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  1. Neural Damage in Experimental Trypanosoma brucei gambiense Infection: Hypothalamic Peptidergic Sleep and Wake-Regulatory Neurons

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    Claudia Laperchia

    2018-02-01

    Full Text Available Neuron populations of the lateral hypothalamus which synthesize the orexin (OX/hypocretin or melanin-concentrating hormone (MCH peptides play crucial, reciprocal roles in regulating wake stability and sleep. The disease human African trypanosomiasis (HAT, also called sleeping sickness, caused by extracellular Trypanosoma brucei (T. b. parasites, leads to characteristic sleep-wake cycle disruption and narcoleptic-like alterations of the sleep structure. Previous studies have revealed damage of OX and MCH neurons during systemic infection of laboratory rodents with the non-human pathogenic T. b. brucei subspecies. No information is available, however, on these peptidergic neurons after systemic infection with T. b. gambiense, the etiological agent of 97% of HAT cases. The present study was aimed at the investigation of immunohistochemically characterized OX and MCH neurons after T. b. gambiense or T. b. brucei infection of a susceptible rodent, the multimammate mouse, Mastomysnatalensis. Cell counts and evaluation of OX fiber density were performed at 4 and 8 weeks post-infection, when parasites had entered the brain parenchyma from the periphery. A significant decrease of OX neurons (about 44% reduction and MCH neurons (about 54% reduction was found in the lateral hypothalamus and perifornical area at 8 weeks in T. b. gambiense-infected M. natalensis. A moderate decrease (21% and 24% reduction, respectively, which did not reach statistical significance, was found after T. b. brucei infection. In two key targets of diencephalic orexinergic innervation, the peri-suprachiasmatic nucleus (SCN region and the thalamic paraventricular nucleus (PVT, densitometric analyses showed a significant progressive decrease in the density of orexinergic fibers in both infection paradigms, and especially during T. b. gambiense infection. Altogether the findings provide novel information showing that OX and MCH neurons are highly vulnerable to chronic

  2. Neural Damage in Experimental Trypanosoma brucei gambiense Infection: The Suprachiasmatic Nucleus

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    Chiara Tesoriero

    2018-02-01

    Full Text Available Trypanosoma brucei (T. b. gambiense is the parasite subspecies responsible for most reported cases of human African trypanosomiasis (HAT or sleeping sickness. This severe infection leads to characteristic disruption of the sleep-wake cycle, recalling attention on the circadian timing system. Most animal models of the disease have been hitherto based on infection of laboratory rodents with the T. b. brucei subspecies, which is not infectious to humans. In these animal models, functional, rather than structural, alterations of the master circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN, have been reported. Information on the SCN after infection with the human pathogenic T. b. gambiense is instead lacking. The present study was aimed at the examination of the SCN after T. b. gambiense infection of a susceptible rodent, the multimammate mouse, Mastomys natalensis, compared with T. b. brucei infection of the same host species. The animals were examined at 4 and 8 weeks post-infection, when parasites (T. b. gambiense or T. b. brucei were detected in the brain parenchyma, indicating that the disease was in the encephalitic stage. Neuron and astrocyte changes were examined with Nissl staining, immunophenotyping and quantitative analyses. Interestingly, significant neuronal loss (about 30% reduction was documented in the SCN during the progression of T. b. gambiense infection. No significant neuronal density changes were found in the SCN of T. b. brucei-infected animals. Neuronal cell counts in the hippocampal dentate gyrus of T. b. gambiense-infected M. natalensis did not point out significant changes, indicating that no widespread neuron loss had occurred in the brain. Marked activation of astrocytes was detected in the SCN after both T. b. gambiense and T. b. brucei infections. Altogether the findings reveal that neurons of the biological clock are highly susceptible to the infection caused by human pathogenic African trypanosomes

  3. Characterization of Trypanosoma brucei gambiense stocks isolated ...

    African Journals Online (AJOL)

    Trypanosoma brucei gambiense was isolated twice from each of 23 patients in Côte d'Ivoire. Genetic characterization using RAPD (Random Primed Amplified Polymorphic DNA) showed additional variability within a given isoenzyme profile (zymodeme), confirming that this fingerprinting method has a higher discriminative ...

  4. Detection of Trypanosoma brucei gambiense and T. b. rhodesiense ...

    African Journals Online (AJOL)

    Detection of Trypanosoma brucei gambiense and T. b. rhodesiense in Glossina fuscipes fuscipes ( Diptera: Glossinidae ) and Stomoxys flies using the polymerase chain reaction (PCR) technique in southern Sudan.

  5. Chimerization at the AQP2–AQP3 locus is the genetic basis of melarsoprol–pentamidine cross-resistance in clinical Trypanosoma brucei gambiense isolates

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    Fabrice E. Graf

    2015-08-01

    Full Text Available Aquaglyceroporin-2 is a known determinant of melarsoprol–pentamidine cross-resistance in Trypanosoma brucei brucei laboratory strains. Recently, chimerization at the AQP2–AQP3 tandem locus was described from melarsoprol–pentamidine cross-resistant Trypanosoma brucei gambiense isolates from sleeping sickness patients in the Democratic Republic of the Congo. Here, we demonstrate that reintroduction of wild-type AQP2 into one of these isolates fully restores drug susceptibility while expression of the chimeric AQP2/3 gene in aqp2–aqp3 null T. b. brucei does not. This proves that AQP2–AQP3 chimerization is the cause of melarsoprol–pentamidine cross-resistance in the T. b. gambiense isolates.

  6. Trypanosoma brucei gambiense: HMI-9 medium containing methylcellulose and human serum supports the continuous axenic in vitro propagation of the bloodstream form.

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    Van Reet, N; Pyana, P P; Deborggraeve, S; Büscher, P; Claes, F

    2011-07-01

    Trypanosoma brucei (T.b.) gambiense causes the chronic form of human African trypanosomiasis or sleeping sickness. One of the major problems with studying T.b. gambiense is the difficulty to isolate it from its original host and the difficult adaptation to in vivo and in vitro mass propagation. The objective of this study was to evaluate if an established method for axenic culture of pleomorphic bloodstream form T.b. brucei strains, based on methylcellulose containing HMI-9 medium, also facilitated the continuous in vitro propagation of other bloodstream form Trypanozoon strains, in particular of T.b. gambiense. Bloodstream form trypanosomes from one T.b. brucei, two T.b. rhodesiense, one T. evansi and seven T.b. gambiense strains were isolated from mouse blood and each was concurrently cultivated in liquid and methylcellulose-containing HMI-9 based medium, either with or without additional human serum supplementation, for over 10 consecutive sub passages. Although HMI-9 based medium supplemented with 1.1% (w/v) methylcellulose supported the continuous cultivation of all non-gambiense strains better than liquid media could, the in vitro cultivation of all gambiense strains was only achieved in HMI-9 based medium containing 1.1% (w/v) methylcellulose, 15% (v/v) fetal calf serum and 5% (v/v) heat-inactivated human serum. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Isolation of Trypanosoma brucei gambiense from cured and relapsed sleeping sickness patients and adaptation to laboratory mice.

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    Patient Pati Pyana

    Full Text Available BACKGROUND: Sleeping sickness due to Trypanosoma brucei (T.b. gambiense is still a major public health problem in some central African countries. Historically, relapse rates around 5% have been observed for treatment with melarsoprol, widely used to treat second stage patients. Later, relapse rates of up to 50% have been recorded in some isolated foci in Angola, Sudan, Uganda and Democratic Republic of the Congo (DRC. Previous investigations are not conclusive on whether decreased sensitivity to melarsoprol is responsible for these high relapse rates. Therefore we aimed to establish a parasite collection isolated from cured as well as from relapsed patients for downstream comparative drug sensitivity profiling. A major constraint for this type of investigation is that T.b. gambiense is particularly difficult to isolate and adapt to classical laboratory rodents. METHODOLOGY/PRINCIPAL FINDINGS: From 360 patients treated in Dipumba hospital, Mbuji-Mayi, D.R. Congo, blood and cerebrospinal fluid (CSF was collected before treatment. From patients relapsing during the 24 months follow-up, the same specimens were collected. Specimens with confirmed parasite presence were frozen in liquid nitrogen in a mixture of Triladyl, egg yolk and phosphate buffered glucose solution. Isolation was achieved by inoculation of the cryopreserved specimens in Grammomys surdaster, Mastomys natalensis and SCID mice. Thus, 85 strains were isolated from blood and CSF of 55 patients. Isolation success was highest in Grammomys surdaster. Forty strains were adapted to mice. From 12 patients, matched strains were isolated before treatment and after relapse. All strains belong to T.b. gambiense type I. CONCLUSIONS AND SIGNIFICANCE: We established a unique collection of T.b. gambiense from cured and relapsed patients, isolated in the same disease focus and within a limited period. This collection is available for genotypic and phenotypic characterisation to investigate the

  8. Melarsoprol sensitivity profile of Trypanosoma brucei gambiense isolates from cured and relapsed sleeping sickness patients from the Democratic Republic of the Congo.

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    Patient Pyana Pati

    2014-10-01

    Full Text Available Sleeping sickness caused by Trypanosoma brucei (T.b. gambiense constitutes a serious health problem in sub-Sahara Africa. In some foci, alarmingly high relapse rates were observed in patients treated with melarsoprol, which used to be the first line treatment for patients in the neurological disease stage. Particularly problematic was the situation in Mbuji-Mayi, East Kasai Province in the Democratic Republic of the Congo with a 57% relapse rate compared to a 5% relapse rate in Masi-Manimba, Bandundu Province. The present study aimed at investigating the mechanisms underlying the high relapse rate in Mbuji-Mayi using an extended collection of recently isolated T.b. gambiense strains from Mbuji-Mayi and from Masi-Manimba.Forty five T.b. gambiense strains were used. Forty one were isolated from patients that were cured or relapsed after melarsoprol treatment in Mbuji-Mayi. In vivo drug sensitivity tests provide evidence of reduced melarsoprol sensitivity in these strains. This reduced melarsoprol sensitivity was not attributable to mutations in TbAT1. However, in all these strains, irrespective of the patient treatment outcome, the two aquaglyceroporin (AQP 2 and 3 genes are replaced by chimeric AQP2/3 genes that may be associated with resistance to pentamidine and melarsoprol. The 4 T.b. gambiense strains isolated in Masi-Manimba contain both wild-type AQP2 and a different chimeric AQP2/3. These findings suggest that the reduced in vivo melarsoprol sensitivity of the Mbuji-Mayi strains and the high relapse rates in that sleeping sickness focus are caused by mutations in the AQP2/AQP3 locus and not by mutations in TbAT1.We conclude that mutations in the TbAQP2/3 locus of the local T.b. gambiense strains may explain the high melarsoprol relapse rates in the Mbuji-Mayi focus but other factors must also be involved in the treatment outcome of individual patients.

  9. Molecular Evidence of a Trypanosoma brucei gambiense Sylvatic Cycle in the Human African Trypanosomiasis Foci of Equatorial Guinea

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    Carlos eCordon-Obras

    2015-07-01

    Full Text Available Gambiense trypanosomiasis is considered an anthroponotic disease. Consequently, control programs are generally aimed at stopping transmission of Trypanosoma brucei gambiense (T. b. gambiense by detecting and treating human cases. However, the persistence of numerous foci despite efforts to eliminate this disease questions this strategy as unique tool to pursue the eradication. The role of animals as a reservoir of T. b. gambiense is still controversial, but could partly explain maintenance of the infection at hypo-endemic levels. In the present study, we evaluated the presence of T. b. gambiense in wild animals in Equatorial Guinea. The infection rate ranged from 0.8% in the insular focus of Luba to more than 12% in Mbini, a focus with a constant trickle of human cases. The parasite was detected in a wide range of animal species including four species never described previously as putative reservoirs. Our study comes to reinforce the hypothesis that animals may play a role in the persistence of T. b. gambiense transmission, being particularly relevant in low transmission settings. Under these conditions the integration of sustained vector control and medical interventions should be considered to achieve the elimination of Gambiense trypanosomiasis.

  10. Trypanosoma brucei gambiense trypanosomiasis in Terego county, northern Uganda, 1996: a lot quality assurance sampling survey.

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    Hutin, Yvan J F; Legros, Dominique; Owini, Vincent; Brown, Vincent; Lee, Evan; Mbulamberi, Dawson; Paquet, Christophe

    2004-04-01

    We estimated the pre-intervention prevalence of Trypanosoma brucei gambiense (Tbg) trypanosomiasis using the lot quality assurance sampling (LQAS) methods in 14 parishes of Terego County in northern Uganda. A total of 826 participants were included in the survey sample in 1996. The prevalence of laboratory confirmed Tbg trypanosomiasis adjusted for parish population sizes was 2.2% (95% confidence interval =1.1-3.2). This estimate was consistent with the 1.1% period prevalence calculated on the basis of cases identified through passive and active screening in 1996-1999. Ranking of parishes in four categories according to LQAS analysis of the 1996 survey predicted the prevalences observed during the first round of active screening in the population in 1997-1998 (P LQAS were validated by the results of the population screening, suggesting that these survey methods may be useful in the pre-intervention phase of sleeping sickness control programs.

  11. Diversity and spation distribution of vectors and hosts of T. brucei gambiense in forest zones of Southern Cameroon: Epidemiological implications

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    Massussi, J.A.; Mbida Mbida, J.A.; Djieto-Lordon, C.; Njiokou, F.; Laveissière, C.; Ploeg, van der J.D.

    2010-01-01

    Host and vector distribution of Trypanosoma brucei gambiense was studied in relation to habitat types and seasons. Six (19.35%) of the 31 mammal species recorded in Bipindi were reservoir hosts. Cercopithecus nictitans was confined to the undisturbed forest and the low intensive shifting cultivation

  12. Comparative Genomics of Glossina palpalis gambiensis and G. morsitans morsitans to Reveal Gene Orthologs Involved in Infection by Trypanosoma brucei gambiense.

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    Hamidou Soumana, Illiassou; Tchicaya, Bernadette; Rialle, Stéphanie; Parrinello, Hugues; Geiger, Anne

    2017-01-01

    Blood-feeding Glossina palpalis gambiense (Gpg) fly transmits the single-celled eukaryotic parasite Trypanosoma brucei gambiense (Tbg), the second Glossina fly African trypanosome pair being Glossina morsitans / T .brucei rhodesiense. Whatever the T. brucei subspecies, whereas the onset of their developmental program in the zoo-anthropophilic blood feeding flies does unfold in the fly midgut, its completion is taking place in the fly salivary gland where does emerge a low size metacyclic trypomastigote population displaying features that account for its establishment in mammals-human individuals included. Considering that the two Glossina - T. brucei pairs introduced above share similarity with respect to the developmental program of this African parasite, we were curious to map on the Glossina morsitans morsitans (Gmm), the Differentially Expressed Genes (DEGs) we listed in a previous study. Briefly, using the gut samples collected at days 3, 10, and 20 from Gpg that were fed or not at day 0 on Tbg-hosting mice, these DGE lists were obtained from RNA seq-based approaches. Here, post the mapping on the quality controlled DEGs on the Gmm genome, the identified ortholog genes were further annotated, the resulting datasets being compared. Around 50% of the Gpg DEGs were shown to have orthologs in the Gmm genome. Under one of the three Glossina midgut sampling conditions, the number of DEGs was even higher when mapping on the Gmm genome than initially recorded. Many Gmm genes annotated as "Hypothetical" were mapped and annotated on many distinct databases allowing some of them to be properly identified. We identify Glossina fly candidate genes encoding (a) a broad panel of proteases as well as (b) chitin-binding proteins, (c) antimicrobial peptide production-Pro3 protein, transferrin, mucin, atttacin, cecropin, etc-to further select in functional studies, the objectives being to probe and validated fly genome manipulation that prevents the onset of the developmental

  13. Trypanosoma brucei gambiense group 1 is distinguished by a unique amino acid substitution in the HpHb receptor implicated in human serum resistance.

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    Rebecca E Symula

    Full Text Available Trypanosoma brucei rhodesiense (Tbr and T. b. gambiense (Tbg, causative agents of Human African Trypanosomiasis (sleeping sickness in Africa, have evolved alternative mechanisms of resisting the activity of trypanosome lytic factors (TLFs, components of innate immunity in human serum that protect against infection by other African trypanosomes. In Tbr, lytic activity is suppressed by the Tbr-specific serum-resistance associated (SRA protein. The mechanism in Tbg is less well understood but has been hypothesized to involve altered activity and expression of haptoglobin haemoglobin receptor (HpHbR. HpHbR has been shown to facilitate internalization of TLF-1 in T.b. brucei (Tbb, a member of the T. brucei species complex that is susceptible to human serum. By evaluating the genetic variability of HpHbR in a comprehensive geographical and taxonomic context, we show that a single substitution that replaces leucine with serine at position 210 is conserved in the most widespread form of Tbg (Tbg group 1 and not found in related taxa, which are either human serum susceptible (Tbb or known to resist lysis via an alternative mechanism (Tbr and Tbg group 2. We hypothesize that this single substitution contributes to reduced uptake of TLF and thus may play a key role in conferring serum resistance to Tbg group 1. In contrast, similarity in HpHbR sequence among isolates of Tbg group 2 and Tbb/Tbr provides further evidence that human serum resistance in Tbg group 2 is likely independent of HpHbR function.

  14. Trypanosoma brucei gambiense adaptation to different mammalian sera is associated with VSG expression site plasticity.

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    Cordon-Obras, Carlos; Cano, Jorge; González-Pacanowska, Dolores; Benito, Agustin; Navarro, Miguel; Bart, Jean-Mathieu

    2013-01-01

    Trypanosoma brucei gambiense infection is widely considered an anthroponosis, although it has also been found in wild and domestic animals. Thus, fauna could act as reservoir, constraining the elimination of the parasite in hypo-endemic foci. To better understand the possible maintenance of T. b. gambiense in local fauna and investigate the molecular mechanisms underlying adaptation, we generated adapted cells lines (ACLs) by in vitro culture of the parasites in different mammalian sera. Using specific antibodies against the Variant Surface Glycoproteins (VSGs) we found that serum ACLs exhibited different VSG variants when maintained in pig, goat or human sera. Although newly detected VSGs were independent of the sera used, the consistent appearance of different VSGs suggested remodelling of the co-transcribed genes at the telomeric Expression Site (VSG-ES). Thus, Expression Site Associated Genes (ESAGs) sequences were analysed to investigate possible polymorphism selection. ESAGs 6 and 7 genotypes, encoding the transferrin receptor (TfR), expressed in different ACLs were characterised. In addition, we quantified the ESAG6/7 mRNA levels and analysed transferrin (Tf) uptake. Interestingly, the best growth occurred in pig and human serum ACLs, which consistently exhibited a predominant ESAG7 genotype and higher Tf uptake than those obtained in calf and goat sera. We also detected an apparent selection of specific ESAG3 genotypes in the pig and human serum ACLs, suggesting that other ESAGs could be involved in the host adaptation processes. Altogether, these results suggest a model whereby VSG-ES remodelling allows the parasite to express a specific set of ESAGs to provide selective advantages in different hosts. Finally, pig serum ACLs display phenotypic adaptation parameters closely related to human serum ACLs but distinct to parasites grown in calf and goat sera. These results suggest a better suitability of swine to maintain T. b. gambiense infection supporting

  15. Gambiense Sleeping Sickness In The Abraka Region Of Delta State ...

    African Journals Online (AJOL)

    Gambiense Sleeping Sickness In The Abraka Region Of Delta State, Nigeria: Passive Case Detection (Pcd) At The Baptist Medical Centre (BMC) Eku 1999 – 2004. ... The highest prevalence of infection was among patients aged between 26-35 years with 35.6% infection rate, 23.3 percent was recorded among those aged ...

  16. Genotypic status of the TbAT1/P2 adenosine transporter of Trypanosoma brucei gambiense isolates from Northwestern Uganda following melarsoprol withdrawal.

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    Anne J N Kazibwe

    Full Text Available BACKGROUND: The development of arsenical and diamidine resistance in Trypanosoma brucei is associated with loss of drug uptake by the P2 purine transporter as a result of alterations in the corresponding T. brucei adenosine transporter 1 gene (TbAT1. Previously, specific TbAT1 mutant type alleles linked to melarsoprol treatment failure were significantly more prevalent in T. b. gambiense from relapse patients at Omugo health centre in Arua district. Relapse rates of up to 30% prompted a shift from melarsoprol to eflornithine (alpha-difluoromethylornithine, DFMO as first-line treatment at this centre. The aim of this study was to determine the status of TbAT1 in recent isolates collected from T. b. gambiense sleeping sickness patients from Arua and Moyo districts in Northwestern Uganda after this shift in first-line drug choice. METHODOLOGY AND RESULTS: Blood and cerebrospinal fluids of consenting patients were collected for DNA preparation and subsequent amplification. All of the 105 isolates from Omugo that we successfully analysed by PCR-RFLP possessed the TbAT1 wild type allele. In addition, PCR/RFLP analysis was performed for 74 samples from Moyo, where melarsoprol is still the first line drug; 61 samples displayed the wild genotype while six were mutant and seven had a mixed pattern of both mutant and wild-type TbAT1. The melarsoprol treatment failure rate at Moyo over the same period was nine out of 101 stage II cases that were followed up at least once. Five of the relapse cases harboured mutant TbAT1, one had the wild type, while no amplification was achieved from the remaining three samples. CONCLUSIONS/SIGNIFICANCE: The apparent disappearance of mutant alleles at Omugo may correlate with melarsoprol withdrawal as first-line treatment. Our results suggest that melarsoprol could successfully be reintroduced following a time lag subsequent to its replacement. A field-applicable test to predict melarsoprol treatment outcome and identify

  17. Characterization of recombinant Trypanosoma brucei gambiense Translationally Controlled Tumor Protein (rTbgTCTP) and its interaction with Glossina midgut bacteria.

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    Bossard, Géraldine; Bartoli, Manon; Fardeau, Marie-Laure; Holzmuller, Philippe; Ollivier, Bernard; Geiger, Anne

    2017-09-03

    In humans, sleeping sickness (i.e. Human African Trypanosomiasis) is caused by the protozoan parasites Trypanosoma brucei gambiense (Tbg) in West and Central Africa, and T. b. rhodesiense in East Africa. We previously showed in vitro that Tbg is able to excrete/secrete a large number of proteins, including Translationally Controlled Tumor Protein (TCTP). Moreover, the tctp gene was described previously to be expressed in Tbg-infected flies. Aside from its involvement in diverse cellular processes, we have investigated a possible alternative role within the interactions occurring between the trypanosome parasite, its tsetse fly vector, and the associated midgut bacteria. In this context, the Tbg tctp gene was synthesized and cloned into the baculovirus vector pAcGHLT-A, and the corresponding protein was produced using the baculovirus Spodoptera frugicola (strain 9) / insect cell system. The purified recombinant protein rTbgTCTP was incubated together with bacteria isolated from the gut of tsetse flies, and was shown to bind to 24 out of the 39 tested bacteria strains belonging to several genera. Furthermore, it was shown to affect the growth of the majority of these bacteria, especially when cultivated under microaerobiosis and anaerobiosis. Finally, we discuss the potential for TCTP to modulate the fly microbiome composition toward favoring trypanosome survival.

  18. Overproduction, purification, crystallization and preliminary X-ray diffraction analysis of Trypanosoma brucei gambiense glycerol kinase

    International Nuclear Information System (INIS)

    Balogun, Emmanuel Oluwadare; Inaoka, Daniel Ken; Kido, Yasutoshi; Shiba, Tomoo; Nara, Takeshi; Aoki, Takashi; Honma, Teruki; Tanaka, Akiko; Inoue, Masayuki; Matsuoka, Shigeru; Michels, Paul A. M.; Harada, Shigeharu; Kita, Kiyoshi

    2010-01-01

    Glycerol kinase from human African trypanosomes has been purified and crystallized for X-ray structure analysis. In the bloodstream forms of human trypanosomes, glycerol kinase (GK; EC 2.7.1.30) is one of the nine glycosomally compartmentalized enzymes that are essential for energy metabolism. In this study, a recombinant Trypanosoma brucei gambiense GK (rTbgGK) with an N-terminal cleavable His 6 tag was overexpressed, purified to homogeneity and crystallized by the sitting-drop vapour-diffusion method using PEG 400 as a precipitant. A complete X-ray diffraction data set to 2.75 Å resolution indicated that the crystals belonged to the orthorhombic space group P2 1 2 1 2 1 , with unit-cell parameters a = 63.84, b = 121.50, c = 154.59 Å. The presence of two rTbgGK molecules in the asymmetric unit gives a Matthews coefficient (V M ) of 2.5 Å 3 Da −1 , corresponding to 50% solvent content

  19. Human and animal Trypanosomes in Côte d'Ivoire form a single breeding population.

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    Paul Capewell

    Full Text Available Trypanosoma brucei is the causative agent of African Sleeping Sickness in humans and contributes to the related veterinary disease, Nagana. T. brucei is segregated into three subspecies based on host specificity, geography and pathology. T. b. brucei is limited to animals (excluding some primates throughout sub-Saharan Africa and is non-infective to humans due to trypanolytic factors found in human serum. T. b. gambiense and T. b. rhodesiense are human infective sub-species. T. b. gambiense is the more prevalent human, causing over 97% of human cases. Study of T. b. gambiense is complicated in that there are two distinct groups delineated by genetics and phenotype. The relationships between the two groups and local T. b. brucei are unclear and may have a bearing on the evolution of the human infectivity traits.A collection of sympatric T. brucei isolates from Côte d'Ivoire, consisting of T. b. brucei and both groups of T. b. gambiense have previously been categorized by isoenzymes, RFLPs and Blood Incubation Infectivity Tests. These samples were further characterized using the group 1 specific marker, TgSGP, and seven microsatellites. The relationships between the T. b. brucei and T. b. gambiense isolates were determined using principal components analysis, neighbor-joining phylogenetics, STRUCTURE, FST, Hardy-Weinberg equilibrium and linkage disequilibrium.Group 1 T. b. gambiense form a clonal genetic group, distinct from group 2 and T. b. brucei, whereas group 2 T. b. gambiense are genetically indistinguishable from local T. b. brucei. There is strong evidence for mating within and between group 2 T. b. gambiense and T. b. brucei. We found no evidence to support the hypothesis that group 2 T. b. gambiense are hybrids of group 1 and T. b. brucei, suggesting that human infectivity has evolved independently in groups 1 and 2 T. b. gambiense.

  20. SHORT COMMUNICATION

    African Journals Online (AJOL)

    2007-05-02

    May 2, 2007 ... caused by morphologically indistinguishable subspecies of Trypanosoma brucei. The two forms are West African sleeping sickness, caused by. T. brucei gambiense and East African sleeping sickness, caused by T. brucei rhodesiense. In Tanzania HAT is one of the major public health problems and was ...

  1. Wild chimpanzees are infected by Trypanosoma brucei

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    Milan Jirků

    2015-12-01

    Finally, we demonstrated that the mandrill serum was able to efficiently lyse T. b. brucei and T. b. rhodesiense, and to some extent T. b. gambiense, while the chimpanzee serum failed to lyse any of these subspecies.

  2. RNA-seq de novo Assembly Reveals Differential Gene Expression in Glossina palpalis gambiensis Infected with Trypanosoma brucei gambiense vs. Non-Infected and Self-Cured Flies.

    Science.gov (United States)

    Hamidou Soumana, Illiassou; Klopp, Christophe; Ravel, Sophie; Nabihoudine, Ibouniyamine; Tchicaya, Bernadette; Parrinello, Hugues; Abate, Luc; Rialle, Stéphanie; Geiger, Anne

    2015-01-01

    Trypanosoma brucei gambiense (Tbg), causing the sleeping sickness chronic form, completes its developmental cycle within the tsetse fly vector Glossina palpalis gambiensis (Gpg) before its transmission to humans. Within the framework of an anti-vector disease control strategy, a global gene expression profiling of trypanosome infected (susceptible), non-infected, and self-cured (refractory) tsetse flies was performed, on their midguts, to determine differential genes expression resulting from in vivo trypanosomes, tsetse flies (and their microbiome) interactions. An RNAseq de novo assembly was achieved. The assembled transcripts were mapped to reference sequences for functional annotation. Twenty-four percent of the 16,936 contigs could not be annotated, possibly representing untranslated mRNA regions, or Gpg- or Tbg-specific ORFs. The remaining contigs were classified into 65 functional groups. Only a few transposable elements were present in the Gpg midgut transcriptome, which may represent active transpositions and play regulatory roles. One thousand three hundred and seventy three genes differentially expressed (DEGs) between stimulated and non-stimulated flies were identified at day-3 post-feeding; 52 and 1025 between infected and self-cured flies at 10 and 20 days post-feeding, respectively. The possible roles of several DEGs regarding fly susceptibility and refractoriness are discussed. The results provide new means to decipher fly infection mechanisms, crucial to develop anti-vector control strategies.

  3. Clinical Presentation and Treatment Outcome of Sleeping Sickness in Sudanese Pre-School Children.

    OpenAIRE

    Eperon, G; Schmid, C; Loutan, L; Chappuis, F

    2007-01-01

    BACKGROUND: Existing data on human African trypanosomiasis (HAT) due to Trypanosoma brucei gambiense among children are limited. Here, we described the demographic, clinical, diagnostic, treatment and outcome characteristics of HAT in pre-school children from Kajo-Keji County, South Sudan in comparison with older patients. METHODS: We did a retrospective analysis of HAT patients treated at the Kiri Sleeping Sickness Treatment Centre (SSTC), Kajo-Keji County, from June 2000 to December 2002. R...

  4. The miRNA and mRNA Signatures of Peripheral Blood Cells in Humans Infected with Trypanosoma brucei gambiense.

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    Smiths Lueong

    Full Text Available Simple, reliable tools for diagnosis of human African Trypanosomiases could ease field surveillance and enhance patient care. In particular, current methods to distinguish patients with (stage II and without (stage I brain involvement require samples of cerebrospinal fluid. We describe here an exploratory study to find out whether miRNAs from peripheral blood leukocytes might be useful in diagnosis of human trypanosomiasis, or for determining the stage of the disease. Using microarrays, we measured miRNAs in samples from Trypanosoma brucei gambiense-infected patients (9 stage I, 10 stage II, 8 seronegative parasite-negative controls and 12 seropositive, but parasite-negative subjects. 8 miRNAs (out of 1205 tested showed significantly lower expression in patients than in seronegative, parasite-negative controls, and 1 showed increased expression. There were no clear differences in miRNAs between patients in different disease stages. The miRNA profiles could not distinguish seropositive, but parasitologically negative samples from controls and results within this group did not correlate with those from the trypanolysis test. Some of the regulated miRNAs, or their predicted mRNA targets, were previously reported changed during other infectious diseases or cancer. We conclude that the changes in miRNA profiles of peripheral blood lymphocytes in human African trypanosomiasis are related to immune activation or inflammation, are probably disease-non-specific, and cannot be used to determine the disease stage. The approach has little promise for diagnostics but might yield information about disease pathology.

  5. Identification of different trypanosome species in the mid-guts of tsetse flies of the Malanga (Kimpese sleeping sickness focus of the Democratic Republic of Congo

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    Simo Gustave

    2012-09-01

    Full Text Available Abstract Background The Malanga sleeping sickness focus of the Democratic Republic of Congo has shown an epidemic evolution of disease during the last century. However, following case detection and treatment, the prevalence of the disease decreased considerably. No active survey has been undertaken in this focus for a couple of years. To understand the current epidemiological status of sleeping sickness as well as the animal African trypanosomiasis in the Malanga focus, we undertook the identification of tsetse blood meals as well as different trypanosome species in flies trapped in this focus. Methods Pyramidal traps were use to trap tsetse flies. All flies caught were identified and live flies were dissected and their mid-guts collected. Fly mid-gut was used for the molecular identification of the blood meal source, as well as for the presence of different trypanosome species. Results About 949 Glossina palpalis palpalis were trapped; 296 (31.2% of which were dissected, 60 (20.3% blood meals collected and 57 (19.3% trypanosome infections identified. The infection rates were 13.4%, 5.1%, 3.5% and 0.4% for Trypanosoma congolense savannah type, Trypanosoma brucei s.l., Trypanosoma congolense forest type and Trypanosoma vivax, respectively. Three mixed infections including Trypanosoma brucei s.l. and Trypanosoma congolense savannah type, and one mixed infection of Trypanosoma vivax and Trypanosoma congolense savannah type were identified. Eleven Trypanosoma brucei gambiense infections were identified; indicating an active circulation of this trypanosome subspecies. Of all the identified blood meals, about 58.3% were identified as being taken on pigs, while 33.3% and 8.3% were from man and other mammals, respectively. Conclusion The presence of Trypanosoma brucei in tsetse mid-guts associated with human blood meals is indicative of an active transmission of this parasite between tsetse and man. The considerable number of pig blood meals combined

  6. Identification of compounds with anti-proliferative activity against Trypanosoma brucei brucei strain 427 by a whole cell viability based HTS campaign.

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    Melissa L Sykes

    Full Text Available Human African Trypanosomiasis (HAT is caused by two trypanosome sub-species, Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense. Drugs available for the treatment of HAT have significant issues related to difficult administration regimes and limited efficacy across species and disease stages. Hence, there is considerable need to find new alternative and less toxic drugs. An approach to identify starting points for new drug candidates is high throughput screening (HTS of large compound library collections. We describe the application of an Alamar Blue based, 384-well HTS assay to screen a library of 87,296 compounds against the related trypanosome subspecies, Trypanosoma brucei brucei bloodstream form lister 427. Primary hits identified against T.b. brucei were retested and the IC(50 value compounds were estimated for T.b. brucei and a mammalian cell line HEK293, to determine a selectivity index for each compound. The screening campaign identified 205 compounds with greater than 10 times selectivity against T.b. brucei. Cluster analysis of these compounds, taking into account chemical and structural properties required for drug-like compounds, afforded a panel of eight compounds for further biological analysis. These compounds had IC(50 values ranging from 0.22 µM to 4 µM with associated selectivity indices ranging from 19 to greater than 345. Further testing against T.b. rhodesiense led to the selection of 6 compounds from 5 new chemical classes with activity against the causative species of HAT, which can be considered potential candidates for HAT early drug discovery. Structure activity relationship (SAR mining revealed components of those hit compound structures that may be important for biological activity. Four of these compounds have undergone further testing to 1 determine whether they are cidal or static in vitro at the minimum inhibitory concentration (MIC, and 2 estimate the time to kill.

  7. Epidemiology of human African trypanosomiasis

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    Franco JR

    2014-08-01

    Full Text Available Jose R Franco,1 Pere P Simarro,1 Abdoulaye Diarra,2 Jean G Jannin1 1World Health Organization, Control of Neglected Tropical Diseases, Innovative and Intensified Disease Management, Geneva, Switzerland; 2World Health Organization, Inter Country Support Team for Central Africa, Regional Office for Africa, Libreville, Gabon Abstract: Human African trypanosomiasis (HAT, or sleeping sickness, is caused by Trypanosoma brucei gambiense, which is a chronic form of the disease present in western and central Africa, and by Trypanosoma brucei rhodesiense, which is an acute disease located in eastern and southern Africa. The rhodesiense form is a zoonosis, with the occasional infection of humans, but in the gambiense form, the human being is regarded as the main reservoir that plays a key role in the transmission cycle of the disease. The gambiense form currently assumes that 98% of the cases are declared; the Democratic Republic of the Congo is the most affected country, with more than 75% of the gambiense cases declared. The epidemiology of the disease is mediated by the interaction of the parasite (trypanosome with the vectors (tsetse flies, as well as with the human and animal hosts within a particular environment. Related to these interactions, the disease is confined in spatially limited areas called “foci”, which are located in Sub-Saharan Africa, mainly in remote rural areas. The risk of contracting HAT is, therefore, determined by the possibility of contact of a human being with an infected tsetse fly. Epidemics of HAT were described at the beginning of the 20th century; intensive activities have been set up to confront the disease, and it was under control in the 1960s, with fewer than 5,000 cases reported in the whole continent. The disease resurged at the end of the 1990s, but renewed efforts from endemic countries, cooperation agencies, and nongovernmental organizations led by the World Health Organization succeeded to raise awareness and

  8. Sleep and rhythm changes at the time of Trypanosoma brucei invasion of the brain parenchyma in the rat.

    Science.gov (United States)

    Seke Etet, Paul F; Palomba, Maria; Colavito, Valeria; Grassi-Zucconi, Gigliola; Bentivoglio, Marina; Bertini, Giuseppe

    2012-05-01

    Human African trypanosomiasis (HAT), or sleeping sickness, is a severe disease caused by Trypanosoma brucei (T.b.). The disease hallmark is sleep alterations. Brain involvement in HAT is a crucial pathogenetic step for disease diagnosis and therapy. In this study, a rat model of African trypanosomiasis was used to assess changes of sleep-wake, rest-activity, and body temperature rhythms in the time window previously shown as crucial for brain parenchyma invasion by T.b. to determine potential biomarkers of this event. Chronic radiotelemetric monitoring in Sprague-Dawley rats was used to continuously record electroencephalogram, electromyogram, rest-activity, and body temperature in the same animals before (baseline recording) and after infection. Rats were infected with T.b. brucei. Data were acquired from 1 to 20 d after infection (parasite neuroinvasion initiates at 11-13 d post-infection in this model), and were compared to baseline values. Sleep parameters were manually scored from electroencephalographic-electromyographic tracings. Circadian rhythms of sleep time, slow-wave activity, rest-activity, and body temperature were studied using cosinor rhythmometry. Results revealed alterations of most of the analyzed parameters. In particular, sleep pattern and sleep-wake organization plus rest-activity and body temperature rhythms exhibited early quantitative and qualitative alterations, which became marked around the time interval crucial for parasite neuroinvasion or shortly after. Data derived from actigrams showed close correspondence with those from hypnograms, suggesting that rest-activity could be useful to monitor sleep-wake alterations in African trypanosomiasis.

  9. Accuracy of individual rapid tests for serodiagnosis of gambiense sleeping sickness in West Africa.

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    Vincent Jamonneau

    2015-02-01

    Full Text Available Individual rapid tests for serodiagnosis (RDT of human African trypanosomiasis (HAT are particularly suited for passive screening and surveillance. However, so far, no large scale evaluation of RDTs has been performed for diagnosis of Trypanosoma brucei gambiense HAT in West Africa. The objective of this study was to assess the diagnostic accuracy of 2 commercial HAT-RDTs on stored plasma samples from West Africa.SD Bioline HAT and HAT Sero-K-Set were performed on 722 plasma samples originating from Guinea and Côte d'Ivoire, including 231 parasitologically confirmed HAT patients, 257 healthy controls, and 234 unconfirmed individuals whose blood tested antibody positive in the card agglutination test but negative by parasitological tests. Immune trypanolysis was performed as a reference test for trypanosome specific antibody presence. Sensitivities in HAT patients were respectively 99.6% for SD Bioline HAT, and 99.1% for HAT Sero-K-Set, specificities in healthy controls were respectively 87.9% and 88.3%. Considering combined positivity in both RDTs, increased the specificity significantly (p ≤ 0.0003 to 93.4%, while 98.7% sensitivity was maintained. Specificities in controls were 98.7-99.6% for the combination of one or two RDTs with trypanolysis, maintaining a sensitivity of at least 98.1%.The observed specificity of the single RDTs was relatively low. Serial application of SD Bioline HAT and HAT Sero-K-Set might offer superior specificity compared to a single RDT, maintaining high sensitivity. The combination of one or two RDTs with trypanolysis seems promising for HAT surveillance.

  10. Excreted/Secreted Proteins from Trypanosome Procyclic Strains

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    Celestine Michelle Atyame Nten

    2010-01-01

    Full Text Available Trypanosoma secretome was shown to be involved in parasite virulence and is suspected of interfering in parasite life-cycle steps such as establishment in the Glossina midgut, metacyclogenesis. Therefore, we attempted to identify the proteins secreted by procyclic strains of T. brucei gambiense and T. brucei brucei, responsible for human and animal trypanosomiasis, respectively. Using mass spectrometry, 427 and 483 nonredundant proteins were characterized in T. brucei brucei and T. brucei gambiense secretomes, respectively; 35% and 42% of the corresponding secretome proteins were specifically secreted by T. brucei brucei and T. brucei gambiense, respectively, while 279 proteins were common to both subspecies. The proteins were assigned to 12 functional classes. Special attention was paid to the most abundant proteases (14 families because of their potential implication in the infection process and nutrient supply. The presence of proteins usually secreted via an exosome pathway suggests that this type of process is involved in trypanosome ESP secretion. The overall results provide leads for further research to develop novel tools for blocking trypanosome transmission.

  11. Identification of trypanosomes in wild animals from Southern Cameroon using the polymerase chain reaction (PCR

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    Herder S.

    2002-12-01

    Full Text Available One possible explanation of the maintenance of many historical foci of sleeping sickness in Central Africa could be the existence of a wild animal reservoir. In this study, PCR was used to detect the different trypanosome species present in wild animal captured by hunters in the southern forest belt of Cameroon (Bipindi. Trypanosomes were also detected by a parasitological method (Quantitative buffy coat : QBC. Parasite could not be isolated in culture medium (Kit for in vitro isolation : KIVI. Specific primers of T. brucei s.l., T. congolense forest type, T. congolense savannah type, T. vivax, T. simiae and T. b. gambiense group 1 were used to identify parasites in the blood of 164 animals belonging to 24 different species including ungulates, rodents, pangolins, carnivores, reptiles and primates. Of the 24 studied species, eight were carrying T. b. gambiense group 1. Those parasites pathogenic to man were found in monkeys (Cercocebus torquatus and Cercopithecus nictitans, in ungulates (Cephalophus dorsalis and C. monticola, in carnivores (Nandinia binotata and Genetta servalina and in rodents (Cricetomys gambianus and Atherurus africanus. 13 species (54 % were carrying T. brucei s.l. identified as non-gambiense group 1.

  12. Targeting the HSP60/10 chaperonin systems of Trypanosoma brucei as a strategy for treating African sleeping sickness.

    Science.gov (United States)

    Abdeen, Sanofar; Salim, Nilshad; Mammadova, Najiba; Summers, Corey M; Goldsmith-Pestana, Karen; McMahon-Pratt, Diane; Schultz, Peter G; Horwich, Arthur L; Chapman, Eli; Johnson, Steven M

    2016-11-01

    Trypanosoma brucei are protozoan parasites that cause African sleeping sickness in humans (also known as Human African Trypanosomiasis-HAT). Without treatment, T. brucei infections are fatal. There is an urgent need for new therapeutic strategies as current drugs are toxic, have complex treatment regimens, and are becoming less effective owing to rising antibiotic resistance in parasites. We hypothesize that targeting the HSP60/10 chaperonin systems in T. brucei is a viable anti-trypanosomal strategy as parasites rely on these stress response elements for their development and survival. We recently discovered several hundred inhibitors of the prototypical HSP60/10 chaperonin system from Escherichia coli, termed GroEL/ES. One of the most potent GroEL/ES inhibitors we discovered was compound 1. While examining the PubChem database, we found that a related analog, 2e-p, exhibited cytotoxicity to Leishmania major promastigotes, which are trypanosomatids highly related to Trypanosoma brucei. Through initial counter-screening, we found that compounds 1 and 2e-p were also cytotoxic to Trypanosoma brucei parasites (EC 50 =7.9 and 3.1μM, respectively). These encouraging initial results prompted us to develop a library of inhibitor analogs and examine their anti-parasitic potential in vitro. Of the 49 new chaperonin inhibitors developed, 39% exhibit greater cytotoxicity to T. brucei parasites than parent compound 1. While many analogs exhibit moderate cytotoxicity to human liver and kidney cells, we identified molecular substructures to pursue for further medicinal chemistry optimization to increase the therapeutic windows of this novel class of chaperonin-targeting anti-parasitic candidates. An intriguing finding from this study is that suramin, the first-line drug for treating early stage T. brucei infections, is also a potent inhibitor of GroEL/ES and HSP60/10 chaperonin systems. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Active transmission of Trypanosoma brucei gambiense Dutton, 1902 ...

    African Journals Online (AJOL)

    Thereafter, palpation for enlarged cervical lymph gland (ECLG) was followed by parasitological examination of aspirate using wet film, haematocrit centrifugation technique (HCT) and mini-anion exchange centrifugation technique (mAECT). Only one confirmed case of sleeping sickness was diagnosed out of the 491 ...

  14. Trypanosoma brucei Invasion and T-Cell Infiltration of the Brain Parenchyma in Experimental Sleeping Sickness: Timing and Correlation with Functional Changes.

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    Claudia Laperchia

    2016-12-01

    Full Text Available The timing of Trypanosoma brucei entry into the brain parenchyma to initiate the second, meningoencephalitic stage of human African trypanosomiasis or sleeping sickness is currently debated and even parasite invasion of the neuropil has been recently questioned. Furthermore, the relationship between neurological features and disease stage are unclear, despite the important diagnostic and therapeutic implications.Using a rat model of chronic Trypanosoma brucei brucei infection we determined the timing of parasite and T-cell neuropil infiltration and its correlation with functional changes. Parasite DNA was detected using trypanosome-specific PCR. Body weight and sleep structure alterations represented by sleep-onset rapid eye movement (SOREM periods, reported in human and experimental African trypanosomiasis, were monitored. The presence of parasites, as well as CD4+ and CD8+ T-cells in the neuropil was assessed over time in the brain of the same animals by immunocytochemistry and quantitative analyses.Trypanosome DNA was present in the brain at day 6 post-infection and increased more than 15-fold by day 21. Parasites and T-cells were observed in the parenchyma from day 9 onwards. Parasites traversing blood vessel walls were observed in the hypothalamus and other brain regions. Body weight gain was reduced from day 7 onwards. SOREM episodes started in most cases early after infection, with an increase in number and duration after parasite neuroinvasion.These findings demonstrate invasion of the neuropil over time, after an initial interval, by parasites and lymphocytes crossing the blood-brain barrier, and show that neurological features can precede this event. The data thus challenge the current clinical and cerebrospinal fluid criteria of disease staging.

  15. Trypanosoma brucei Invasion and T-Cell Infiltration of the Brain Parenchyma in Experimental Sleeping Sickness: Timing and Correlation with Functional Changes.

    Science.gov (United States)

    Laperchia, Claudia; Palomba, Maria; Seke Etet, Paul F; Rodgers, Jean; Bradley, Barbara; Montague, Paul; Grassi-Zucconi, Gigliola; Kennedy, Peter G E; Bentivoglio, Marina

    2016-12-01

    The timing of Trypanosoma brucei entry into the brain parenchyma to initiate the second, meningoencephalitic stage of human African trypanosomiasis or sleeping sickness is currently debated and even parasite invasion of the neuropil has been recently questioned. Furthermore, the relationship between neurological features and disease stage are unclear, despite the important diagnostic and therapeutic implications. Using a rat model of chronic Trypanosoma brucei brucei infection we determined the timing of parasite and T-cell neuropil infiltration and its correlation with functional changes. Parasite DNA was detected using trypanosome-specific PCR. Body weight and sleep structure alterations represented by sleep-onset rapid eye movement (SOREM) periods, reported in human and experimental African trypanosomiasis, were monitored. The presence of parasites, as well as CD4+ and CD8+ T-cells in the neuropil was assessed over time in the brain of the same animals by immunocytochemistry and quantitative analyses. Trypanosome DNA was present in the brain at day 6 post-infection and increased more than 15-fold by day 21. Parasites and T-cells were observed in the parenchyma from day 9 onwards. Parasites traversing blood vessel walls were observed in the hypothalamus and other brain regions. Body weight gain was reduced from day 7 onwards. SOREM episodes started in most cases early after infection, with an increase in number and duration after parasite neuroinvasion. These findings demonstrate invasion of the neuropil over time, after an initial interval, by parasites and lymphocytes crossing the blood-brain barrier, and show that neurological features can precede this event. The data thus challenge the current clinical and cerebrospinal fluid criteria of disease staging.

  16. The Oral Antimalarial Drug Tafenoquine Shows Activity against Trypanosoma brucei.

    Science.gov (United States)

    Carvalho, Luis; Martínez-García, Marta; Pérez-Victoria, Ignacio; Manzano, José Ignacio; Yardley, Vanessa; Gamarro, Francisco; Pérez-Victoria, José M

    2015-10-01

    The protozoan parasite Trypanosoma brucei causes human African trypanosomiasis, or sleeping sickness, a neglected tropical disease that requires new, safer, and more effective treatments. Repurposing oral drugs could reduce both the time and cost involved in sleeping sickness drug discovery. Tafenoquine (TFQ) is an oral antimalarial drug belonging to the 8-aminoquinoline family which is currently in clinical phase III. We show here that TFQ efficiently kills different T. brucei spp. in the submicromolar concentration range. Our results suggest that TFQ accumulates into acidic compartments and induces a necrotic process involving cell membrane disintegration and loss of cytoplasmic content, leading to parasite death. Cell lysis is preceded by a wide and multitarget drug action, affecting the lysosome, mitochondria, and acidocalcisomes and inducing a depolarization of the mitochondrial membrane potential, elevation of intracellular Ca(2+), and production of reactive oxygen species. This is the first report of an 8-aminoquinoline demonstrating significant in vitro activity against T. brucei. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  17. Sleeping sickness in travelers - do they really sleep?

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    Karin Urech

    2011-11-01

    Full Text Available The number of imported Human African Trypanosomiasis (HAT cases in non-endemic countries has increased over the last years. The objective of this analysis is to describe the clinical presentation of HAT in Caucasian travelers. Literature was screened (MEDLINE, Pubmed using the terms "Human African Trypanosomiasis", "travelers" and "expatriates"; all European languages except Slavic ones were included. Publications without clinical description of patients were only included in the epidemiological analysis. Forty-five reports on Caucasians with T.b. rhodesiense and 15 with T.b. gambiense infections were included in the analysis of the clinical parameters. Both species have presented with fever (T.b. rhodesiense 97.8% and T.b. gambiense 93.3%, headache (50% each and a trypanosomal chancre (T.b. rhodesiense 84.4%, T.b. gambiense 46.7%. While sleeping disorders dominate the clinical presentation of HAT in endemic regions, there have been only rare reports in travelers: insomnia (T.b. rhodesiense 7.1%, T.b. gambiense 21.4%, diurnal somnolence (T.b. rhodesiense 4.8%, T.b. gambiense none. Surprisingly, jaundice has been seen in 24.2% of the Caucasian T.b. rhodesiense patients, but has never been described in HAT patients in endemic regions. These results contrast to the clinical presentation of T.b. gambiense and T.b. rhodesiense HAT in Africans in endemic regions, where the presentation of chronic T.b. gambiense and acute T.b. rhodesiense HAT is different. The analysis of 14 reports on T.b. gambiense HAT in Africans living in a non-endemic country shows that neurological symptoms such as somnolence (46.2%, motor deficit (64.3% and reflex anomalies (14.3% as well as psychiatric symptoms such as hallucinations (21.4% or depression (21.4% may dominate the clinical picture. Often, the diagnosis has been missed initially: some patients have even been hospitalized in psychiatric clinics. In travelers T.b. rhodesiense and gambiense present as acute illnesses

  18. Sensitivity and Specificity of a Prototype Rapid Diagnostic Test for the Detection of Trypanosoma brucei gambiense Infection: A Multi-centric Prospective Study.

    Science.gov (United States)

    Bisser, Sylvie; Lumbala, Crispin; Nguertoum, Etienne; Kande, Victor; Flevaud, Laurence; Vatunga, Gedeao; Boelaert, Marleen; Büscher, Philippe; Josenando, Theophile; Bessell, Paul R; Biéler, Sylvain; Ndung'u, Joseph M

    2016-04-01

    A major challenge in the control of human African trypanosomiasis (HAT) is lack of reliable diagnostic tests that are rapid and easy to use in remote areas where the disease occurs. In Trypanosoma brucei gambiense HAT, the Card Agglutination Test for Trypanosomiasis (CATT) has been the reference screening test since 1978, usually on whole blood, but also in a 1/8 dilution (CATT 1/8) to enhance specificity. However, the CATT is not available in a single format, requires a cold chain for storage, and uses equipment that requires electricity. A solution to these challenges has been provided by rapid diagnostic tests (RDT), which have recently become available. A prototype immunochromatographic test, the SD BIOLINE HAT, based on two native trypanosomal antigens (VSG LiTat 1.3 and VSG LiTat 1.5) has been developed. We carried out a non-inferiority study comparing this prototype to the CATT 1/8 in field settings. The prototype SD BIOLINE HAT, the CATT Whole Blood and CATT 1/8 were systematically applied on fresh blood samples obtained from 14,818 subjects, who were prospectively enrolled through active and passive screening in clinical studies in three endemic countries of central Africa: Angola, the Democratic Republic of the Congo and the Central African Republic. One hundred and forty nine HAT cases were confirmed by parasitology. The sensitivity and specificity of the prototype SD BIOLINE HAT was 89.26% (95% confidence interval (CI) = 83.27-93.28) and 94.58% (95% CI = 94.20-94.94) respectively. The sensitivity and specificity of the CATT on whole blood were 93.96% (95% CI = 88.92-96.79) and 95.91% (95% CI = 95.58-96.22), and of the CATT 1/8 were 89.26% (95% CI = 83.27-93.28) and 98.88% (95% CI = 98.70-99.04) respectively. After further optimization, the prototype SD BIOLINE HAT could become an alternative to current screening methods in primary healthcare settings in remote, resource-limited regions where HAT typically occurs.

  19. Some liver function indices and blood parameters in T. brucei ...

    African Journals Online (AJOL)

    JTEkanem

    symptoms of African sleeping sickness9. Despite the prolific research ... is a disease for which both man and other animals whether ... on some symptoms caused by T. brucei infection. .... immune response is insufficient to clear infection21-23.

  20. The flagellum of Trypanosoma brucei: new tricks from an old dog

    Science.gov (United States)

    Ralston, Katherine S.; Hill, Kent L.

    2010-01-01

    African trypanosomes, i.e. Trypanosoma brucei and related sub-species, are devastating human and animal pathogens that cause significant human mortality and limit sustained economic development in sub-Saharan Africa. Trypanosoma brucei is a highly motile protozoan parasite and coordinated motility is central to both disease pathogenesis in the mammalian host and parasite development in the tsetse fly vector. Since motility is critical for parasite development and pathogenesis, understanding unique aspects of the T. brucei flagellum may uncover novel targets for therapeutic intervention in African sleeping sickness. Moreover, studies of conserved features of the T. brucei flagellum are directly relevant to understanding fundamental aspects of flagellum and cilium function in other eukaryotes, making T. brucei an important model system. The T. brucei flagellum contains a canonical 9 + 2 axoneme, together with additional features that are unique to kinetoplastids and a few closely-related organisms. Until recently, much of our knowledge of the structure and function of the trypanosome flagellum was based on analogy and inference from other organisms. There has been an explosion in functional studies in T. brucei in recent years, revealing conserved as well as novel and unexpected structural and functional features of the flagellum. Most notably, the flagellum has been found to be an essential organelle, with critical roles in parasite motility, morphogenesis, cell division and immune evasion. This review highlights recent discoveries on the T. brucei flagellum. PMID:18472102

  1. Is there a suburban sleeping sickness in Libreville? | Kohagne ...

    African Journals Online (AJOL)

    Background: The transmission of sleeping sickness occurs primarily in rural areas, and exposed populations are those living from rural activities such as agriculture, fishing, animal husbandry or hunting. However, urban and suburban foci are more and more reported in T. b. gambiense areas. In Libreville town, sleeping ...

  2. Epidemiology of Sleeping Sickness in Boffa (Guinea): Where Are the Trypanosomes?

    Science.gov (United States)

    Kagbadouno, Moise Saa; Camara, Mamadou; Rouamba, Jeremi; Rayaisse, Jean-Baptiste; Traoré, Ibrahima Sory; Camara, Oumou; Onikoyamou, Mory Fassou; Courtin, Fabrice; Ravel, Sophie; de Meeûs, Thierry; Bucheton, Bruno; Jamonneau, Vincent; Solano, Philippe

    2012-01-01

    Human African Trypanosomiasis (HAT) in West Africa is a lethal, neglected disease caused by Trypanosoma brucei gambiense transmitted by the tsetse Glossina palpalis gambiensis. Although the littoral part of Guinea with its typical mangrove habitat is the most prevalent area in West Africa, very few data are available on the epidemiology of the disease in such biotopes. As part of a HAT elimination project in Guinea, we carried a cross-sectional study of the distribution and abundance of people, livestock, tsetse and trypanosomes in the focus of Boffa. An exhaustive census of the human population was done, together with spatial mapping of the area. Entomological data were collected, a human medical survey was organized together with a survey in domestic animals. In total, 45 HAT cases were detected out of 14445 people who attended the survey, these latter representing 50.9% of the total population. Potential additional carriers of T. b. gambiense were also identified by the trypanolysis test (14 human subjects and two domestic animals). No trypanosome pathogenic to animals were found, neither in the 874 tsetse dissected nor in the 300 domestic animals sampled. High densities of tsetse were found in places frequented by humans, such as pirogue jetties, narrow mangrove channels and watering points. The prevalence of T. b. gambiense in humans, combined to low attendance of the population at risk to medical surveys, and to an additional proportion of human and animal carriers of T. b. gambiense who are not treated, highlights the limits of strategies targeting HAT patients only. In order to stop T. b. gambiense transmission, vector control should be added to the current strategy of case detection and treatment. Such an integrated strategy will combine medical surveillance to find and treat cases, and vector control activities to protect people from the infective bites of tsetse. PMID:23272259

  3. A tropical tale: how Naja nigricollis venom beats Trypanosoma brucei

    DEFF Research Database (Denmark)

    Martos Esteban, Andrea; Laustsen, Andreas Hougaard; Carrington, Mark

    Trypanosoma brucei is a parasitic protozoan species capable to infecting insect vectors whose bite further produces African sleeping sickness inhuman beings [1]. During the parasite’s extracellular life in the mammalian host,its outer coat, mainly composed of Variable Surface Glycoproteins (VSGs)...

  4. The detection and treatment of human African trypanosomiasis

    Directory of Open Access Journals (Sweden)

    Bouteille B

    2012-06-01

    Full Text Available Bernard Bouteille,1 Alain Buguet21Laboratory of Parasitology, Dupuytren University Hospital of Limoges, France; 2Polyclinic Marie-Louise Poto-Djembo, Pointe-Noire, CongoAbstract: Human African trypanosomiasis (HAT is caused by the injection of Trypanosoma brucei (T. b. gambiense or T. b. rhodesiense by Glossina, the tsetse fly. Three historical eras followed the exclusive clinical approach of the 19th century. At the turn of the century, the “initial research” era was initiated because of the dramatic spread of HAT throughout intertropical Africa, and scientists discovered the agent and its vector. Two entities, recurrent fever and sleeping sickness, were then considered a continuum between hemolymphatic stage 1 and meningoencephalitic stage 2. Treatments were developed. Soon after World War I, specific services and mobile teams were created, initiating the “epidemiological” era, during which populations were visited, screened, and treated. As a result, by 1960, annual new cases were rare. New mass screening and staging tools were then developed in a third, “modern” era, especially to counter a new epidemic wave. Currently, diagnosis still relies on microscopic detection of trypanosomes without (wet and thick blood films or with concentration techniques (capillary tube centrifugation, miniature anion-exchange centrifugation technique. Staging is a vital step.Stage 1 patients are treated on site with pentamidine or suramin. However, stage 2 patients are treated in specialized facilities, using drugs that are highly toxic and/or that require complex administration procedures (melarsoprol, eflornithine, or nifurtimox-eflornithine combination therapy. Suramin and melarsoprol are the only medications active against Rhodesian HAT. Staging still relies on cerebrospinal fluid examination for trypanosome detection and white blood cell counts: stage 1, absence of trypanosomes, white blood cell counts ≤ 5/µL; stage 2, presence of

  5. Estimating and mapping the population at risk of sleeping sickness.

    Directory of Open Access Journals (Sweden)

    Pere P Simarro

    Full Text Available Human African trypanosomiasis (HAT, also known as sleeping sickness, persists as a public health problem in several sub-Saharan countries. Evidence-based, spatially explicit estimates of population at risk are needed to inform planning and implementation of field interventions, monitor disease trends, raise awareness and support advocacy. Comprehensive, geo-referenced epidemiological records from HAT-affected countries were combined with human population layers to map five categories of risk, ranging from "very high" to "very low," and to estimate the corresponding at-risk population.Approximately 70 million people distributed over a surface of 1.55 million km(2 are estimated to be at different levels of risk of contracting HAT. Trypanosoma brucei gambiense accounts for 82.2% of the population at risk, the remaining 17.8% being at risk of infection from T. b. rhodesiense. Twenty-one million people live in areas classified as moderate to very high risk, where more than 1 HAT case per 10,000 inhabitants per annum is reported.Updated estimates of the population at risk of sleeping sickness were made, based on quantitative information on the reported cases and the geographic distribution of human population. Due to substantial methodological differences, it is not possible to make direct comparisons with previous figures for at-risk population. By contrast, it will be possible to explore trends in the future. The presented maps of different HAT risk levels will help to develop site-specific strategies for control and surveillance, and to monitor progress achieved by ongoing efforts aimed at the elimination of sleeping sickness.

  6. Response of Tripanosoma brucei brucei –induced anaemia to a ...

    African Journals Online (AJOL)

    A study was therefore carried out to determine the effect of the preparation on packed cell volume (PCV) and haemoglobin (Hb) concentrations in anaemic rabbits. The PCV and Hb concentrations of healthy rabbits infected with Trypanosoma brucei brucei were monitored for 49 days. T. b. brucei produced a significant ...

  7. Novel molecular mechanism for targeting the parasite Trypanosoma brucei with snake venom toxins

    DEFF Research Database (Denmark)

    Martos Esteban, Andrea; Laustsen, Andreas Hougaard; Carrington, Mark

    Trypanosoma brucei is a parasitic protozoan species capable to infecting insect vectors whose bite further produces African sleeping sickness inhuman beings. During parasites’extracellular lives in the mammalian host, its outer coat, mainly composedof Variable surface glycoproteins (VSGs)[2...

  8. Trypanosoma brucei solanesyl-diphosphate synthase localizes to the mitochondrion

    Czech Academy of Sciences Publication Activity Database

    Lai, D.-H.; Bontempi, E. J.; Lukeš, Julius

    2012-01-01

    Roč. 183, č. 2 (2012), s. 189-192 ISSN 0166-6851 R&D Projects: GA ČR(CZ) GAP305/11/2179 Institutional support: RVO:60077344 Keywords : Trypanosoma brucei * Sleeping sickness * Ubiquinone * Solanesyl-diphosphate synthase * Digitonin permeabilization * In situ tagging Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.734, year: 2012 http://www.sciencedirect.com/science/article/pii/S0166685112000539

  9. Phenolic Constituents of Medicinal Plants with Activity against Trypanosoma brucei

    Directory of Open Access Journals (Sweden)

    Ya Nan Sun

    2016-04-01

    Full Text Available Neglected tropical diseases (NTDs affect over one billion people all over the world. These diseases are classified as neglected because they impact populations in areas with poor financial conditions and hence do not attract sufficient research investment. Human African Trypanosomiasis (HAT or sleeping sickness, caused by the parasite Trypanosoma brucei, is one of the NTDs. The current therapeutic interventions for T. brucei infections often have toxic side effects or require hospitalization so that they are not available in the rural environments where HAT occurs. Furthermore, parasite resistance is increasing, so that there is an urgent need to identify novel lead compounds against this infection. Recognizing the wide structural diversity of natural products, we desired to explore and identify novel antitrypanosomal chemotypes from a collection of natural products obtained from plants. In this study, 440 pure compounds from various medicinal plants were tested against T. brucei by in a screening using whole cell in vitro assays. As the result, twenty-two phenolic compounds exhibited potent activity against cultures of T. brucei. Among them, eight compounds—4, 7, 11, 14, 15, 18, 20, and 21—showed inhibitory activity against T. brucei, with IC50 values below 5 µM, ranging from 0.52 to 4.70 μM. Based on these results, we attempt to establish some general trends with respect to structure-activity relationships, which indicate that further investigation and optimization of these derivatives might enable the preparation of potentially useful compounds for treating HAT.

  10. Taxonomy Icon Data: Trypanosoma brucei [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available Trypanosoma brucei Trypanosoma brucei Trypanosoma_brucei_L.png Trypanosoma_brucei_NL.png Trypanoso...ma_brucei_S.png Trypanosoma_brucei_NS.png http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Trypanoso...ma+brucei&t=L http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Trypanosoma+brucei&t=NL http://bioscie...ncedbc.jp/taxonomy_icon/icon.cgi?i=Trypanosoma+brucei&t=S http://biosciencedbc.jp.../taxonomy_icon/icon.cgi?i=Trypanosoma+brucei&t=NS http://togodb.biosciencedbc.jp/togodb/view/taxonomy_icon_comment_en?species_id=121 ...

  11. Meiosis and Haploid Gametes in the Pathogen Trypanosoma brucei

    OpenAIRE

    Peacock, Lori; Bailey, Mick; Carrington, Mark; Gibson, Wendy

    2014-01-01

    Summary In eukaryote pathogens, sex is an important driving force in spreading genes for drug resistance, pathogenicity, and virulence [1]. For the parasitic trypanosomes that cause African sleeping sickness, mating occurs during transmission by the tsetse vector [2, 3] and involves meiosis [4], but haploid gametes have not yet been identified. Here, we show that meiosis is a normal part of development in the insect salivary glands for all subspecies of Trypanosoma brucei, including the human...

  12. Monitoring the use of nifurtimox-eflornithine combination therapy (NECT in the treatment of second stage gambiense human African trypanosomiasis

    Directory of Open Access Journals (Sweden)

    Franco JR

    2012-08-01

    Full Text Available Jose R Franco,1 Pere P Simarro,1 Abdoulaye Diarra,2 Jose A Ruiz-Postigo,3 Mireille Samo,1 Jean G Jannin11World Health Organization, Control of Neglected Tropical Diseases, Innovative and Intensified Disease Management, Geneva, Switzerland; 2World Health Organization, Regional Office for Africa, Brazzaville, Congo; 3World Health Organization, Communicable Disease Control, Control of Tropical Diseases and Zoonoses Regional Office for the Eastern Mediterranean, Cairo, EgyptAbstract: After inclusion of the nifurtimox-eflornithine combination therapy (NECT in the Model List of Essential Medicines for the treatment of second-stage gambiense human African trypanosomiasis (HAT, the World Health Organization, in collaboration with National Sleeping Sickness Control Programs and nongovernmental organizations set up a pharmacovigilance system to assess the safety and efficacy of NECT during its routine use. Data were collected for 1735 patients treated with NECT in nine disease endemic countries during 2010–2011. At least one adverse event (AE was described in 1043 patients (60.1% and a total of 3060 AE were reported. Serious adverse events (SAE were reported for 19 patients (1.1% of treated, leading to nine deaths (case fatality rate of 0.5%. The most frequent AE were gastrointestinal disorders (vomiting/nausea and abdominal pain, followed by headache, musculoskeletal pains, and vertigo. The most frequent SAE and cause of death were convulsions, fever, and coma that were considered as reactive encephalopathy. Two hundred and sixty-two children below 15 years old were treated. The characteristics of AE were similar to adults, but the major AE were less frequent in children with only one SAE and no deaths registered in this group. Gastrointestinal problems (vomiting and abdominal pain were more frequent than in adults, but musculoskeletal pains, vertigo, asthenia, neuropsychiatric troubles (headaches, seizures, tremors, hallucinations, insomnia were less

  13. Non-cytochrome mediated mitochondrial ATP production in bloodstream form Trypanosoma brucei brucei

    NARCIS (Netherlands)

    Bienen, E. J.; Maturi, R. K.; Pollakis, G.; Clarkson, A. B.

    1993-01-01

    The life cycle of Trypanosoma brucei brucei involves a series of differentiation steps characterized by marked changes in mitochondrial development and function. The bloodstream forms of this parasite completely lack cytochromes and have not been considered to have any Krebs cycle function. It has

  14. Stearoyl-CoA desaturase is an essential enzyme for the parasitic protist Trypanosoma brucei

    Energy Technology Data Exchange (ETDEWEB)

    Alloatti, Andres [Instituto de Biologia Molecular y Celular de Rosario (IBR), CONICET, Facultad de Ciencias Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, Santa Fe (Argentina); Gupta, Shreedhara; Gualdron-Lopez, Melisa; Nguewa, Paul A. [Research Unit for Tropical Diseases, de Duve Institute and Laboratory of Biochemistry, Universite Catholique de Louvain, Brussels (Belgium); Altabe, Silvia G. [Instituto de Biologia Molecular y Celular de Rosario (IBR), CONICET, Facultad de Ciencias Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, Santa Fe (Argentina); Deumer, Gladys; Wallemacq, Pierre [Department of Clinical Chemistry, Cliniques Universitaires Saint-Luc, LTAP, Universite Catholique de Louvain, Brussels (Belgium); Michels, Paul A.M. [Research Unit for Tropical Diseases, de Duve Institute and Laboratory of Biochemistry, Universite Catholique de Louvain, Brussels (Belgium); Uttaro, Antonio D., E-mail: toniuttaro@yahoo.com.ar [Instituto de Biologia Molecular y Celular de Rosario (IBR), CONICET, Facultad de Ciencias Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, Santa Fe (Argentina)

    2011-08-26

    Highlights: {yields} Inhibiting {Delta}9 desaturase drastically changes T. brucei's fatty-acid composition. {yields} Isoxyl specifically inhibits the {Delta}9 desaturase causing a growth arrest. {yields} RNA interference of desaturase expression causes a similar effect. {yields} Feeding T. brucei-infected mice with Isoxyl decreases the parasitemia. {yields} 70% of Isoxyl-treated mice survived the trypanosome infection. -- Abstract: Trypanosoma brucei, the etiologic agent of sleeping sickness, is exposed to important changes in nutrients and temperature during its life cycle. To adapt to these changes, the fluidity of its membranes plays a crucial role. This fluidity, mediated by the fatty-acid composition, is regulated by enzymes named desaturases. We have previously shown that the oleoyl desaturase is essential for Trypanosoma cruzi and T. brucei. In this work, we present experimental support for the relevance of stearoyl-CoA desaturase (SCD) for T. brucei's survival, in both its insect or procyclic-form (PCF) and bloodstream-form (BSF) stages. We evaluated this essentiality in two different ways: by generating a SCD knocked-down parasite line using RNA interference, and by chemical inhibition of the enzyme with two compounds, Isoxyl and a thiastearate with the sulfur atom at position 10 (10-TS). The effective concentration for 50% growth inhibition (EC{sub 50}) of PCF was 1.0 {+-} 0.2 {mu}M for Isoxyl and 5 {+-} 2 {mu}M for 10-TS, whereas BSF appeared more susceptible with EC{sub 50} values 0.10 {+-} 0.03 {mu}M (Isoxyl) and 1.0 {+-} 0.6 {mu}M (10-TS). RNA interference showed to be deleterious for both stages of the parasite. In addition, T. brucei-infected mice were fed with Isoxyl, causing a reduction of the parasitemia and an increase of the rodents' survival.

  15. Stearoyl-CoA desaturase is an essential enzyme for the parasitic protist Trypanosoma brucei

    International Nuclear Information System (INIS)

    Alloatti, Andres; Gupta, Shreedhara; Gualdron-Lopez, Melisa; Nguewa, Paul A.; Altabe, Silvia G.; Deumer, Gladys; Wallemacq, Pierre; Michels, Paul A.M.; Uttaro, Antonio D.

    2011-01-01

    Highlights: → Inhibiting Δ9 desaturase drastically changes T. brucei's fatty-acid composition. → Isoxyl specifically inhibits the Δ9 desaturase causing a growth arrest. → RNA interference of desaturase expression causes a similar effect. → Feeding T. brucei-infected mice with Isoxyl decreases the parasitemia. → 70% of Isoxyl-treated mice survived the trypanosome infection. -- Abstract: Trypanosoma brucei, the etiologic agent of sleeping sickness, is exposed to important changes in nutrients and temperature during its life cycle. To adapt to these changes, the fluidity of its membranes plays a crucial role. This fluidity, mediated by the fatty-acid composition, is regulated by enzymes named desaturases. We have previously shown that the oleoyl desaturase is essential for Trypanosoma cruzi and T. brucei. In this work, we present experimental support for the relevance of stearoyl-CoA desaturase (SCD) for T. brucei's survival, in both its insect or procyclic-form (PCF) and bloodstream-form (BSF) stages. We evaluated this essentiality in two different ways: by generating a SCD knocked-down parasite line using RNA interference, and by chemical inhibition of the enzyme with two compounds, Isoxyl and a thiastearate with the sulfur atom at position 10 (10-TS). The effective concentration for 50% growth inhibition (EC 50 ) of PCF was 1.0 ± 0.2 μM for Isoxyl and 5 ± 2 μM for 10-TS, whereas BSF appeared more susceptible with EC 50 values 0.10 ± 0.03 μM (Isoxyl) and 1.0 ± 0.6 μM (10-TS). RNA interference showed to be deleterious for both stages of the parasite. In addition, T. brucei-infected mice were fed with Isoxyl, causing a reduction of the parasitemia and an increase of the rodents' survival.

  16. Essential Assembly Factor Rpf2 Forms Novel Interactions within the 5S RNP in Trypanosoma brucei.

    Science.gov (United States)

    Kamina, Anyango D; Jaremko, Daniel; Christen, Linda; Williams, Noreen

    2017-01-01

    Ribosome biogenesis is a highly complex and conserved cellular process that is responsible for making ribosomes. During this process, there are several assembly steps that function as regulators to ensure proper ribosome formation. One of these steps is the assembly of the 5S ribonucleoprotein particle (5S RNP) in the central protuberance of the 60S ribosomal subunit. In eukaryotes, the 5S RNP is composed of 5S rRNA, ribosomal proteins L5 and L11, and assembly factors Rpf2 and Rrs1. Our laboratory previously showed that in Trypanosoma brucei , the 5S RNP is composed of 5S rRNA, L5, and trypanosome-specific RNA binding proteins P34 and P37. In this study, we characterize an additional component of the 5S RNP, the T. brucei homolog of Rpf2. This is the first study to functionally characterize interactions mediated by Rpf2 in an organism other than fungi. T . brucei Rpf2 (TbRpf2) was identified from tandem affinity purification using extracts prepared from protein A-tobacco etch virus (TEV)-protein C (PTP)-tagged L5, P34, and P37 cell lines, followed by mass spectrometry analysis. We characterized the binding interactions between TbRpf2 and the previously characterized members of the T. brucei 5S RNP. Our studies show that TbRpf2 mediates conserved binding interactions with 5S rRNA and L5 and that TbRpf2 also interacts with trypanosome-specific proteins P34 and P37. We performed RNA interference (RNAi) knockdown of TbRpf2 and showed that this protein is essential for the survival of the parasites and is critical for proper ribosome formation. These studies provide new insights into a critical checkpoint in the ribosome biogenesis pathway in T. brucei . IMPORTANCE Trypanosoma brucei is the parasitic protozoan that causes African sleeping sickness. Ribosome assembly is essential for the survival of this parasite through the different host environments it encounters during its life cycle. The assembly of the 5S ribonucleoprotein particle (5S RNP) functions as one of

  17. Genetic control of resistance to Trypanosoma brucei brucei infection in mice

    Czech Academy of Sciences Publication Activity Database

    Šíma, Matyáš; Havelková, Helena; Quan, L.; Svobodová, M.; Jarošíková, T.; Vojtíšková, Jarmila; Stassen, A. P. M.; Demant, P.; Lipoldová, Marie

    2011-01-01

    Roč. 5, č. 6 (2011), e1173 ISSN 1935-2735 R&D Projects: GA AV ČR IAA500520606; GA MŠk(CZ) LC06009 Grant - others:NIH-NCI(US) 1R01CA127162-01 Institutional research plan: CEZ:AV0Z50520514 Keywords : Trypanosoma brucei brucei * mouse recombinant congenic strains * Tbbr Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.716, year: 2011

  18. In vitro susceptibility of Trypanosoma brucei brucei to selected essential oils and their major components.

    Science.gov (United States)

    Costa, Sonya; Cavadas, Cláudia; Cavaleiro, Carlos; Salgueiro, Lígia; do Céu Sousa, Maria

    2018-07-01

    Aiming for discovering effective and harmless antitrypanosomal agents, 17 essential oils and nine major components were screened for their effects on T. b. brucei. The essential oils were obtained by hydrodistillation from fresh plant material and analyzed by GC and GC-MS. The trypanocidal activity was assessed using blood stream trypomastigotes cultures of T. b. brucei and the colorimetric resazurin method. The MTT test was used to assess the cytotoxicity of essential oils on macrophage cells and Selectivity Indexes were calculated. Of the 17 essential oils screened three showed high trypanocidal activity (IC 50  oils had no cytotoxic effects on macrophage cells showing the highest values of Selectivity Index (63.4, 9.0 and 11.8, respectively). The oils of Distichoselinum tenuifolium, Lavandula viridis, Origanum virens, Seseli tortuosom, Syzygium aromaticum, and Thymbra capitata also exhibited activity (IC 50 of 10-25 μg/mL) but showed cytotoxicity on macrophages. Of the nine compounds tested, α-pinene (IC 50 of 2.9 μg/mL) and citral (IC 50 of 18.9 μg/mL) exhibited the highest anti-trypanosomal activities. Citral is likely the active component of C. citratus and α-pinene is responsible for the antitrypanosomal effects of J. oxycedrus. The present work leads us to propose the J. oxycedrus, C. citratus and L. luisieri oils as valuable sources of new molecules for African Sleeping Sickness treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Analytical purification of a 60-kDa target protein of artemisinin detected in Trypanosoma brucei brucei

    Directory of Open Access Journals (Sweden)

    Benetode Konziase

    2015-12-01

    Full Text Available Here we describe the isolation and purity determination of Trypanosoma brucei (T. b. brucei candidate target proteins of artemisinin. The candidate target proteins were detected and purified from their biological source (T. b. brucei lysate using the diazirine-free biotinylated probe 5 for an affinity binding to a streptavidin-tagged resin and, subsequently, the labeled target proteins were purified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE. We herein showed the electrophoresis gel and the immunoblotting film containing the 60-kDa trypanosomal candidate target protein of artemisinin as a single band, which was visualized on-gel by the reverse-staining method and on a Western blotting film by enhanced chemiluminescence. The data provided in this article are related to the original research article “Biotinylated probes of artemisinin with labeling affinity toward Trypanosoma brucei brucei target proteins”, by Konziase (Anal. Biochem., vol. 482, 2015, pp. 25–31. http://dx.doi.org/10.1016/j.ab.2015.04.020.

  20. Escaping deleterious immune response in their hosts: lessons from trypanosomatids

    Directory of Open Access Journals (Sweden)

    Anne eGeiger

    2016-05-01

    Full Text Available The Trypanosomatidae family includes the genera Trypanosoma and Leishmania, protozoan parasites displaying complex digenetic life cycles requiring a vertebrate host and an insect vector. Trypanosoma brucei gambiense, T. cruzi and Leishmania spp are important human pathogens causing Human African Trypanosomiasis (HAT or Sleeping Sickness, Chagas’ disease, and various clinical forms of Leishmaniasis, respectively. They are transmitted to humans by tsetse flies, triatomine bugs or sandflies and affect millions of people worldwide.In humans, extracellular African trypanosomes (T. brucei evade the hosts’ immune defences, allowing their transmission to the next host, via the tsetse vector. By contrast, T. cruzi and Leishmania sp. have developed a complex intracellular lifestyle, also preventing several mechanisms to circumvent the host’s immune response.This review seeks to set out the immune evasion strategies developed by the different trypanosomatids resulting from parasite-host interactions and, will focus on: clinical and epidemiological importance of diseases; life cycles: parasites-hosts-vectors; innate immunity: key steps for trypanosomatids in invading hosts; deregulation of antigen presenting cells; disruption of efficient specific immunity; and the immune responses used for parasite proliferation.

  1. Escaping Deleterious Immune Response in Their Hosts: Lessons from Trypanosomatids

    Science.gov (United States)

    Geiger, Anne; Bossard, Géraldine; Sereno, Denis; Pissarra, Joana; Lemesre, Jean-Loup; Vincendeau, Philippe; Holzmuller, Philippe

    2016-01-01

    The Trypanosomatidae family includes the genera Trypanosoma and Leishmania, protozoan parasites displaying complex digenetic life cycles requiring a vertebrate host and an insect vector. Trypanosoma brucei gambiense, Trypanosoma cruzi, and Leishmania spp. are important human pathogens causing human African trypanosomiasis (HAT or sleeping sickness), Chagas’ disease, and various clinical forms of Leishmaniasis, respectively. They are transmitted to humans by tsetse flies, triatomine bugs, or sandflies, and affect millions of people worldwide. In humans, extracellular African trypanosomes (T. brucei) evade the hosts’ immune defenses, allowing their transmission to the next host, via the tsetse vector. By contrast, T. cruzi and Leishmania sp. have developed a complex intracellular lifestyle, also preventing several mechanisms to circumvent the host’s immune response. This review seeks to set out the immune evasion strategies developed by the different trypanosomatids resulting from parasite–host interactions and will focus on: clinical and epidemiological importance of diseases; life cycles: parasites–hosts–vectors; innate immunity: key steps for trypanosomatids in invading hosts; deregulation of antigen-presenting cells; disruption of efficient specific immunity; and the immune responses used for parasite proliferation. PMID:27303406

  2. In vitro activity of commercial formulation and active principle of ...

    African Journals Online (AJOL)

    The in vitro trypanocidal activities of 4 commercial formulations Ornidyl®, Pentamidine isethionate®, Germanin® and Lampit® and their corresponding active principles (Dl-difluoromethylornithine, pentamidine isethionate, suramine and 5-nitrofuran) were compared against Trypanosoma brucei gambiense. Differences of ...

  3. Development of Trypanosomosis Agglutination Card Test (TACT ...

    African Journals Online (AJOL)

    In a bid to improve field diagnosis of animal trypanosomosis in tsetse-infested African countries, TACT utilizing fixed and stabilized procyclic antigen from culture-derived Trypanosoma brucei gambiense isolate IL2343 was developed and evaluated in Uganda. Its diagnostic sensitivity was evaluated using blood samples ...

  4. CHARACTERIZATION AND ANTIPARASITIC ACTIVITY OF BENZOPHENONE THIOSEMICARBAZONES ON Trypanosoma brucei brucei

    Directory of Open Access Journals (Sweden)

    Georges C. Accrombessi

    2011-02-01

    Full Text Available The structure of four synthesized thiosemicarbazones, substituted or not, of benzophenone has been confirmed by spectrometrical analysis IR, NMR 1H and 13C. Their anti-trypanosomal activities were evaluated on Trypanosoma brucei brucei. Among these compounds, benzophenone 4 phenyl-3-thiosemicarbazone 4 has the highest activity with the half-inhibitory concentration (IC50 = 8.48 micromolar (µM. Benzophenone 4-methyl-3-thiosemicarbazone 3 and benzophenone thiosemicarbazone 1 showed moderate anti-trypanosomal activity with IC50 values equal to 23.27 µM and 67.17 µM respectively. Benzophenone 2 methyl-3-thiosemicarbazone 2 showed no activity up to IC50 = 371.74 µM.

  5. ATG24 Represses Autophagy and Differentiation and Is Essential for Homeostasy of the Flagellar Pocket in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Ana Brennand

    Full Text Available We have previously identified homologs for nearly half of the approximately 30 known yeast Atg's in the genome database of the human sleeping sickness parasite Trypanosoma brucei. So far, only a few of these homologs have their role in autophagy experimentally confirmed. Among the candidates was the ortholog of Atg24 that is involved in pexophagy in yeast. In T. brucei, the peroxisome-like organelles named glycosomes harbor core metabolic processes, especially glycolysis. In the autotrophic yeast, autophagy is essential for adaptation to different nutritional environments by participating in the renewal of the peroxisome population. We hypothesized that autophagic turnover of the parasite's glycosomes plays a role in differentiation during its life cycle, which demands adaptation to different host environments and associated dramatic changes in nutritional conditions. We therefore characterized T. brucei ATG24, the T. brucei ortholog of yeast Atg24 and mammalian SNX4, and found it to have a regulatory role in autophagy and differentiation as well as endocytic trafficking. ATG24 partially localized on endocytic membranes where it was recruited via PI3-kinase III/VPS34. ATG24 silencing severely impaired receptor-mediated endocytosis of transferrin, but not adsorptive uptake of a lectin, and caused a major enlargement of the flagellar pocket. ATG24 silencing approximately doubled the number of autophagosomes, suggesting a role in repressing autophagy, and strongly accelerated differentiation, in accordance with a role of autophagy in parasite differentiation. Overexpression of the two isoforms of T. brucei ATG8 fused to GFP slowed down differentiation, possibly by a dominant-negative effect. This was overcome by ATG24 depletion, further supporting its regulatory role.

  6. Serum total proteins and creatinine levels in experimental gambian ...

    African Journals Online (AJOL)

    Attempt was therefore made to evaluate the effect of two strains of Trypanosoma brucei gambiense on total proteins and other serum biochemical parameters using vervet monkeys as a model. The outcome of both strains in vervet monkeys was traumatic as the monkeys died from infection 12 – 15 weeks post infection while ...

  7. Adenylate Cyclases of Trypanosoma brucei, Environmental Sensors and Controllers of Host Innate Immune Response.

    Science.gov (United States)

    Salmon, Didier

    2018-04-25

    Trypanosoma brucei , etiological agent of Sleeping Sickness in Africa, is the prototype of African trypanosomes, protozoan extracellular flagellate parasites transmitted by saliva ( Salivaria ). In these parasites the molecular controls of the cell cycle and environmental sensing are elaborate and concentrated at the flagellum. Genomic analyses suggest that these parasites appear to differ considerably from the host in signaling mechanisms, with the exception of receptor-type adenylate cyclases (AC) that are topologically similar to receptor-type guanylate cyclase (GC) of higher eukaryotes but control a new class of cAMP targets of unknown function, the cAMP response proteins (CARPs), rather than the classical protein kinase A cAMP effector (PKA). T. brucei possesses a large polymorphic family of ACs, mainly associated with the flagellar membrane, and these are involved in inhibition of the innate immune response of the host prior to the massive release of immunomodulatory factors at the first peak of parasitemia. Recent evidence suggests that in T. brucei several insect-specific AC isoforms are involved in social motility, whereas only a few AC isoforms are involved in cytokinesis control of bloodstream forms, attesting that a complex signaling pathway is required for environmental sensing. In this review, after a general update on cAMP signaling pathway and the multiple roles of cAMP, I summarize the existing knowledge of the mechanisms by which pathogenic microorganisms modulate cAMP levels to escape immune defense.

  8. Adenylate Cyclases of Trypanosoma brucei, Environmental Sensors and Controllers of Host Innate Immune Response

    Directory of Open Access Journals (Sweden)

    Didier Salmon

    2018-04-01

    Full Text Available Trypanosoma brucei, etiological agent of Sleeping Sickness in Africa, is the prototype of African trypanosomes, protozoan extracellular flagellate parasites transmitted by saliva (Salivaria. In these parasites the molecular controls of the cell cycle and environmental sensing are elaborate and concentrated at the flagellum. Genomic analyses suggest that these parasites appear to differ considerably from the host in signaling mechanisms, with the exception of receptor-type adenylate cyclases (AC that are topologically similar to receptor-type guanylate cyclase (GC of higher eukaryotes but control a new class of cAMP targets of unknown function, the cAMP response proteins (CARPs, rather than the classical protein kinase A cAMP effector (PKA. T. brucei possesses a large polymorphic family of ACs, mainly associated with the flagellar membrane, and these are involved in inhibition of the innate immune response of the host prior to the massive release of immunomodulatory factors at the first peak of parasitemia. Recent evidence suggests that in T. brucei several insect-specific AC isoforms are involved in social motility, whereas only a few AC isoforms are involved in cytokinesis control of bloodstream forms, attesting that a complex signaling pathway is required for environmental sensing. In this review, after a general update on cAMP signaling pathway and the multiple roles of cAMP, I summarize the existing knowledge of the mechanisms by which pathogenic microorganisms modulate cAMP levels to escape immune defense.

  9. Characterization of Trypanosoma brucei brucei S-adenosyl-L-methionine decarboxylase and its inhibition by Berenil, pentamidine and methylglyoxal bis(guanylhydrazone).

    Science.gov (United States)

    Bitonti, A J; Dumont, J A; McCann, P P

    1986-01-01

    Trypanosoma brucei brucei S-adenosyl-L-methionine (AdoMet) decarboxylase was found to be relatively insensitive to activation by putrescine as compared with the mammalian enzyme, being stimulated by only 50% over a 10,000-fold range of putrescine concentrations. The enzyme was not stimulated by up to 10 mM-Mg2+. The Km for AdoMet was 30 microM, similar to that of other eukaryotic AdoMet decarboxylases. T.b. brucei AdoMet decarboxylase activity was apparently irreversibly inhibited in vitro by Berenil and reversibly by pentamidine and methylglyoxal bis(guanylhydrazone). Berenil also inhibited trypanosomal AdoMet decarboxylase by 70% within 4 h after administration to infected rats and markedly increased the concentration of putrescine in trypanosomes that were exposed to the drug in vivo. Spermidine and spermine blocked the curative effect of Berenil on model mouse T.b. brucei infections. This effect of the polyamines was probably not due to reversal of Berenil's inhibitory effects on the AdoMet decarboxylase. PMID:3800910

  10. Troglitazone induces differentiation in Trypanosoma brucei

    International Nuclear Information System (INIS)

    Denninger, Viola; Figarella, Katherine; Schoenfeld, Caroline; Brems, Stefanie; Busold, Christian; Lang, Florian; Hoheisel, Joerg; Duszenko, Michael

    2007-01-01

    Trypanosoma brucei, a protozoan parasite causing sleeping sickness, is transmitted by the tsetse fly and undergoes a complex lifecycle including several defined stages within the insect vector and its mammalian host. In the latter, differentiation from the long slender to the short stumpy form is induced by a yet unknown factor of trypanosomal origin. Here we describe that some thiazolidinediones are also able to induce differentiation. In higher eukaryotes, thiazolidinediones are involved in metabolism and differentiation processes mainly by binding to the intracellular receptor peroxisome proliferator activated receptor γ. Our studies focus on the effects of troglitazone on bloodstream form trypanosomes. Differentiation was monitored using mitochondrial markers (membrane potential, succinate dehydrogenase activity, inhibition of oxygen uptake by KCN, amount of cytochrome transcripts), morphological changes (Transmission EM and light microscopy), and transformation experiments (loss of the Variant Surface Glycoprotein coat and increase of dihydroliponamide dehydrogenase activity). To further investigate the mechanisms responsible for these changes, microarray analyses were performed, showing an upregulation of expression site associated gene 8 (ESAG8), a potential differentiation regulator

  11. Expression of interferon-inducible chemokines and sleep/wake changes during early encephalitis in experimental African trypanosomiasis.

    Science.gov (United States)

    Laperchia, Claudia; Tesoriero, Chiara; Seke-Etet, Paul F; La Verde, Valentina; Colavito, Valeria; Grassi-Zucconi, Gigliola; Rodgers, Jean; Montague, Paul; Kennedy, Peter G E; Bentivoglio, Marina

    2017-08-01

    Human African trypanosomiasis or sleeping sickness, caused by the parasite Trypanosoma brucei, leads to neuroinflammation and characteristic sleep/wake alterations. The relationship between the onset of these alterations and the development of neuroinflammation is of high translational relevance, but remains unclear. This study investigates the expression of interferon (IFN)-γ and IFN-inducible chemokine genes in the brain, and the levels of CXCL10 in the serum and cerebrospinal fluid prior to and during the encephalitic stage of trypanosome infection, and correlates these with sleep/wake changes in a rat model of the disease. The expression of genes encoding IFN-γ, CXCL9, CXCL10, and CXCL11 was assessed in the brain of rats infected with Trypanosoma brucei brucei and matched controls using semi-quantitative end-point RT-PCR. Levels of CXCL10 in the serum and cerebrospinal fluid were determined using ELISA. Sleep/wake states were monitored by telemetric recording. Using immunohistochemistry, parasites were found in the brain parenchyma at 14 days post-infection (dpi), but not at 6 dpi. Ifn-γ, Cxcl9, Cxcl10 and Cxcl11 mRNA levels showed moderate upregulation by 14 dpi followed by further increase between 14 and 21 dpi. CXCL10 concentration in the cerebrospinal fluid increased between 14 and 21 dpi, preceded by a rise in the serum CXCL10 level between 6 and 14 dpi. Sleep/wake pattern fragmentation was evident at 14 dpi, especially in the phase of wake predominance, with intrusion of sleep episodes into wakefulness. The results show a modest increase in Cxcl9 and Cxcl11 transcripts in the brain and the emergence of sleep/wake cycle fragmentation in the initial encephalitic stage, followed by increases in Ifn-γ and IFN-dependent chemokine transcripts in the brain and of CXCL10 in the cerebrospinal fluid. The latter parameter and sleep/wake alterations could provide combined humoral and functional biomarkers of the early encephalitic stage in African trypanosomiasis.

  12. Expression of interferon-inducible chemokines and sleep/wake changes during early encephalitis in experimental African trypanosomiasis.

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    Claudia Laperchia

    2017-08-01

    Full Text Available Human African trypanosomiasis or sleeping sickness, caused by the parasite Trypanosoma brucei, leads to neuroinflammation and characteristic sleep/wake alterations. The relationship between the onset of these alterations and the development of neuroinflammation is of high translational relevance, but remains unclear. This study investigates the expression of interferon (IFN-γ and IFN-inducible chemokine genes in the brain, and the levels of CXCL10 in the serum and cerebrospinal fluid prior to and during the encephalitic stage of trypanosome infection, and correlates these with sleep/wake changes in a rat model of the disease.The expression of genes encoding IFN-γ, CXCL9, CXCL10, and CXCL11 was assessed in the brain of rats infected with Trypanosoma brucei brucei and matched controls using semi-quantitative end-point RT-PCR. Levels of CXCL10 in the serum and cerebrospinal fluid were determined using ELISA. Sleep/wake states were monitored by telemetric recording. Using immunohistochemistry, parasites were found in the brain parenchyma at 14 days post-infection (dpi, but not at 6 dpi. Ifn-γ, Cxcl9, Cxcl10 and Cxcl11 mRNA levels showed moderate upregulation by 14 dpi followed by further increase between 14 and 21 dpi. CXCL10 concentration in the cerebrospinal fluid increased between 14 and 21 dpi, preceded by a rise in the serum CXCL10 level between 6 and 14 dpi. Sleep/wake pattern fragmentation was evident at 14 dpi, especially in the phase of wake predominance, with intrusion of sleep episodes into wakefulness.The results show a modest increase in Cxcl9 and Cxcl11 transcripts in the brain and the emergence of sleep/wake cycle fragmentation in the initial encephalitic stage, followed by increases in Ifn-γ and IFN-dependent chemokine transcripts in the brain and of CXCL10 in the cerebrospinal fluid. The latter parameter and sleep/wake alterations could provide combined humoral and functional biomarkers of the early encephalitic stage in African

  13. Proteome remodelling during development from blood to insect-form Trypanosoma brucei quantified by SILAC and mass spectrometry

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    Gunasekera Kapila

    2012-10-01

    Full Text Available Abstract Background Trypanosoma brucei is the causative agent of human African sleeping sickness and Nagana in cattle. In addition to being an important pathogen T. brucei has developed into a model system in cell biology. Results Using Stable Isotope Labelling of Amino acids in Cell culture (SILAC in combination with mass spectrometry we determined the abundance of >1600 proteins in the long slender (LS, short stumpy (SS mammalian bloodstream form stages relative to the procyclic (PC insect-form stage. In total we identified 2645 proteins, corresponding to ~30% of the total proteome and for the first time present a comprehensive overview of relative protein levels in three life stages of the parasite. Conclusions We can show the extent of pre-adaptation in the SS cells, especially at the level of the mitochondrial proteome. The comparison to a previously published report on monomorphic in vitro grown bloodstream and procyclic T. brucei indicates a loss of stringent regulation particularly of mitochondrial proteins in these cells when compared to the pleomorphic in vivo situation. In order to better understand the different levels of gene expression regulation in this organism we compared mRNA steady state abundance with the relative protein abundance-changes and detected moderate but significant correlation indicating that trypanosomes possess a significant repertoire of translational and posttranslational mechanisms to regulate protein abundance.

  14. Metabolic reprogramming during the Trypanosoma brucei life cycle [version 2; referees: 4 approved

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    Terry K. Smith

    2017-05-01

    Full Text Available Cellular metabolic activity is a highly complex, dynamic, regulated process that is influenced by numerous factors, including extracellular environmental signals, nutrient availability and the physiological and developmental status of the cell. The causative agent of sleeping sickness, Trypanosoma brucei, is an exclusively extracellular protozoan parasite that encounters very different extracellular environments during its life cycle within the mammalian host and tsetse fly insect vector. In order to meet these challenges, there are significant alterations in the major energetic and metabolic pathways of these highly adaptable parasites. This review highlights some of these metabolic changes in this early divergent eukaryotic model organism.

  15. Metabolic reprogramming during the Trypanosoma brucei life cycle [version 1; referees: 4 approved

    Directory of Open Access Journals (Sweden)

    Terry K. Smith

    2017-05-01

    Full Text Available Cellular metabolic activity is a highly complex, dynamic, regulated process that is influenced by numerous factors, including extracellular environmental signals, nutrient availability and the physiological and developmental status of the cell. The causative agent of sleeping sickness, Trypanosoma brucei, is an exclusively extracellular protozoan parasite that encounters very different extracellular environments during its life cycle within the mammalian host and tsetse fly insect vector. In order to meet these challenges, there are significant alterations in the major energetic and metabolic pathways of these highly adaptable parasites. This review highlights some of these metabolic changes in this early divergent eukaryotic model organism.

  16. Classical clinical signs in rats experimemtally infected with Trypanosoma brucei

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    Nwoha Rosemary Ijeoma Ogechi

    2015-02-01

    Full Text Available Objective: To investigate clinical signs in Trypanosoma brucei infection in albino rats. Methods: Fourteen rats grouped into 2 with 7 rats in each group were used to determine classical clinical manifestation of Trypanosoma brucei infection in rats. Group A rats were uninfected control and Group B rats were infected with Trypanosoma brucei. Results: Parasitaemia was recorded in Group B by (3.86±0.34 d and the peak of parasitaemia was observed at Day 5 post infection. Classical signs observed included squint eyes, raised whiskers, lethargy, no weight loss, pyrexia, isolation from the other rats, and starry hair coat. Conclusions: These signs could be diagnostic or aid in diagnosis of Trypanosoma brucei infection in rats.

  17. Regulation and spatial organization of PCNA in Trypanosoma brucei

    International Nuclear Information System (INIS)

    Kaufmann, Doris; Gassen, Alwine; Maiser, Andreas; Leonhardt, Heinrich; Janzen, Christian J.

    2012-01-01

    Highlights: ► Characterization of the proliferating cell nuclear antigen in Trypanosoma brucei (TbPCNA). ► TbPCNA is a suitable marker to detect replication in T. brucei. ► TbPCNA distribution and regulation is different compared to closely related parasites T. cruzi and Leishmania donovani. -- Abstract: As in most eukaryotic cells, replication is regulated by a conserved group of proteins in the early-diverged parasite Trypanosoma brucei. Only a few components of the replication machinery have been described in this parasite and regulation, sub-nuclear localization and timing of replication are not well understood. We characterized the proliferating cell nuclear antigen in T. brucei (TbPCNA) to establish a spatial and temporal marker for replication. Interestingly, PCNA distribution and regulation is different compared to the closely related parasites Trypanosoma cruzi and Leishmania donovani. TbPCNA foci are clearly detectable during S phase of the cell cycle but in contrast to T. cruzi they are not preferentially located at the nuclear periphery. Furthermore, PCNA seems to be degraded when cells enter G2 phase in T. brucei suggesting different modes of replication regulation or functions of PCNA in these closely related eukaryotes.

  18. Exploring the Trypanosoma brucei Hsp83 potential as a target for structure guided drug design.

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    Juan Carlos Pizarro

    Full Text Available Human African trypanosomiasis is a neglected parasitic disease that is fatal if untreated. The current drugs available to eliminate the causative agent Trypanosoma brucei have multiple liabilities, including toxicity, increasing problems due to treatment failure and limited efficacy. There are two approaches to discover novel antimicrobial drugs--whole-cell screening and target-based discovery. In the latter case, there is a need to identify and validate novel drug targets in Trypanosoma parasites. The heat shock proteins (Hsp, while best known as cancer targets with a number of drug candidates in clinical development, are a family of emerging targets for infectious diseases. In this paper, we report the exploration of T. brucei Hsp83--a homolog of human Hsp90--as a drug target using multiple biophysical and biochemical techniques. Our approach included the characterization of the chemical sensitivity of the parasitic chaperone against a library of known Hsp90 inhibitors by means of differential scanning fluorimetry (DSF. Several compounds identified by this screening procedure were further studied using isothermal titration calorimetry (ITC and X-ray crystallography, as well as tested in parasite growth inhibitions assays. These experiments led us to the identification of a benzamide derivative compound capable of interacting with TbHsp83 more strongly than with its human homologs and structural rationalization of this selectivity. The results highlight the opportunities created by subtle structural differences to develop new series of compounds to selectively target the Trypanosoma brucei chaperone and effectively kill the sleeping sickness parasite.

  19. Regulation and spatial organization of PCNA in Trypanosoma brucei

    Energy Technology Data Exchange (ETDEWEB)

    Kaufmann, Doris; Gassen, Alwine [University of Munich (LMU), Department Biology I, Genetics, Grosshaderner Str. 2-4, 82152 Martinsried (Germany); Maiser, Andreas; Leonhardt, Heinrich [University of Munich (LMU), Department Biology II, Grosshaderner Str. 2-4, 82152 Martinsried (Germany); Janzen, Christian J., E-mail: christian.janzen@uni-wuerzburg.de [University of Munich (LMU), Department Biology I, Genetics, Grosshaderner Str. 2-4, 82152 Martinsried (Germany)

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer Characterization of the proliferating cell nuclear antigen in Trypanosoma brucei (TbPCNA). Black-Right-Pointing-Pointer TbPCNA is a suitable marker to detect replication in T. brucei. Black-Right-Pointing-Pointer TbPCNA distribution and regulation is different compared to closely related parasites T. cruzi and Leishmania donovani. -- Abstract: As in most eukaryotic cells, replication is regulated by a conserved group of proteins in the early-diverged parasite Trypanosoma brucei. Only a few components of the replication machinery have been described in this parasite and regulation, sub-nuclear localization and timing of replication are not well understood. We characterized the proliferating cell nuclear antigen in T. brucei (TbPCNA) to establish a spatial and temporal marker for replication. Interestingly, PCNA distribution and regulation is different compared to the closely related parasites Trypanosoma cruzi and Leishmania donovani. TbPCNA foci are clearly detectable during S phase of the cell cycle but in contrast to T. cruzi they are not preferentially located at the nuclear periphery. Furthermore, PCNA seems to be degraded when cells enter G2 phase in T. brucei suggesting different modes of replication regulation or functions of PCNA in these closely related eukaryotes.

  20. The activity of aminoglycoside antibiotics against Trypanosoma brucei.

    Science.gov (United States)

    Maina, N W; Kinyanjui, B; Onyango, J D; Auma, J E; Croj, S

    1998-01-01

    The trypanocidal activity of four aminoglycosides was determined against Trypanosoma brucei in vitro. The drug activity in descending order, was as follows; paromomycin kanamycin>gentamycin > neomycin. Paromomycin bad the highest activity and the concentration that inhibited 50% of trypanosome growth (IC50) was 11.4microM. The effect of paromomycin on the causative agents of the East African form of sleeping sickness - T.b. rhodesiense KETRI 265, 2285, 2545, 2562 and EATRO 110,112, 1152 was subsequently assessed. Variations sensitivities between the trypanosome populations were observed and IC50 values ranging from 13.01 to 43.06 microM recorded. However, when paromomycin was administered intraperitoneally (i.p) at 500 mg/kg, it was not effective in curing mice infected with T. b. rhodesienseKETRI 2545 the most drug-sensitive isolate in vitro. Lack of in vivo activity may be because the trypanosome is an extracellular parasite. The pharmacokinetics of paromomycin in the mouse model need to be determined.

  1. Trypanosoma brucei metabolite indolepyruvate decreases HIF-1α and glycolysis in macrophages as a mechanism of innate immune evasion.

    Science.gov (United States)

    McGettrick, Anne F; Corcoran, Sarah E; Barry, Paul J G; McFarland, Jennifer; Crès, Cécile; Curtis, Anne M; Franklin, Edward; Corr, Sinéad C; Mok, K Hun; Cummins, Eoin P; Taylor, Cormac T; O'Neill, Luke A J; Nolan, Derek P

    2016-11-29

    The parasite Trypanasoma brucei causes African trypanosomiasis, known as sleeping sickness in humans and nagana in domestic animals. These diseases are a major burden in the 36 sub-Saharan African countries where the tsetse fly vector is endemic. Untreated trypanosomiasis is fatal and the current treatments are stage-dependent and can be problematic during the meningoencephalitic stage, where no new therapies have been developed in recent years and the current drugs have a low therapeutic index. There is a need for more effective treatments and a better understanding of how these parasites evade the host immune response will help in this regard. The bloodstream form of T. brucei excretes significant amounts of aromatic ketoacids, including indolepyruvate, a transamination product of tryptophan. This study demonstrates that this process is essential in bloodstream forms, is mediated by a specialized isoform of cytoplasmic aminotransferase and, importantly, reveals an immunomodulatory role for indolepyruvate. Indolepyruvate prevents the LPS-induced glycolytic shift in macrophages. This effect is the result of an increase in the hydroxylation and degradation of the transcription factor hypoxia-inducible factor-1α (HIF-1α). The reduction in HIF-1α levels by indolepyruvate, following LPS or trypanosome activation, results in a decrease in production of the proinflammatory cytokine IL-1β. These data demonstrate an important role for indolepyruvate in immune evasion by T. brucei.

  2. Triacylglycerol Storage in Lipid Droplets in Procyclic Trypanosoma brucei.

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    Stefan Allmann

    Full Text Available Carbon storage is likely to enable adaptation of trypanosomes to nutritional challenges or bottlenecks during their stage development and migration in the tsetse. Lipid droplets are candidates for this function. This report shows that feeding of T. brucei with oleate results in a 4-5 fold increase in the number of lipid droplets, as quantified by confocal fluorescence microscopy and by flow cytometry of BODIPY 493/503-stained cells. The triacylglycerol (TAG content also increased 4-5 fold, and labeled oleate is incorporated into TAG. Fatty acid carbon can thus be stored as TAG in lipid droplets under physiological growth conditions in procyclic T. brucei. β-oxidation has been suggested as a possible catabolic pathway for lipids in T. brucei. A single candidate gene, TFEα1 with coding capacity for a subunit of the trifunctional enzyme complex was identified. TFEα1 is expressed in procyclic T. brucei and present in glycosomal proteomes, Unexpectedly, a TFEα1 gene knock-out mutant still expressed wild-type levels of previously reported NADP-dependent 3-hydroxyacyl-CoA dehydrogenase activity, and therefore, another gene encodes this enzymatic activity. Homozygous Δtfeα1/Δtfeα1 null mutant cells show a normal growth rate and an unchanged glycosomal proteome in procyclic T. brucei. The decay kinetics of accumulated lipid droplets upon oleate withdrawal can be fully accounted for by the dilution effect of cell division in wild-type and Δtfeα1/Δtfeα1 cells. The absence of net catabolism of stored TAG in procyclic T. brucei, even under strictly glucose-free conditions, does not formally exclude a flux through TAG, in which biosynthesis equals catabolism. Also, the possibility remains that TAG catabolism is completely repressed by other carbon sources in culture media or developmentally activated in post-procyclic stages in the tsetse.

  3. Minimum Information Loss Based Multi-kernel Learning for Flagellar Protein Recognition in Trypanosoma Brucei

    KAUST Repository

    Wang, Jim Jing-Yan

    2014-12-01

    Trypanosma brucei (T. Brucei) is an important pathogen agent of African trypanosomiasis. The flagellum is an essential and multifunctional organelle of T. Brucei, thus it is very important to recognize the flagellar proteins from T. Brucei proteins for the purposes of both biological research and drug design. In this paper, we investigate computationally recognizing flagellar proteins in T. Brucei by pattern recognition methods. It is argued that an optimal decision function can be obtained as the difference of probability functions of flagella protein and the non-flagellar protein for the purpose of flagella protein recognition. We propose to learn a multi-kernel classification function to approximate this optimal decision function, by minimizing the information loss of such approximation which is measured by the Kull back-Leibler (KL) divergence. An iterative multi-kernel classifier learning algorithm is developed to minimize the KL divergence for the problem of T. Brucei flagella protein recognition, experiments show its advantage over other T. Brucei flagellar protein recognition and multi-kernel learning methods. © 2014 IEEE.

  4. In vivo trypanocidal activity of Nymphaea lotus Linn. methanol extract against Trypanosoma brucei brucei

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    Muhammad Haruna Garba

    2015-10-01

    Full Text Available Objective: To evaluate the antitrypanosomal potentials of methanol extract of Nymphaea lotus Linn. (N. lotus with the aim of obtaining a new lead for formulating safe, inexpensive, nontoxic and readily available trypanocidal drugs. Methods: Seventy percent (v/v (methanol/water crude extract of N. lotus was evaluated for antitrypanosomal activity in experimental trypanosomiasis using Trypanosoma brucei bruceiinfected mice. Infected mice in different groups were administered intraperitoneally 100, 200, 300 and 400 mg/kg body weight/day of the crude for two weeks, while a positive control group was treated with standard drug, berenil. Results: The crude extract at a dose of 100 mg/kg body weight/day was more effective than the higher doses in completely clearing parasites from the blood of mice infected with Trypanosoma brucei brucei. Pre-treatment of healthy mice with the crude extract for 5 days before infection did not prevent the establishment of the infection, indicating that the extract had no prophylactic activity. Subinoculation of the blood and cerebrospinal fluid drawn from the cured mice into healthy mice failed to produce any infection within 50 days post inoculation. Administration of 1 000 mg/kg body weight of the crude extract led to the death of 50% of the experimental animals indicating a high level of toxicity of the extract at higher doses. Conclusions: This study has demonstrated the potency of the crude extract of N. lotus in treating experimental trypanosomiasis at lower doses.

  5. Estimating the burden of rhodesiense sleeping sickness during an outbreak in Serere, eastern Uganda

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    Coleman Paul G

    2008-03-01

    Full Text Available Abstract Background Zoonotic sleeping sickness, or HAT (Human African Trypanosomiasis, caused by infection with Trypanosoma brucei rhodesiense, is an under-reported and neglected tropical disease. Previous assessments of the disease burden expressed as Disability-Adjusted Life Years (DALYs for this infection have not distinguished T.b. rhodesiense from infection with the related, but clinically distinct Trypanosoma brucei gambiense form. T.b. rhodesiense occurs focally, and it is important to assess the burden at the scale at which resource-allocation decisions are made. Methods The burden of T.b. rhodesiense was estimated during an outbreak of HAT in Serere, Uganda. We identified the unique characteristics affecting the burden of rhodesiense HAT such as age, severity, level of under-reporting and duration of hospitalisation, and use field data and empirical estimates of these to model the burden imposed by this and other important diseases in this study population. While we modelled DALYs using standard methods, we also modelled uncertainty of our parameter estimates through a simulation approach. We distinguish between early and late stage HAT morbidity, and used disability weightings appropriate for the T.b. rhodesiense form of HAT. We also use a model of under-reporting of HAT to estimate the contribution of un-reported mortality to the overall disease burden in this community, and estimate the cost-effectiveness of hospital-based HAT control. Results Under-reporting accounts for 93% of the DALY estimate of rhodesiense HAT. The ratio of reported malaria cases to reported HAT cases in the same health unit was 133:1, however, the ratio of DALYs was 3:1. The age productive function curve had a close correspondence with the HAT case distribution, and HAT cases occupied more patient admission time in Serere during 1999 than all other infectious diseases other than malaria. The DALY estimate for HAT in Serere shows that the burden is much greater

  6. Divergent Small Tim Homologues Are Associated with TbTim17 and Critical for the Biogenesis of TbTim17 Protein Complexes in Trypanosoma brucei

    Science.gov (United States)

    Smith, Joseph T.; Singha, Ujjal K.; Misra, Smita

    2018-01-01

    ABSTRACT The small Tim proteins belong to a group of mitochondrial intermembrane space chaperones that aid in the import of mitochondrial inner membrane proteins with internal targeting signals. Trypanosoma brucei, the protozoan parasite that causes African trypanosomiasis, possesses multiple small Tim proteins that include homologues of T. brucei Tim9 (TbTim9) and Tim10 (TbTim10) and a unique small Tim that shares homology with both Tim8 and Tim13 (TbTim8/13). Here, we found that these three small TbTims are expressed as soluble mitochondrial intermembrane space proteins. Coimmunoprecipitation and mass spectrometry analysis showed that the small TbTims stably associated with each other and with TbTim17, the major component of the mitochondrial inner membrane translocase in T. brucei. Yeast two-hybrid analysis indicated direct interactions among the small TbTims; however, their interaction patterns appeared to be different from those of their counterparts in yeast and humans. Knockdown of the small TbTims reduced cell growth and decreased the steady-state level of TbTim17 and T. brucei ADP/ATP carrier (TbAAC), two polytopic mitochondrial inner membrane proteins. Knockdown of small TbTims also reduced the matured complexes of TbTim17 in mitochondria. Depletion of any of the small TbTims reduced TbTim17 import moderately but greatly hampered the stability of the TbTim17 complexes in T. brucei. Altogether, our results revealed that TbTim9, TbTim10, and TbTim8/13 interact with each other, associate with TbTim17, and play a crucial role in the integrity and maintenance of the levels of TbTim17 complexes. IMPORTANCE Trypanosoma brucei is the causative agent of African sleeping sickness. The parasite’s mitochondrion represents a useful source for potential chemotherapeutic targets. Similarly to yeast and humans, mitochondrial functions depend on the import of proteins that are encoded in the nucleus and made in the cytosol. Even though the machinery involved in this

  7. New heterocyclic compounds: Synthesis and antitrypanosomal properties.

    Science.gov (United States)

    Pomel, S; Dubar, F; Forge, D; Loiseau, P M; Biot, C

    2015-08-15

    Three new series of quinoline, quinolone, and benzimidazole derivatives were synthesized and evaluated in vitro against Trypanosoma brucei gambiense. In the quinoline series, the metallo antimalarial drug candidate (ferroquine, FQ) and its ruthenium analogue (ruthenoquine, RQ, compound 13) showed the highest in vitro activities with IC50 values around 0.1 μM. Unfortunately, both compounds failed to cure Trypanosoma brucei brucei infected mice in vivo. The other heterocyclic compounds were active in vitro with IC50 values varying from 0.8 to 34 μM. One of the most interesting results was a fluoroquinolone derivative (compound 2) that was able to offer a survival time of 8 days after a treatment at the single dose of 100 μmol/kg by intraperitoneal route. Although no clear-cut structure-activity relationships emerged, further pharmacomodulations are worth to be developed in this series. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Studies on the glycosome of Trypanosoma brucei

    International Nuclear Information System (INIS)

    Aman, R.A.

    1985-01-01

    Glycosomes (microbodies) have been purified from bloodstream form Trypanosoma brucei by an improved procedure involving freezing and thawing live organisms in 15% glycerol prior to cell disruption. Highly purified organelles of bloodstream form T. brucei contain 11 major proteins of which 8 tentatively identified glycolytic enzymes make up about 90% of the total glycosomal protein. Treatment of these intact isolated organelles with the bisimidoester dimethylsuberimidate (DMSI) resulted in crosslinking of all glycosomal proteins into a large complex suggestive of juxtapositioning of the glycosomal proteins. The crosslinked complex was capable of catalyzing the multienzyme conversion of glucose to glycerol-3-phosphate but did not possess any special kinetic features different from those of the unaggregated enzymes represented by solubilized glycosomes. The multienzyme reaction had a lab phase associated with it and [ 14 C]-glucose label incorporation into sugar phosphate intermediates was effectively competed by unlabeled intermediates. Glycosomes were also purified from culture form T. brucei by several different procedures. Comparison of highly purified organelles from the two different life stages of the organism showed reduced specific activities and contents of the early glycolytic enzymes in organelles from the culture form with a decrease from 87% to 35% of the contribution of glycolytic enzymes to the total glycosomal protein

  9. Transcriptome Profiling of Trypanosoma brucei Development in the Tsetse Fly Vector Glossina morsitans.

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    Amy F Savage

    Full Text Available African trypanosomes, the causative agents of sleeping sickness in humans and nagana in animals, have a complex digenetic life cycle between a mammalian host and an insect vector, the blood-feeding tsetse fly. Although the importance of the insect vector to transmit the disease was first realized over a century ago, many aspects of trypanosome development in tsetse have not progressed beyond a morphological analysis, mainly due to considerable challenges to obtain sufficient material for molecular studies. Here, we used high-throughput RNA-Sequencing (RNA-Seq to profile Trypanosoma brucei transcript levels in three distinct tissues of the tsetse fly, namely the midgut, proventriculus and salivary glands. Consistent with current knowledge and providing a proof of principle, transcripts coding for procyclin isoforms and several components of the cytochrome oxidase complex were highly up-regulated in the midgut transcriptome, whereas transcripts encoding metacyclic VSGs (mVSGs and the surface coat protein brucei alanine rich protein or BARP were extremely up-regulated in the salivary gland transcriptome. Gene ontology analysis also supported the up-regulation of biological processes such as DNA metabolism and DNA replication in the proventriculus transcriptome and major changes in signal transduction and cyclic nucleotide metabolism in the salivary gland transcriptome. Our data highlight a small repertoire of expressed mVSGs and potential signaling pathways involving receptor-type adenylate cyclases and members of a surface carboxylate transporter family, called PADs (Proteins Associated with Differentiation, to cope with the changing environment, as well as RNA-binding proteins as a possible global regulators of gene expression.

  10. Evaluation of In Vitro Activity of Essential Oils against Trypanosoma brucei brucei and Trypanosoma evansi

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    Nathan Habila

    2010-01-01

    Full Text Available Essential oils (EOs from Cymbopogon citratus (CC, Eucalyptus citriodora (EC, Eucalyptus camaldulensis (ED, and Citrus sinensis (CS were obtained by hydrodistillation process. The EOs were evaluated in vitro for activity against Trypanosoma brucei brucei (Tbb and Trypanosoma evansi (T. evansi. The EOs were found to possess antitrypanosomal activity in vitro in a dose-dependent pattern in a short period of time. The drop in number of parasite over time was achieved doses of 0.4 g/ml, 0.2 g/mL, and 0.1 g/mL for all the EOs. The concentration of 0.4 g/mL CC was more potent at 3 minutes and 2 minutes for Tbb and T. evansi, respectively. The GC-MS analysis of the EOs revealed presence of Cyclobutane (96.09% in CS, 6-octenal (77.11% in EC, Eucalyptol (75% in ED, and Citral (38.32% in CC among several other organic compounds. The results are discussed in relation to trypanosome chemotherapy.

  11. PHYTOREMEDIATION POTENTIAL OF Vigna unguiculata IN A ...

    African Journals Online (AJOL)

    FRANK

    Following the first appearance of T. b. gambiense parasitaemia, the animals developed ... of sleep and wakefulness between weeks 8 and 10 when the animals were in the classical diurnal sleepiness with 8 -. 10 sleep ..... transgenic mice.

  12. Protein functional links in Trypanosoma brucei, identified by gene fusion analysis

    Directory of Open Access Journals (Sweden)

    Trimpalis Philip

    2011-07-01

    Full Text Available Abstract Background Domain or gene fusion analysis is a bioinformatics method for detecting gene fusions in one organism by comparing its genome to that of other organisms. The occurrence of gene fusions suggests that the two original genes that participated in the fusion are functionally linked, i.e. their gene products interact either as part of a multi-subunit protein complex, or in a metabolic pathway. Gene fusion analysis has been used to identify protein functional links in prokaryotes as well as in eukaryotic model organisms, such as yeast and Drosophila. Results In this study we have extended this approach to include a number of recently sequenced protists, four of which are pathogenic, to identify fusion linked proteins in Trypanosoma brucei, the causative agent of African sleeping sickness. We have also examined the evolution of the gene fusion events identified, to determine whether they can be attributed to fusion or fission, by looking at the conservation of the fused genes and of the individual component genes across the major eukaryotic and prokaryotic lineages. We find relatively limited occurrence of gene fusions/fissions within the protist lineages examined. Our results point to two trypanosome-specific gene fissions, which have recently been experimentally confirmed, one fusion involving proteins involved in the same metabolic pathway, as well as two novel putative functional links between fusion-linked protein pairs. Conclusions This is the first study of protein functional links in T. brucei identified by gene fusion analysis. We have used strict thresholds and only discuss results which are highly likely to be genuine and which either have already been or can be experimentally verified. We discuss the possible impact of the identification of these novel putative protein-protein interactions, to the development of new trypanosome therapeutic drugs.

  13. Mechanism of Trypanosoma brucei gambiense resistance to human serum

    DEFF Research Database (Denmark)

    Uzureau, Pierrick; Uzureau, Sophie; Lecordier, Laurence

    2013-01-01

    GP), which prevents APOL1 toxicity and induces stiffening of membranes upon interaction with lipids. Two additional features contribute to resistance to TLFs: reduction of sensitivity to APOL1 requiring cysteine protease activity, and TbHpHbR inactivation due to a L210S substitution. According...

  14. Mating compatibility in the parasitic protist Trypanosoma brucei.

    Science.gov (United States)

    Peacock, Lori; Ferris, Vanessa; Bailey, Mick; Gibson, Wendy

    2014-02-21

    Genetic exchange has been described in several kinetoplastid parasites, but the most well-studied mating system is that of Trypanosoma brucei, the causative organism of African sleeping sickness. Sexual reproduction takes place in the salivary glands (SG) of the tsetse vector and involves meiosis and production of haploid gametes. Few genetic crosses have been carried out to date and consequently there is little information about the mating compatibility of different trypanosomes. In other single-celled eukaryotes, mating compatibility is typically determined by a system of two or more mating types (MT). Here we investigated the MT system in T. brucei. We analysed a large series of F1, F2 and back crosses by pairwise co-transmission of red and green fluorescent cloned cell lines through experimental tsetse flies. To analyse each cross, trypanosomes were cloned from fly SG containing a mixture of both parents, and genotyped by microsatellites and molecular karyotype. To investigate mating compatibility at the level of individual cells, we directly observed the behaviour of SG-derived gametes in intra- or interclonal mixtures of red and green fluorescent trypanosomes ex vivo. Hybrid progeny were found in all F1 and F2 crosses and most of the back crosses. The success of individual crosses was highly variable as judged by the number of hybrid clones produced, suggesting a range of mating compatibilities among F1 progeny. As well as hybrids, large numbers of recombinant genotypes resulting from intraclonal mating (selfers) were found in some crosses. In ex vivo mixtures, red and green fluorescent trypanosome gametes were observed to pair up and interact via their flagella in both inter- and intraclonal combinations. While yellow hybrid trypanosomes were frequently observed in interclonal mixtures, such evidence of cytoplasmic exchange was rare in the intraclonal mixtures. The outcomes of individual crosses, particularly back crosses, were variable in numbers of both

  15. Antitrypanosomal effect of methanolic extract of Zingiber officinale (ginger on Trypanosoma brucei brucei-infected Wistar mice

    Directory of Open Access Journals (Sweden)

    P. I. Kobo

    2014-10-01

    Full Text Available Aim: The study was carried out to determine the in vivo antitrypanosomal effect of methanolic extract of Zingiber officinale (ginger in Trypanosoma brucei brucei-infected mice. Materials and Methods: Twenty-five mice were randomly allocated into five groups of five animals each. Group I and II were given Tween 80 (1 ml/kg and diminazene aceturate (3.5 mg/kg to serve as untreated and treated controls, respectively. Groups III-V received the extract at 200, 400 and 800 mg/kg body weight, respectively. All treatments were given for 6 consecutive days and through the oral route. The mean body weight, mean survival period and daily level of parasitaemia were evaluated. Results: Acute toxicity showed the extract to be relatively safe. There was an insignificant increase in body weight and survival rate of mice treated with the extract. The level of parasitaemia in the extract treated groups was decreased. Conclusion: This study shows the in vivo potential of methanolic extract of Z. officinale in the treatment of trypanosomiasis.

  16. Intraclonal mating occurs during tsetse transmission of Trypanosoma brucei

    Directory of Open Access Journals (Sweden)

    Ferris Vanessa

    2009-09-01

    Full Text Available Abstract Background Mating in Trypanosoma brucei is a non-obligatory event, triggered by the co-occurrence of different strains in the salivary glands of the vector. Recombinants that result from intra- rather than interclonal mating have been detected, but only in crosses of two different trypanosome strains. This has led to the hypothesis that when trypanosomes recognize a different strain, they release a diffusible factor or pheromone that triggers mating in any cell in the vicinity whether it is of the same or a different strain. This idea assumes that the trypanosome can recognize self and non-self, although there is as yet no evidence for the existence of mating types in T. brucei. Results We investigated intraclonal mating in T. b. brucei by crossing red and green fluorescent lines of a single strain, so that recombinant progeny can be detected in the fly by yellow fluorescence. For strain 1738, seven flies had both red and green trypanosomes in the salivary glands and, in three, yellow trypanosomes were also observed, although they could not be recovered for subsequent analysis. Nonetheless, both red and non-fluorescent clones from these flies had recombinant genotypes as judged by microsatellite and karyotype analyses, and some also had raised DNA contents, suggesting recombination or genome duplication. Strain J10 produced similar results indicative of intraclonal mating. In contrast, trypanosome clones recovered from other flies showed that genotypes can be transmitted with fidelity. When a yellow hybrid clone expressing both red and green fluorescent protein genes was transmitted, the salivary glands contained a mixture of fluorescent-coloured trypanosomes, but only yellow and red clones were recovered. While loss of the GFP gene in the red clones could have resulted from gene conversion, some of these clones showed loss of heterozygosity and raised DNA contents as in the other single strain transmissions. Our observations suggest

  17. Interaction between Trypanosoma brucei and Haemonchus ...

    African Journals Online (AJOL)

    In order to investigate the immunomodulatory influence of concurrent T. brucei and H. contortus infection in West African Dwarf (WAD) goats, 28 infected and 7 uninfected (control) of 8-9 months old male WAD goats were studied. The infected goats were separated into resistant (Class 1) and susceptible (Class 2) Faecal ...

  18. Endogenous sterol biosynthesis is important for mitochondrial function and cell morphology in procyclic forms of Trypanosoma brucei.

    Science.gov (United States)

    Pérez-Moreno, Guiomar; Sealey-Cardona, Marco; Rodrigues-Poveda, Carlos; Gelb, Michael H; Ruiz-Pérez, Luis Miguel; Castillo-Acosta, Víctor; Urbina, Julio A; González-Pacanowska, Dolores

    2012-10-01

    Sterol biosynthesis inhibitors are promising entities for the treatment of trypanosomal diseases. Insect forms of Trypanosoma brucei, the causative agent of sleeping sickness, synthesize ergosterol and other 24-alkylated sterols, yet also incorporate cholesterol from the medium. While sterol function has been investigated by pharmacological manipulation of sterol biosynthesis, molecular mechanisms by which endogenous sterols influence cellular processes remain largely unknown in trypanosomes. Here we analyse by RNA interference, the effects of a perturbation of three specific steps of endogenous sterol biosynthesis in order to dissect the role of specific intermediates in proliferation, mitochondrial function and cellular morphology in procyclic cells. A decrease in the levels of squalene synthase and squalene epoxidase resulted in a depletion of cellular sterol intermediates and end products, impaired cell growth and led to aberrant morphologies, DNA fragmentation and a profound modification of mitochondrial structure and function. In contrast, cells deficient in sterol methyl transferase, the enzyme involved in 24-alkylation, exhibited a normal growth phenotype in spite of a complete abolition of the synthesis and content of 24-alkyl sterols. Thus, the data provided indicates that while the depletion of squalene and post-squalene endogenous sterol metabolites results in profound cellular defects, bulk 24-alkyl sterols are not strictly required to support growth in insect forms of T. brucei in vitro. Copyright © 2012 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

  19. Meiosis and haploid gametes in the pathogen Trypanosoma brucei.

    Science.gov (United States)

    Peacock, Lori; Bailey, Mick; Carrington, Mark; Gibson, Wendy

    2014-01-20

    In eukaryote pathogens, sex is an important driving force in spreading genes for drug resistance, pathogenicity, and virulence. For the parasitic trypanosomes that cause African sleeping sickness, mating occurs during transmission by the tsetse vector and involves meiosis, but haploid gametes have not yet been identified. Here, we show that meiosis is a normal part of development in the insect salivary glands for all subspecies of Trypanosoma brucei, including the human pathogens. By observing insect-derived trypanosomes during the window of peak expression of meiosis-specific genes, we identified promastigote-like (PL) cells that interacted with each other via their flagella and underwent fusion, as visualized by the mixing of cytoplasmic red and green fluorescent proteins. PL cells had a short, wide body, a very long anterior flagellum, and either one or two kinetoplasts, but only the anterior kinetoplast was associated with the flagellum. Measurement of nuclear DNA contents showed that PL cells were haploid relative to diploid metacyclics. Trypanosomes are among the earliest diverging eukaryotes, and our results support the hypothesis that meiosis and sexual reproduction are ubiquitous in eukaryotes and likely to have been early innovations. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Deciphering RNA Regulatory Elements Involved in the Developmental and Environmental Gene Regulation of Trypanosoma brucei.

    Science.gov (United States)

    Gazestani, Vahid H; Salavati, Reza

    2015-01-01

    Trypanosoma brucei is a vector-borne parasite with intricate life cycle that can cause serious diseases in humans and animals. This pathogen relies on fine regulation of gene expression to respond and adapt to variable environments, with implications in transmission and infectivity. However, the involved regulatory elements and their mechanisms of actions are largely unknown. Here, benefiting from a new graph-based approach for finding functional regulatory elements in RNA (GRAFFER), we have predicted 88 new RNA regulatory elements that are potentially involved in the gene regulatory network of T. brucei. We show that many of these newly predicted elements are responsive to both transcriptomic and proteomic changes during the life cycle of the parasite. Moreover, we found that 11 of predicted elements strikingly resemble previously identified regulatory elements for the parasite. Additionally, comparison with previously predicted motifs on T. brucei suggested the superior performance of our approach based on the current limited knowledge of regulatory elements in T. brucei.

  1. Trypanosoma brucei mitochondrial respiratome: Composition and organization in procyclic form

    KAUST Repository

    Acestor, Nathalie

    2011-05-24

    The mitochondrial respiratory chain is comprised of four different protein complexes (I-IV), which are responsible for electron transport and generation of proton gradient in the mitochondrial intermembrane space. This proton gradient is then used by F oF 1-ATP synthase (complex V) to produce ATP by oxidative phosphorylation. In this study, the respiratory complexes I, II, and III were affinity purified from Trypanosoma brucei procyclic form cells and their composition was determined by mass spectrometry. The results along with those that we previously reported for complexes IV and V showed that the respiratome of Trypanosoma is divergent because many of its proteins are unique to this group of organisms. The studies also identified two mitochondrial subunit proteins of respiratory complex IV that are encoded by edited RNAs. Proteomics data from analyses of complexes purified using numerous tagged component proteins in each of the five complexes were used to generate the first predicted protein-protein interaction network of the Trypanosoma brucei respiratory chain. These results provide the first comprehensive insight into the unique composition of the respiratory complexes in Trypanosoma brucei, an early diverged eukaryotic pathogen. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Haematological indices in Trypanosoma brucei brucei (Federe isolate infected Nigerian donkeys (Equus asinus treated with homidium and isometamidium chloride of ciprofloxacin in broiler chickens after single intravenous and intraingluvial administration

    Directory of Open Access Journals (Sweden)

    Queen Nneka Oparah

    2017-03-01

    Full Text Available The efficacy of intramuscular administration of Homidium chloride (Novidium® and Isometamidium chloride (Sécuridium® in Nigerian donkeys (Equus asinus experimentally infected with T. b. brucei (Federe isolate was investigated. Changes in haematological and serum biochemical indices were evaluated using clinical haematology and biochemistry methods. Red blood cell (RBC count for the negative control group was significantly higher than for the positive control, Novidium® and Sécuridium®-treatment groups. Haemoglobin (Hb concentration significantly reduced in the infected untreated group compared with other groups. Packed cell volume (PCV was significantly different between negative and positive controls, and also between the infected untreated and treatment groups. There was significant reduction in platelet counts post-infection and post-treatment. Mean corpuscular volume (MCV increased significantly in the treatment groups while mean corpuscular haemoglobin concentration (MCHC significantly reduced only in the Sécuridium®-treatment group. Lymphocyte count for infected untreated was non-significantly higher than for the uninfected controls, but treatment with both trypanocides recorded further increases, which were higher compared with that of the uninfected group. Post infection and treatment, aspartate aminotransferase (AST levels increased significantly. There were non-significant differences in electrolyte ion concentrations across the groups except for chloride ion which recorded a significant reduction in the Novidium®-treatment group. This experiment revealed that Nigerian donkeys infected with T. brucei brucei (Federe isolate developed symptoms of trypanosomosis; anaemia, lymphocytosis and thrombocytopenia. Treatment with the trypanocides ameliorated effects of the infection, and results suggest that immunosuppression may not be a substantial clinical manifestation of T. brucei brucei (Federe isolate trypanosomosis in Nigerian

  3. Crystal structure of arginine methyltransferase 6 from Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Chongyuan Wang

    Full Text Available Arginine methylation plays vital roles in the cellular functions of the protozoan Trypanosoma brucei. The T. brucei arginine methyltransferase 6 (TbPRMT6 is a type I arginine methyltransferase homologous to human PRMT6. In this study, we report the crystal structures of apo-TbPRMT6 and its complex with the reaction product S-adenosyl-homocysteine (SAH. The structure of apo-TbPRMT6 displays several features that are different from those of type I PRMTs that were structurally characterized previously, including four stretches of insertion, the absence of strand β15, and a distinct dimerization arm. The comparison of the apo-TbPRMT6 and SAH-TbPRMT6 structures revealed the fine rearrangements in the active site upon SAH binding. The isothermal titration calorimetry results demonstrated that SAH binding greatly increases the affinity of TbPRMT6 to a substrate peptide derived from bovine histone H4. The western blotting and mass spectrometry results revealed that TbPRMT6 methylates bovine histone H4 tail at arginine 3 but cannot methylate several T. brucei histone tails. In summary, our results highlight the structural differences between TbPRMT6 and other type I PRMTs and reveal that the active site rearrangement upon SAH binding is important for the substrate binding of TbPRMT6.

  4. Diagnostic Accuracy and Feasibility of Serological Tests on Filter Paper Samples for Outbreak Detection of T.b. gambiense Human African Trypanosomiasis

    Science.gov (United States)

    Hasker, Epco; Lutumba, Pascal; Mumba, Dieudonné; Lejon, Veerle; Büscher, Phillipe; Kande, Victor; Muyembe, Jean Jacques; Menten, Joris; Robays, Jo; Boelaert, Marleen

    2010-01-01

    Control of human African trypanosomiasis (HAT) in the Democratic Republic of Congo is based on mass population screening by mobile teams; a costly and labor-intensive approach. We hypothesized that blood samples collected on filter paper by village health workers and processed in a central laboratory might be a cost-effective alternative. We estimated sensitivity and specificity of micro-card agglutination test for trypanosomiasis (micro-CATT) and enzyme-linked immunosorbent assay (ELISA)/T.b. gambiense on filter paper samples compared with parasitology-based case classification and used the results in a Monte Carlo simulation of a lot quality assurance sampling (LQAS) approach. Micro-CATT and ELISA/T.b. gambiense showed acceptable sensitivity (92.7% [95% CI 87.4–98.0%] and 82.2% [95% CI 75.3–90.4%]) and very high specificity (99.4% [95% CI 99.0–99.9%] and 99.8% [95% CI 99.5–100%]), respectively. Conditional on high sample size per lot (≥ 60%), both tests could reliably distinguish a 2% from a zero prevalence at village level. Alternatively, these tests could be used to identify individual HAT suspects for subsequent confirmation. PMID:20682885

  5. Fluorine walk: The impact of fluorine in quinolone amides on their activity against African sleeping sickness.

    Science.gov (United States)

    Berninger, Michael; Erk, Christine; Fuß, Antje; Skaf, Joseph; Al-Momani, Ehab; Israel, Ina; Raschig, Martina; Güntzel, Paul; Samnick, Samuel; Holzgrabe, Ulrike

    2018-05-25

    Human African Trypanosomiasis, also known as African sleeping sickness, is caused by the parasitic protozoa of the genus Trypanosoma. If there is no pharmacological intervention, the parasites can cross the blood-brain barrier (BBB), inevitably leading to death of the patients. Previous investigation identified the quinolone amide GHQ168 as a promising lead compound having a nanomolar activity against T. b. brucei. Here, the role of a fluorine substitution at different positions was investigated in regard to toxicity, pharmacokinetics, and antitrypanosomal activity. This 'fluorine walk' led to new compounds with improved metabolic stability and consistent activity against T. b. brucei. The ability of the new quinolone amides to cross the BBB was confirmed using an 18 F-labelled quinolone amide derivative by means of ex vivo autoradiography of a murine brain. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  6. Role of cytokines in Trypanosoma brucei-induced anaemia: A ...

    African Journals Online (AJOL)

    species Trypanosoma brucei that are transmitted by a tsetse fly (Glossina spp.) ... of autologous immunoglobulin antibodies on the red cell surfaces and also to ... development for the detection and management of anaemia in trypanosomiasis.

  7. Malleable Mitochondrion of Trypanosoma brucei

    Czech Academy of Sciences Publication Activity Database

    Verner, Zdeněk; Basu, Somsuvro; Benz, C.; Dixit, S.; Dobáková, Eva; Faktorová, Drahomíra; Hashimi, Hassan; Horáková, Eva; Huang, Zhenqiu; Paris, Zdeněk; Peña-Diaz, Priscila; Ridlon, L.; Týč, Jiří; Wildridge, David; Zíková, Alena; Lukeš, Julius

    2015-01-01

    Roč. 315, 2015 Feb 07 (2015), s. 73-151 ISSN 1937-6448 R&D Projects: GA ČR GAP302/12/2513; GA MŠk LL1205; GA MŠk(CZ) EE2.3.30.0032; GA MŠk LH12104; GA ČR GAP305/12/2261 EU Projects: European Commission(XE) 316304 Institutional support: RVO:60077344 Keywords : Kinetoplast * Metabolism * Mitochondrial transport * Mitochondrion * RNA import * T. brucei * Trypanosome * kDNA Subject RIV: EE - Microbiology, Virology Impact factor: 3.752, year: 2015

  8. What controls glycolysis in bloodstream form Trypanosoma brucei?

    NARCIS (Netherlands)

    Bakker, B.M.; Michels, P.A.M.; Opperdoes, F.R.; Westerhoff, H.V.

    1999-01-01

    On the basis of the experimentally determined kinetic properties of the trypanosomal enzymes, the question is addressed of which step limits the glycolytic flux in bloodstream form Trypanosoma brucei. There appeared to be no single answer; in the physiological range, control shifted between the

  9. Anti-trypanosomal effect of Malva sylvestris (Malvaceae) extract on a ...

    African Journals Online (AJOL)

    Methods: Sleeping sickness was induced by the intraperitoneal injection of ... count in the blood and CSF of mice with Trypanosoma brucei brucei-induced sleeping sickness compared ... The whole plant of Malva sylvestris was collected ... The animals were anesthetized by ... significantly (p < 0.01) improved the weight of.

  10. No gold standard estimation of the sensitivity and specificity of two molecular diagnostic protocols for Trypanosoma brucei spp. in Western Kenya.

    Directory of Open Access Journals (Sweden)

    Barend Mark de Clare Bronsvoort

    2010-01-01

    Full Text Available African animal trypanosomiasis is caused by a range of tsetse transmitted protozoan parasites includingTrypanosoma vivax, Trypanosoma congolense and Trypansoma brucei. In Western Kenya and other parts of East Africa two subspecies of T. brucei, T.b. brucei and the zoonoticT.b. rhodesiense, co-circulate in livestock. A range of polymerase chain reactions (PCR have been developed as important molecular diagnostic tools for epidemiological investigations of T. brucei s.l. in the animal reservoir and of its zoonotic potential. Quantification of the relative performance of different diagnostic PCRs is essential to ensure comparability of studies. This paper describes an evaluation of two diagnostic test systems for T. brucei using a T. brucei s.l. specific PCR [1] and a single nested PCR targeting the Internal Transcribed Spacer (ITS regions of trypanosome ribosomal DNA [2]. A Bayesian formulation of the Hui-Walter latent class model was employed to estimate their test performance in the absence of a gold standard test for detecting T.brucei s.l. infections in ear-vein blood samples from cattle, pig, sheep and goat populations in Western Kenya, stored on Whatman FTA cards. The results indicate that the system employing the T. brucei s.l. specific PCR (Se1=0.760 had a higher sensitivity than the ITS-PCR (Se2=0.640; both have high specificity (Sp1=0.998; Sp2=0.997. The true prevalences for livestock populations were estimated (pcattle=0.091, ppigs=0.066, pgoats=0.005, psheep=0.006, taking into account the uncertainties in the specificity and sensitivity of the two test systems. Implications of test performance include the required survey sample size; due to its higher sensitivity and specificity, the T. brucei s.l. specific PCR requires a consistently smaller sample size than the ITS-PCR for the detection of T. brucei s.l. However the ITS-PCR is able to simultaneously screen samples for other pathogenic trypanosomes and may thus be, overall, a better

  11. Interactions among Trypanosoma brucei RAD51 paralogues in DNA repair and antigenic variation

    Science.gov (United States)

    Dobson, Rachel; Stockdale, Christopher; Lapsley, Craig; Wilkes, Jonathan; McCulloch, Richard

    2011-01-01

    Homologous recombination in Trypanosoma brucei is used for moving variant surface glycoprotein (VSG) genes into expression sites during immune evasion by antigenic variation. A major route for such VSG switching is gene conversion reactions in which RAD51, a universally conserved recombinase, catalyses homology-directed strand exchange. In any eukaryote, RAD51-directed strand exchange in vivo is mediated by further factors, including RAD51-related proteins termed Rad51 paralogues. These appear to be ubiquitously conserved, although their detailed roles in recombination remain unclear. In T. brucei, four putative RAD51 paralogue genes have been identified by sequence homology. Here we show that all four RAD51 paralogues act in DNA repair, recombination and RAD51 subnuclear dynamics, though not equivalently, while mutation of only one RAD51 paralogue gene significantly impedes VSG switching. We also show that the T. brucei RAD51 paralogues interact, and that the complexes they form may explain the distinct phenotypes of the mutants as well as observed expression interdependency. Finally, we document the Rad51 paralogues that are encoded by a wide range of protists, demonstrating that the Rad51 paralogue repertoire in T. brucei is unusually large among microbial eukaryotes and that one member of the protein family corresponds with a key, conserved eukaryotic Rad51 paralogue. PMID:21615552

  12. Changes in blood sugar levels of rats experimentally infected with Trypanosoma brucei and treated with imidocarb dipropionate and diminazene aceturate

    Directory of Open Access Journals (Sweden)

    Nwoha Rosemary Ijeoma Ogechi

    2016-01-01

    Full Text Available Objective: To determine the effect of Trypanosoma brucei (T. brucei on blood sugar level of infected rats. Methods: The experiment was done with 42 albino rats grouped into 3 groups of 14 members each. Group A was uninfected (control group, Group B was infected with T. brucei and treated with diminazene aceturate, and Group C was infected with T. brucei and treated with imidocarb dipropionate. Blood samples were collected from the media canthus of the experimental rats on Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 for the assessment of change in blood sugar levels. The blood sugar levels were determined with a glucometer (Accu-chek active serial No. GN: 10023338. Results: By 4 to 5 days post infection, there was a significant increase (P 0.05 was observed in the groups when compared with the control group till Day 12 of the experiment. Conclusions: T. brucei caused a significant increase in blood sugar of infected rats.

  13. An Atypical Mitochondrial Carrier That Mediates Drug Action in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Juan P de Macêdo

    2015-05-01

    Full Text Available Elucidating the mechanism of action of trypanocidal compounds is an important step in the development of more efficient drugs against Trypanosoma brucei. In a screening approach using an RNAi library in T. brucei bloodstream forms, we identified a member of the mitochondrial carrier family, TbMCP14, as a prime candidate mediating the action of a group of anti-parasitic choline analogs. Depletion of TbMCP14 by inducible RNAi in both bloodstream and procyclic forms increased resistance of parasites towards the compounds by 7-fold and 3-fold, respectively, compared to uninduced cells. In addition, down-regulation of TbMCP14 protected bloodstream form mitochondria from a drug-induced decrease in mitochondrial membrane potential. Conversely, over-expression of the carrier in procyclic forms increased parasite susceptibility more than 13-fold. Metabolomic analyses of parasites over-expressing TbMCP14 showed increased levels of the proline metabolite, pyrroline-5-carboxylate, suggesting a possible involvement of TbMCP14 in energy production. The generation of TbMCP14 knock-out parasites showed that the carrier is not essential for survival of T. brucei bloodstream forms, but reduced parasite proliferation under standard culture conditions. In contrast, depletion of TbMCP14 in procyclic forms resulted in growth arrest, followed by parasite death. The time point at which parasite proliferation stopped was dependent on the major energy source, i.e. glucose versus proline, in the culture medium. Together with our findings that proline-dependent ATP production in crude mitochondria from TbMCP14-depleted trypanosomes was reduced compared to control mitochondria, the study demonstrates that TbMCP14 is involved in energy production in T. brucei. Since TbMCP14 belongs to a trypanosomatid-specific clade of mitochondrial carrier family proteins showing very poor similarity to mitochondrial carriers of mammals, it may represent an interesting target for drug

  14. Effect of rearing diet on the infection rate in flies released for the control of tsetse populations by sterile males

    International Nuclear Information System (INIS)

    Maudlin, I.

    1990-01-01

    In areas where sleeping sickness is endemic, it is the practice of sterile insect technique (SIT) programmes to give sterilized males a bloodmeal before release into the wild in order to reduce the risk of these released flies acting as disease vectors. This strategy has been adopted because of experimental evidence which showed that it was essential to infect flies at their first feed to establish a Tripanosoma brucei gambiense or T. b rhodesiense infection in tsetse flies. The aim of the work was to test artificial tsetse diets produced in the IAEA Laboratory at Seibersdorf in order to determine whether they were as effective as whole blood in inhibiting T. brucei sensu lato (sl) infections in flies. Seven artificial diets were tested with T.b. rhodesiense; Glossina morsitans morsitans males were fed one meal of the diet and then starved for 3 days before the infective feed. None of these diets significantly altered the infection rate of the treated flies and the seven groups produced statistically homogeneous results, with a mean midgut rate of 16% (control flies fed pig blood: 17%). Flies infected as tenerals with the same trypanosome stock produced midgut rates of 61%. Three of the diets were also tested with a T. congolense stock. There were no significant differences between flies fed artificial (mean midgut infection rate: 15%) and whole blood diets (19%). G. m. morsitans infected as tenerals with this trypanosome stock produced midgut rates of 66%. As with T. brucei sl infections, teneral flies were far more likely to develop a T. congolense infection than fed flies; this result suggests that all the tsetse flies used in SIT programmes should be fed before release in order to reduce the risk both to man and his livestock. Artificial diets are as effective as whole blood in inhibiting trypanosome infections. The effect of bloodmeal on the fly infection rates is discussed in relation to lectin production in fed flies. (author). 13 refs, 2 tabs

  15. Novel sterol metabolic network of Trypanosoma brucei procyclic and bloodstream forms

    Science.gov (United States)

    Nes, Craigen R.; Singha, Ujjal K.; Liu, Jialin; Ganapathy, Kulothungan; Villalta, Fernando; Waterman, Michael R.; Lepesheva, Galina I.; Chaudhuri, Minu; Nes, W. David

    2012-01-01

    Trypanosoma brucei is the protozoan parasite that causes African trypanosomiasis, a neglected disease of people and animals. Co-metabolite analysis, labelling studies using [methyl-2H3]-methionine and substrate/product specificities of the cloned 24-SMT (sterol C24-methyltransferase) and 14-SDM (sterol C14-demethylase) from T. brucei afforded an uncommon sterol metabolic network that proceeds from lanosterol and 31-norlanosterol to ETO [ergosta-5,7,25(27)-trien-3β-ol], 24-DTO [dimethyl ergosta-5,7,25(27)-trienol] and ergosterol [ergosta-5,7,22(23)-trienol]. To assess the possible carbon sources of ergosterol biosynthesis, specifically 13C-labelled specimens of lanosterol, acetate, leucine and glucose were administered to T. brucei and the 13C distributions found were in accord with the operation of the acetate–mevalonate pathway, with leucine as an alternative precursor, to ergostenols in either the insect or bloodstream form. In searching for metabolic signatures of procyclic cells, we observed that the 13C-labelling treatments induce fluctuations between the acetyl-CoA (mitochondrial) and sterol (cytosolic) synthetic pathways detected by the progressive increase in 13C-ergosterol production (control sterol synthesis that is further fluctuated in the cytosol, yielding distinct sterol profiles in relation to cell demands on growth. PMID:22176028

  16. Gene fusion analysis in the battle against the African endemic sleeping sickness.

    Directory of Open Access Journals (Sweden)

    Philip Trimpalis

    Full Text Available The protozoan Trypanosoma brucei causes African Trypanosomiasis or sleeping sickness in humans, which can be lethal if untreated. Most available pharmacological treatments for the disease have severe side-effects. The purpose of this analysis was to detect novel protein-protein interactions (PPIs, vital for the parasite, which could lead to the development of drugs against this disease to block the specific interactions. In this work, the Domain Fusion Analysis (Rosetta Stone method was used to identify novel PPIs, by comparing T. brucei to 19 organisms covering all major lineages of the tree of life. Overall, 49 possible protein-protein interactions were detected, and classified based on (a statistical significance (BLAST e-value, domain length etc., (b their involvement in crucial metabolic pathways, and (c their evolutionary history, particularly focusing on whether a protein pair is split in T. brucei and fused in the human host. We also evaluated fusion events including hypothetical proteins, and suggest a possible molecular function or involvement in a certain biological process. This work has produced valuable results which could be further studied through structural biology or other experimental approaches so as to validate the protein-protein interactions proposed here. The evolutionary analysis of the proteins involved showed that, gene fusion or gene fission events can happen in all organisms, while some protein domains are more prone to fusion and fission events and present complex evolutionary patterns.

  17. Cyclical appearance of African trypanosomes in the cerebrospinal fluid: new insights in how trypanosomes enter the CNS.

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    Stefan Mogk

    Full Text Available It is textbook knowledge that human infective forms of Trypanosoma brucei, the causative agent of sleeping sickness, enter the brain across the blood-brain barrier after an initial phase of weeks (rhodesiense or months (gambiense in blood. Based on our results using an animal model, both statements seem questionable. As we and others have shown, the first infection relevant crossing of the blood brain border occurs via the choroid plexus, i.e. via the blood-CSF barrier. In addition, counting trypanosomes in blood-free CSF obtained by an atlanto-occipital access revealed a cyclical infection in CSF that was directly correlated to the trypanosome density in blood infection. We also obtained conclusive evidence of organ infiltration, since parasites were detected in tissues outside the blood vessels in heart, spleen, liver, eye, testis, epididymis, and especially between the cell layers of the pia mater including the Virchow-Robin space. Interestingly, in all organs except pia mater, heart and testis, trypanosomes showed either a more or less degraded appearance of cell integrity by loss of the surface coat (VSG, loss of the microtubular cytoskeleton and loss of the intracellular content, or where taken up by phagocytes and degraded intracellularly within lysosomes. This is also true for trypanosomes placed intrathecally into the brain parenchyma using a stereotactic device. We propose a different model of brain infection that is in accordance with our observations and with well-established facts about the development of sleeping sickness.

  18. Relationship between Trypanosoma brucei rhodesiense genetic diversity and clinical spectrum among sleeping sickness patients in Uganda.

    Science.gov (United States)

    Kato, Charles D; Mugasa, Claire M; Nanteza, Ann; Matovu, Enock; Alibu, Vincent P

    2017-10-27

    Human African trypanosomiasis (HAT) due to Trypanosoma brucei rhodesiense in East and southern Africa is reported to be clinically diverse. We tested the hypothesis that this clinical diversity is associated with a variation in trypanosome genotypes. Trypanosome DNA isolated from HAT patients was genotyped using 7 microsatellite markers directly from blood spotted FTA cards following a whole genome amplification. All markers were polymorphic and identified 17 multi-locus genotypes with 56% of the isolates having replicate genotypes. We did not observe any significant clustering between isolates and bootstrap values across major tree nodes were insignificant. When genotypes were compared among patients with varying clinical presentation or outcome, replicate genotypes were observed at both extremes showing no significant association between genetic diversity and clinical outcome. Our study shows that T. b. rhodesiense isolates are homogeneous within a focus and that observed clinical diversity may not be associated with parasite genetic diversity. Other factors like host genetics and environmental factors might be involved in determining clinical diversity. Our study may be important in designing appropriate control measures that target the parasite.

  19. Rab23 is a flagellar protein in Trypanosoma brucei

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    Field Mark C

    2011-06-01

    Full Text Available Abstract Background Rab small GTPases are important mediators of membrane transport, and orthologues frequently retain similar locations and functions, even between highly divergent taxa. In metazoan organisms Rab23 is an important negative regulator of Sonic hedgehog signaling and is crucial for correct development and differentiation of cellular lineages by virtue of an involvement in ciliary recycling. Previously, we reported that Trypanosoma brucei Rab23 localized to the nuclear envelope 1, which is clearly inconsistent with the mammalian location and function. As T. brucei is unicellular the potential that Rab23 has no role in cell signaling was possible. Here we sought to further investigate the role(s of Rab23 in T. brucei to determine if Rab23 was an example of a Rab protein with divergent function in distinct taxa. Methods/major findings The taxonomic distribution of Rab23 was examined and compared with the presence of flagella/cilia in representative taxa. Despite evidence for considerable secondary loss, we found a clear correlation between a conventional flagellar structure and the presence of a Rab23 orthologue in the genome. By epitope-tagging, Rab23 was localized and found to be present at the flagellum throughout the cell cycle. However, RNAi knockdown did not result in a flagellar defect, suggesting that Rab23 is not required for construction or maintenance of the flagellum. Conclusions The location of Rab23 at the flagellum is conserved between mammals and trypanosomes and the Rab23 gene is restricted to flagellated organisms. These data may suggest the presence of a Rab23-mediated signaling mechanism in trypanosomes.

  20. Structures of Trypanosoma brucei methionyl-tRNA synthetase with urea-based inhibitors provide guidance for drug design against sleeping sickness.

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    Cho Yeow Koh

    2014-04-01

    Full Text Available Methionyl-tRNA synthetase of Trypanosoma brucei (TbMetRS is an important target in the development of new antitrypanosomal drugs. The enzyme is essential, highly flexible and displaying a large degree of changes in protein domains and binding pockets in the presence of substrate, product and inhibitors. Targeting this protein will benefit from a profound understanding of how its structure adapts to ligand binding. A series of urea-based inhibitors (UBIs has been developed with IC50 values as low as 19 nM against the enzyme. The UBIs were shown to be orally available and permeable through the blood-brain barrier, and are therefore candidates for development of drugs for the treatment of late stage human African trypanosomiasis. Here, we expand the structural diversity of inhibitors from the previously reported collection and tested for their inhibitory effect on TbMetRS and on the growth of T. brucei cells. The binding modes and binding pockets of 14 UBIs are revealed by determination of their crystal structures in complex with TbMetRS at resolutions between 2.2 Å to 2.9 Å. The structures show binding of the UBIs through conformational selection, including occupancy of the enlarged methionine pocket and the auxiliary pocket. General principles underlying the affinity of UBIs for TbMetRS are derived from these structures, in particular the optimum way to fill the two binding pockets. The conserved auxiliary pocket might play a role in binding tRNA. In addition, a crystal structure of a ternary TbMetRS•inhibitor•AMPPCP complex indicates that the UBIs are not competing with ATP for binding, instead are interacting with ATP through hydrogen bond. This suggests a possibility that a general 'ATP-engaging' binding mode can be utilized for the design and development of inhibitors targeting tRNA synthetases of other disease-causing pathogen.

  1. RNA-Seq analysis validates the use of culture-derived Trypanosoma brucei and provides new markers for mammalian and insect life-cycle stages.

    Science.gov (United States)

    Naguleswaran, Arunasalam; Doiron, Nicholas; Roditi, Isabel

    2018-04-02

    Trypanosoma brucei brucei, the parasite causing Nagana in domestic animals, is closely related to the parasites causing sleeping sickness, but does not infect humans. In addition to its importance as a pathogen, the relative ease of genetic manipulation and an innate capacity for RNAi extend its use as a model organism in cell and infection biology. During its development in its mammalian and insect (tsetse fly) hosts, T. b. brucei passes through several different life-cycle stages. There are currently four life-cycle stages that can be cultured: slender forms and stumpy forms, which are equivalent to forms found in the mammal, and early and late procyclic forms, which are equivalent to forms in the tsetse midgut. Early procyclic forms show coordinated group movement (social motility) on semi-solid surfaces, whereas late procyclic forms do not. RNA-Seq was performed on biological replicates of each life-cycle stage. These constitute the first datasets for culture-derived slender and stumpy bloodstream forms and early and late procyclic forms. Expression profiles confirmed that genes known to be stage-regulated in the animal and insect hosts were also regulated in culture. Sequence reads of 100-125 bases provided sufficient precision to uncover differential expression of closely related genes. More than 100 transcripts showed peak expression in stumpy forms, including adenylate cyclases and several components of inositol metabolism. Early and late procyclic forms showed differential expression of 73 transcripts, a number of which encoded proteins that were previously shown to be stage-regulated. Moreover, two adenylate cyclases previously shown to reduce social motility are up-regulated in late procyclic forms. This study validates the use of cultured bloodstream forms as alternatives to animal-derived parasites and yields new markers for all four stages. In addition to underpinning recent findings that early and late procyclic forms are distinct life-cycle stages

  2. Overview of the Diagnostic Methods Used in the Field for Human African Trypanosomiasis: What Could Change in the Next Years?

    Directory of Open Access Journals (Sweden)

    Julien Bonnet

    2015-01-01

    Full Text Available Sleeping sickness is a parasitic infection caused by two species of trypanosomes (Trypanosoma brucei gambiense and rhodesiense, transmitted by the tsetse fly. The disease eventually affects the central nervous system, resulting in severe neurological symptoms. Without treatment, death is inevitable. During the first stage of the disease, infected patients are mildly symptomatic and early detection of infection allows safer treatment (administered on an outpatient basis which can avoid death; routine screening of the exposed population is necessary, especially in areas of high endemicity. The current therapeutic treatment of this disease, especially in stage 2, can cause complications and requires a clinical surveillance for several days. A good stage diagnosis of the disease is the cornerstone for delivering the adequate treatment. The task faced by the medical personnel is further complicated by the lack of support from local health infrastructure, which is at best weak, but often nonexistent. Therefore it is crucial to look for new more efficient technics for the diagnosis of stage which are also best suited to use in the field, in areas not possessing high-level health facilities. This review, after an overview of the disease, summarizes the current diagnosis procedures and presents the advances in the field.

  3. Serum Iron and Nitric Oxide Production in Trypanosoma brucei ...

    African Journals Online (AJOL)

    JTEkanem

    reduction in the serum iron status and a modulation of nitric oxide synthase activity of T. brucei infected rats. ... inflammation and tissue damage15. ... The serum iron level was determined ... concentration or of total nitrate and nitrite ... 15. 16. 17. 18. Days. S e ru m iro n lev e l mg. /ml. Infected treated. Infected untreated. 0.

  4. A Trypanosoma brucei kinesin heavy chain promotes parasite growth by triggering host arginase activity.

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    Géraldine De Muylder

    2013-10-01

    Full Text Available In order to promote infection, the blood-borne parasite Trypanosoma brucei releases factors that upregulate arginase expression and activity in myeloid cells.By screening a cDNA library of T. brucei with an antibody neutralizing the arginase-inducing activity of parasite released factors, we identified a Kinesin Heavy Chain isoform, termed TbKHC1, as responsible for this effect. Following interaction with mouse myeloid cells, natural or recombinant TbKHC1 triggered SIGN-R1 receptor-dependent induction of IL-10 production, resulting in arginase-1 activation concomitant with reduction of nitric oxide (NO synthase activity. This TbKHC1 activity was IL-4Rα-independent and did not mirror M2 activation of myeloid cells. As compared to wild-type T. brucei, infection by TbKHC1 KO parasites was characterized by strongly reduced parasitaemia and prolonged host survival time. By treating infected mice with ornithine or with NO synthase inhibitor, we observed that during the first wave of parasitaemia the parasite growth-promoting effect of TbKHC1-mediated arginase activation resulted more from increased polyamine production than from reduction of NO synthesis. In late stage infection, TbKHC1-mediated reduction of NO synthesis appeared to contribute to liver damage linked to shortening of host survival time.A kinesin heavy chain released by T. brucei induces IL-10 and arginase-1 through SIGN-R1 signaling in myeloid cells, which promotes early trypanosome growth and favors parasite settlement in the host. Moreover, in the late stage of infection, the inhibition of NO synthesis by TbKHC1 contributes to liver pathogenicity.

  5. Challenges in the diagnosis and management of sleeping sickness in Tanzania: a case report.

    Science.gov (United States)

    Sindato, C; Kibona, S N; Nkya, G M; Mbilu, T J N K; Manga, C; Kaboya, J S; Rawille, F

    2008-07-01

    In Tanzania sleeping sickness presents a serious threat to human health with a country-wide average of 400 cases reported annually. Both wild and domestic animals have been found to play a significant role in the epidemiology of sleeping sickness. Serengeti National Park in northern Tanzania, has experienced a number of sleeping sickness epidemics since 1922. The epidemics were associated with abundant game animals in the areas and Glossina swynnertoni was incriminated as the main vector. However since 2001 there has been no case of sleeping sickness reported from the park. This case report highlights on the possibility of resurgence and challenges in the diagnosis and management of sleeping sickness in Serengeti. A 38 years old Tanzanian man working in the Serengeti National Park who had experienced various tsetse bites was presented with a febrile condition and history of unsuccessful case management at different health facilities. Blood and cerebrospinal fluid (CSF) samples were examined for the presence oftrypanosomes using wet film, Field's stain and concentration techniques. Typanosoma brucei rhodesiense were detected in both the blood and CSF samples. The patient was treated successfully with melarsoprol. The results of this case study highlight the possibility of resurgence of sleeping sickness in the park hence calls for the need to create more awareness among the community and clinicians. There is need for early reporting to health facility and strengthening the diagnostic capacity of healthcare facilities in and around national parks endemic for sleeping sickness.

  6. Antiparasitic activity of diallyl trisulfide (Dasuansu) on human and animal pathogenic protozoa (Trypanosoma sp., Entamoeba histolytica and Giardia lamblia) in vitro.

    Science.gov (United States)

    Lun, Z R; Burri, C; Menzinger, M; Kaminsky, R

    1994-03-01

    Garlic (Allium sativum L.) and one of its major components, allicin, have been known to have antibacterial and antifungal activity for a long time. Diallyl trisulfide is a chemically stable final transformation product of allicin which was synthesized in 1981 in China and used for treatment of bacterial, fungal and parasitic infections in man. The activity of diallyl trisulfide was investigated in several important protozoan parasites in vitro. The IC50 (concentration which inhibits metabolism or growth of parasites by 50%) for Trypanosoma brucei brucei, T.b. rhodesiense, T.b. gambiense, T. evansi, T. congolense and T. equiperdum was in the range of 0.8-5.5 micrograms/ml. IC50 values were 59 micrograms/ml for Entamoeba histolytica and 14 micrograms/ml for Giardia lamblia. The cytotoxicity of the compound was evaluated on two fibroblast cell lines (MASEF, Mastomys natalensis embryo fibroblast and HEFL-12, human embryo fibroblast) in vitro. The maximum tolerated concentration for both cell lines was 25 micrograms/ml. The results indicate that the compound has potential to be used for treatment of several human and animal parasitic diseases.

  7. Telomeric expression sites are highly conserved in Trypanosoma brucei.

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    Christiane Hertz-Fowler

    Full Text Available Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs. The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology.

  8. Identification of TOEFAZ1-interacting proteins reveals key regulators of Trypanosoma brucei cytokinesis.

    Science.gov (United States)

    Hilton, Nicholas A; Sladewski, Thomas E; Perry, Jenna A; Pataki, Zemplen; Sinclair-Davis, Amy N; Muniz, Richard S; Tran, Holly L; Wurster, Jenna I; Seo, Jiwon; de Graffenried, Christopher L

    2018-05-21

    The protist parasite Trypanosoma brucei is an obligate extracellular pathogen that retains its highly-polarized morphology during cell division and has evolved a novel cytokinetic process independent of non-muscle myosin II. The polo-like kinase homolog TbPLK is essential for transmission of cell polarity during division and for cytokinesis. We previously identified a putative TbPLK substrate named Tip of the Extending FAZ 1 (TOEFAZ1) as an essential kinetoplastid-specific component of the T. brucei cytokinetic machinery. We performed a proximity-dependent biotinylation (BioID) screen using TOEFAZ1 as a means to identify additional proteins that are involved in cytokinesis. Using quantitative proteomic methods, we identified nearly 500 TOEFAZ1-proximal proteins and characterized 59 in further detail. Among the candidates, we identified an essential putative phosphatase that regulates the expression level and localization of both TOEFAZ1 and TbPLK, a previously uncharacterized protein that is necessary for the assembly of a new cell posterior, and a microtubule plus-end directed orphan kinesin that is required for completing cleavage furrow ingression. The identification of these proteins provides new insight into T. brucei cytokinesis and establishes TOEFAZ1 as a key component of this essential and uniquely-configured process in kinetoplastids. This article is protected by copyright. All rights reserved. © 2018 John Wiley & Sons Ltd.

  9. Structure of a Trypanosoma brucei α/β-hydrolase fold protein with unknown function

    International Nuclear Information System (INIS)

    Merritt, Ethan A.; Holmes, Margaret; Buckner, Frederick S.; Van Voorhis, Wesley C.; Quartly, Erin; Phizicky, Eric M.; Lauricella, Angela; Luft, Joseph; DeTitta, George; Neely, Helen; Zucker, Frank; Hol, Wim G. J.

    2008-01-01

    T. brucei gene Tb10.6k15.0140 codes for an α/β-hydrolase fold protein of unknown function. The 2.2 Å crystal structure shows that members of this sequence family retain a conserved Ser residue at the expected site of a catalytic nucleophile, but that trypanosomatid sequences lack structural homologs for the other expected residues of the catalytic triad. The structure of a structural genomics target protein, Tbru020260AAA from Trypanosoma brucei, has been determined to a resolution of 2.2 Å using multiple-wavelength anomalous diffraction at the Se K edge. This protein belongs to Pfam sequence family PF08538 and is only distantly related to previously studied members of the α/β-hydrolase fold family. Structural superposition onto representative α/β-hydrolase fold proteins of known function indicates that a possible catalytic nucleophile, Ser116 in the T. brucei protein, lies at the expected location. However, the present structure and by extension the other trypanosomatid members of this sequence family have neither sequence nor structural similarity at the location of other active-site residues typical for proteins with this fold. Together with the presence of an additional domain between strands β6 and β7 that is conserved in trypanosomatid genomes, this suggests that the function of these homologs has diverged from other members of the fold family

  10. Spliced leader RNA silencing (SLS - a programmed cell death pathway in Trypanosoma brucei that is induced upon ER stress

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    Michaeli Shulamit

    2012-05-01

    Full Text Available Abstract Trypanosoma brucei is the causative agent of African sleeping sickness. The parasite cycles between its insect (procyclic form and mammalian hosts (bloodstream form. Trypanosomes lack conventional transcription regulation, and their genes are transcribed in polycistronic units that are processed by trans-splicing and polyadenylation. In trans-splicing, which is essential for processing of each mRNA, an exon, the spliced leader (SL is added to all mRNAs from a small RNA, the SL RNA. Trypanosomes lack the machinery for the unfolded protein response (UPR, which in other eukaryotes is induced under endoplasmic reticulum (ER stress. Trypanosomes respond to such stress by changing the stability of mRNAs, which are essential for coping with the stress. However, under severe ER stress that is induced by blocking translocation of proteins to the ER, treatment of cells with chemicals that induce misfolding in the ER, or extreme pH, trypanosomes elicit the spliced leader silencing (SLS pathway. In SLS, the transcription of the SL RNA gene is extinguished, and tSNAP42, a specific SL RNA transcription factor, fails to bind to its cognate promoter. SLS leads to complete shut-off of trans-splicing. In this review, I discuss the UPR in mammals and compare it to the ER stress response in T. brucei leading to SLS. I summarize the evidence supporting the notion that SLS is a programmed cell death (PCD pathway that is utilized by the parasites to substitute for the apoptosis observed in higher eukaryotes under prolonged ER stress. I present the hypothesis that SLS evolved to expedite the death process, and rapidly remove from the population unfit parasites that, by elimination via SLS, cause minimal damage to the parasite population.

  11. A target-based high throughput screen yields Trypanosoma brucei hexokinase small molecule inhibitors with antiparasitic activity.

    Directory of Open Access Journals (Sweden)

    Elizabeth R Sharlow

    2010-04-01

    Full Text Available The parasitic protozoan Trypanosoma brucei utilizes glycolysis exclusively for ATP production during infection of the mammalian host. The first step in this metabolic pathway is mediated by hexokinase (TbHK, an enzyme essential to the parasite that transfers the gamma-phospho of ATP to a hexose. Here we describe the identification and confirmation of novel small molecule inhibitors of bacterially expressed TbHK1, one of two TbHKs expressed by T. brucei, using a high throughput screening assay.Exploiting optimized high throughput screening assay procedures, we interrogated 220,233 unique compounds and identified 239 active compounds from which ten small molecules were further characterized. Computation chemical cluster analyses indicated that six compounds were structurally related while the remaining four compounds were classified as unrelated or singletons. All ten compounds were approximately 20-17,000-fold more potent than lonidamine, a previously identified TbHK1 inhibitor. Seven compounds inhibited T. brucei blood stage form parasite growth (0.03brucei parasites, Leishmania promastigotes, and mammalian cell lines. Analysis of two structurally related compounds, ebselen and SID 17387000, revealed that both were mixed inhibitors of TbHK1 with respect to ATP. Additionally, both compounds inhibited parasite lysate-derived HK activity. None of the compounds displayed structural similarity to known hexokinase inhibitors or human African trypanosomiasis therapeutics.The novel chemotypes identified here could represent leads for future therapeutic development against the African trypanosome.

  12. Procyclic Trypanosoma brucei do not use Krebs cycle activity for energy generation

    NARCIS (Netherlands)

    Weelden, van S.W.H.; Fast, B.; Vogt, A.; Meer, van der P.; Saas, J.; Hellemond, van J.J.; Tielens, A.G.M.; Boshart, M.

    2003-01-01

    The importance of a functional Krebs cycle for energy generation in the procyclic stage of Trypanosoma brucei was investigated under physiological conditions during logarithmic phase growth of a pleomorphic parasite strain. Wild type procyclic cells and mutants with targeted deletion of the gene

  13. Design and Synthesis of Brain Penetrant Trypanocidal N-Myristoyltransferase Inhibitors.

    Science.gov (United States)

    Bayliss, Tracy; Robinson, David A; Smith, Victoria C; Brand, Stephen; McElroy, Stuart P; Torrie, Leah S; Mpamhanga, Chido; Norval, Suzanne; Stojanovski, Laste; Brenk, Ruth; Frearson, Julie A; Read, Kevin D; Gilbert, Ian H; Wyatt, Paul G

    2017-12-14

    N-Myristoyltransferase (NMT) represents a promising drug target within the parasitic protozoa Trypanosoma brucei (T. brucei), the causative agent for human African trypanosomiasis (HAT) or sleeping sickness. We have previously validated T. brucei NMT as a promising druggable target for the treatment of HAT in both stages 1 and 2 of the disease. We report on the use of the previously reported DDD85646 (1) as a starting point for the design of a class of potent, brain penetrant inhibitors of T. brucei NMT.

  14. Studies on the localization of Trypanosoma brucei in the female reproductive tract of bka mice and hooded lister rats

    International Nuclear Information System (INIS)

    Chipepa, J.A.S.; Brown, H.; Holmes, P.

    1991-01-01

    A study was conducted to establish whether Trypanosoma brucei migrated preferentially to the reproductive tracts of female BKA mice, or Hooded Lister rats and lodged there as the site of choice compared to other organs. Blood flow to the reproductive tracts, the liver and spleen was measured using red blood cells labelled with chromium- 51. The distribution of trypanosomes labelled with 75 Se-methionine. The average percentage of the blood flow to the reproductive tract was 0.21Plus or minus0.08 in mice, while the mean concentration of trypanosomes there was 0.30% in both mice and rats. Blood flow to the liver was lower than the percentage distribution of Se-labelled T.Brucei(5.17Plus or minus1.34 versus 8.1Plus or Minus1.2). There were, on the contrary, less labelled trypanosomes as compared to the mean blood flow to the spleen (0.54% plus or minus0.18 versus 2.10%pPlus or minus0.88). After 24 hours there were adequate numbers of T. brucei in the reproductive tract to cause parasitaemia in recipient mice. From these preliminary data it was concluded that T. brucei did not lodge in the reproductive organ system a site of choice. (author). 9 refs., 3 tabs

  15. Novel 1,2-dihydroquinazolin-2-ones: Design, synthesis, and biological evaluation against Trypanosoma brucei.

    Science.gov (United States)

    Pham, ThanhTruc; Walden, Madeline; Butler, Christopher; Diaz-Gonzalez, Rosario; Pérez-Moreno, Guiomar; Ceballos-Pérez, Gloria; Gomez-Pérez, Veronica; García-Hernández, Raquel; Zecca, Henry; Krakoff, Emma; Kopec, Brian; Ichire, Ogar; Mackenzie, Caden; Pitot, Marika; Ruiz, Luis Miguel; Gamarro, Francisco; González-Pacanowska, Dolores; Navarro, Miguel; Dounay, Amy B

    2017-08-15

    In 2014, a published report of the high-throughput screen of>42,000 kinase inhibitors from GlaxoSmithKline against T. brucei identified 797 potent and selective hits. From this rich data set, we selected NEU-0001101 (1) for hit-to-lead optimization. Through our preliminary compound synthesis and SAR studies, we have confirmed the previously reported activity of 1 in a T. brucei cell proliferation assay and have identified alternative groups to replace the pyridyl ring in 1. Pyrazole 24 achieves improvements in both potency and lipophilicity relative to 1, while also showing good in vitro metabolic stability. The SAR developed on 24 provides new directions for further optimization of this novel scaffold for anti-trypanosomal drug discovery. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. A combined CXCL10, CXCL8 and H-FABP panel for the staging of human African trypanosomiasis patients.

    Directory of Open Access Journals (Sweden)

    Alexandre Hainard

    2009-06-01

    Full Text Available Human African trypanosomiasis (HAT, also known as sleeping sickness, is a parasitic tropical disease. It progresses from the first, haemolymphatic stage to a neurological second stage due to invasion of parasites into the central nervous system (CNS. As treatment depends on the stage of disease, there is a critical need for tools that efficiently discriminate the two stages of HAT. We hypothesized that markers of brain damage discovered by proteomic strategies and inflammation-related proteins could individually or in combination indicate the CNS invasion by the parasite.Cerebrospinal fluid (CSF originated from parasitologically confirmed Trypanosoma brucei gambiense patients. Patients were staged on the basis of CSF white blood cell (WBC count and presence of parasites in CSF. One hundred samples were analysed: 21 from stage 1 (no trypanosomes in CSF and 5 WBC/microL patients. The concentration of H-FABP, GSTP-1 and S100beta in CSF was measured by ELISA. The levels of thirteen inflammation-related proteins (IL-1ra, IL-1beta, IL-6, IL-9, IL-10, G-CSF, VEGF, IFN-gamma, TNF-alpha, CCL2, CCL4, CXCL8 and CXCL10 were determined by bead suspension arrays.CXCL10 most accurately distinguished stage 1 and stage 2 patients, with a sensitivity of 84% and specificity of 100%. Rule Induction Like (RIL analysis defined a panel characterized by CXCL10, CXCL8 and H-FABP that improved the detection of stage 2 patients to 97% sensitivity and 100% specificity.This study highlights the value of CXCL10 as a single biomarker for staging T. b. gambiense-infected HAT patients. Further combination of CXCL10 with H-FABP and CXCL8 results in a panel that efficiently rules in stage 2 HAT patients. As these molecules could potentially be markers of other CNS infections and disorders, these results should be validated in a larger multi-centric cohort including other inflammatory diseases such as cerebral malaria and active tuberculosis.

  17. Trypanosoma brucei Mitochondrial Respiratome: Composition and Organization in Procyclic Form

    Czech Academy of Sciences Publication Activity Database

    Acestor, N.; Zíková, Alena; Dalley, R. A.; Anupama, A.; Panigrahi, A. K.; Stuart, K. D.

    2011-01-01

    Roč. 10, č. 9 (2011), s. 1-14 ISSN 1535-9476 R&D Projects: GA ČR GP204/09/P563 Institutional research plan: CEZ:AV0Z60220518 Keywords : SUCCINATE DEHYDROGENASE * EDITED MESSENGER-RNA * COMPLEX-I * TRYPANOSOMA-BRUCEI * UBIQUINONE OXIDOREDUCTASE * TAP-TAG * PROTEIN INTERACTION * ALTERNATIVE OXIDASE * STATISTICAL-MODEL * MASS-SPECTROMETRY Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.398, year: 2011

  18. Arterial blood pressure changes in acute T. brucei infection of dogs ...

    African Journals Online (AJOL)

    The aim of this study is to find out the usefulness of serial arterial blood pressure measurements in predicting severity and outcome of acute Trypanosoma brucei infection in dogs. Twenty adult dogs of mixed sexes and aged between 2 and 5 years were used for this study. The dogs were of good cardiac health and were ...

  19. Trypanosoma brucei Co-opts NK Cells to Kill Splenic B2 B Cells.

    Directory of Open Access Journals (Sweden)

    Deborah Frenkel

    2016-07-01

    Full Text Available After infection with T. brucei AnTat 1.1, C57BL/6 mice lost splenic B2 B cells and lymphoid follicles, developed poor parasite-specific antibody responses, lost weight, became anemic and died with fulminating parasitemia within 35 days. In contrast, infected C57BL/6 mice lacking the cytotoxic granule pore-forming protein perforin (Prf1-/- retained splenic B2 B cells and lymphoid follicles, developed high-titer antibody responses against many trypanosome polypeptides, rapidly suppressed parasitemia and did not develop anemia or lose weight for at least 60 days. Several lines of evidence show that T. brucei infection-induced splenic B cell depletion results from natural killer (NK cell-mediated cytotoxicity: i B2 B cells were depleted from the spleens of infected intact, T cell deficient (TCR-/- and FcγRIIIa deficient (CD16-/- C57BL/6 mice excluding a requirement for T cells, NKT cell, or antibody-dependent cell-mediated cytotoxicity; ii administration of NK1.1 specific IgG2a (mAb PK136 but not irrelevant IgG2a (myeloma M9144 prevented infection-induced B cell depletion consistent with a requirement for NK cells; iii splenic NK cells but not T cells or NKT cells degranulated in infected C57BL/6 mice co-incident with B cell depletion evidenced by increased surface expression of CD107a; iv purified NK cells from naïve C57BL/6 mice killed purified splenic B cells from T. brucei infected but not uninfected mice in vitro indicating acquisition of an NK cell activating phenotype by the post-infection B cells; v adoptively transferred C57BL/6 NK cells prevented infection-induced B cell population growth in infected Prf1-/- mice consistent with in vivo B cell killing; vi degranulated NK cells in infected mice had altered gene and differentiation antigen expression and lost cytotoxic activity consistent with functional exhaustion, but increased in number as infection progressed indicating continued generation. We conclude that NK cells in T. brucei

  20. Chemical characterisation of Nigerian red propolis and its biological activity against Trypanosoma Brucei.

    Science.gov (United States)

    Omar, Ruwida M K; Igoli, John; Gray, Alexander I; Ebiloma, Godwin Unekwuojo; Clements, Carol; Fearnley, James; Ebel, Ru Angeli Edrada; Zhang, Tong; De Koning, Harry P; Watson, David G

    2016-01-01

    A previous study showed the unique character of Nigerian red propolis from Rivers State, Nigeria (RSN), with regards to chemical composition and activity against Trypanosoma brucei in comparison with other African propolis. To carry out fractionation and biological testing of Nigerian propolis in order to isolate compounds with anti-trypanosomal activity. To compare the composition of the RSN propolis with the composition of Brazilian red propolis. Profiling was carried out using HPLC-UV-ELSD and HPLC-Orbitrap-FTMS on extracts of two samples collected from RSN with data extraction using MZmine software. Isolation was carried out by normal phase and reversed phase MPLC. Elucidation of the compounds with a purity > 95% was performed by 1D/2D NMR HRMS and HRLC-MS(n) . Ten phenolic compounds were isolated or in the case of liquiritigenin partially purified. Data for nine of these correlated with literature reports of known compounds i.e. one isoflavanone, calycosin (1); two flavanones, liquiritigenin (2) and pinocembrin (5); an isoflavan, vestitol (3); a pterocarpan, medicarpin (4); two prenylflavanones, 8-prenylnaringenin (7) and 6-prenylnaringenin (8); and two geranyl flavonoids, propolin D (9) and macarangin (10). The tenth was elucidated as a previously undescribed dihydrobenzofuran (6). The isolated compounds were tested against Trypanosoma brucei and displayed moderate to high activity. Some of the compounds tested had similar activity against wild type T. brucei and two strains displaying pentamidine resistance. Nigerian propolis from RSN has some similarities with Brazilian red propolis. The propolis displayed anti-trypanosomal activity at a potentially useful level. Copyright © 2015 John Wiley & Sons, Ltd.

  1. Central Nervous System Parasitosis and Neuroinflammation Ameliorated by Systemic IL-10 Administration in Trypanosoma brucei-Infected Mice.

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    Jean Rodgers

    Full Text Available Invasion of the central nervous system (CNS by African trypanosomes represents a critical step in the development of human African trypanosomiasis. In both clinical cases and experimental mouse infections it has been demonstrated that predisposition to CNS invasion is associated with a type 1 systemic inflammatory response. Using the Trypanosoma brucei brucei GVR35 experimental infection model, we demonstrate that systemic delivery of the counter-inflammatory cytokine IL-10 lowers plasma IFN-γ and TNF-α concentrations, CNS parasitosis and ameliorates neuro-inflammatory pathology and clinical symptoms of disease. The results provide evidence that CNS invasion may be susceptible to immunological attenuation.

  2. The promoter for a variant surface glycoprotein gene expression site in Trypanosoma brucei

    NARCIS (Netherlands)

    Zomerdijk, J. C.; Ouellette, M.; ten Asbroek, A. L.; Kieft, R.; Bommer, A. M.; Clayton, C. E.; Borst, P.

    1990-01-01

    The variant-specific surface glycoprotein (VSG) gene 221 of Trypanosoma brucei is transcribed as part of a 60 kb expression site (ES). We have identified the promoter controlling this multigene transcription unit by the use of 221 chromosome-enriched DNA libraries and VSG gene 221 expression site

  3. Three Redox States of Trypanosoma brucei Alternative Oxidase Identified by Infrared Spectroscopy and Electrochemistry

    Science.gov (United States)

    Maréchal, Amandine; Kido, Yasutoshi; Kita, Kiyoshi; Moore, Anthony L.; Rich, Peter R.

    2009-01-01

    Electrochemistry coupled with Fourier transform infrared (IR) spectroscopy was used to investigate the redox properties of recombinant alternative ubiquinol oxidase from Trypanosoma brucei, the organism responsible for African sleeping sickness. Stepwise reduction of the fully oxidized resting state of recombinant alternative ubiquinol oxidase revealed two distinct IR redox difference spectra. The first of these, signal 1, titrates in the reductive direction as an n = 2 Nernstian component with an apparent midpoint potential of 80 mV at pH 7.0. However, reoxidation of signal 1 in the same potential range under anaerobic conditions did not occur and only began with potentials in excess of 500 mV. Reoxidation by introduction of oxygen was also unsuccessful. Signal 1 contained clear features that can be assigned to protonation of at least one carboxylate group, further perturbations of carboxylic and histidine residues, bound ubiquinone, and a negative band at 1554 cm−1 that might arise from a radical in the fully oxidized protein. A second distinct IR redox difference spectrum, signal 2, appeared more slowly once signal 1 had been reduced. This component could be reoxidized with potentials above 100 mV. In addition, when both signals 1 and 2 were reduced, introduction of oxygen caused rapid oxidation of both components. These data are interpreted in terms of the possible active site structure and mechanism of oxygen reduction to water. PMID:19767647

  4. Handling uncertainty in dynamic models: the pentose phosphate pathway in Trypanosoma brucei.

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    Eduard J Kerkhoven

    Full Text Available Dynamic models of metabolism can be useful in identifying potential drug targets, especially in unicellular organisms. A model of glycolysis in the causative agent of human African trypanosomiasis, Trypanosoma brucei, has already shown the utility of this approach. Here we add the pentose phosphate pathway (PPP of T. brucei to the glycolytic model. The PPP is localized to both the cytosol and the glycosome and adding it to the glycolytic model without further adjustments leads to a draining of the essential bound-phosphate moiety within the glycosome. This phosphate "leak" must be resolved for the model to be a reasonable representation of parasite physiology. Two main types of theoretical solution to the problem could be identified: (i including additional enzymatic reactions in the glycosome, or (ii adding a mechanism to transfer bound phosphates between cytosol and glycosome. One example of the first type of solution would be the presence of a glycosomal ribokinase to regenerate ATP from ribose 5-phosphate and ADP. Experimental characterization of ribokinase in T. brucei showed that very low enzyme levels are sufficient for parasite survival, indicating that other mechanisms are required in controlling the phosphate leak. Examples of the second type would involve the presence of an ATP:ADP exchanger or recently described permeability pores in the glycosomal membrane, although the current absence of identified genes encoding such molecules impedes experimental testing by genetic manipulation. Confronted with this uncertainty, we present a modeling strategy that identifies robust predictions in the context of incomplete system characterization. We illustrate this strategy by exploring the mechanism underlying the essential function of one of the PPP enzymes, and validate it by confirming the model predictions experimentally.

  5. Minimum Information Loss Based Multi-kernel Learning for Flagellar Protein Recognition in Trypanosoma Brucei

    KAUST Repository

    Wang, Jim Jing-Yan; Gao, Xin

    2014-01-01

    for the purposes of both biological research and drug design. In this paper, we investigate computationally recognizing flagellar proteins in T. Brucei by pattern recognition methods. It is argued that an optimal decision function can be obtained as the difference

  6. Aquaglyceroporin-null trypanosomes display glycerol transport defects and respiratory-inhibitor sensitivity.

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    Laura Jeacock

    2017-03-01

    Full Text Available Aquaglyceroporins (AQPs transport water and glycerol and play important roles in drug-uptake in pathogenic trypanosomatids. For example, AQP2 in the human-infectious African trypanosome, Trypanosoma brucei gambiense, is responsible for melarsoprol and pentamidine-uptake, and melarsoprol treatment-failure has been found to be due to AQP2-defects in these parasites. To further probe the roles of these transporters, we assembled a T. b. brucei strain lacking all three AQP-genes. Triple-null aqp1-2-3 T. b. brucei displayed only a very moderate growth defect in vitro, established infections in mice and recovered effectively from hypotonic-shock. The aqp1-2-3 trypanosomes did, however, display glycerol uptake and efflux defects. They failed to accumulate glycerol or to utilise glycerol as a carbon-source and displayed increased sensitivity to salicylhydroxamic acid (SHAM, octyl gallate or propyl gallate; these inhibitors of trypanosome alternative oxidase (TAO can increase intracellular glycerol to toxic levels. Notably, disruption of AQP2 alone generated cells with glycerol transport defects. Consistent with these findings, AQP2-defective, melarsoprol-resistant clinical isolates were sensitive to the TAO inhibitors, SHAM, propyl gallate and ascofuranone, relative to melarsoprol-sensitive reference strains. We conclude that African trypanosome AQPs are dispensable for viability and osmoregulation but they make important contributions to drug-uptake, glycerol-transport and respiratory-inhibitor sensitivity. We also discuss how the AQP-dependent inverse sensitivity to melarsoprol and respiratory inhibitors described here might be exploited.

  7. Comparative analysis of the kinomes of three pathogenic trypanosomatids: Leishmania major, Trypanosoma brucei and Trypanosoma cruzi

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    Ward Pauline N

    2005-09-01

    Full Text Available Abstract Background The trypanosomatids Leishmania major, Trypanosoma brucei and Trypanosoma cruzi cause some of the most debilitating diseases of humankind: cutaneous leishmaniasis, African sleeping sickness, and Chagas disease. These protozoa possess complex life cycles that involve development in mammalian and insect hosts, and a tightly coordinated cell cycle ensures propagation of the highly polarized cells. However, the ways in which the parasites respond to their environment and coordinate intracellular processes are poorly understood. As a part of an effort to understand parasite signaling functions, we report the results of a genome-wide analysis of protein kinases (PKs of these three trypanosomatids. Results Bioinformatic searches of the trypanosomatid genomes for eukaryotic PKs (ePKs and atypical PKs (aPKs revealed a total of 176 PKs in T. brucei, 190 in T. cruzi and 199 in L. major, most of which are orthologous across the three species. This is approximately 30% of the number in the human host and double that of the malaria parasite, Plasmodium falciparum. The representation of various groups of ePKs differs significantly as compared to humans: trypanosomatids lack receptor-linked tyrosine and tyrosine kinase-like kinases, although they do possess dual-specificity kinases. A relative expansion of the CMGC, STE and NEK groups has occurred. A large number of unique ePKs show no strong affinity to any known group. The trypanosomatids possess few ePKs with predicted transmembrane domains, suggesting that receptor ePKs are rare. Accessory Pfam domains, which are frequently present in human ePKs, are uncommon in trypanosomatid ePKs. Conclusion Trypanosomatids possess a large set of PKs, comprising approximately 2% of each genome, suggesting a key role for phosphorylation in parasite biology. Whilst it was possible to place most of the trypanosomatid ePKs into the seven established groups using bioinformatic analyses, it has not been

  8. IL-6 is Upregulated in Late-Stage Disease in Monkeys Experimentally Infected with Trypanosoma brucei rhodesiense

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    Dawn Nyawira Maranga

    2013-01-01

    Full Text Available The management of human African trypanosomiasis (HAT is constrained by lack of simple-to-use diagnostic, staging, and treatment tools. The search for novel biomarkers is, therefore, essential in the fight against HAT. The current study aimed at investigating the potential of IL-6 as an adjunct parameter for HAT stage determination in vervet monkey model. Four adult vervet monkeys (Chlorocebus aethiops were experimentally infected with Trypanosoma brucei rhodesiense and treated subcuratively at 28 days after infection (dpi to induce late stage disease. Three noninfected monkeys formed the control group. Cerebrospinal fluid (CSF and blood samples were obtained at weekly intervals and assessed for various biological parameters. A typical HAT-like infection was observed. The late stage was characterized by significant (P<0.05 elevation of CSF IL-6, white blood cell count, and total protein starting 35 dpi with peak levels of these parameters coinciding with relapse parasitaemia. Brain immunohistochemical staining revealed an increase in brain glial fibrillary acidic protein expression indicative of reactive astrogliosis in infected animals which were euthanized in late-stage disease. The elevation of IL-6 in CSF which accompanied other HAT biomarkers indicates onset of parasite neuroinvasion and show potential for use as an adjunct late-stage disease biomarker in the Rhodesian sleeping sickness.

  9. Ethyl Pyruvate Emerges as a Safe and Fast Acting Agent against Trypanosoma brucei by Targeting Pyruvate Kinase Activity.

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    Netsanet Worku

    Full Text Available Human African Trypanosomiasis (HAT also called sleeping sickness is an infectious disease in humans caused by an extracellular protozoan parasite. The disease, if left untreated, results in 100% mortality. Currently available drugs are full of severe drawbacks and fail to escape the fast development of trypanosoma resistance. Due to similarities in cell metabolism between cancerous tumors and trypanosoma cells, some of the current registered drugs against HAT have also been tested in cancer chemotherapy. Here we demonstrate for the first time that the simple ester, ethyl pyruvate, comprises such properties.The current study covers the efficacy and corresponding target evaluation of ethyl pyruvate on T. brucei cell lines using a combination of biochemical techniques including cell proliferation assays, enzyme kinetics, phasecontrast microscopic video imaging and ex vivo toxicity tests. We have shown that ethyl pyruvate effectively kills trypanosomes most probably by net ATP depletion through inhibition of pyruvate kinase (Ki = 3.0±0.29 mM. The potential of ethyl pyruvate as a trypanocidal compound is also strengthened by its fast acting property, killing cells within three hours post exposure. This has been demonstrated using video imaging of live cells as well as concentration and time dependency experiments. Most importantly, ethyl pyruvate produces minimal side effects in human red cells and is known to easily cross the blood-brain-barrier. This makes it a promising candidate for effective treatment of the two clinical stages of sleeping sickness. Trypanosome drug-resistance tests indicate irreversible cell death and a low incidence of resistance development under experimental conditions.Our results present ethyl pyruvate as a safe and fast acting trypanocidal compound and show that it inhibits the enzyme pyruvate kinase. Competitive inhibition of this enzyme was found to cause ATP depletion and cell death. Due to its ability to easily cross

  10. Nifurtimox plus Eflornithine for late-stage sleeping sickness in Uganda: a case series.

    Directory of Open Access Journals (Sweden)

    Francesco Checchi

    2007-11-01

    Full Text Available We report efficacy and safety outcomes from a prospective case series of 31 late-stage T.b. gambiense sleeping sickness (Human African Trypanosomiasis, HAT patients treated with a combination of nifurtimox and eflornithine (N+E in Yumbe, northwest Uganda in 2002-2003, following on a previously reported terminated trial in nearby Omugo, in which 17 patients received the combination under the same conditions.Eligible sequential late-stage patients received 400 mg/Kg/day eflornithine (Ornidyl, Sanofi-Aventis for seven days plus 15 mg/Kg/day (20 mg for children <15 years old nifurtimox (Lampit, Bayer AG for ten days. Efficacy (primary outcome was monitored for 24 months post discharge. Clinical and laboratory adverse events (secondary outcome were monitored during treatment. All 31 patients were discharged alive, but two died post-discharge of non-HAT and non-treatment causes, and one was lost to follow-up. Efficacy ranged from 90.3% to 100.0% according to analysis approach. Five patients experienced major adverse events during treatment, and neutropenia was common (9/31 patients.Combined with the previous group of 17 trial patients, this case series yields a group of 48 patients treated with N+E, among whom no deaths judged to be treatment- or HAT-related, no treatment terminations and no relapses have been noted, a very favourable outcome in the context of late-stage disease. N+E could be the most promising combination regimen available for sleeping sickness, and deserves further evaluation.

  11. The F1 -ATPase from Trypanosoma brucei is elaborated by three copies of an additional p18-subunit.

    Science.gov (United States)

    Gahura, Ondřej; Šubrtová, Karolína; Váchová, Hana; Panicucci, Brian; Fearnley, Ian M; Harbour, Michael E; Walker, John E; Zíková, Alena

    2018-02-01

    The F-ATPases (also called the F 1 F o -ATPases or ATP synthases) are multi-subunit membrane-bound molecular machines that produce ATP in bacteria and in eukaryotic mitochondria and chloroplasts. The structures and enzymic mechanisms of their F 1 -catalytic domains are highly conserved in all species investigated hitherto. However, there is evidence that the F-ATPases from the group of protozoa known as Euglenozoa have novel features. Therefore, we have isolated pure and active F 1 -ATPase from the euglenozoan parasite, Trypanosoma brucei, and characterized it. All of the usual eukaryotic subunits (α, β, γ, δ, and ε) were present in the enzyme, and, in addition, two unique features were detected. First, each of the three α-subunits in the F 1 -domain has been cleaved by proteolysis in vivo at two sites eight residues apart, producing two assembled fragments. Second, the T. brucei F 1 -ATPase has an additional subunit, called p18, present in three copies per complex. Suppression of expression of p18 affected in vitro growth of both the insect and infectious mammalian forms of T. brucei. It also reduced the levels of monomeric and multimeric F-ATPase complexes and diminished the in vivo hydrolytic activity of the enzyme significantly. These observations imply that p18 plays a role in the assembly of the F 1 domain. These unique features of the F 1 -ATPase extend the list of special characteristics of the F-ATPase from T. brucei, and also, demonstrate that the architecture of the F 1 -ATPase complex is not strictly conserved in eukaryotes. © 2017 Federation of European Biochemical Societies.

  12. Major surface glycoproteins of insect forms of Trypanosoma brucei are not essential for cyclical transmission by tsetse.

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    Erik Vassella

    Full Text Available Procyclic forms of Trypanosoma brucei reside in the midgut of tsetse flies where they are covered by several million copies of glycosylphosphatidylinositol-anchored proteins known as procyclins. It has been proposed that procyclins protect parasites against proteases and/or participate in tropism, directing them from the midgut to the salivary glands. There are four different procyclin genes, each subject to elaborate levels of regulation. To determine if procyclins are essential for survival and transmission of T. brucei, all four genes were deleted and parasite fitness was compared in vitro and in vivo. When co-cultured in vitro, the null mutant and wild type trypanosomes (tagged with cyan fluorescent protein maintained a near-constant equilibrium. In contrast, when flies were infected with the same mixture, the null mutant was rapidly overgrown in the midgut, reflecting a reduction in fitness in vivo. Although the null mutant is patently defective in competition with procyclin-positive parasites, on its own it can complete the life cycle and generate infectious metacyclic forms. The procyclic form of T. brucei thus differs strikingly from the bloodstream form, which does not tolerate any perturbation of its variant surface glycoprotein coat, and from other parasites such as Plasmodium berghei, which requires the circumsporozoite protein for successful transmission to a new host.

  13. Agrochemicals against malaria, sleeping sickness, leishmaniasis and Chagas disease.

    Science.gov (United States)

    Witschel, Matthias; Rottmann, Matthias; Kaiser, Marcel; Brun, Reto

    2012-01-01

    In tropical regions, protozoan parasites can cause severe diseases with malaria, leishmaniasis, sleeping sickness, and Chagas disease standing in the forefront. Many of the drugs currently being used to treat these diseases have been developed more than 50 years ago and can cause severe adverse effects. Above all, resistance to existing drugs is widespread and has become a serious problem threatening the success of control measures. In order to identify new antiprotozoal agents, more than 600 commercial agrochemicals have been tested on the pathogens causing the above mentioned diseases. For all of the pathogens, compounds were identified with similar or even higher activities than the currently used drugs in applied in vitro assays. Furthermore, in vivo activity was observed for the fungicide/oomyceticide azoxystrobin, and the insecticide hydramethylnon in the Plasmodium berghei mouse model, and for the oomyceticide zoxamide in the Trypanosoma brucei rhodesiense STIB900 mouse model, respectively.

  14. Antiprotozoal activity of medicinal plants used by Iquitos-Nauta road communities in Loreto (Peru).

    Science.gov (United States)

    Vásquez-Ocmín, Pedro; Cojean, Sandrine; Rengifo, Elsa; Suyyagh-Albouz, Soulaf; Amasifuen Guerra, Carlos A; Pomel, Sébastien; Cabanillas, Billy; Mejía, Kember; Loiseau, Philippe M; Figadère, Bruno; Maciuk, Alexandre

    2018-01-10

    In the Peruvian Amazon, the use of medicinal plants is a common practice. However, there is few documented information about the practical aspects of their use and few scientific validation. The starting point for this work was a set of interviews of people living in rural communities from the Peruvian Amazon about their uses of plants. Protozoan diseases are a public health issue in the Amazonian communities, who partly cope with it by using traditional remedies. Validation of these traditional practices contributes to public health care efficiency and may help identify new antiprotozoal compounds. to inventory and validate the use of medicinal plants by rural people of Loreto region. Rural mestizos were interviewed about traditional medication of parasite infections with medicinal plants. Ethnopharmacological surveys were undertaken in two villages along Iquitos-Nauta road (Loreto region, Peru), namely 13 de Febrero and El Dorado communities. Forty-six plants were collected according to their traditional use for the treatment of parasitic diseases, 50 ethanolic extracts (different parts for some of the plants) were tested in vitro on Plasmodium falciparum (3D7 sensitive strain and W2 chloroquine resistant strain), Leishmania donovani LV9 strain and Trypanosoma brucei gambiense. Cytotoxic assessment (HUVEC cells) of the active extracts was performed. Two of the most active plants were submitted to preliminary bioguided fractionation to ascertain and explore their activities. From the initial plants list, 10 were found to be active on P. falciparum, 15 on L. donovani and 2 on the three parasites. The ethanolic extract from Costus curvibracteatus (Costaceae) leaves and Grias neuberthii (Lecythidaceae) bark showed strong in vitro activity on P. falciparum (sensitive and resistant strain) and L. donovani and moderate activity on T. brucei gambiense. The Amazonian forest communities in Peru represents a source of knowledge on the use of medicinal plants. In this work

  15. Trypanocidal action of bisphosphonium salts through a mitochondrial target in bloodstream form Trypanosoma brucei

    Czech Academy of Sciences Publication Activity Database

    Alkhaldi, A.A.M.; Martínek, Jan; Panicucci, Brian; Dardonville, C.; Zíková, Alena; de Koning, H.P.

    2016-01-01

    Roč. 6, č. 1 (2016), s. 23-34 ISSN 2211-3207 R&D Projects: GA MŠk LL1205 Institutional support: RVO:60077344 Keywords : Trypanosoma brucei * mitochondrion * FoF1 ATPase * succinate dehydrogenase * phosphonium salt * SDH complex Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.809, year: 2016

  16. Anti-Parasitic Activities of Allium sativum and Allium cepa against Trypanosoma b. brucei and Leishmania tarentolae.

    Science.gov (United States)

    Krstin, Sonja; Sobeh, Mansour; Braun, Markus Santhosh; Wink, Michael

    2018-04-21

    Background: Garlics and onions have been used for the treatment of diseases caused by parasites and microbes since ancient times. Trypanosomiasis and leishmaniasis are a concern in many areas of the world, especially in poor countries. Methods: Trypanosoma brucei brucei and Leishmania tarentolae were used to investigate the anti-parasitic effects of dichloromethane extracts of Allium sativum (garlic) and Allium cepa (onion) bulbs. As a confirmation of known antimicrobial activities, they were studied against a selection of G-negative, G-positive bacteria and two fungi. Chemical analyses were performed using high-performance liquid chromatography (HPLC) and electrospray ionization-mass spectrometry (LC-ESI-MS/MS). Results: Chemical analyses confirmed the abundance of several sulfur secondary metabolites in garlic and one (zwiebelane) in the onion extract. Both extracts killed both types of parasites efficiently and inhibited the Trypanosoma brucei trypanothione reductase irreversibly. In addition, garlic extract decreased the mitochondrial membrane potential in trypanosomes. Garlic killed the fungi C. albicans and C. parapsilosis more effectively than the positive control. The combinations of garlic and onion with common trypanocidal and leishmanicidal drugs resulted in a synergistic or additive effect in 50% of cases. Conclusion: The mechanism for biological activity of garlic and onion appears to be related to the amount and the profile of sulfur-containing compounds. It is most likely that vital substances inside the parasitic cell, like trypanothione reductase, are inhibited through disulfide bond formation between SH groups of vital redox compounds and sulfur-containing secondary metabolites.

  17. Functional characterisation and drug target validation of a mitotic kinesin-13 in Trypanosoma brucei.

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    Kuan Yoow Chan

    2010-08-01

    Full Text Available Mitotic kinesins are essential for faithful chromosome segregation and cell proliferation. Therefore, in humans, kinesin motor proteins have been identified as anti-cancer drug targets and small molecule inhibitors are now tested in clinical studies. Phylogenetic analyses have assigned five of the approximately fifty kinesin motor proteins coded by Trypanosoma brucei genome to the Kinesin-13 family. Kinesins of this family have unusual biochemical properties because they do not transport cargo along microtubules but are able to depolymerise microtubules at their ends, therefore contributing to the regulation of microtubule length. In other eukaryotic genomes sequenced to date, only between one and three Kinesin-13s are present. We have used immunolocalisation, RNAi-mediated protein depletion, biochemical in vitro assays and a mouse model of infection to study the single mitotic Kinesin-13 in T. brucei. Subcellular localisation of all five T. brucei Kinesin-13s revealed distinct distributions, indicating that the expansion of this kinesin family in kinetoplastids is accompanied by functional diversification. Only a single kinesin (TbKif13-1 has a nuclear localisation. Using active, recombinant TbKif13-1 in in vitro assays we experimentally confirm the depolymerising properties of this kinesin. We analyse the biological function of TbKif13-1 by RNAi-mediated protein depletion and show its central role in regulating spindle assembly during mitosis. Absence of the protein leads to abnormally long and bent mitotic spindles, causing chromosome mis-segregation and cell death. RNAi-depletion in a mouse model of infection completely prevents infection with the parasite. Given its essential role in mitosis, proliferation and survival of the parasite and the availability of a simple in vitro activity assay, TbKif13-1 has been identified as an excellent potential drug target.

  18. Inhibitors of the mitochondrial cytochrome b-c1 complex inhibit the cyanide-insensitive respiration of Trypanosoma brucei.

    Science.gov (United States)

    Turrens, J F; Bickar, D; Lehninger, A L

    1986-06-01

    The cyanide-insensitive respiration of bloodstream trypomastigote forms of Trypanosoma brucei (75 +/- 8 nmol O2 min-1(mg protein)-1) is completely inhibited by the mitochondrial ubiquinone-like inhibitors 2-hydroxy-3-undecyl-1,4-naphthoquinone (UHNQ) and 5-n-undecyl-6-hydroxy-4,7-dioxobenzothiazole (UHDBT). The Ki values for UHDBT (30 nM) and UHNQ (2 microM) are much lower than the reported Ki for salicylhydroxamic acid (SHAM) (5 microM), a widely used inhibitor of the cyanide-insensitive oxidase. UHNQ also stimulated the glycerol-3-phosphate-dependent reduction of phenazine methosulfate, demonstrating that the site of UHNQ inhibition is on the terminal oxidase of the cyanide-insensitive respiration of T. brucei. These results suggest that a ubiquinone-like compound may act as an electron carrier between the two enzymatic components of the cyanide-insensitive glycerol-3-phosphate oxidase.

  19. γ-Tubulin complex in Trypanosoma brucei: molecular composition, subunit interdependence and requirement for axonemal central pair protein assembly.

    Science.gov (United States)

    Zhou, Qing; Li, Ziyin

    2015-11-01

    γ-Tubulin complex constitutes a key component of the microtubule-organizing center and nucleates microtubule assembly. This complex differs in complexity in different organisms: the budding yeast contains the γ-tubulin small complex (γTuSC) composed of γ-tubulin, gamma-tubulin complex protein (GCP)2 and GCP3, whereas animals contain the γ-tubulin ring complex (γTuRC) composed of γTuSC and three additional proteins, GCP4, GCP5 and GCP6. In Trypanosoma brucei, the composition of the γ-tubulin complex remains elusive, and it is not known whether it also regulates assembly of the subpellicular microtubules and the spindle microtubules. Here we report that the γ-tubulin complex in T. brucei is composed of γ-tubulin and three GCP proteins, GCP2-GCP4, and is primarily localized in the basal body throughout the cell cycle. Depletion of GCP2 and GCP3, but not GCP4, disrupted the axonemal central pair microtubules, but not the subpellicular microtubules and the spindle microtubules. Furthermore, we showed that the γTuSC is required for assembly of two central pair proteins and that γTuSC subunits are mutually required for stability. Together, these results identified an unusual γ-tubulin complex in T. brucei, uncovered an essential role of γTuSC in central pair protein assembly, and demonstrated the interdependence of individual γTuSC components for maintaining a stable complex. © 2015 John Wiley & Sons Ltd.

  20. Antitrypanosomal compounds from the essential oil and extracts of Keetia leucantha leaves with inhibitor activity on Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase.

    Science.gov (United States)

    Bero, J; Beaufay, C; Hannaert, V; Hérent, M-F; Michels, P A; Quetin-Leclercq, J

    2013-02-15

    Keetia leucantha is a West African tree used in traditional medicine to treat several diseases among which parasitic infections. The dichloromethane extract of leaves was previously shown to possess growth-inhibitory activities on Plasmodium falciparum, Trypanosoma brucei brucei and Leishmania mexicana mexicana with low or no cytotoxicity (>100 μg/ml on human normal fibroblasts) (Bero et al. 2009, 2011). In continuation of our investigations on the antitrypanosomal compounds from this dichloromethane extract, we analyzed by GC-FID and GC-MS the essential oil of its leaves obtained by hydrodistillation and the major triterpenic acids in this extract by LC-MS. Twenty-seven compounds were identified in the oil whose percentages were calculated using the normalization method. The essential oil, seven of its constituents and the three triterpenic acids were evaluated for their antitrypanosomal activity on Trypanosoma brucei brucei bloodstream forms (Tbb BSF) and procyclic forms (Tbb PF) to identify an activity on the glycolytic process of trypanosomes. The oil showed an IC(50) of 20.9 μg/ml on Tbb BSF and no activity was observed on Tbb PF. The best antitrypanosomal activity was observed for ursolic acid with IC(50) of 2.5 and 6.5 μg/ml respectively on Tbb BSF and Tbb PF. The inhibitory activity on a glycolytic enzyme of T. brucei, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), was also evaluated for betulinic acid, olenaolic acid, ursolic acid, phytol, α-ionone and β-ionone. The three triterpenic acids and β-ionone showed inhibitory activities on GAPDH with oleanolic acid being the most active with an inhibition of 72.63% at 20 μg/ml. This paper reports for the first time the composition and antitrypanosomal activity of the essential oil of Keetia leucantha. Several of its constituents and three triterpenic acids present in the dichloromethane leaves extract showed a higher antitrypanosomal activity on bloodstream forms of Tbb as compared to procyclic forms

  1. Sleep Sleeping Patch

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The Sleep Sleeping Patch is a new kind of external patch based on modern sleep medicine research achievements, which uses the internationally advanced transdermal therapeutic system (TTS). The Sleep Sleeping Patch transmits natural sleep inducers such as peppermint and liquorice extracts and melatonin through the skin to induce sleep. Clinical research proves that the Sleep Sleeping Patch can effectively improve insomnia and the quality of sleep. Highly effective: With the modern TTS therapy,

  2. Sleeping sickness in Buikwe South Health sub-district: Neuroinfection situation report.

    Science.gov (United States)

    Dobrodenkova, Silvia

    2013-09-01

    The aim of this paper is to describe the incidence of Trypanosoma brucei rhodesiense sleeping sickness in the last functioning treatment centre in Buikwe South HSD in Southeast Uganda, in Mukono District, for a 19-year period (1989-2008). This is a report on the treatment outcome, structure of population affected, comparison with the published data on general incidence of T. b rhodesiensae in Uganda and functioning of sleeping sickness control program. Cross-sectional sleeping sickness data from 1989 to 2008 were collected retrospectively in 2009 at Buikwe Sleeping Sickness Center to identify case counts and measures of disease magnitude per sub-county per year. Data were collected from all available records of sleeping sickness patients. Case counts from the Buikwe South sub-counties, and even some neighboring sub-counties for 19 years (1989-2008) were collected and analyzed by Microsoft Excel and EpiInfo program. In the period from 1989 to 2008, 372 cases of sleeping sickness were diagnosed and treated. Children under 5 years were 12 (3.22%) - males 6, females 6, patients in the age from 6 to 15 years were 51 (13.7%) - males 30, females 21, and patients above 15 were 309 (83.06%) - males 176, females 133. In the category 5-15 years and above 15 years there was a significant gender difference closely connected to the professional exposure. The oldest patient was 80 years old, the youngest was 3 moths old. The average age of the patients was 30.8 years. From all 372 patients with trypanosomiasis 30 had died - 10 females and 20 males, which means 8% case fatality. The case fatality rate in the late stage of the disease was 14%. From this group 6 patients (20%) had negative BS. The average interval between the diagnosis and death was 14.4 days, in 10 patients the exact date of death was not recorded. Average age of the patients that died was 30.6 years. Sleeping sickness still remains a serious public health problem. Since the preventive and educational activities

  3. The γ-tubulin complex in Trypanosoma brucei: molecular composition, subunit interdependence and requirement for axonemal central pair protein assembly

    Science.gov (United States)

    Zhou, Qing; Li, Ziyin

    2015-01-01

    The γ-tubulin complex constitutes a key component of the microtubule-organizing center and nucleates microtubule assembly. This complex differs in complexity in different organisms: the budding yeast contains the γ-tubulin small complex (γTuSC) composed of γ-tubulin, GCP2 and GCP3, whereas animals contain the γ-tubulin ring complex (γTuRC) composed of γTuSC and three additional proteins, GCP4, GCP5 and GCP6. In Trypanosoma brucei, the composition of the γ-tubulin complex remains elusive, and it is not known whether it also regulates assembly of the subpellicular microtubules and the spindle microtubules. Here we report that the γ-tubulin complex in T. brucei is composed of γ-tubulin and three GCP proteins, GCP2-GCP4, and is primarily localized in the basal body throughout the cell cycle. Depletion of GCP2 and GCP3, but not GCP4, disrupted the axonemal central pair microtubules, but not the subpellicular microtubules and the spindle microtubules. Furthermore, we showed that the γTuSC is required for assembly of two central pair proteins and that γTuSC subunits are mutually required for stability. Together, these results identified an unusual γ-tubulin complex in T. brucei, uncovered an essential role of γTuSC in central pair protein assembly, and demonstrated the interdependence of individual γTuSC components for maintaining a stable complex. PMID:26224545

  4. Peptide-targeted delivery of a pH sensor for quantitative measurements of intraglycosomal pH in live Trypanosoma brucei.

    Science.gov (United States)

    Lin, Sheng; Morris, Meredith T; Ackroyd, P Christine; Morris, James C; Christensen, Kenneth A

    2013-05-28

    Studies of dynamic changes in organelles of protozoan parasite Trypanosoma brucei have been limited, in part because of the difficulty of targeting analytical probes to specific subcellular compartments. Here we demonstrate application of a ratiometric probe for pH quantification in T. brucei glycosomes. The probe consists of a peptide encoding the peroxisomal targeting sequence (F-PTS1, acetyl-CKGGAKL) coupled to fluorescein, which responds to pH. When incubated with living parasites, the probe is internalized within vesicular structures that colocalize with a glycosomal marker. Inhibition of uptake of F-PTS1 at 4 °C and pulse-chase colocalization with fluorescent dextran suggested that the probe is initially taken up by non-receptor-mediated endocytosis but is subsequently transported separately from dextran and localized within glycosomes, prior to the final fusion of labeled glycosomes and lysosomes as part of glycosomal turnover. Intraorganellar measurements and pH calibration with F-PTS1 in T. brucei glycosomes indicate that the resting glycosomal pH under physiological conditions is 7.4 ± 0.2. However, incubation in glucose-depleted buffer triggered mild acidification of the glycosome over a period of 20 min, with a final observed pH of 6.8 ± 0.3. This glycosomal acidification was reversed by reintroduction of glucose. Coupling of ratiometric fluorescent sensors and reporters to PTS peptides offers an invaluable tool for monitoring in situ glycosomal response(s) to changing environmental conditions and could be applied to additional kinetoplastid parasites.

  5. THE CYTOSOLIC AND GLYCOSOMAL GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE FROM TRYPANOSOMA-BRUCEI - KINETIC-PROPERTIES AND COMPARISON WITH HOMOLOGOUS ENZYMES

    NARCIS (Netherlands)

    LAMBEIR, AM; LOISEAU, AM; KUNTZ, DA; VELLIEUX, FM; MICHELS, PAM; OPPERDOES, FR

    1991-01-01

    The protozoan haemoflagellate Trypanosoma brucei has two NAD-dependent glyceraldehyde-3-phosphate dehydrogenase isoenzymes, each with a different localization within the cell. One isoenzyme is found in the cytosol, as in other eukaryotes, while the other is found in the glycosome, a microbody-like

  6. The Chemical Characterization of Nigerian Propolis samples and Their Activity Against Trypanosoma brucei.

    Science.gov (United States)

    Omar, Ruwida; Igoli, John O; Zhang, Tong; Gray, Alexander I; Ebiloma, Godwin U; Clements, Carol J; Fearnley, James; Edrada Ebel, RuAngeli; Paget, Tim; de Koning, Harry P; Watson, David G

    2017-04-19

    Profiling of extracts from twelve propolis samples collected from eight regions in Nigeria was carried out using high performance liquid chromatography (LC) coupled with evaporative light scattering (ELSD), ultraviolet detection (UV) and mass spectrometry (MS), gas chromatography mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR). Principal component analysis (PCA) of the processed LC-MS data demonstrated the varying chemical composition of the samples. Most of the samples were active against Trypanosoma b. brucei with the highest activity being in the samples from Southern Nigeria. The more active samples were fractionated in order to isolate the component(s) responsible for their activity using medium pressure liquid chromatography (MPLC). Three xanthones, 1,3,7-trihydroxy-2,8-di-(3-methylbut-2-enyl)xanthone, 1,3,7-trihydroxy-4,8-di-(3-methylbut-2-enyl)xanthone a previously undescribed xanthone and three triterpenes: ambonic acid, mangiferonic acid and a mixture of α-amyrin with mangiferonic acid (1:3) were isolated and characterised by NMR and LC-MS. These compounds all displayed strong inhibitory activity against T.b. brucei but none of them had higher activity than the crude extracts. Partial least squares (PLS) modelling of the anti-trypanosomal activity of the sample extracts using the LC-MS data indicated that high activity in the extracts, as judged from LCMS 2 data, could be correlated to denticulatain isomers in the extracts.

  7. A haptoglobin-hemoglobin receptor conveys innate immunity to Trypanosoma brucei in humans

    DEFF Research Database (Denmark)

    Vanhollebeke, Benoit; De Muylder, Géraldine; Nielsen, Marianne J

    2008-01-01

    The protozoan parasite Trypanosoma brucei is lysed by apolipoprotein L-I, a component of human high-density lipoprotein (HDL) particles that are also characterized by the presence of haptoglobin-related protein. We report that this process is mediated by a parasite glycoprotein receptor, which...... binds the haptoglobin-hemoglobin complex with high affinity for the uptake and incorporation of heme into intracellular hemoproteins. In mice, this receptor was required for optimal parasite growth and the resistance of parasites to the oxidative burst by host macrophages. In humans, the trypanosome...... immunity against the parasite....

  8. Mitochondrial tRNA import in Trypanosoma brucei is independent of thiolation and the Rieske protein

    Czech Academy of Sciences Publication Activity Database

    Paris, Zdeněk; RUBIO, M. A. T.; Lukeš, Julius; Alfonzo, J. D.

    2009-01-01

    Roč. 15, č. 7 (2009), s. 1398-1406 ISSN 1355-8382 R&D Projects: GA ČR GA204/06/1558; GA MŠk LC07032; GA MŠk 2B06129 Institutional research plan: CEZ:AV0Z60220518 Keywords : T. brucei * tRNA import * 2-thiolation * RIC * Rieske * Fe-S cluster Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.198, year: 2009

  9. Molecular Confirmation of Trypanosoma evansi and Babesia bigemina in Cattle from Lower Egypt

    Directory of Open Access Journals (Sweden)

    Mahmoud M. Elhaig, Abdelfattah Selim, Mohamed M. Mahmoud and Eman K El-Gayar

    2016-11-01

    Full Text Available Trypanosomosis and babesiosis are economically important vector-borne diseases for animal health and productivity in developing countries. In Egypt, molecular epidemiological surveys on such diseases are scarce. In the present study, we examined 475 healthy and 25 clinically diagnosed cattle from three provinces in Lower Egypt, for Trypanosoma (T. and Babesia (B. infections using an ITS1 PCR assay that confirmed Trypanosoma species presence and an 18S rRNA assay that detected B. bigemina. Results confirmed Trypanosoma spp. and B. bigemina presence in 30.4% and 11% individuals, respectively, with eight animals (1.6% being co-infected with both hemoparasites. Subsequent type-specific PCRs revealed that all Trypanosoma PCR positive samples corresponded to T. evansi and that none of the animals harboured T. brucei gambiense or T. brucei rhodesiense. Nucleotide sequencing of the variable surface glycoprotein revealed the T. evansi cattle strain to be most closely related (99% nucleotide sequence identity to strains previously detected in dromedary camels in Egypt, while the 18S rRNA gene phylogeny confirmed the presence of a unique B. bigemina haplotype closely related to strains from Turkey and Brazil. Statistically significant differences in PCR prevalence were noted with respect to gender, clinical status and locality. These results confirm the presence of high numbers of carrier animals and signal the need for expanded surveillance and control efforts.

  10. Occurrence, clinical manifestation and the epidemiological implications of naturally occurring canine trypanosomosis in western Kenya

    Directory of Open Access Journals (Sweden)

    G.O. Matete

    2003-11-01

    Full Text Available Domestic dogs were screened for Trypanosoma brucei infection using the haematocrit centrifugation technique as part of routine active surveillance exercises in the Busia and Teso districts of Kenya. The purpose was to assess the role of dogs as sentinels for the occurrence of human sleeping sickness. Out of 200 dogs screened, five were found to be infected at the various test sites. These five succumbed to the disease within four weeks, and exhibited a distinct and pronounced corneal opacity before death. Blood from two naturally infected dogs were tested for the presence of the serum resistance associated (SRA gene and one tested positive, confirming it as human infective (T. brucei rhodesiense prevalence (0.5 %. It is considered that the occurrence of this clinical sign could be used as an early warning prediction of future outbreaks. This type of prediction could form an integral part of an indigenous technical knowledge set in areas lying at the edges of the tsetse (Glossina belts where T. brucei is the main trypanosome species that affects dogs. The occurrence of corneal opacity in dogs could indicate a rise in the levels of T. brucei a proportion of which could be human infective T. b. rhodesiense circulating in the population early enough before disease outbreak occurs. It is thought that during sleeping sickness epidemics the domestic dog will be the first casualty rapidly succumbing to disease long before it is noticed in man. Prompt prediction of disease outbreaks would thus enable early interventions that would reduce the morbidity, mortality and the general economic losses associated with sleeping sickness to be instituted.

  11. Adaptations in the glucose metabolism of procyclic Trypanosoma brucei isolates from Tsetse flies and during differentiation of bloodstream forms.

    NARCIS (Netherlands)

    van Grinsven, K.W.A.; van den Abbeele, J.; van den Bossche, P.; van Hellemond, J.J.; Tielens, A.G.M.

    2009-01-01

    Procyclic forms of Trypanosoma brucei isolated from the midguts of infected tsetse flies, or freshly transformed from a strain that is close to field isolates, do not use a complete Krebs cycle. Furthermore, short stumpy bloodstream forms produce acetate and are apparently metabolically preadapted

  12. KREX2 is not essential for either procyclic or bloodstream form Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Jason Carnes

    Full Text Available Most mitochondrial mRNAs in Trypanosoma brucei require RNA editing for maturation and translation. The edited RNAs primarily encode proteins of the oxidative phosphorylation system. These parasites undergo extensive changes in energy metabolism between the insect and bloodstream stages which are mirrored by alterations in RNA editing. Two U-specific exonucleases, KREX1 and KREX2, are both present in protein complexes (editosomes that catalyze RNA editing but the relative roles of each protein are not known.The requirement for KREX2 for RNA editing in vivo was assessed in both procyclic (insect and bloodstream form parasites by methods that use homologous recombination for gene elimination. These studies resulted in null mutant cells in which both alleles were eliminated. The viability of these cells demonstrates that KREX2 is not essential in either life cycle stage, despite certain defects in RNA editing in vivo. Furthermore, editosomes isolated from KREX2 null cells require KREX1 for in vitro U-specific exonuclease activity.KREX2 is a U-specific exonuclease that is dispensable for RNA editing in vivo in T. brucei BFs and PFs. This result suggests that the U deletion activity, which is required for RNA editing, is primarily mediated in vivo by KREX1 which is normally found associated with only one type of editosome. The retention of the KREX2 gene implies a non-essential role or a role that is essential in other life cycle stages or conditions.

  13. Mitochondrial translation factors of Trypanosoma brucei: elongation factor-Tu has a unique subdomain that is essential for its function

    Czech Academy of Sciences Publication Activity Database

    Cristodero, M.; Mani, J.; Oeljeklaus, S.; Aeberhard, L.; Hashimi, Hassan; Ramrath, D.J.F.; Lukeš, Julius; Warscheid, B.; Schneider, A.

    2013-01-01

    Roč. 90, č. 4 (2013), s. 744-755 ISSN 0950-382X R&D Projects: GA ČR GAP305/12/2261 Institutional support: RVO:60077344 Keywords : mitochondrial translation * Trypanosoma brucei * EF-Tu Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.026, year: 2013

  14. Repurposing a Library of Human Cathepsin L Ligands: Identification of Macrocyclic Lactams as Potent Rhodesain and Trypanosoma brucei Inhibitors.

    Science.gov (United States)

    Giroud, Maude; Dietzel, Uwe; Anselm, Lilli; Banner, David; Kuglstatter, Andreas; Benz, Jörg; Blanc, Jean-Baptiste; Gaufreteau, Delphine; Liu, Haixia; Lin, Xianfeng; Stich, August; Kuhn, Bernd; Schuler, Franz; Kaiser, Marcel; Brun, Reto; Schirmeister, Tanja; Kisker, Caroline; Diederich, François; Haap, Wolfgang

    2018-04-26

    Rhodesain (RD) is a parasitic, human cathepsin L (hCatL) like cysteine protease produced by Trypanosoma brucei ( T. b.) species and a potential drug target for the treatment of human African trypanosomiasis (HAT). A library of hCatL inhibitors was screened, and macrocyclic lactams were identified as potent RD inhibitors ( K i < 10 nM), preventing the cell-growth of Trypanosoma brucei rhodesiense (IC 50 < 400 nM). SARs addressing the S2 and S3 pockets of RD were established. Three cocrystal structures with RD revealed a noncovalent binding mode of this ligand class due to oxidation of the catalytic Cys25 to a sulfenic acid (Cys-SOH) during crystallization. The P-glycoprotein efflux ratio was measured and the in vivo brain penetration in rats determined. When tested in vivo in acute HAT model, the compounds permitted up to 16.25 (vs 13.0 for untreated controls) mean days of survival.

  15. Zoonotic trypanosomes in South East Asia : attempts to control Trypanosoma lewisi using human and animal trypanocidal drugs

    OpenAIRE

    Desquesnes, M.; Yangtara, S.; Kunphukhieo, P.; Jittapalapong, S.; Herder, Stéphane

    2016-01-01

    Beside typical human trypanosomes responsible of sleeping sickness in Africa and Chagas disease in Latin America, there is a growing number of reported atypical human infections due to Trypanosoma evansi, a livestock parasite, or Trypanosoma lewisi, a rat parasite, especially in Asia. Drugs available for the treatment of T. brucei ssp. in humans are obviously of choice for the control of T. evansi because it is derived from T. brucei. However, concerning T. lewisi, there is an urgent need to ...

  16. Changes in the serum profiles of lipids and cholesterol in sheep ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-06-17

    Jun 17, 2008 ... Trypanosomosis (trypanosomiasis), a disease caused in domestic and wild ... as Human African Trypanosomosis or sleeping sickness; namely, T. brucei .... jugular veins were then severed in order to collect sufficient blood.

  17. Trypanosoma brucei TbIF1 inhibits the essential F1-ATPase in the infectious form of the parasite.

    Directory of Open Access Journals (Sweden)

    Brian Panicucci

    2017-04-01

    Full Text Available The mitochondrial (mt FoF1-ATP synthase of the digenetic parasite, Trypanosoma brucei, generates ATP during the insect procyclic form (PF, but becomes a perpetual consumer of ATP in the mammalian bloodstream form (BF, which lacks a canonical respiratory chain. This unconventional dependence on FoF1-ATPase is required to maintain the essential mt membrane potential (Δψm. Normally, ATP hydrolysis by this rotary molecular motor is restricted to when eukaryotic cells experience sporadic hypoxic conditions, during which this compulsory function quickly depletes the cellular ATP pool. To protect against this cellular treason, the highly conserved inhibitory factor 1 (IF1 binds the enzyme in a manner that solely inhibits the hydrolytic activity. Intriguingly, we were able to identify the IF1 homolog in T. brucei (TbIF1, but determined that its expression in the mitochondrion is tightly regulated throughout the life cycle as it is only detected in PF cells. TbIF1 appears to primarily function as an emergency brake in PF cells, where it prevented the restoration of the Δψm by FoF1-ATPase when respiration was chemically inhibited. In vitro, TbIF1 overexpression specifically inhibits the hydrolytic activity but not the synthetic capability of the FoF1-ATP synthase in PF mitochondria. Furthermore, low μM amounts of recombinant TbIF1 achieve the same inhibition of total mt ATPase activity as the FoF1-ATPase specific inhibitors, azide and oligomycin. Therefore, even minimal ectopic expression of TbIF1 in BF cells proved lethal as the indispensable Δψm collapsed due to inhibited FoF1-ATPase. In summary, we provide evidence that T. brucei harbors a natural and potent unidirectional inhibitor of the vital FoF1-ATPase activity that can be exploited for future structure-based drug design.

  18. Proximity Interactions among Basal Body Components in Trypanosoma brucei Identify Novel Regulators of Basal Body Biogenesis and Inheritance

    Directory of Open Access Journals (Sweden)

    Hung Quang Dang

    2017-01-01

    Full Text Available The basal body shares similar architecture with centrioles in animals and is involved in nucleating flagellar axonemal microtubules in flagellated eukaryotes. The early-branching Trypanosoma brucei possesses a motile flagellum nucleated from the basal body that consists of a mature basal body and an adjacent pro-basal body. Little is known about the basal body proteome and its roles in basal body biogenesis and flagellar axoneme assembly in T. brucei. Here, we report the identification of 14 conserved centriole/basal body protein homologs and 25 trypanosome-specific basal body proteins. These proteins localize to distinct subdomains of the basal body, and several of them form a ring-like structure surrounding the basal body barrel. Functional characterization of representative basal body proteins revealed distinct roles in basal body duplication/separation and flagellar axoneme assembly. Overall, this work identified novel proteins required for basal body duplication and separation and uncovered new functions of conserved basal body proteins in basal body duplication and separation, highlighting an unusual mechanism of basal body biogenesis and inheritance in this early divergent eukaryote.

  19. Processing of the glycosomal matrix-protein import receptor PEX5 of Trypanosoma brucei

    International Nuclear Information System (INIS)

    Gualdrón-López, Melisa; Michels, Paul A.M.

    2013-01-01

    Highlights: ► Most eukaryotic cells have a single gene for the peroxin PEX5. ► PEX5 is sensitive to in vitro proteolysis in distantly related organisms. ► TbPEX5 undergoes N-terminal truncation in vitro and possibly in vivo. ► Truncated TbPEX5 is still capable of binding PTS1-containing proteins. ► PEX5 truncation is physiologically relevant or an evolutionary conserved artifact. -- Abstract: Glycolysis in kinetoplastid protists such as Trypanosoma brucei is compartmentalized in peroxisome-like organelles called glycosomes. Glycosomal matrix-protein import involves a cytosolic receptor, PEX5, which recognizes the peroxisomal-targeting signal type 1 (PTS1) present at the C-terminus of the majority of matrix proteins. PEX5 appears generally susceptible to in vitro proteolytic processing. On western blots of T. brucei, two PEX5 forms are detected with apparent M r of 100 kDa and 72 kDa. 5′-RACE-PCR showed that TbPEX5 is encoded by a unique transcript that can be translated into a protein of maximally 72 kDa. However, recombinant PEX5 migrates aberrantly in SDS–PAGE with an apparent M r of 100 kDa, similarly as observed for the native peroxin. In vitro protease susceptibility analysis of native and 35 S-labelled PEX5 showed truncation of the 100 kDa form at the N-terminal side by unknown parasite proteases, giving rise to the 72 kDa form which remains functional for PTS1 binding. The relevance of these observations is discussed

  20. Processing of the glycosomal matrix-protein import receptor PEX5 of Trypanosoma brucei

    Energy Technology Data Exchange (ETDEWEB)

    Gualdrón-López, Melisa [Research Unit for Tropical Diseases, de Duve Institute, Université catholique de Louvain, Brussels (Belgium); Michels, Paul A.M., E-mail: paul.michels@uclouvain.be [Research Unit for Tropical Diseases, de Duve Institute, Université catholique de Louvain, Brussels (Belgium)

    2013-02-01

    Highlights: ► Most eukaryotic cells have a single gene for the peroxin PEX5. ► PEX5 is sensitive to in vitro proteolysis in distantly related organisms. ► TbPEX5 undergoes N-terminal truncation in vitro and possibly in vivo. ► Truncated TbPEX5 is still capable of binding PTS1-containing proteins. ► PEX5 truncation is physiologically relevant or an evolutionary conserved artifact. -- Abstract: Glycolysis in kinetoplastid protists such as Trypanosoma brucei is compartmentalized in peroxisome-like organelles called glycosomes. Glycosomal matrix-protein import involves a cytosolic receptor, PEX5, which recognizes the peroxisomal-targeting signal type 1 (PTS1) present at the C-terminus of the majority of matrix proteins. PEX5 appears generally susceptible to in vitro proteolytic processing. On western blots of T. brucei, two PEX5 forms are detected with apparent M{sub r} of 100 kDa and 72 kDa. 5′-RACE-PCR showed that TbPEX5 is encoded by a unique transcript that can be translated into a protein of maximally 72 kDa. However, recombinant PEX5 migrates aberrantly in SDS–PAGE with an apparent M{sub r} of 100 kDa, similarly as observed for the native peroxin. In vitro protease susceptibility analysis of native and {sup 35}S-labelled PEX5 showed truncation of the 100 kDa form at the N-terminal side by unknown parasite proteases, giving rise to the 72 kDa form which remains functional for PTS1 binding. The relevance of these observations is discussed.

  1. Sierra Leone Journal of Biomedical Research 38 Original Article

    African Journals Online (AJOL)

    ). 38 ... Sleeping sickness or Human African Trypanosomiasis (HAT) caused by Trypanosoma brucei .... end of the 1930th produced new social and .... use) resulted in the radical diminishing of the game ..... strains isolated from pigs in Liberia.

  2. Blocking variant surface glycoprotein synthesis alters endoplasmic reticulum exit sites/Golgi homeostasis in Trypanosoma brucei.

    Science.gov (United States)

    Ooi, Cher-Pheng; Smith, Terry K; Gluenz, Eva; Wand, Nadina Vasileva; Vaughan, Sue; Rudenko, Gloria

    2018-06-01

    The predominant secretory cargo of bloodstream form Trypanosoma brucei is variant surface glycoprotein (VSG), comprising ~10% total protein and forming a dense protective layer. Blocking VSG translation using Morpholino oligonucleotides triggered a precise pre-cytokinesis arrest. We investigated the effect of blocking VSG synthesis on the secretory pathway. The number of Golgi decreased, particularly in post-mitotic cells, from 3.5 ± 0.6 to 2.0 ± 0.04 per cell. Similarly, the number of endoplasmic reticulum exit sites (ERES) in post-mitotic cells dropped from 3.9 ± 0.6 to 2.7 ± 0.1 eight hours after blocking VSG synthesis. The secretory pathway was still functional in these stalled cells, as monitored using Cathepsin L. Rates of phospholipid and glycosylphosphatidylinositol-anchor biosynthesis remained relatively unaffected, except for the level of sphingomyelin which increased. However, both endoplasmic reticulum and Golgi morphology became distorted, with the Golgi cisternae becoming significantly dilated, particularly at the trans-face. Membrane accumulation in these structures is possibly caused by reduced budding of nascent vesicles due to the drastic reduction in the total amount of secretory cargo, that is, VSG. These data argue that the total flux of secretory cargo impacts upon the biogenesis and maintenance of secretory structures and organelles in T. brucei, including the ERES and Golgi. © 2018 The Authors. Traffic published by John Wiley & Sons Ltd.

  3. Dynamics of Mitochondrial RNA-Binding Protein Complex in Trypanosoma brucei and Its Petite Mutant under Optimized Immobilization Conditions

    Czech Academy of Sciences Publication Activity Database

    Huang, Zhenqiu; Kaltenbrunner, S.; Šimková, Eva; Staněk, David; Lukeš, Julius; Hashimi, Hassan

    2014-01-01

    Roč. 13, č. 9 (2014), s. 1232-1240 ISSN 1535-9778 R&D Projects: GA ČR GAP305/12/2261; GA MŠk(CZ) EE2.3.30.0032 Institutional support: RVO:60077344 ; RVO:68378050 Keywords : mitochondrion * Trypanosoma brucei * YFP Subject RIV: EB - Genetics ; Molecular Biology; EB - Genetics ; Molecular Biology (UMG-J) Impact factor: 2.820, year: 2014

  4. Exosome secretion affects social motility in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Dror Eliaz

    2017-03-01

    Full Text Available Extracellular vesicles (EV secreted by pathogens function in a variety of biological processes. Here, we demonstrate that in the protozoan parasite Trypanosoma brucei, exosome secretion is induced by stress that affects trans-splicing. Following perturbations in biogenesis of spliced leader RNA, which donates its spliced leader (SL exon to all mRNAs, or after heat-shock, the SL RNA is exported to the cytoplasm and forms distinct granules, which are then secreted by exosomes. The exosomes are formed in multivesicular bodies (MVB utilizing the endosomal sorting complexes required for transport (ESCRT, through a mechanism similar to microRNA secretion in mammalian cells. Silencing of the ESCRT factor, Vps36, compromised exosome secretion but not the secretion of vesicles derived from nanotubes. The exosomes enter recipient trypanosome cells. Time-lapse microscopy demonstrated that cells secreting exosomes or purified intact exosomes affect social motility (SoMo. This study demonstrates that exosomes are delivered to trypanosome cells and can change their migration. Exosomes are used to transmit stress signals for communication between parasites.

  5. Metabolomics Identifies Multiple Candidate Biomarkers to Diagnose and Stage Human African Trypanosomiasis.

    Directory of Open Access Journals (Sweden)

    Isabel M Vincent

    2016-12-01

    Full Text Available Treatment for human African trypanosomiasis is dependent on the species of trypanosome causing the disease and the stage of the disease (stage 1 defined by parasites being present in blood and lymphatics whilst for stage 2, parasites are found beyond the blood-brain barrier in the cerebrospinal fluid (CSF. Currently, staging relies upon detecting the very low number of parasites or elevated white blood cell numbers in CSF. Improved staging is desirable, as is the elimination of the need for lumbar puncture. Here we use metabolomics to probe samples of CSF, plasma and urine from 40 Angolan patients infected with Trypanosoma brucei gambiense, at different disease stages. Urine samples provided no robust markers indicative of infection or stage of infection due to inherent variability in urine concentrations. Biomarkers in CSF were able to distinguish patients at stage 1 or advanced stage 2 with absolute specificity. Eleven metabolites clearly distinguished the stage in most patients and two of these (neopterin and 5-hydroxytryptophan showed 100% specificity and sensitivity between our stage 1 and advanced stage 2 samples. Neopterin is an inflammatory biomarker previously shown in CSF of stage 2 but not stage 1 patients. 5-hydroxytryptophan is an important metabolite in the serotonin synthetic pathway, the key pathway in determining somnolence, thus offering a possible link to the eponymous symptoms of "sleeping sickness". Plasma also yielded several biomarkers clearly indicative of the presence (87% sensitivity and 95% specificity and stage of disease (92% sensitivity and 81% specificity. A logistic regression model including these metabolites showed clear separation of patients being either at stage 1 or advanced stage 2 or indeed diseased (both stages versus control.

  6. Melarsoprol cyclodextrin inclusion complexes as promising oral candidates for the treatment of human African trypanosomiasis.

    Directory of Open Access Journals (Sweden)

    Jean Rodgers

    2011-09-01

    Full Text Available Human African trypanosomiasis (HAT, or sleeping sickness, results from infection with the protozoan parasites Trypanosoma brucei (T. b. gambiense or T. b. rhodesiense and is invariably fatal if untreated. There are 60 million people at risk from the disease throughout sub-Saharan Africa. The infection progresses from the haemolymphatic stage where parasites invade the blood, lymphatics and peripheral organs, to the late encephalitic stage where they enter the central nervous system (CNS to cause serious neurological disease. The trivalent arsenical drug melarsoprol (Arsobal is the only currently available treatment for CNS-stage T. b. rhodesiense infection. However, it must be administered intravenously due to the presence of propylene glycol solvent and is associated with numerous adverse reactions. A severe post-treatment reactive encephalopathy occurs in about 10% of treated patients, half of whom die. Thus melarsoprol kills 5% of all patients receiving it. Cyclodextrins have been used to improve the solubility and reduce the toxicity of a wide variety of drugs. We therefore investigated two melarsoprol cyclodextrin inclusion complexes; melarsoprol hydroxypropyl-β-cyclodextrin and melarsoprol randomly-methylated-β-cyclodextrin. We found that these compounds retain trypanocidal properties in vitro and cure CNS-stage murine infections when delivered orally, once per day for 7-days, at a dosage of 0.05 mmol/kg. No overt signs of toxicity were detected. Parasite load within the brain was rapidly reduced following treatment onset and magnetic resonance imaging showed restoration of normal blood-brain barrier integrity on completion of chemotherapy. These findings strongly suggest that complexed melarsoprol could be employed as an oral treatment for CNS-stage HAT, delivering considerable improvements over current parenteral chemotherapy.

  7. Transferrin coupled azanthraquinone enhances the killing effect on trypanosomes. The role of lysosomal mannosidase

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    Nok A.J.

    2002-12-01

    Full Text Available Partially purified azanthraquinone (AQ extract from Mitracarpus scaber was coupled to bovine transferrin (Tf using azidophenyl glyoxal (APG. The AQ-APG-Tf conjugate was found to possess an enhanced in vitro trypanocidal activity against Trypanosoma congolense and T. brucei brucei. At low concentrations of 0.39-90 mg/ml, the conjugate diminished the growth of T. congolense and T. b. brucei dose dependently at the logarithmic phase. Both parasites were more sensitive to AQ-APG-Tf than to the free (AQ extract. Growth inhibition on the parasites by the free extract was observed at 20-200 mg/ml. The total activity of the lysosomal enzyme a-mannosidase was reduced in the T. congolense cells treated with AQ-APG-Tf in a dose related pattern. However, the activity of the mannosidase in the T. b. brucei treated cells is less affected. The AQ-APG-Tf is more effective on a mannosidase than free AQ, eight and four fold for T. congolense and T. b. brucei respectively. The results are discussed as regards the potency of using transferrin as suitable drug carrier in the chemotherapy of Human sleeping sickness.

  8. The Aurora Kinase in Trypanosoma brucei plays distinctive roles in metaphase-anaphase transition and cytokinetic initiation.

    Directory of Open Access Journals (Sweden)

    Ziyin Li

    2009-09-01

    Full Text Available Aurora B kinase is an essential regulator of chromosome segregation with the action well characterized in eukaryotes. It is also implicated in cytokinesis, but the detailed mechanism remains less clear, partly due to the difficulty in separating the latter from the former function in a growing cell. A chemical genetic approach with an inhibitor of the enzyme added to a synchronized cell population at different stages of the cell cycle would probably solve this problem. In the deeply branched parasitic protozoan Trypanosoma brucei, an Aurora B homolog, TbAUK1, was found to control both chromosome segregation and cytokinetic initiation by evidence from RNAi and dominant negative mutation. To clearly separate these two functions, VX-680, an inhibitor of TbAUK1, was added to a synchronized T. brucei procyclic cell population at different cell cycle stages. The unique trans-localization pattern of the chromosomal passenger complex (CPC, consisting of TbAUK1 and two novel proteins TbCPC1 and TbCPC2, was monitored during mitosis and cytokinesis by following the migration of the proteins tagged with enhanced yellow fluorescence protein in live cells with time-lapse video microscopy. Inhibition of TbAUK1 function in S-phase, prophase or metaphase invariably arrests the cells in the metaphase, suggesting an action of TbAUK1 in promoting metaphase-anaphase transition. TbAUK1 inhibition in anaphase does not affect mitotic exit, but prevents trans-localization of the CPC from the spindle midzone to the anterior tip of the new flagellum attachment zone for cytokinetic initiation. The CPC in the midzone is dispersed back to the two segregated nuclei, while cytokinesis is inhibited. In and beyond telophase, TbAUK1 inhibition has no effect on the progression of cytokinesis or the subsequent G1, S and G2 phases until a new metaphase is attained. There are thus two clearly distinct points of TbAUK1 action in T. brucei: the metaphase-anaphase transition and

  9. In Silico Identification and in Vitro Activity of Novel Natural Inhibitors of Trypanosoma brucei Glyceraldehyde-3-phosphate-dehydrogenase.

    Science.gov (United States)

    Herrmann, Fabian C; Lenz, Mairin; Jose, Joachim; Kaiser, Marcel; Brun, Reto; Schmidt, Thomas J

    2015-09-03

    As part of our ongoing efforts to identify natural products with activity against pathogens causing neglected tropical diseases, we are currently performing an extensive screening of natural product (NP) databases against a multitude of protozoan parasite proteins. Within this project, we screened a database of NPs from a commercial supplier, AnalytiCon Discovery (Potsdam, Germany), against Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase (TbGAPDH), a glycolytic enzyme whose inhibition deprives the parasite of energy supply. NPs acting as potential inhibitors of the mentioned enzyme were identified using a pharmacophore-based virtual screening and subsequent docking of the identified hits into the active site of interest. In a set of 700 structures chosen for the screening, 13 (1.9%) were predicted to possess significant affinity towards the enzyme and were therefore tested in an in vitro enzyme assay using recombinant TbGAPDH. Nine of these in silico hits (69%) showed significant inhibitory activity at 50 µM, of which two geranylated benzophenone derivatives proved to be particularly active with IC50 values below 10 µM. These compounds also showed moderate in vitro activity against T. brucei rhodesiense and may thus represent interesting starting points for further optimization.

  10. Trypanosoma brucei TBRGG1, a mitochondrial oligo(U)-binding protein that co-localizes with an in vitro RNA editing activity

    NARCIS (Netherlands)

    Vanhamme, L.; Perez-Morga, D.; Marchal, C.; Speijer, D.; Lambert, L.; Geuskens, M.; Alexandre, S.; Ismaïli, N.; Göringer, U.; Benne, R.; Pays, E.

    1998-01-01

    We report the characterization of a Trypanosoma brucei 75-kDa protein of the RGG (Arg-Gly-Gly) type, termed TBRGG1. Dicistronic and monocistronic transcripts of the TBRGG1 gene were produced by both alternative splicing and polyadenylation. TBRGG1 was found in two or three forms that differ in their

  11. Secondary Metabolites from Vietnamese Marine Invertebrates with Activity against Trypanosoma brucei and T. cruzi

    Directory of Open Access Journals (Sweden)

    Nguyen Phuong Thao

    2014-06-01

    Full Text Available Marine-derived natural products from invertebrates comprise an extremely diverse and promising source of the compounds from a wide variety of structural classes. This study describes the discovery of five marine natural products with activity against Trypanosoma species by natural product library screening using whole cell in vitro assays. We investigated the anti-trypanosomal activity of the extracts from the soft corals and echinoderms living in Vietnamese seas. Of the samples screened, the methanolic extracts of several marine organisms exhibited potent activities against cultures of Trypanosoma brucei and T. cruzi (EC50 < 5.0 μg/mL. Among the compounds isolated from these extracts, laevigatol B (1 from Lobophytum crassum and L. laevigatum, (24S-ergost-4-ene-3-one (2 from Sinularia dissecta, astropectenol A (3 from Astropecten polyacanthus, and cholest-8-ene-3β,5α,6β,7α-tetraol (4 from Diadema savignyi showed inhibitory activity against T. brucei with EC50 values ranging from 1.57 ± 0.14 to 14.6 ± 1.36 μM, relative to the positive control, pentamidine (EC50 = 0.015 ± 0.003 μM. Laevigatol B (1 and 5α-cholest-8(14-ene-3β,7α-diol (5 exhibited also significant inhibitory effects on T. cruzi. The cytotoxic activity of the pure compounds on mammalian cells was also assessed and found to be insignificant in all cases. This is the first report on the inhibitory effects of marine organisms collected in Vietnamese seas against Trypanosoma species responsible for neglected tropical diseases.

  12. Genetic Dissociation of Daily Sleep and Sleep Following Thermogenetic Sleep Deprivation in Drosophila.

    Science.gov (United States)

    Dubowy, Christine; Moravcevic, Katarina; Yue, Zhifeng; Wan, Joy Y; Van Dongen, Hans P A; Sehgal, Amita

    2016-05-01

    Sleep rebound-the increase in sleep that follows sleep deprivation-is a hallmark of homeostatic sleep regulation that is conserved across the animal kingdom. However, both the mechanisms that underlie sleep rebound and its relationship to habitual daily sleep remain unclear. To address this, we developed an efficient thermogenetic method of inducing sleep deprivation in Drosophila that produces a substantial rebound, and applied the newly developed method to assess sleep rebound in a screen of 1,741 mutated lines. We used data generated by this screen to identify lines with reduced sleep rebound following thermogenetic sleep deprivation, and to probe the relationship between habitual sleep amount and sleep following thermogenetic sleep deprivation in Drosophila. To develop a thermogenetic method of sleep deprivation suitable for screening, we thermogenetically stimulated different populations of wake-promoting neurons labeled by Gal4 drivers. Sleep rebound following thermogenetically-induced wakefulness varies across the different sets of wake-promoting neurons that were stimulated, from very little to quite substantial. Thermogenetic activation of neurons marked by the c584-Gal4 driver produces both strong sleep loss and a substantial rebound that is more consistent within genotypes than rebound following mechanical or caffeine-induced sleep deprivation. We therefore used this driver to induce sleep deprivation in a screen of 1,741 mutagenized lines generated by the Drosophila Gene Disruption Project. Flies were subjected to 9 h of sleep deprivation during the dark period and released from sleep deprivation 3 h before lights-on. Recovery was measured over the 15 h following sleep deprivation. Following identification of lines with reduced sleep rebound, we characterized baseline sleep and sleep depth before and after sleep deprivation for these hits. We identified two lines that consistently exhibit a blunted increase in the duration and depth of sleep after

  13. The Silicon Trypanosome : A Test Case of Iterative Model Extension in Systems Biology

    NARCIS (Netherlands)

    Achcar, Fiona; Fadda, Abeer; Haanstra, Jurgen R.; Kerkhoven, Eduard J.; Kim, Dong-Hyun; Leroux, Alejandro E.; Papamarkou, Theodore; Rojas, Federico; Bakker, Barbara M.; Barrett, Michael P.; Clayton, Christine; Girolami, Mark; Krauth-Siegel, R. Luise; Matthews, Keith R.; Breitling, Rainer; Poole, RK

    2014-01-01

    The African trypanosome, Ttypanosoma brucei, is a unicellular parasite causing African Trypanosomiasis (sleeping sickness in humans and nagana in animals). Due to some of its unique properties, it has emerged as a popular model organism in systems biology. A predictive quantitative model of

  14. Functional and structural insights revealed by molecular dynamics simulations of an essential RNA editing ligase in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Rommie E Amaro

    2007-11-01

    Full Text Available RNA editing ligase 1 (TbREL1 is required for the survival of both the insect and bloodstream forms of Trypanosoma brucei, the parasite responsible for the devastating tropical disease African sleeping sickness. The type of RNA editing that TbREL1 is involved in is unique to the trypanosomes, and no close human homolog is known to exist. In addition, the high-resolution crystal structure revealed several unique features of the active site, making this enzyme a promising target for structure-based drug design. In this work, two 20 ns atomistic molecular dynamics (MD simulations are employed to investigate the dynamics of TbREL1, both with and without the ATP substrate present. The flexibility of the active site, dynamics of conserved residues and crystallized water molecules, and the interactions between TbREL1 and the ATP substrate are investigated and discussed in the context of TbREL1's function. Differences in local and global motion upon ATP binding suggest that two peripheral loops, unique to the trypanosomes, may be involved in interdomain signaling events. Notably, a significant structural rearrangement of the enzyme's active site occurs during the apo simulations, opening an additional cavity adjacent to the ATP binding site that could be exploited in the development of effective inhibitors directed against this protozoan parasite. Finally, ensemble averaged electrostatics calculations over the MD simulations reveal a novel putative RNA binding site, a discovery that has previously eluded scientists. Ultimately, we use the insights gained through the MD simulations to make several predictions and recommendations, which we anticipate will help direct future experimental studies and structure-based drug discovery efforts against this vital enzyme.

  15. Population genetics of Trypanosoma brucei rhodesiense: clonality and diversity within and between foci.

    Directory of Open Access Journals (Sweden)

    Craig W Duffy

    2013-11-01

    Full Text Available African trypanosomes are unusual among pathogenic protozoa in that they can undergo their complete morphological life cycle in the tsetse fly vector with mating as a non-obligatory part of this development. Trypanosoma brucei rhodesiense, which infects humans and livestock in East and Southern Africa, has classically been described as a host-range variant of the non-human infective Trypanosoma brucei that occurs as stable clonal lineages. We have examined T. b. rhodesiense populations from East (Uganda and Southern (Malawi Africa using a panel of microsatellite markers, incorporating both spatial and temporal analyses. Our data demonstrate that Ugandan T. b. rhodesiense existed as clonal populations, with a small number of highly related genotypes and substantial linkage disequilibrium between pairs of loci. However, these populations were not stable as the dominant genotypes changed and the genetic diversity also reduced over time. Thus these populations do not conform to one of the criteria for strict clonality, namely stability of predominant genotypes over time, and our results show that, in a period in the mid 1990s, the previously predominant genotypes were not detected but were replaced by a novel clonal population with limited genetic relationship to the original population present between 1970 and 1990. In contrast, the Malawi T. b. rhodesiense population demonstrated significantly greater diversity and evidence for frequent genetic exchange. Therefore, the population genetics of T. b. rhodesiense is more complex than previously described. This has important implications for the spread of the single copy T. b. rhodesiense gene that allows human infectivity, and therefore the epidemiology of the human disease, as well as suggesting that these parasites represent an important organism to study the influence of optional recombination upon population genetic dynamics.

  16. Anti-trypanosomal activity of cationic N-heterocyclic carbene gold(I) complexes.

    Science.gov (United States)

    Winter, Isabel; Lockhauserbäumer, Julia; Lallinger-Kube, Gertrud; Schobert, Rainer; Ersfeld, Klaus; Biersack, Bernhard

    2017-06-01

    Two gold(I) N-heterocyclic carbene complexes 1a and 1b were tested for their anti-trypanosomal activity against Trypanosoma brucei parasites. Both gold compounds exhibited excellent anti-trypanosomal activity (IC 50 =0.9-3.0nM). The effects of the gold complexes 1a and 1b on the T. b. brucei cytoskeleton were evaluated. Rapid detachment of the flagellum from the cell body occurred after treatment with the gold complexes. In addition, a quick and complete degeneration of the parasitic cytoskeleton was induced by the gold complexes, only the microtubules of the detached flagellum remained intact. Both gold compounds 1a and 1b feature selective anti-trypanosomal agents and were distinctly more active against T. b. brucei cells than against human HeLa cells. Thus, the gold complexes 1a and 1b feature promising drug candidates for the treatment of trypanosome infections such as sleeping sickness (human African Trypanosomiasis caused by Trypanosoma brucei parasites). Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Trypanosoma brucei TbIF1 inhibits the essential Finf1/inf-ATPase in the infectious form of the parasite

    Czech Academy of Sciences Publication Activity Database

    Panicucci, Brian; Gahura, Ondřej; Zíková, Alena

    2017-01-01

    Roč. 11, č. 4 (2017), č. článku e0005552. ISSN 1935-2735 R&D Projects: GA MŠk(CZ) EE2.3.30.0032; GA ČR GA17-22248S; GA MŠk LL1205 Institutional support: RVO:60077344 Keywords : mt * TblF1 * Trypanosoma brucei Subject RIV: EE - Microbiology, Virology OBOR OECD: Infectious Diseases Impact factor: 3.834, year: 2016

  18. In Silico Identification and in Vitro Activity of Novel Natural Inhibitors of Trypanosoma brucei Glyceraldehyde-3-phosphate-dehydrogenase

    Directory of Open Access Journals (Sweden)

    Fabian C. Herrmann

    2015-09-01

    Full Text Available As part of our ongoing efforts to identify natural products with activity against pathogens causing neglected tropical diseases, we are currently performing an extensive screening of natural product (NP databases against a multitude of protozoan parasite proteins. Within this project, we screened a database of NPs from a commercial supplier, AnalytiCon Discovery (Potsdam, Germany, against Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase (TbGAPDH, a glycolytic enzyme whose inhibition deprives the parasite of energy supply. NPs acting as potential inhibitors of the mentioned enzyme were identified using a pharmacophore-based virtual screening and subsequent docking of the identified hits into the active site of interest. In a set of 700 structures chosen for the screening, 13 (1.9% were predicted to possess significant affinity towards the enzyme and were therefore tested in an in vitro enzyme assay using recombinant TbGAPDH. Nine of these in silico hits (69% showed significant inhibitory activity at 50 µM, of which two geranylated benzophenone derivatives proved to be particularly active with IC50 values below 10 µM. These compounds also showed moderate in vitro activity against T. brucei rhodesiense and may thus represent interesting starting points for further optimization.

  19. Mosaic VSGs and the scale of Trypanosoma brucei antigenic variation.

    Directory of Open Access Journals (Sweden)

    James P J Hall

    Full Text Available A main determinant of prolonged Trypanosoma brucei infection and transmission and success of the parasite is the interplay between host acquired immunity and antigenic variation of the parasite variant surface glycoprotein (VSG coat. About 0.1% of trypanosome divisions produce a switch to a different VSG through differential expression of an archive of hundreds of silent VSG genes and pseudogenes, but the patterns and extent of the trypanosome diversity phenotype, particularly in chronic infection, are unclear. We applied longitudinal VSG cDNA sequencing to estimate variant richness and test whether pseudogenes contribute to antigenic variation. We show that individual growth peaks can contain at least 15 distinct variants, are estimated computationally to comprise many more, and that antigenically distinct 'mosaic' VSGs arise from segmental gene conversion between donor VSG genes or pseudogenes. The potential for trypanosome antigenic variation is probably much greater than VSG archive size; mosaic VSGs are core to antigenic variation and chronic infection.

  20. Investigating the Chaperone Properties of a Novel Heat Shock Protein, Hsp70.c, from Trypanosoma brucei

    Directory of Open Access Journals (Sweden)

    Adélle Burger

    2014-01-01

    Full Text Available The neglected tropical disease, African Trypanosomiasis, is fatal and has a crippling impact on economic development. Heat shock protein 70 (Hsp70 is an important molecular chaperone that is expressed in response to stress and Hsp40 acts as its co-chaperone. These proteins play a wide range of roles in the cell and they are required to assist the parasite as it moves from a cold blooded insect vector to a warm blooded mammalian host. A novel cytosolic Hsp70, from Trypanosoma brucei, TbHsp70.c, contains an acidic substrate binding domain and lacks the C-terminal EEVD motif. The ability of a cytosolic Hsp40 from Trypanosoma brucei J protein 2, Tbj2, to function as a co-chaperone of TbHsp70.c was investigated. The main objective was to functionally characterize TbHsp70.c to further expand our knowledge of parasite biology. TbHsp70.c and Tbj2 were heterologously expressed and purified and both proteins displayed the ability to suppress aggregation of thermolabile MDH and chemically denatured rhodanese. ATPase assays revealed a 2.8-fold stimulation of the ATPase activity of TbHsp70.c by Tbj2. TbHsp70.c and Tbj2 both demonstrated chaperone activity and Tbj2 functions as a co-chaperone of TbHsp70.c. In vivo heat stress experiments indicated upregulation of the expression levels of TbHsp70.c.

  1. Sleep Applications to Assess Sleep Quality.

    Science.gov (United States)

    Fietze, Ingo

    2016-12-01

    This article highlights the potential uses that smartphone applications may have for helping those with sleep problems. Applications in smartphones offer the promised possibility of detection of sleep. From the author's own experience, one can also conclude that sleep applications are approximately as good as polysomnography in detection of sleep time, similar to the conventional wearable actimeters. In the future, sleep applications will help to further enhance awareness of sleep health and to distinguish those who actually poorly and only briefly sleep from those who suffer more likely from paradox insomnia. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Characterization of a Novel Class I Transcription Factor A (CITFA) Subunit That Is Indispensable for Transcription by the Multifunctional RNA Polymerase I of Trypanosoma brucei

    KAUST Repository

    Nguyen, T. N.; Nguyen, B. N.; Lee, J. H.; Panigrahi, A. K.; Gunzl, A.

    2012-01-01

    Trypanosoma brucei is the only organism known to have evolved a multifunctional RNA polymerase I (pol I) system that is used to express the parasite's ribosomal RNAs, as well as its major cell surface antigens, namely, the variant surface

  3. The 2’-O-ribose methyltransferase for cap 1 of spliced leader RNA and U1 small nuclear RNA in Trypanosoma brucei

    Czech Academy of Sciences Publication Activity Database

    Zamudio, J. R.; Mittra, B.; Foldynová-Trantírková, Silvie; Zeiner, G. M.; Lukeš, Julius; Bujnicki, J. M.; Sturm, N. R.; Campbell, D. A.

    2007-01-01

    Roč. 27, č. 17 (2007), s. 6084-6092 ISSN 0270-7306 R&D Projects: GA MŠk 2B06129; GA MŠk LC07032 Institutional research plan: CEZ:AV0Z60220518 Keywords : methylation * Trypanosoma brucei * methyltransferase * RNA interference Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.420, year: 2007

  4. Cell Cycle Inhibition To Treat Sleeping Sickness

    Directory of Open Access Journals (Sweden)

    Conrad L. Epting

    2017-09-01

    Full Text Available African trypanosomiasis is caused by infection with the protozoan parasite Trypanosoma brucei. During infection, this pathogen divides rapidly to high density in the bloodstream of its mammalian host in a manner similar to that of leukemia. Like all eukaryotes, T. brucei has a cell cycle involving the de novo synthesis of DNA regulated by ribonucleotide reductase (RNR, which catalyzes the conversion of ribonucleotides into their deoxy form. As an essential enzyme for the cell cycle, RNR is a common target for cancer chemotherapy. We hypothesized that inhibition of RNR by genetic or pharmacological means would impair parasite growth in vitro and prolong the survival of infected animals. Our results demonstrate that RNR inhibition is highly effective in suppressing parasite growth both in vitro and in vivo. These results support drug discovery efforts targeting the cell cycle, not only for African trypanosomiasis but possibly also for other infections by eukaryotic pathogens.

  5. Dihydroquinazolines as a novel class of Trypanosoma brucei trypanothione reductase inhibitors: discovery, synthesis, and characterization of their binding mode by protein crystallography.

    Science.gov (United States)

    Patterson, Stephen; Alphey, Magnus S; Jones, Deuan C; Shanks, Emma J; Street, Ian P; Frearson, Julie A; Wyatt, Paul G; Gilbert, Ian H; Fairlamb, Alan H

    2011-10-13

    Trypanothione reductase (TryR) is a genetically validated drug target in the parasite Trypanosoma brucei , the causative agent of human African trypanosomiasis. Here we report the discovery, synthesis, and development of a novel series of TryR inhibitors based on a 3,4-dihydroquinazoline scaffold. In addition, a high resolution crystal structure of TryR, alone and in complex with substrates and inhibitors from this series, is presented. This represents the first report of a high resolution complex between a noncovalent ligand and this enzyme. Structural studies revealed that upon ligand binding the enzyme undergoes a conformational change to create a new subpocket which is occupied by an aryl group on the ligand. Therefore, the inhibitor, in effect, creates its own small binding pocket within the otherwise large, solvent exposed active site. The TryR-ligand structure was subsequently used to guide the synthesis of inhibitors, including analogues that challenged the induced subpocket. This resulted in the development of inhibitors with improved potency against both TryR and T. brucei parasites in a whole cell assay.

  6. Independent Analysis of the Flagellum Surface and Matrix Proteomes Provides Insight into Flagellum Signaling in Mammalian-infectious Trypanosoma brucei*

    Science.gov (United States)

    Oberholzer, Michael; Langousis, Gerasimos; Nguyen, HoangKim T.; Saada, Edwin A.; Shimogawa, Michelle M.; Jonsson, Zophonias O.; Nguyen, Steven M.; Wohlschlegel, James A.; Hill, Kent L.

    2011-01-01

    The flagellum of African trypanosomes is an essential and multifunctional organelle that functions in motility, cell morphogenesis, and host-parasite interaction. Previous studies of the trypanosome flagellum have been limited by the inability to purify flagella without first removing the flagellar membrane. This limitation is particularly relevant in the context of studying flagellum signaling, as signaling requires surface-exposed proteins in the flagellar membrane and soluble signaling proteins in the flagellar matrix. Here we employ a combination of genetic and mechanical approaches to purify intact flagella from the African trypanosome, Trypanosoma brucei, in its mammalian-infectious stage. We combined flagellum purification with affinity-purification of surface-exposed proteins to conduct independent proteomic analyses of the flagellum surface and matrix fractions. The proteins identified encompass a broad range of molecular functionalities, including many predicted to function in signaling. Immunofluorescence and RNA interference studies demonstrate flagellum localization and function for proteins identified and provide insight into mechanisms of flagellum attachment and motility. The flagellum surface proteome includes many T. brucei-specific proteins and is enriched for proteins up-regulated in the mammalian-infectious stage of the parasite life-cycle. The combined results indicate that the flagellum surface presents a diverse and dynamic host-parasite interface that is well-suited for host-parasite signaling. PMID:21685506

  7. Sleep less and bite more: sleep disorders associated with occlusal loads during sleep.

    Science.gov (United States)

    Kato, Takafumi; Yamaguchi, Taihiko; Okura, Kazuo; Abe, Susumu; Lavigne, Gilles J

    2013-04-01

    Occlusal overload during sleep is a significant clinical issue that has negative impacts on the maintenance of teeth and the longevity of dental prostheses. Sleep is usually viewed as an 'out-of-functional' mode for masticatory muscles. However, orodental structures and prostheses are not free from occlusal loads during sleep since masticatory muscles can be activated at a low level within normal sleep continuity. Thus, an increase in masticatory muscle contractions, by whatever the cause, can be associated with a risk of increased occlusal loads during sleep. Among such conditions, sleep bruxism (SB) is a type of sleep-related movement disorders with potential load challenge to the tooth and orofacial structures. Patients with SB usually report frequent tooth grinding noises during sleep and there is a consecutive increase in number and strength of rhythmic masticatory muscle activity (RMMA). Other types of masticatory muscle contractions can be non-specifically activated during sleep, such as brief contractions with tooth tapping, sleep talking, non-rhythmic contractions related to non-specific body movements, etc.; these occur more frequently in sleep disorders. Studies have shown that clinical signs and symptoms of SB can be found in patients with sleep disorders. In addition, sleep becomes compromised with aging process, and a prevalence of most sleep disorders is high in the elderly populations, in which prosthodontic rehabilitations are more required. Therefore, the recognition and understanding of the role of sleep disorders can provide a comprehensive vision for prosthodontic rehabilitations when prosthodontists manage complex orodental cases needing interdisciplinary collaborations between dentistry and sleep medicine. Copyright © 2013 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

  8. Sleep-Active Neurons: Conserved Motors of Sleep

    Science.gov (United States)

    Bringmann, Henrik

    2018-01-01

    Sleep is crucial for survival and well-being. This behavioral and physiological state has been studied in all major genetically accessible model animals, including rodents, fish, flies, and worms. Genetic and optogenetic studies have identified several neurons that control sleep, making it now possible to compare circuit mechanisms across species. The “motor” of sleep across animal species is formed by neurons that depolarize at the onset of sleep to actively induce this state by directly inhibiting wakefulness. These sleep-inducing neurons are themselves controlled by inhibitory or activating upstream pathways, which act as the “drivers” of the sleep motor: arousal inhibits “sleep-active” neurons whereas various sleep-promoting “tiredness” pathways converge onto sleep-active neurons to depolarize them. This review provides the first overview of sleep-active neurons across the major model animals. The occurrence of sleep-active neurons and their regulation by upstream pathways in both vertebrate and invertebrate species suggests that these neurons are general and ancient components that evolved early in the history of nervous systems. PMID:29618588

  9. Sleep Disorders

    DEFF Research Database (Denmark)

    Rahbek Kornum, Birgitte; Mignot, Emmanuel

    2014-01-01

    mediates circadian regulation of sleep. Misalignment with the rhythm of the sun results in circadian disorders and jet lag. The molecular basis of homeostatic sleep regulation is mostly unknown. A network of mutually inhibitory brain nuclei regulates sleep states and sleep-wake transitions. Abnormalities...... in these networks create sleep disorders, including rapid eye movement sleep behavior disorder, sleep walking, and narcolepsy. Physiological changes associated with sleep can be imbalanced, resulting in excess movements such as periodic leg movements during sleep or abnormal breathing in obstructive sleep apneas....... As every organ in the body is affected by sleep directly or indirectly, sleep and sleep-associated disorders are frequent and only now starting to be understood....

  10. Adolescents' sleep behaviors and perceptions of sleep.

    Science.gov (United States)

    Noland, Heather; Price, James H; Dake, Joseph; Telljohann, Susan K

    2009-05-01

    Sleep duration affects the health of children and adolescents. Shorter sleep durations have been associated with poorer academic performance, unintentional injuries, and obesity in adolescents. This study extends our understanding of how adolescents perceive and deal with their sleep issues. General education classes were randomly selected from a convenience sample of three high schools in the Midwest. Three hundred eighty-four ninth- to twelfth-grade students (57%) completed a self-administered valid and reliable questionnaire on sleep behaviors and perceptions of sleep. Most respondents (91.9%) obtained inadequate sleep (sleep each week night. The majority indicated that not getting enough sleep had the following effects on them: being more tired during the day (93.7%), having difficulty paying attention (83.6%), lower grades (60.8%), increase in stress (59.0%), and having difficulty getting along with others (57.7%). Some students reported engaging in harmful behaviors to help them sleep: taking sleeping pills (6.0%), smoking a cigarette to relax (5.7%), and drinking alcohol in the evening (2.9%). Students who received fewer hours of sleep were significantly more likely to report being stressed (p = .02) and were more likely to be overweight (p = .04). Inadequate sleep time may be contributing to adolescent health problems such as increased stress and obesity. Findings indicate a need for sleep hygiene education for adolescents and their parents. A long-term solution to chronic sleep deprivation among high school students could include delaying high school start times, such as was done successfully in the Minneapolis Public School District.

  11. TbPIF5 is a Trypanosoma brucei mitochondrial DNA helicase involved in processing of minicircle Okazaki fragments.

    Directory of Open Access Journals (Sweden)

    Beiyu Liu

    2009-09-01

    Full Text Available Trypanosoma brucei's mitochondrial genome, kinetoplast DNA (kDNA, is a giant network of catenated DNA rings. The network consists of a few thousand 1 kb minicircles and several dozen 23 kb maxicircles. Here we report that TbPIF5, one of T. brucei's six mitochondrial proteins related to Saccharomyces cerevisiae mitochondrial DNA helicase ScPIF1, is involved in minicircle lagging strand synthesis. Like its yeast homolog, TbPIF5 is a 5' to 3' DNA helicase. Together with other enzymes thought to be involved in Okazaki fragment processing, TbPIF5 localizes in vivo to the antipodal sites flanking the kDNA. Minicircles in wild type cells replicate unidirectionally as theta-structures and are unusual in that Okazaki fragments are not joined until after the progeny minicircles have segregated. We now report that overexpression of TbPIF5 causes premature removal of RNA primers and joining of Okazaki fragments on theta structures. Further elongation of the lagging strand is blocked, but the leading strand is completed and the minicircle progeny, one with a truncated H strand (ranging from 0.1 to 1 kb, are segregated. The minicircles with a truncated H strand electrophorese on an agarose gel as a smear. This replication defect is associated with kinetoplast shrinkage and eventual slowing of cell growth. We propose that TbPIF5 unwinds RNA primers after lagging strand synthesis, thus facilitating processing of Okazaki fragments.

  12. Obstructive sleep apnea alters sleep stage transition dynamics.

    Directory of Open Access Journals (Sweden)

    Matt T Bianchi

    2010-06-01

    Full Text Available Enhanced characterization of sleep architecture, compared with routine polysomnographic metrics such as stage percentages and sleep efficiency, may improve the predictive phenotyping of fragmented sleep. One approach involves using stage transition analysis to characterize sleep continuity.We analyzed hypnograms from Sleep Heart Health Study (SHHS participants using the following stage designations: wake after sleep onset (WASO, non-rapid eye movement (NREM sleep, and REM sleep. We show that individual patient hypnograms contain insufficient number of bouts to adequately describe the transition kinetics, necessitating pooling of data. We compared a control group of individuals free of medications, obstructive sleep apnea (OSA, medical co-morbidities, or sleepiness (n = 374 with mild (n = 496 or severe OSA (n = 338. WASO, REM sleep, and NREM sleep bout durations exhibited multi-exponential temporal dynamics. The presence of OSA accelerated the "decay" rate of NREM and REM sleep bouts, resulting in instability manifesting as shorter bouts and increased number of stage transitions. For WASO bouts, previously attributed to a power law process, a multi-exponential decay described the data well. Simulations demonstrated that a multi-exponential process can mimic a power law distribution.OSA alters sleep architecture dynamics by decreasing the temporal stability of NREM and REM sleep bouts. Multi-exponential fitting is superior to routine mono-exponential fitting, and may thus provide improved predictive metrics of sleep continuity. However, because a single night of sleep contains insufficient transitions to characterize these dynamics, extended monitoring of sleep, probably at home, would be necessary for individualized clinical application.

  13. Effect of experimental single Ancylostoma caninum and mixed infections of Trypanosoma brucei and Trypanosoma congolense on the humoural immune response to anti-rabies vaccination in dogs

    Directory of Open Access Journals (Sweden)

    Nwoha Rosemary Ijeoma Ogechi

    2015-06-01

    Full Text Available Objective: To determine the effect of Ancylostoma caninum (A. caninum and trypanosome parasites on the immune response to vaccination in dogs in endemic environments. Methods: Sixteen dogs for the experiment were grouped into 4 of 4 members each. Group I was the uninfected control one, and GPII was infected with A. caninum; GPIII was infected with A. caninum/Trypanosoma congolense (T. congolense, and GPIV was infected with Trypanosoma brucei (T. brucei/A. caninum. The dogs were first vaccinated with antirabies vaccine before infecting GPII, GPIII and GPIV with A. caninum which were done 4 weeks after vaccination. By 2-week post-vaccination, trypanosome parasites were superimposed on both GPIII and GPIV. A secondary vaccination was given to GPI, GPII, GPIII, and GPIV by Week 12 of the experiment (4 weeks post treatment. Results: The prepatent period was (3.00 ± 1.40 days, in the conjunct infection of T. brucei/ A. caninum. It was (9.00 ± 1.10 days, in conjunct T. congolense/A. caninum. The prepatent period of A. caninum was (14.0 ± 2.0 days in the single A. caninum group and (13.0 ± 1.0 days in the conjunct trypanosome/A. caninum. At the 1st week after vaccination, the antibody titer in all the vaccinated groups (GPI, GPII, GPIII, and GPIV significantly increased (P < 0.05 and peaked at the 3rd week after vaccination. Following infections, there were marked significant decreases (P < 0.05 in the antibody production against rabies in GPII, GPIII and GPIV. The significant decrease (P < 0.05 in antibody titer was highest in the conjunct groups (GPIII and GPIV compared to the single infection (GPII. Treatment with diminazene aceturate and mebendazole did not significantly improve antibody response in the dogs. A secondary vaccination administered at the 12th week after the primary vaccination significantly increased (P < 0.05 the antibody titer with a peak at the 3rd week after the secondary vaccination. Conclusions: It was therefore concluded

  14. Sleep Habits and Sleep Problems in Healthy Preschoolers.

    Science.gov (United States)

    Murthy, C L Srinivasa; Bharti, Bhavneet; Malhi, Prahbhjot; Khadwal, Alka

    2015-07-01

    To describe the sleep patterns and problems in children aged between 12 and 36 mo of age. This cross sectional survey was collected over a span of 1 y in Advanced Pediatric Centre, PGIMER, Chandigarh and crèches of Chandigarh. Children in the age group of 12 to 36 mo were included in study. Children with chronic illness, developmental delay, seizure disorder and lack of consent were excluded. A total of 368 children were enrolled. Main outcome measures were sleep duration over 1 to 3 y of life; sleep behavior at onset, during and waking of sleep and parent reported sleep problems and their predictors. The average duration of sleep was 12.5 h (S.D = 1.9). The mean total sleep duration and mean day time sleep duration decreased, while mean night time sleep increased as the age advanced from 12 to 36 mo. Following were the frequency of sleep habits seen in the index study; bed time routine was seen only in 68(18.5 %), a regular bed time ritual was seen in 281(76.4 %), 329(89.4 %) children frequently required 0-20 min time to fall asleep, 11(3 %) parents used sleep inducing drugs. Night waking (1 to 3 times a night) was seen in 297(80.7 %) and its frequency declined with age. Parent reported sleep problems were seen in 12.8 % (47/368). Lack of co-sleeping and night waking were considered as strongest predictors of parent reported sleep problems. Toddlers' sleep duration, night waking behavior, and day time naps decrease as the age progress while night time sleep duration increases with age. Lack of co-sleeping and night waking are considered as strongest predictors of parent reported sleep problems.

  15. Sleep

    Science.gov (United States)

    ... Institute (NHLBI). 1 Mood. Sleep affects your mood. Insufficient sleep can cause irritability that can lead to trouble with relationships, ... basics/understanding_sleep.htm#dynamic_activity Centers for Disease ... insufficient rest or sleep among adults—United States, 2008. MMWR, 58 (42), ...

  16. Immediate postarousal sleep dynamics: an important determinant of sleep stability in obstructive sleep apnea.

    Science.gov (United States)

    Younes, Magdy; Hanly, Patrick J

    2016-04-01

    Arousability from sleep is increasingly recognized as an important determinant of the clinical spectrum of sleep disordered breathing (SDB). Patients with SDB display a wide range of arousability. The reason for these differences is not known. We hypothesized that differences in the speed with which sleep deepens following arousals/awakenings (postarousal sleep dynamics) is a major determinant of these differences in arousability in patients with SDB. We analyzed 40 preexisting clinical polysomnography records from patients with a range of SDB severity (apnea-hypopnea index 5-135/h). Sleep depth was determined every 3 s using the odds ratio product (ORP) method, a continuous index of sleep depth (0 = deep sleep, 2.5 = full wakefulness) that correlates strongly (r = 0.98) with arousability (Younes M, Ostrowski M, Soiferman M, Younes H, Younes M, Raneri J, and Hanly P. Sleep 38: 641-654, 2015). Time course of ORP was determined from end of arousal until the next arousal. All arousals were analyzed (142 ± 65/polysomnogram). ORP increased from 0.58 ± 0.32 during sleep to 1.67 ± 0.35 during arousals. ORP immediately (first 9 s) following arousals/awakenings (ORP-9) ranged from 0.21(very deep sleep) to 1.71 (highly arousable state) in different patients. In patients with high ORP-9, sleep deepened slowly (over minutes) beyond 9 s but only if no arousals/awakenings recurred. ORP-9 correlated strongly with average non-rapid eye movement sleep depth (r = 0.87, P sleep architecture. We conclude that postarousal sleep dynamics are highly variable among patients with sleep-disordered breathing and largely determine average sleep depth and continuity. Copyright © 2016 the American Physiological Society.

  17. PLS-Prediction and Confirmation of Hydrojuglone Glucoside as the Antitrypanosomal Constituent of Juglans Spp.

    Directory of Open Access Journals (Sweden)

    Therese Ellendorff

    2015-05-01

    Full Text Available Naphthoquinones (NQs occur naturally in a large variety of plants. Several NQs are highly active against protozoans, amongst them the causative pathogens of neglected tropical diseases such as human African trypanosomiasis (sleeping sickness, Chagas disease and leishmaniasis. Prominent NQ-producing plants can be found among Juglans spp. (Juglandaceae with juglone derivatives as known constituents. In this study, 36 highly variable extracts were prepared from different plant parts of J. regia, J. cinerea and J. nigra. For all extracts, antiprotozoal activity was determined against the protozoans Trypanosoma cruzi, T. brucei rhodesiense and Leishmania donovani. In addition, an LC-MS fingerprint was recorded for each extract. With each extract’s fingerprint and the data on in vitro growth inhibitory activity against T. brucei rhodesiense a Partial Least Squares (PLS regression model was calculated in order to obtain an indication of compounds responsible for the differences in bioactivity between the 36 extracts. By means of PLS, hydrojuglone glucoside was predicted as an active compound against T. brucei and consequently isolated and tested in vitro. In fact, the pure compound showed activity against T. brucei at a significantly lower cytotoxicity towards mammalian cells than established antiprotozoal NQs such as lapachol.

  18. Cancer in the parasitic protozoans Trypanosoma brucei and Toxoplasma gondii.

    Science.gov (United States)

    Lun, Zhao-Rong; Lai, De-Hua; Wen, Yan-Zi; Zheng, Ling-Ling; Shen, Ji-Long; Yang, Ting-Bo; Zhou, Wen-Liang; Qu, Liang-Hu; Hide, Geoff; Ayala, Francisco J

    2015-07-21

    Cancer is a general name for more than 100 malignant diseases. It is postulated that all cancers start from a single abnormal cell that grows out of control. Untreated cancers can cause serious consequences and deaths. Great progress has been made in cancer research that has significantly improved our knowledge and understanding of the nature and mechanisms of the disease, but the origins of cancer are far from being well understood due to the limitations of suitable model systems and to the complexities of the disease. In view of the fact that cancers are found in various species of vertebrates and other metazoa, here, we suggest that cancer also occurs in parasitic protozoans such as Trypanosoma brucei, a blood parasite, and Toxoplasma gondii, an obligate intracellular pathogen. Without treatment, these protozoan cancers may cause severe disease and death in mammals, including humans. The simpler genomes of these single-cell organisms, in combination with their complex life cycles and fascinating life cycle differentiation processes, may help us to better understand the origins of cancers and, in particular, leukemias.

  19. Megazol and its bioisostere 4H-1,2,4-triazole: comparing the trypanocidal, cytotoxic and genotoxic activities and their in vitro and in silico interactions with the Trypanosoma brucei nitroreductase enzyme

    Directory of Open Access Journals (Sweden)

    Alcione Silva de Carvalho

    2014-06-01

    Full Text Available Megazol (7 is a 5-nitroimidazole that is highly active against Trypanosoma cruzi and Trypanosoma brucei, as well as drug-resistant forms of trypanosomiasis. Compound 7 is not used clinically due to its mutagenic and genotoxic properties, but has been largely used as a lead compound. Here, we compared the activity of 7 with its 4H-1,2,4-triazole bioisostere (8 in bloodstream forms of T. brucei and T. cruzi and evaluated their activation by T. brucei type I nitroreductase (TbNTR enzyme. We also analysed the cytotoxic and genotoxic effects of these compounds in whole human blood using Comet and fluorescein diacetate/ethidium bromide assays. Although the only difference between 7 and 8 is the substitution of sulphur (in the thiadiazole in 7 for nitrogen (in the triazole in 8, the results indicated that 8 had poorer antiparasitic activity than 7 and was not genotoxic, whereas 7 presented this effect. The determination of Vmax indicated that although 8 was metabolised more rapidly than 7, it bounds to the TbNTR with better affinity, resulting in equivalent kcat/KM values. Docking assays of 7 and 8 performed within the active site of a homology model of the TbNTR indicating that 8 had greater affinity than 7.

  20. Physical neighborhood and social environment, beliefs about sleep, sleep hygiene behaviors, and sleep quality among African Americans.

    Science.gov (United States)

    Nam, Soohyun; Whittemore, Robin; Jung, Sunyoung; Latkin, Carl; Kershaw, Trace; Redeker, Nancy S

    2018-06-01

    African Americans (AAs) have a higher prevalence of sleep disorders than other racial/ethnic groups. However, little is known about the relationships among individual and neighborhood factors related to sleep quality in AAs. The purposes of this study were to (1) describe beliefs about sleep, sleep hygiene behaviors, and sleep quality among AAs; and (2) examine the relationships among sociodemographic characteristics, neighborhood environment, beliefs about sleep, sleep hygiene behaviors, and sleep quality. We conducted a cross-sectional study of 252 AA men and women in the Greater New Haven, CT, USA community. We assessed their sociodemographic characteristics, neighborhood environment, beliefs about sleep, sleep hygiene, and sleep quality with the following measures, respectively: the Neighborhood Environment Scale, the brief version of Dysfunctional Beliefs and Attitudes about Sleep, the Sleep Hygiene Practice Scale, the Pittsburgh Sleep Quality Index. We performed descriptive statistics, correlations and multiple hierarchical regression. About 72% of the participants (mean age: 53.88 ± 14.17 years, 77.8% women) reported experiencing sleep disturbance. People with poor sleep quality were more likely to report poorer neighborhood social environment (social cohesion), poorer overall neighborhood environment, more dysfunctional beliefs toward sleep, and poorer sleep hygiene than those who had good sleep quality. In the final multivariate model that controlled for a number of chronic comorbid conditions, neighborhood environment, beliefs about sleep, and sleep hygiene behaviors were significantly associated with sleep quality. Future efforts are needed to improve sleep among AAs by considering both the individual's belief about sleep, sleep hygiene behaviors and neighborhood factors. Copyright © 2018 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.

  1. Sleep physiology and sleep disorders in childhood

    Directory of Open Access Journals (Sweden)

    El Shakankiry HM

    2011-09-01

    Full Text Available Hanan M El ShakankiryKing Fahd University Hospital, Al Dammam University, Al Khobar, Kingdom of Saudi ArabiaAbstract: Sleep has long been considered as a passive phenomenon, but it is now clear that it is a period of intense brain activity involving higher cortical functions. Overall, sleep affects every aspect of a child's development, particularly higher cognitive functions. Sleep concerns are ranked as the fifth leading concern of parents. Close to one third of all children suffer from sleep disorders, the prevalence of which is increased in certain pediatric populations, such as children with special needs, children with psychiatric or medical diagnoses and children with autism or pervasive developmental disorders. The paper reviews sleep physiology and the impact, classification, and management of sleep disorders in the pediatric age group.Keywords: sleep physiology, sleep disorders, childhood, epilepsy

  2. I sleep, because we sleep: a synthesis on the role of culture in sleep behavior research.

    Science.gov (United States)

    Airhihenbuwa, C O; Iwelunmor, J I; Ezepue, C J; Williams, N J; Jean-Louis, G

    2016-02-01

    The aim of this study was to synthesize the literature on the cultural aspects of sleep and their relevance to behavioral sleep research. A narrative synthesis of the existing literature on sleep was conducted with a focus on its biological, sociological, political, and anthropological aspects. This synthesis was guided by the PEN-3 cultural model, developed by the primary author. The findings highlight the cross-cultural contexts within which people sleep and the role of varied sleeping arrangements in influencing sleep behavior and perspectives. Furthermore, the contexts in which sleep occurs, coupled with the influence of the family, and the positive aspects of sleep helped illustrate why cultural aspects of sleep are vital for a broader understanding of sleep. The authors conclude by highlighting the need to integrate studies on the biological, sociological, and political aspects of sleep. Our examination of the literature strongly suggests that careful assessment of epidemiological and clinical sleep data should consider the cultural aspects of sleep as well as the context in which sleep occurs, the role of the family, and positive aspects of sleep. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Train hard, sleep well? Perceived training load, sleep quantity and sleep stage distribution in elite level athletes.

    Science.gov (United States)

    Knufinke, Melanie; Nieuwenhuys, Arne; Geurts, Sabine A E; Møst, Els I S; Maase, Kamiel; Moen, Maarten H; Coenen, Anton M L; Kompier, Michiel A J

    2018-04-01

    Sleep is essential for recovery and performance in elite athletes. While it is generally assumed that exercise benefits sleep, high training load may jeopardize sleep and hence limit adequate recovery. To examine this, the current study assessed objective sleep quantity and sleep stage distributions in elite athletes and calculated their association with perceived training load. Mixed-methods. Perceived training load, actigraphy and one-channel EEG recordings were collected among 98 elite athletes during 7 consecutive days of regular training. Actigraphy revealed total sleep durations of 7:50±1:08h, sleep onset latencies of 13±15min, wake after sleep onset of 33±17min and sleep efficiencies of 88±5%. Distribution of sleep stages indicated 51±9% light sleep, 21±8% deep sleep, and 27±7% REM sleep. On average, perceived training load was 5.40±2.50 (scale 1-10), showing large daily variability. Mixed-effects models revealed no alteration in sleep quantity or sleep stage distributions as a function of day-to-day variation in preceding training load (all p's>.05). Results indicate healthy sleep durations, but elevated wake after sleep onset, suggesting a potential need for sleep optimization. Large proportions of deep sleep potentially reflect an elevated recovery need. With sleep quantity and sleep stage distributions remaining irresponsive to variations in perceived training load, it is questionable whether athletes' current sleep provides sufficient recovery after strenuous exercise. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  4. REM sleep complicates period adding bifurcations from monophasic to polyphasic sleep behavior in a sleep-wake regulatory network model for human sleep

    OpenAIRE

    Kalmbach, K.; Booth, V.; Behn, C. G. Diniz

    2017-01-01

    The structure of human sleep changes across development as it consolidates from the polyphasic sleep of infants to the single nighttime sleep period typical in adults. Across this same developmental period, time scales of the homeostatic sleep drive, the physiological drive to sleep that increases with time spent awake, also change and presumably govern the transition from polyphasic to monophasic sleep behavior. Using a physiologically-based, sleep-wake regulatory network model for human sle...

  5. Sustained sleep fragmentation induces sleep homeostasis in mice

    KAUST Repository

    Baud, Maxime O.; Magistretti, Pierre J.; Petit, Jean Marie

    2015-01-01

    Study Objectives: Sleep fragmentation (SF) is an integral feature of sleep apnea and other prevalent sleep disorders. Although the effect of repetitive arousals on cognitive performance is well documented, the effects of long-term SF on electroencephalography (EEG) and molecular markers of sleep homeostasis remain poorly investigated. To address this question, we developed a mouse model of chronic SF and characterized its effect on EEG spectral frequencies and the expression of genes previously linked to sleep homeostasis including clock genes, heat shock proteins, and plasticity-related genes. Design: N/A. Setting: Animal sleep research laboratory. Participants : Sixty-six C57BL6/J adult mice. Interventions: Instrumental sleep disruption at a rate of 60/h during 14 days Measurements and Results: Locomotor activity and EEG were recorded during 14 days of SF followed by recovery for 2 days. Despite a dramatic number of arousals and decreased sleep bout duration, SF minimally reduced total quantity of sleep and did not significantly alter its circadian distribution. Spectral analysis during SF revealed a homeostatic drive for slow wave activity (SWA; 1-4 Hz) and other frequencies as well (4-40 Hz). Recordings during recovery revealed slow wave sleep consolidation and a transient rebound in SWA, and paradoxical sleep duration. The expression of selected genes was not induced following chronic SF. Conclusions: Chronic sleep fragmentation (SF) increased sleep pressure confirming that altered quality with preserved quantity triggers core sleep homeostasis mechanisms. However, it did not induce the expression of genes induced by sleep loss, suggesting that these molecular pathways are not sustainably activated in chronic diseases involving SF.

  6. Sustained sleep fragmentation induces sleep homeostasis in mice

    KAUST Repository

    Baud, Maxime O.

    2015-04-01

    Study Objectives: Sleep fragmentation (SF) is an integral feature of sleep apnea and other prevalent sleep disorders. Although the effect of repetitive arousals on cognitive performance is well documented, the effects of long-term SF on electroencephalography (EEG) and molecular markers of sleep homeostasis remain poorly investigated. To address this question, we developed a mouse model of chronic SF and characterized its effect on EEG spectral frequencies and the expression of genes previously linked to sleep homeostasis including clock genes, heat shock proteins, and plasticity-related genes. Design: N/A. Setting: Animal sleep research laboratory. Participants : Sixty-six C57BL6/J adult mice. Interventions: Instrumental sleep disruption at a rate of 60/h during 14 days Measurements and Results: Locomotor activity and EEG were recorded during 14 days of SF followed by recovery for 2 days. Despite a dramatic number of arousals and decreased sleep bout duration, SF minimally reduced total quantity of sleep and did not significantly alter its circadian distribution. Spectral analysis during SF revealed a homeostatic drive for slow wave activity (SWA; 1-4 Hz) and other frequencies as well (4-40 Hz). Recordings during recovery revealed slow wave sleep consolidation and a transient rebound in SWA, and paradoxical sleep duration. The expression of selected genes was not induced following chronic SF. Conclusions: Chronic sleep fragmentation (SF) increased sleep pressure confirming that altered quality with preserved quantity triggers core sleep homeostasis mechanisms. However, it did not induce the expression of genes induced by sleep loss, suggesting that these molecular pathways are not sustainably activated in chronic diseases involving SF.

  7. Sleep disorders and work performance: findings from the 2008 National Sleep Foundation Sleep in America poll.

    Science.gov (United States)

    Swanson, Leslie M; Arnedt, J Todd; Rosekind, Mark R; Belenky, Gregory; Balkin, Thomas J; Drake, Christopher

    2011-09-01

    Chronic sleep deprivation is common among workers, and has been associated with negative work outcomes, including absenteeism and occupational accidents. The objective of the present study is to characterize reciprocal relationships between sleep and work. Specifically, we examined how sleep impacts work performance and how work affects sleep in individuals not at-risk for a sleep disorder; assessed work performance outcomes for individuals at-risk for sleep disorders, including insomnia, obstructive sleep apnea (OSA) and restless legs syndrome (RLS); and characterized work performance impairments in shift workers (SW) at-risk for shift work sleep disorders relative to SW and day workers. One-thousand Americans who work 30 h per week or more were asked questions about employment, work performance and sleep in the National Sleep Foundation's 2008 Sleep in America telephone poll. Long work hours were associated with shorter sleep times, and shorter sleep times were associated with more work impairments. Thirty-seven percent of respondents were classified as at-risk for any sleep disorder. These individuals had more negative work outcomes as compared with those not at-risk for a sleep disorder. Presenteeism was a significant problem for individuals with insomnia symptoms, OSA and RLS as compared with respondents not at-risk. These results suggest that long work hours may contribute to chronic sleep loss, which may in turn result in work impairment. Risk for sleep disorders substantially increases the likelihood of negative work outcomes, including occupational accidents, absenteeism and presenteeism. © 2010 European Sleep Research Society.

  8. Shining evolutionary light on human sleep and sleep disorders.

    Science.gov (United States)

    Nunn, Charles L; Samson, David R; Krystal, Andrew D

    2016-01-01

    Sleep is essential to cognitive function and health in humans, yet the ultimate reasons for sleep-i.e. 'why' sleep evolved-remain mysterious. We integrate findings from human sleep studies, the ethnographic record, and the ecology and evolution of mammalian sleep to better understand sleep along the human lineage and in the modern world. Compared to other primates, sleep in great apes has undergone substantial evolutionary change, with all great apes building a sleeping platform or 'nest'. Further evolutionary change characterizes human sleep, with humans having the shortest sleep duration, yet the highest proportion of rapid eye movement sleep among primates. These changes likely reflect that our ancestors experienced fitness benefits from being active for a greater portion of the 24-h cycle than other primates, potentially related to advantages arising from learning, socializing and defending against predators and hostile conspecifics. Perspectives from evolutionary medicine have implications for understanding sleep disorders; we consider these perspectives in the context of insomnia, narcolepsy, seasonal affective disorder, circadian rhythm disorders and sleep apnea. We also identify how human sleep today differs from sleep through most of human evolution, and the implications of these changes for global health and health disparities. More generally, our review highlights the importance of phylogenetic comparisons in understanding human health, including well-known links between sleep, cognitive performance and health in humans. © The Author(s) 2016. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

  9. Benefits of Sleep Extension on Sustained Attention and Sleep Pressure Before and During Total Sleep Deprivation and Recovery.

    Science.gov (United States)

    Arnal, Pierrick J; Sauvet, Fabien; Leger, Damien; van Beers, Pascal; Bayon, Virginie; Bougard, Clément; Rabat, Arnaud; Millet, Guillaume Y; Chennaoui, Mounir

    2015-12-01

    To investigate the effects of 6 nights of sleep extension on sustained attention and sleep pressure before and during total sleep deprivation and after a subsequent recovery sleep. Subjects participated in two experimental conditions (randomized cross-over design): extended sleep (EXT, 9.8 ± 0.1 h (mean ± SE) time in bed) and habitual sleep (HAB, 8.2 ± 0.1 h time in bed). In each condition, subjects performed two consecutive phases: (1) 6 nights of either EXT or HAB (2) three days in-laboratory: baseline, total sleep deprivation and after 10 h of recovery sleep. Residential sleep extension and sleep performance laboratory (continuous polysomnographic recording). 14 healthy men (age range: 26-37 years). EXT vs. HAB sleep durations prior to total sleep deprivation. Total sleep time and duration of all sleep stages during the 6 nights were significantly higher in EXT than HAB. EXT improved psychomotor vigilance task performance (PVT, both fewer lapses and faster speed) and reduced sleep pressure as evidenced by longer multiple sleep latencies (MSLT) at baseline compared to HAB. EXT limited PVT lapses and the number of involuntary microsleeps during total sleep deprivation. Differences in PVT lapses and speed and MSLT at baseline were maintained after one night of recovery sleep. Six nights of extended sleep improve sustained attention and reduce sleep pressure. Sleep extension also protects against psychomotor vigilance task lapses and microsleep degradation during total sleep deprivation. These beneficial effects persist after one night of recovery sleep. © 2015 Associated Professional Sleep Societies, LLC.

  10. Sleep and Sleep Problems: From Birth to 3

    Science.gov (United States)

    Du Mond, Courtney; Mindell, Jodi A.

    2011-01-01

    Sleep is an important aspect of a child's early development and is essential to family well-being. During their first 3 years, infants and toddlers spend more than 50% of their lives sleeping. However, concerns about sleep and sleep problems are among the most common issues brought to the attention of pediatricians. Although sleep is one of the…

  11. Effect of Daytime Exercise on Sleep Eeg and Subjective Sleep

    Science.gov (United States)

    Sasazawa, Y.; Kawada, T.; Kiryu, Y.

    1997-08-01

    This study was designed to assess the effects of daytime physical exercise on the quality of objective and subjective sleep by examining all-night sleep EEGs. The subjects were five male students, aged 19 to 20 years, who were in the habit of performing regular daytime exercise. The sleep polygraphic parameters in this study were sleep stage time as a percentage of total sleep time (%S1, %S2, %S(3+4), %SREM, %MT), time in bed (TIB), sleep time (ST), total sleep time (TST), sleep onset latency (SOL), waking from sleep, sleep efficiency, number of awakenings, number of stage shifts, number of spindles, and percentages of α and δ waves, all of which were determined by an automatic computer analysis system. The OSA questionnaire was used to investigate subjective sleep. The five scales of the OSA used were sleepiness, sleep maintenance, worry, integrated sleep feeling, and sleep initiation. Each sleep parameter was compared in the exercise and the non-exercise groups. Two-way analysis of variance was applied using subject factor and exercise factor. The main effect of the subject was significant in all parameters and the main effect of exercise in %S(3+4), SOL and sleep efficiency, among the objective sleep parameters. The main effects of the subject, except sleepiness, were significant, as was the main effect of exercise on sleep initiation, among the subjective sleep parameters. These findings suggest that daytime exercise shortened sleep latency and prolonged slow-wave sleep, and that the subjects fell asleep more easily on exercise days. There were also significant individual differences in both the objective and subjective sleep parameters.

  12. Unihemispheric sleep and asymmetrical sleep: behavioral, neurophysiological, and functional perspectives

    Directory of Open Access Journals (Sweden)

    Mascetti GG

    2016-07-01

    Full Text Available Gian Gastone Mascetti Department of General Psychology, University of Padova, Padova, Italy Abstract: Sleep is a behavior characterized by a typical body posture, both eyes' closure, raised sensory threshold, distinctive electrographic signs, and a marked decrease of motor activity. In addition, sleep is a periodically necessary behavior and therefore, in the majority of animals, it involves the whole brain and body. However, certain marine mammals and species of birds show a different sleep behavior, in which one cerebral hemisphere sleeps while the other is awake. In dolphins, eared seals, and manatees, unihemispheric sleep allows them to have the benefits of sleep, breathing, thermoregulation, and vigilance. In birds, antipredation vigilance is the main function of unihemispheric sleep, but in domestic chicks, it is also associated with brain lateralization or dominance in the control of behavior. Compared to bihemispheric sleep, unihemispheric sleep would mean a reduction of the time spent sleeping and of the associated recovery processes. However, the behavior and health of aquatic mammals and birds does not seem at all impaired by the reduction of sleep. The neural mechanisms of unihemispheric sleep are unknown, but assuming that the neural structures involved in sleep in cetaceans, seals, and birds are similar to those of terrestrial mammals, it is suggested that they involve the interaction of structures of the hypothalamus, basal forebrain, and brain stem. The neural mechanisms promoting wakefulness dominate one side of the brain, while those promoting sleep predominates the other side. For cetaceans, unihemispheric sleep is the only way to sleep, while in seals and birds, unihemispheric sleep events are intermingled with bihemispheric and rapid eye movement sleep events. Electroencephalogram hemispheric asymmetries are also reported during bihemispheric sleep, at awakening, and at sleep onset, as well as being associated with a use

  13. Unihemispheric sleep and asymmetrical sleep: behavioral, neurophysiological, and functional perspectives.

    Science.gov (United States)

    Mascetti, Gian Gastone

    2016-01-01

    Sleep is a behavior characterized by a typical body posture, both eyes' closure, raised sensory threshold, distinctive electrographic signs, and a marked decrease of motor activity. In addition, sleep is a periodically necessary behavior and therefore, in the majority of animals, it involves the whole brain and body. However, certain marine mammals and species of birds show a different sleep behavior, in which one cerebral hemisphere sleeps while the other is awake. In dolphins, eared seals, and manatees, unihemispheric sleep allows them to have the benefits of sleep, breathing, thermoregulation, and vigilance. In birds, antipredation vigilance is the main function of unihemispheric sleep, but in domestic chicks, it is also associated with brain lateralization or dominance in the control of behavior. Compared to bihemispheric sleep, unihemispheric sleep would mean a reduction of the time spent sleeping and of the associated recovery processes. However, the behavior and health of aquatic mammals and birds does not seem at all impaired by the reduction of sleep. The neural mechanisms of unihemispheric sleep are unknown, but assuming that the neural structures involved in sleep in cetaceans, seals, and birds are similar to those of terrestrial mammals, it is suggested that they involve the interaction of structures of the hypothalamus, basal forebrain, and brain stem. The neural mechanisms promoting wakefulness dominate one side of the brain, while those promoting sleep predominates the other side. For cetaceans, unihemispheric sleep is the only way to sleep, while in seals and birds, unihemispheric sleep events are intermingled with bihemispheric and rapid eye movement sleep events. Electroencephalogram hemispheric asymmetries are also reported during bihemispheric sleep, at awakening, and at sleep onset, as well as being associated with a use-dependent process (local sleep).

  14. Sleep Deficiency and Sleep Health Problems in Chinese Adolescents

    Directory of Open Access Journals (Sweden)

    Victor Kang

    2012-01-01

    Full Text Available A survey of sleep schedules, sleep health, and the impact on school performance was conducted in 585 adolescents in a high school in China. A high level of early and circadian-disadvantaged sleep/wake schedules during weekdays was observed. Significantly shorter sleep duration on weekdays was reported ( P < 0.0001. Older teenagers slept significantly less than the younger teenagers ( P < 0.0001. Complaints of inadequate sleep and sleepiness during weekdays were prevalent. Night awakenings were reported in 32.2% of students. Students with a sleep length of less than 7 hours, complaint of inadequate sleep, or excessive daytime sleepiness during weekdays were more likely to report an adverse effect of poor sleep on performance. The present observations are qualitatively similar to those reported in our study in American adolescents, particularly with respect to Chinese adolescents exhibiting a similar sleep deficiency on weekdays. We concluded that sleep deficiency and sleep health problems were prevalent in the participating adolescents in China, and were perceived to adversely affect school performance.

  15. Aging induced ER stress alters sleep and sleep homeostasis

    Science.gov (United States)

    Brown, Marishka K.; Chan, May T.; Zimmerman, John E.; Pack, Allan I.; Jackson, Nicholas E.; Naidoo, Nirinjini

    2014-01-01

    Alterations in the quality, quantity and architecture of baseline and recovery sleep have been shown to occur during aging. Sleep deprivation induces endoplasmic reticular (ER) stress and upregulates a protective signaling pathway termed the unfolded protein response (UPR). The effectiveness of the adaptive UPR is diminished by age. Previously, we showed that endogenous chaperone levels altered recovery sleep in Drosophila melanogaster. We now report that acute administration of the chemical chaperone sodium 4-phenylbutyrate (PBA) reduces ER stress and ameliorates age-associated sleep changes in Drosophila. PBA consolidates both baseline and recovery sleep in aging flies. The behavioral modifications of PBA are linked to its suppression of ER stress. PBA decreased splicing of x-box binding protein 1 (XBP1) and upregulation of phosphorylated elongation initiation factor 2 α (p-eIF2α), in flies that were subjected to sleep deprivation. We also demonstrate that directly activating ER stress in young flies fragments baseline sleep and alters recovery sleep. Alleviating prolonged/sustained ER stress during aging contributes to sleep consolidation and improves recovery sleep/ sleep debt discharge. PMID:24444805

  16. [The NHG guideline 'Sleep problems and sleeping pills'

    NARCIS (Netherlands)

    Damen-van Beek, Z.; Lucassen, P.L.; Gorgels, W.J.M.J.; Smelt, A.F.; Knuistingh Neven, A.; Bouma, M.

    2015-01-01

    - The Dutch College of General Practitioners' (NHG) guideline 'Sleep problems and sleeping pills' provides recommendations for the diagnosis and treatment of the most prevalent sleep problems and for the management of chronic users of sleeping pills.- The preferred approach for sleeplessness is not

  17. Channel-forming activities in the glycosomal fraction from the bloodstream form of Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Melisa Gualdron-López

    Full Text Available BACKGROUND: Glycosomes are a specialized form of peroxisomes (microbodies present in unicellular eukaryotes that belong to the Kinetoplastea order, such as Trypanosoma and Leishmania species, parasitic protists causing severe diseases of livestock and humans in subtropical and tropical countries. The organelles harbour most enzymes of the glycolytic pathway that is responsible for substrate-level ATP production in the cell. Glycolysis is essential for bloodstream-form Trypanosoma brucei and enzymes comprising this pathway have been validated as drug targets. Glycosomes are surrounded by a single membrane. How glycolytic metabolites are transported across the glycosomal membrane is unclear. METHODS/PRINCIPAL FINDINGS: We hypothesized that glycosomal membrane, similarly to membranes of yeast and mammalian peroxisomes, contains channel-forming proteins involved in the selective transfer of metabolites. To verify this prediction, we isolated a glycosomal fraction from bloodstream-form T. brucei and reconstituted solubilized membrane proteins into planar lipid bilayers. The electrophysiological characteristics of the channels were studied using multiple channel recording and single channel analysis. Three main channel-forming activities were detected with current amplitudes 70-80 pA, 20-25 pA, and 8-11 pA, respectively (holding potential +10 mV and 3.0 M KCl as an electrolyte. All channels were in fully open state in a range of voltages ±150 mV and showed no sub-conductance transitions. The channel with current amplitude 20-25 pA is anion-selective (P(K+/P(Cl-∼0.31, while the other two types of channels are slightly selective for cations (P(K+/P(Cl- ratios ∼1.15 and ∼1.27 for the high- and low-conductance channels, respectively. The anion-selective channel showed an intrinsic current rectification that may suggest a functional asymmetry of the channel's pore. CONCLUSIONS/SIGNIFICANCE: These results indicate that the membrane of glycosomes

  18. Challenges in the diagnosis and management of sleeping sickness ...

    African Journals Online (AJOL)

    Blood and cerebrospinal fluid (CSF) samples were examined for the presence of trypanosomes using wet film, Field\\'s stain and concentration techniques. Typanosoma brucei rhodesiense were detected in both the blood and CSF samples. The patient was treated successfully with melarsoprol. The results of this case study ...

  19. Gratitude influences sleep through the mechanism of pre-sleep cognitions.

    Science.gov (United States)

    Wood, Alex M; Joseph, Stephen; Lloyd, Joanna; Atkins, Samuel

    2009-01-01

    To test whether individual differences in gratitude are related to sleep after controlling for neuroticism and other traits. To test whether pre-sleep cognitions are the mechanism underlying this relationship. A cross-sectional questionnaire study was conducted with a large (186 males, 215 females) community sample (ages=18-68 years, mean=24.89, S.D.=9.02), including 161 people (40%) scoring above 5 on the Pittsburgh Sleep Quality Index, indicating clinically impaired sleep. Measures included gratitude, the Pittsburgh Sleep Quality Index (PSQI), self-statement test of pre-sleep cognitions, the Mini-IPIP scales of Big Five personality traits, and the Social Desirability Scale. Gratitude predicted greater subjective sleep quality and sleep duration, and less sleep latency and daytime dysfunction. The relationship between gratitude and each of the sleep variables was mediated by more positive pre-sleep cognitions and less negative pre-sleep cognitions. All of the results were independent of the effect of the Big Five personality traits (including neuroticism) and social desirability. This is the first study to show that a positive trait is related to good sleep quality above the effect of other personality traits, and to test whether pre-sleep cognitions are the mechanism underlying the relationship between any personality trait and sleep. The study is also the first to show that trait gratitude is related to sleep and to explain why this occurs, suggesting future directions for research, and novel clinical implications.

  20. Healthy Sleep Habits

    Science.gov (United States)

    ... Sleep Apnea Testing CPAP Healthy Sleep Habits Healthy Sleep Habits Your behaviors during the day, and especially ... team at an AASM accredited sleep center . Quick Sleep Tips Follow these tips to establish healthy sleep ...

  1. Obstructive Sleep Apnea

    Science.gov (United States)

    ... find out more. Obstructive Sleep Apnea (OSA) Obstructive Sleep Apnea (OSA) Obstructive sleep apnea (OSA) is a ... find out more. Obstructive Sleep Apnea (OSA) Obstructive Sleep Apnea (OSA) Obstructive sleep apnea (OSA) is a ...

  2. Three-dimensional structure of the Trypanosome flagellum suggests that the paraflagellar rod functions as a biomechanical spring.

    Directory of Open Access Journals (Sweden)

    Louise C Hughes

    Full Text Available Flagellum motility is critical for normal human development and for transmission of pathogenic protozoa that cause tremendous human suffering worldwide. Biophysical principles underlying motility of eukaryotic flagella are conserved from protists to vertebrates. However, individual cells exhibit diverse waveforms that depend on cell-specific elaborations on basic flagellum architecture. Trypanosoma brucei is a uniflagellated protozoan parasite that causes African sleeping sickness. The T. brucei flagellum is comprised of a 9+2 axoneme and an extra-axonemal paraflagellar rod (PFR, but the three-dimensional (3D arrangement of the underlying structural units is poorly defined. Here, we use dual-axis electron tomography to determine the 3D architecture of the T. brucei flagellum. We define the T. brucei axonemal repeating unit. We observe direct connections between the PFR and axonemal dyneins, suggesting a mechanism by which mechanochemical signals may be transmitted from the PFR to axonemal dyneins. We find that the PFR itself is comprised of overlapping laths organized into distinct zones that are connected through twisting elements at the zonal interfaces. The overall structure has an underlying 57 nm repeating unit. Biomechanical properties inferred from PFR structure lead us to propose that the PFR functions as a biomechanical spring that may store and transmit energy derived from axonemal beating. These findings provide insight into the structural foundations that underlie the distinctive flagellar waveform that is a hallmark of T. brucei cell motility.

  3. Sleep Problems

    Science.gov (United States)

    ... For Consumers Consumer Information by Audience For Women Sleep Problems Share Tweet Linkedin Pin it More sharing ... 101 KB) En Español Medicines to Help You Sleep Tips for Better Sleep Basic Facts about Sleep ...

  4. Decrease in monocular sleep after sleep deprivation in the domestic chicken

    NARCIS (Netherlands)

    Boerema, AS; Riedstra, B; Strijkstra, AM

    2003-01-01

    We investigated the trade-off between sleep need and alertness, by challenging chickens to modify their monocular sleep. We sleep deprived domestic chickens (Gallus domesticus) to increase their sleep need. We found that in response to sleep deprivation the fraction of monocular sleep within sleep

  5. Sleep Disorders

    Science.gov (United States)

    ... the day, even if you have had enough sleep? You might have a sleep disorder. The most common kinds are Insomnia - a hard time falling or staying asleep Sleep apnea - breathing interruptions during sleep Restless legs syndrome - ...

  6. Sleep-dependent memory consolidation in patients with sleep disorders.

    Science.gov (United States)

    Cipolli, Carlo; Mazzetti, Michela; Plazzi, Giuseppe

    2013-04-01

    Sleep can improve the off-line memory consolidation of new items of declarative and non-declarative information in healthy subjects, whereas acute sleep loss, as well as sleep restriction and fragmentation, impair consolidation. This suggests that, by modifying the amount and/or architecture of sleep, chronic sleep disorders may also lead to a lower gain in off-line consolidation, which in turn may be responsible for the varying levels of impaired performance at memory tasks usually observed in sleep-disordered patients. The experimental studies conducted to date have shown specific impairments of sleep-dependent consolidation overall for verbal and visual declarative information in patients with primary insomnia, for verbal declarative information in patients with obstructive sleep apnoeas, and for visual procedural skills in patients with narcolepsy-cataplexy. These findings corroborate the hypothesis that impaired consolidation is a consequence of the chronically altered organization of sleep. Moreover, they raise several novel questions as to: a) the reversibility of consolidation impairment in the case of effective treatment, b) the possible negative influence of altered prior sleep also on the encoding of new information, and c) the relationships between altered sleep and memory impairment in patients with other (medical, psychiatric or neurological) diseases associated with quantitative and/or qualitative changes of sleep architecture. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Sleep and sleep disorders in Don Quixote.

    Science.gov (United States)

    Iranzo, Alex; Santamaria, Joan; de Riquer, Martín

    2004-01-01

    In Don Quijote de la Mancha, Miguel de Cervantes presents Don Quixote as an amazing character of the 17th century who suffers from delusions and illusions, believing himself to be a medieval knight errant. Besides this neuropsychiatric condition, Cervantes included masterful descriptions of several sleep disorders such as insomnia, sleep deprivation, disruptive loud snoring and rapid eye movement sleep behaviour disorder. In addition, he described the occurrence of physiological, vivid dreams and habitual, post-prandial sleepiness--the siesta. Cervantes' concept of sleep as a passive state where all cerebral activities are almost absent is in conflict with his description of abnormal behaviours during sleep and vivid, fantastic dreams. His concept of sleep was shared by his contemporary, Shakespeare, and could have been influenced by the reading of the classical Spanish book of psychiatry Examen de Ingenios (1575).

  8. Obstructive Sleep Apnea

    Medline Plus

    Full Text Available ... find out more. Obstructive Sleep Apnea (OSA) Obstructive Sleep Apnea (OSA) Obstructive sleep apnea (OSA) is a ... find out more. Obstructive Sleep Apnea (OSA) Obstructive Sleep Apnea (OSA) Obstructive sleep apnea (OSA) is a ...

  9. Sleep Insufficiency, Sleep Health Problems and Performance in High School Students

    Directory of Open Access Journals (Sweden)

    Xue Ming

    2011-01-01

    Full Text Available A survey on sleep schedule, sleep health, school performance and school start times was conducted in 1,941 adolescents. A high level of early and circadian-disadvantaged sleep/wake schedules during weekdays was observed. Shorter sleep duration on weekdays was reported, especially in upper classmen. Complaints of inadequate sleep and sleepiness during weekdays, alarm clock use, and napping were prevalent. Night awakening and prolonged sleep onset were common and associated with poor school performance. Students with a sleep length of less than 7 hours on both weekdays and weekends exhibited poorer performance, while those who made up this sleep loss on weekends did not. The total number of poor sleep factors in an individual also correlated with poor school performance. Earlier school start times were associated with a perception of poor sleep quality, shorter sleep duration and more sleep health problems. We conclude that sleep inadequacies and sleep health problems were prevalent in this population, especially in those who started school earlier in the morning, and that these poor sleep factors were associated with school performance.

  10. Sleep Tips: 7 Steps to Better Sleep

    Science.gov (United States)

    ... turn every night. Consider simple tips for better sleep, from setting a sleep schedule to including physical activity in your daily ... factors that can interfere with a good night's sleep — from work stress and family responsibilities to unexpected ...

  11. Train hard, sleep well? Perceived training load, sleep quantity and sleep stage distribution in elite level athletes

    NARCIS (Netherlands)

    Knufinke, M.; Nieuwenhuys, A.; Geurts, S.A.E.; Mø st, E.I.S.; Maase, K.; Moen, M.H.; Coenen, A.M.L.; Kompier, M.A.J.

    2018-01-01

    Objectives: Sleep is essential for recovery and performance in elite athletes. While it is generally assumed that exercise benefits sleep, high training load may jeopardize sleep and hence limit adequate recovery. To examine this, the current study assessed objective sleep quantity and sleep stage

  12. Infant sleep problems: The sleep characteristics of the "Don't Know" response.

    Science.gov (United States)

    Tsai, Shao-Yu; Lee, Chien-Chang; Chen, Li-Chiou; Tung, Yi-Ching

    2018-01-01

    To examine the sleep characteristics of infants with parentally reported sleep problems, with parentally reported no sleep problems and with parentally reported uncertain sleep conditions. Infant sleep problems are recognized as a major health issue worldwide. However, in our daily clinical practices, it is not uncommon for parents not to know whether their infant sleep is problematic. A prospective study conducted between 2012 - 2015 where 219 parents completed questionnaires and infants wore an actigraph monitor for 7 days. Multinomial logistic regression models were used to evaluate the actigraphic and parentally reported infant sleep behaviours between the groups. Thirty-two (14.61%) parents did not know whether their infant sleep was problematic and 118 (53.88%) parents considered their infant sleep a problem. Compared with infants without sleep problems, infants with uncertain sleep conditions had significantly increased odds of having shortened longest sleep duration according to parental report. A significant association was found for infants without sleep problems compared with those with sleep problems who had significantly more wake after sleep onset as measured by actigraphy, as well as reduced longest sleep duration according to parental report. Infants with uncertain sleep conditions have the same problematic sleep behaviours resembling those of children with reported sleep problems. Healthcare professionals should actively disseminate sleep knowledge to help parents interpret infant sleep behaviours and consider possible intervention strategies for improving parental sleep-related knowledge and infant sleep. © 2017 John Wiley & Sons Ltd.

  13. Sleep in childhood and adolescence: age-specific sleep characteristics, common sleep disturbances and associated difficulties.

    Science.gov (United States)

    Barclay, Nicola L; Gregory, Alice M

    2014-01-01

    Sleep changes throughout the lifespan, with particularly salient alterations occurring during the first few years of life, as well as during the transition from childhood to adolescence. Such changes are partly the result of brain maturation; complex changes in the organisation of the circadian system; as well as changes in daily routine, environmental demands and responsibilities. Despite the automaticity of sleep, given that it is governed by a host of complex mechanisms, there are times when sleep becomes disturbed. Sleep disturbances in childhood are common and may stem from behavioural difficulties or abnormalities in physiological processes-and, in some cases manifest into diagnosable sleep disorders. As well as occurring exclusively, childhood sleep disturbances often co-occur with other difficulties. The purpose of this chapter is to outline the neurobiology of typical sleep/wake processes, and describe changes in sleep physiology and architecture from birth to adulthood. Furthermore, common childhood sleep disorders are described as are their associations with other traits, including all of the syndromes presented in this handbook: ASDs, ADHD, schizophrenia and emotional/behavioural difficulties. Throughout, we attempt to explain possible mechanisms underlying these disorders and their associations.

  14. Sleep Hygiene and Sleep Quality of Third-Trimester Pregnant Women.

    Science.gov (United States)

    Tsai, Shao-Yu; Lee, Chien-Nan; Wu, Wei-Wen; Landis, Carol A

    2016-02-01

    The purpose of this descriptive study was to examine the associations of sleep hygiene and actigraphy measures of sleep with self-reported sleep quality in 197 pregnant women in northern Taiwan. Third-trimester pregnant women completed the Sleep Hygiene Practice Scale (SHPS) and the Pittsburgh Sleep Quality Index (PSQI) as well as the Center for Epidemiologic Studies-Depression Scale (CES-D), and wore an actigraph for 7 consecutive days. Student's t-test was used to compare the SHPS scores and means as well as variability of actigraphy sleep variables between poor sleepers (i.e., PSQI global score >5) and good sleepers (i.e., PSQI global score ≤5). Compared to good sleepers, poor sleepers reported significantly worse sleep hygiene, with higher SHPS scores and higher sleep schedule, arousal-related behavior, and sleep environment subscale scores. Poor sleepers had significantly greater intra-individual variability of sleep onset latency, total nighttime sleep, and wake after sleep onset than good sleepers. In stepwise linear regression, older maternal age (p = .01), fewer employment hours per week (p = .01), higher CES-D total score (p hygiene intervention in women during pregnancy. © 2015 Wiley Periodicals, Inc.

  15. Sleep in Othello

    Science.gov (United States)

    Dimsdale, Joel E.

    2009-01-01

    Some of our best descriptions of sleep disorders come from literature. While Shakespeare is well known for his references to insomnia and sleep walking, his works also demonstrate a keen awareness of many other sleep disorders. This paper examines sleep themes in Shakespeare's play Othello. The play indicates Shakespeare's astute eye for sleep deprivation, sexual parasomnias, and effects of stress and drugs on sleep. Citation: Dimsdale JE. Sleep in Othello. J Clin Sleep Med 2009;5(3):280-281. PMID:19960651

  16. Shining evolutionary light on human sleep and sleep disorders.

    OpenAIRE

    Krystal, Andrew; Nunn, CL; Samson, DR; Krystal, AD

    2016-01-01

    Sleep is essential to cognitive function and health in humans, yet the ultimate reasons for sleep-i.e. 'why' sleep evolved-remain mysterious. We integrate findings from human sleep studies, the ethnographic record, and the ecology and evolution of mammalia

  17. Sleep disorders - overview

    Science.gov (United States)

    Insomnia; Narcolepsy; Hypersomina; Daytime sleepiness; Sleep rhythm; Sleep disruptive behaviors; Jet lag ... excessive daytime sleepiness) Problems sticking to a regular sleep schedule (sleep rhythm problem) Unusual behaviors during sleep ( ...

  18. Aging induced endoplasmic reticulum stress alters sleep and sleep homeostasis.

    Science.gov (United States)

    Brown, Marishka K; Chan, May T; Zimmerman, John E; Pack, Allan I; Jackson, Nicholas E; Naidoo, Nirinjini

    2014-06-01

    Alterations in the quality, quantity, and architecture of baseline and recovery sleep have been shown to occur during aging. Sleep deprivation induces endoplasmic reticular (ER) stress and upregulates a protective signaling pathway termed the unfolded protein response. The effectiveness of the adaptive unfolded protein response is diminished by age. Previously, we showed that endogenous chaperone levels altered recovery sleep in Drosophila melanogaster. We now report that acute administration of the chemical chaperone sodium 4-phenylbutyrate (PBA) reduces ER stress and ameliorates age-associated sleep changes in Drosophila. PBA consolidates both baseline and recovery sleep in aging flies. The behavioral modifications of PBA are linked to its suppression of ER stress. PBA decreased splicing of X-box binding protein 1 and upregulation of phosphorylated elongation initiation factor 2 α, in flies that were subjected to sleep deprivation. We also demonstrate that directly activating ER stress in young flies fragments baseline sleep and alters recovery sleep. Alleviating prolonged or sustained ER stress during aging contributes to sleep consolidation and improves recovery sleep or sleep debt discharge. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Adolescents' Sleep Behaviors and Perceptions of Sleep

    Science.gov (United States)

    Noland, Heather; Price, James H.; Dake, Joseph; Telljohann, Susan K.

    2009-01-01

    Background: Sleep duration affects the health of children and adolescents. Shorter sleep durations have been associated with poorer academic performance, unintentional injuries, and obesity in adolescents. This study extends our understanding of how adolescents perceive and deal with their sleep issues. Methods: General education classes were…

  20. Effects of different sleep deprivation protocols on sleep perception in healthy volunteers.

    Science.gov (United States)

    Goulart, Leonardo I; Pinto, Luciano R; Perlis, Michael L; Martins, Raquel; Caboclo, Luis Otavio; Tufik, Sergio; Andersen, Monica L

    2014-10-01

    To investigate whether different protocols of sleep deprivation modify sleep perception. The effects of total sleep deprivation (TD) and selective rapid eye movement (REM) sleep deprivation (RD) on sleep perception were analyzed in normal volunteers. Thirty-one healthy males with normal sleep were randomized to one of three conditions: (i) normal uninterrupted sleep; (ii) four nights of RD; or (iii) two nights of TD. Morning perception of total sleep time was evaluated for each condition. Sleep perception was estimated using total sleep time (in hours) as perceived by the volunteer divided by the total sleep time (in hours) measured by polysomnography (PSG). The final value of this calculation was defined as the perception index (PI). There were no significant differences among the three groups of volunteers in the total sleep time measured by PSG or in the perception of total sleep time at baseline condition. Volunteers submitted to RD exhibited lower sleep PI scores as compared with controls during the sleep deprivation period (P sleep deprivation reduced the ability of healthy young volunteers to perceive their total sleep time when compared with time measured by PSG. The data reinforce the influence of sleep deprivation on sleep perception. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Sleep location and parent-perceived sleep outcomes in older infants.

    Science.gov (United States)

    Mindell, Jodi A; Leichman, Erin S; Walters, Russel M

    2017-11-01

    Initial studies indicate more independent and consolidated sleep in the first few months in infants who sleep separately. Little is known, however, about the relationship of sleep location (separate room, room-sharing, bed-sharing) with sleep outcomes in older infants (ages 6-12 months). It was expected that those who sleep in a separate room would have better parent-perceived sleep outcomes and more positive sleep health behaviors. Parents of 6236 infants (6-12 months) in the United States (US) and 3798 in an international sample (Australia, Brazil, Canada, Great Britain, and New Zealand) completed a smartphone app-based expanded version of the validated Brief Infant Sleep Questionnaire. A total of 37.2% of the infants in the US and 48.4% in the international sample slept in a separate room. In both samples, infants who slept in a separate room as opposed to room-sharing or bed-sharing had parent-perceived sleep outcomes and sleep-related behaviors that reflected earlier bedtimes, shorter time to fall asleep, more nighttime and total sleep, and increased sleep consolidation. They were also more likely to have a consistent bedtime routine and to fall asleep independently, as well as less likely to feed to sleep at bedtime and during the night. In addition, parents of separate room sleepers perceived bedtime to be less difficult and sleep to be better overall. Overall, 6- to 12-month-old infants who slept in a separate room had better reported sleep outcomes and fewer parent-perceived disturbances at bedtime than infants who room-shared with their parents, as well compared to those who slept in their parents' bed. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. A Multispecies Approach to Co-Sleeping : Integrating Human-Animal Co-Sleeping Practices into Our Understanding of Human Sleep.

    Science.gov (United States)

    Smith, Bradley P; Hazelton, Peta C; Thompson, Kirrilly R; Trigg, Joshua L; Etherton, Hayley C; Blunden, Sarah L

    2017-09-01

    Human sleeping arrangements have evolved over time and differ across cultures. The majority of adults share their bed at one time or another with a partner or child, and many also sleep with pets. In fact, around half of dog and cat owners report sharing a bed or bedroom with their pet(s). However, interspecies co-sleeping has been trivialized in the literature relative to interpersonal or human-human co-sleeping, receiving little attention from an interdisciplinary psychological perspective. In this paper, we provide a historical outline of the "civilizing process" that has led to current sociocultural conceptions of sleep as an individual, private function crucial for the functioning of society and the health of individuals. We identify similar historical processes at work in the formation of contemporary constructions of socially normative sleeping arrangements for humans and animals. Importantly, since previous examinations of co-sleeping practices have anthropocentrically framed this topic, the result is an incomplete understanding of co-sleeping practices. By using dogs as an exemplar of human-animal co-sleeping, and comparing human-canine sleeping with adult-child co-sleeping, we determine that both forms of co-sleeping share common factors for establishment and maintenance, and often result in similar benefits and drawbacks. We propose that human-animal and adult-child co-sleeping should be approached as legitimate and socially relevant forms of co-sleeping, and we recommend that co-sleeping be approached broadly as a social practice involving relations with humans and other animals. Because our proposition is speculative and derived from canine-centric data, we recommend ongoing theoretical refinement grounded in empirical research addressing co-sleeping between humans and multiple animal species.

  3. Central sleep apnea

    Science.gov (United States)

    Sleep apnea - central; Obesity - central sleep apnea; Cheyne-Stokes - central sleep apnea; Heart failure - central sleep apnea ... Central sleep apnea results when the brain temporarily stops sending signals to the muscles that control breathing. The condition ...

  4. Mammalian sleep

    Science.gov (United States)

    Staunton, Hugh

    2005-05-01

    This review examines the biological background to the development of ideas on rapid eye movement sleep (REM sleep), so-called paradoxical sleep (PS), and its relation to dreaming. Aspects of the phenomenon which are discussed include physiological changes and their anatomical location, the effects of total and selective sleep deprivation in the human and animal, and REM sleep behavior disorder, the latter with its clinical manifestations in the human. Although dreaming also occurs in other sleep phases (non-REM or NREM sleep), in the human, there is a contingent relation between REM sleep and dreaming. Thus, REM is taken as a marker for dreaming and as REM is distributed ubiquitously throughout the mammalian class, it is suggested that other mammals also dream. It is suggested that the overall function of REM sleep/dreaming is more important than the content of the individual dream; its function is to place the dreamer protagonist/observer on the topographical world. This has importance for the developing infant who needs to develop a sense of self and separateness from the world which it requires to navigate and from which it is separated for long periods in sleep. Dreaming may also serve to maintain a sense of ‘I’ness or “self” in the adult, in whom a fragility of this faculty is revealed in neurological disorders.

  5. Assessing sleep in adolescents through a better understanding of sleep physiology.

    Science.gov (United States)

    George, Nancy M; Davis, Jean E

    2013-06-01

    Adolescents need about nine hours of sleep per night, yet most teens get far less. Inadequate sleep has consequences not only for academic performance but also for mental and physical health; it has been linked to lowered resilience and an increased risk of cardiovascular and metabolic diseases. It's imperative that assessment of sleep become a routine part of adolescent health care. An understanding of sleep physiology is essential to helping nurses better assess and manage sleep deprivation in this population. Sleep assessment involves evaluating the three main aspects of sleep: amount, quality, and architecture. The authors provide an overview of sleep physiology, describe sleep changes that occur during adolescence, and discuss the influence of these changes on adolescent health. They also provide simple questions that nurses can use to assess sleep and risk factors for disrupted sleep, and discuss patient education and other interventions.

  6. Sleep Behaviors and Sleep Quality in Children with Autism Spectrum Disorders

    Science.gov (United States)

    Souders, Margaret C.; Mason, Thorton B. A.; Valladares, Otto; Bucan, Maja; Levy, Susan E.; Mandell, David S.; Weaver, Terri E.; Pinto-Martin, Jennifer

    2009-01-01

    Study Objectives: (1) Compare sleep behaviors of children with autism spectrum disorders (ASD) with sleep behaviors of typically developing (TD) children using the Children's Sleep Habits Questionnaire (CSHQ); (2) compare sleep quality—defined as mean activity, sleep latency, number of awakenings, sleep efficiency and total sleep time—of the cohort of children with ASD and TD, as measured by 10 nights of actigraphy; and (3) estimate the prevalence of sleep disturbances in the ASD and TD cohorts. Design: Descriptive cross-sectional study. Setting: The Children's Hospital of Philadelphia. Participants: Randomly selected children from the Regional Autism Center. The ASD cohort of 59 children, aged 4 to 10 years, (26 with autism, 21 with pervasive developmental disorder-not otherwise specified [PDD-NOS], and 12 with Asperger disorder) were compared with 40 TD control subjects. Measurements and Results: The CSHQ, sleep diaries, and 10 nights of actigraphy using the Sadeh algorithm of children with ASD and TD control subjects were compared. CSHQ showed 66.1% of parents of children with ASD (62.5% autism, 76.2% PDD-NOS, 58.3% Asperger disorder) and 45% of parents of the control subjects reported that their children had sleep problems. Actigraphic data showed that 66.7% of children with ASD (75% autism, 52.4% PDD-NOS, 75% Asperger disorder) and 45.9% of the control subjects had disturbed sleep. Conclusions: The prevalence estimate of 45% for mild sleep disturbances in the TD cohort highlights pediatric sleep debt as a public health problem of concern. The prevalence estimate of 66% for moderate sleep disturbances in the ASD cohort underscores the significant sleep problems that the families of these children face. The predominant sleep disorders in the ASD cohort were behavioral insomnia sleep-onset type and insomnia due to PDD. Citation: Souders MC; Mason TBA; Valladares O; Bucan M; Levy SE; Mandell DS; Weaver TE; Pinto-Martin D. Sleep behaviors and sleep quality in

  7. Unraveling the Neurobiology of Sleep and Sleep Disorders Using Drosophila.

    Science.gov (United States)

    Chakravarti, L; Moscato, E H; Kayser, M S

    2017-01-01

    Sleep disorders in humans are increasingly appreciated to be not only widespread but also detrimental to multiple facets of physical and mental health. Recent work has begun to shed light on the mechanistic basis of sleep disorders like insomnia, restless legs syndrome, narcolepsy, and a host of others, but a more detailed genetic and molecular understanding of how sleep goes awry is lacking. Over the past 15 years, studies in Drosophila have yielded new insights into basic questions regarding sleep function and regulation. More recently, powerful genetic approaches in the fly have been applied toward studying primary human sleep disorders and other disease states associated with dysregulated sleep. In this review, we discuss the contribution of Drosophila to the landscape of sleep biology, examining not only fundamental advances in sleep neurobiology but also how flies have begun to inform pathological sleep states in humans. © 2017 Elsevier Inc. All rights reserved.

  8. Associations between sleep duration, sleep quality and diabetic retinopathy.

    Directory of Open Access Journals (Sweden)

    Nicholas Y Q Tan

    Full Text Available Abnormal durations of sleep have been associated with risk of diabetes. However, it is not clear if sleep duration is associated with diabetic retinopathy (DR.In a cross-sectional study, we included 1,231 (Malay, n = 395; Indian, n = 836 adults (mean age 64.4 ± 9.0 years, 50.4% female with diabetes from the second visit of two independent population-based cohort studies (2011-15 in Singapore. Self-reported habitual sleep duration was categorized as short (<6 h, normal (6≤ h <8, and long (≥8 h. Questionnaires were administered to detect risk of obstructive sleep apnea (OSA, excessive daytime sleepiness, and insomnia, all of which may indicate poor quality of sleep. The associations between sleep-related characteristics with moderate DR and vision-threatening DR (VTDR were analysed using logistic regression models adjusted for potential confounders.Prevalence of moderate DR and VTDR in the study population were 10.5% and 6.3% respectively. The mean duration of sleep was 6.4 ± 1.5 h. Compared to normal sleep duration, both short and long sleep durations were associated with moderate DR with multivariable odds ratio (95% confidence interval of 1.73 (1.03-2.89 and 2.17 (1.28-3.66 respectively. Long sleep duration (2.37 [1.16-4.89], high risk of OSA (2.24 [1.09-4.75], and excessive daytime sleepiness (3.27 [1.02-10.30] were separately associated with VTDR.Sleep duration had a U-shaped association with moderate DR; long sleep duration, excessive daytime sleepiness and high risk of OSA were positively associated with VTDR.

  9. Are there associations between sleep bruxism, chronic stress, and sleep quality?

    Science.gov (United States)

    Ohlmann, Brigitte; Bömicke, Wolfgang; Habibi, Yasamin; Rammelsberg, Peter; Schmitter, Marc

    2018-07-01

    The purpose of this study was to identify associations between definite sleep bruxism, as defined by the American academy of sleep medicine, and chronic stress and sleep quality. Sleep bruxism was determined by use of questionnaires, assessment of clinical symptoms, and recording of electromyographic and electrocardiographic data (recorded by the Bruxoff ® device). The study included 67 participants. Of these, 38 were identified as bruxers and 29 as non-bruxers. The 38 bruxers were further classified as 17 moderate and 21 intense bruxers. Self-reported stress and self-reported sleep quality were determined by use of the validated questionnaires "Trier Inventory for the Assessment of Chronic Stress" (TICS) and the "Pittsburgh Sleep Quality Index" (PSQI). No statistically significant association was found between sleep bruxism and self-reported stress or sleep quality. However, a significant association between specific items of chronic stress and poor sleep quality was identified. The results of this study indicate an association between subjective sleep quality and subjective chronic stress, irrespective of the presence or absence of sleep bruxism. Chronic stress and sleep quality do not seem to be associated with sleep bruxism. (clinical trial no. NCT03039985). Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. Can sleep deprivation studies explain why human adults sleep?

    Science.gov (United States)

    Brown, Lee K

    2012-11-01

    This review will concentrate on the consequences of sleep deprivation in adult humans. These findings form a paradigm that serves to demonstrate many of the critical functions of the sleep states. The drive to obtain food, water, and sleep constitutes important vegetative appetites throughout the animal kingdom. Unlike nutrition and hydration, the reasons for sleep have largely remained speculative. When adult humans are nonspecifically sleep-deprived, systemic effects may include defects in cognition, vigilance, emotional stability, risk-taking, and, possibly, moral reasoning. Appetite (for foodstuffs) increases and glucose intolerance may ensue. Procedural, declarative, and emotional memory are affected. Widespread alterations of immune function and inflammatory regulators can be observed, and functional MRI reveals profound changes in regional cerebral activity related to attention and memory. Selective deprivation of rapid eye movement (REM) sleep, on the contrary, appears to be more activating and to have lesser effects on immunity and inflammation. The findings support a critical need for sleep due to the widespread effects on the adult human that result from nonselective sleep deprivation. The effects of selective REM deprivation appear to be different and possibly less profound, and the functions of this sleep state remain enigmatic.

  11. The Sleeping Cerebellum.

    Science.gov (United States)

    Canto, Cathrin B; Onuki, Yoshiyuki; Bruinsma, Bastiaan; van der Werf, Ysbrand D; De Zeeuw, Chris I

    2017-05-01

    We sleep almost one-third of our lives and sleep plays an important role in critical brain functions like memory formation and consolidation. The role of sleep in cerebellar processing, however, constitutes an enigma in the field of neuroscience; we know little about cerebellar sleep-physiology, cerebro-cerebellar interactions during sleep, or the contributions of sleep to cerebellum-dependent memory consolidation. Likewise, we do not understand why cerebellar malfunction can lead to changes in the sleep-wake cycle and sleep disorders. In this review, we evaluate how sleep and cerebellar processing may influence one another and highlight which scientific routes and technical approaches could be taken to uncover the mechanisms underlying these interactions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Effect of mandibular advancement device on sleep bruxism score and sleep quality.

    Science.gov (United States)

    Solanki, Nehal; Singh, Balendra Pratap; Chand, Pooran; Siddharth, Ramashankar; Arya, Deeksha; Kumar, Lakshya; Tripathi, Suryakant; Jivanani, Hemant; Dubey, Abhishek

    2017-01-01

    The use of mandibular advancement devices (MADs) in the treatment of sleep bruxism is gaining widespread importance. However, the effects of MADs on sleep bruxism scores, sleep quality, and occlusal force are not clear. The purpose of this clinical study was to analyze the effect of MADs on sleep bruxism scores, sleep quality, and occlusal force. This uncontrolled before and after study enrolled 30 participants with sleep bruxism. Outcomes assessed were sleep quality, sleep bruxism scores (sleep bruxism bursts and sleep bruxism episodes/hour), and occlusal force before and after 15 and 30 days of using a MAD. Sleep bruxism scores were assessed by ambulatory polysomnography and sleep quality by using the Pittsburgh sleep quality index (PSQI). Occlusal force was recorded by using a digital gnathodynamometer in the first molar region on both sides. Statistical analysis was done by 1-factor repeated measures ANOVA (α=.05). Statistically significant reductions in sleep bruxism bursts/h, sleep bruxism episodes/h, and PSQI scores were found after 15 and 30 days of using a MAD (Pbruxism scores, sleep quality, and reduction in occlusal force in sleep bruxism participants after using MADs. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

  13. Sleep and cognition.

    Science.gov (United States)

    Deak, Maryann C; Stickgold, Robert

    2010-07-01

    Sleep is a complex physiologic state, the importance of which has long been recognized. Lack of sleep is detrimental to humans and animals. Over the past decade, an important link between sleep and cognitive processing has been established. Sleep plays an important role in consolidation of different types of memory and contributes to insightful, inferential thinking. While the mechanism by which memories are processed in sleep remains unknown, several experimental models have been proposed. This article explores the link between sleep and cognition by reviewing (1) the effects of sleep deprivation on cognition, (2) the influence of sleep on consolidation of declarative and non-declarative memory, and (3) some proposed models of how sleep facilitates memory consolidation in sleep. Copyright © 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. Copyright © 2010 John Wiley & Sons, Ltd.

  14. Sleep Disturbance, Sleep Duration, and Inflammation: A Systematic Review and Meta-Analysis of Cohort Studies and Experimental Sleep Deprivation.

    Science.gov (United States)

    Irwin, Michael R; Olmstead, Richard; Carroll, Judith E

    2016-07-01

    Sleep disturbance is associated with inflammatory disease risk and all-cause mortality. Here, we assess global evidence linking sleep disturbance, sleep duration, and inflammation in adult humans. A systematic search of English language publications was performed, with inclusion of primary research articles that characterized sleep disturbance and/or sleep duration or performed experimental sleep deprivation and assessed inflammation by levels of circulating markers. Effect sizes (ES) and 95% confidence intervals (CI) were extracted and pooled using a random effect model. A total of 72 studies (n > 50,000) were analyzed with assessment of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor α (TNFα). Sleep disturbance was associated with higher levels of CRP (ES .12; 95% CI = .05-.19) and IL-6 (ES .20; 95% CI = .08-.31). Shorter sleep duration, but not the extreme of short sleep, was associated with higher levels of CRP (ES .09; 95% CI = .01-.17) but not IL-6 (ES .03; 95% CI: -.09 to .14). The extreme of long sleep duration was associated with higher levels of CRP (ES .17; 95% CI = .01-.34) and IL-6 (ES .11; 95% CI = .02-20). Neither sleep disturbances nor sleep duration was associated with TNFα. Neither experimental sleep deprivation nor sleep restriction was associated with CRP, IL-6, or TNFα. Some heterogeneity among studies was found, but there was no evidence of publication bias. Sleep disturbance and long sleep duration, but not short sleep duration, are associated with increases in markers of systemic inflammation. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  15. Sleep in Othello

    OpenAIRE

    Dimsdale, Joel E.

    2009-01-01

    Some of our best descriptions of sleep disorders come from literature. While Shakespeare is well known for his references to insomnia and sleep walking, his works also demonstrate a keen awareness of many other sleep disorders. This paper examines sleep themes in Shakespeare's play Othello. The play indicates Shakespeare's astute eye for sleep deprivation, sexual parasomnias, and effects of stress and drugs on sleep.

  16. Sleep/Wake Patterns and Parental Perceptions of Sleep in Children Born Preterm

    Science.gov (United States)

    Biggs, Sarah N.; Meltzer, Lisa J.; Tapia, Ignacio E.; Traylor, Joel; Nixon, Gillian M.; Horne, Rosemary S.C.; Doyle, Lex W.; Asztalos, Elizabeth; Mindell, Jodi A.; Marcus, Carole L.

    2016-01-01

    Study Objectives: To compare sleep/wake patterns in children born preterm in Australia vs Canada and determine cultural differences in the relationship between parental perception of sleep and actual sleep behaviors. Methods: Australian and Canadian children born preterm were recruited from the Caffeine for Apnea of Prematurity trial (n = 188, 5–12 y) and underwent 14 days actigraphy monitoring. Parents completed the National Sleep Foundation 2004 Sleep in America questionnaire. Cross-cultural differences in sleep characteristics assessed by actigraphy and parent-reported questionnaire were examined. Correlational analyses determined the associations between parental perceptions of child sleep need and sleep behavior. Results: Actigraphy showed preterm children obtained, on average, 8 h sleep/night, one hour less than population recommendations for their age. There was no difference in total sleep time (TST) between Australian and Canadian cohorts; however, bed and wake times were earlier in Australian children. Bedtimes and TST varied by 60 minutes from night to night in both cohorts. Parent-reported child TST on the National Sleep Foundation questionnaire was 90 minutes longer than recorded by actigraphy. Both bedtime and TST on weekdays and weekends were related to parental perception of child sleep need in the Australian cohort. Only TST on weekdays was related to parental perception of child sleep need in the Canadian cohort. Conclusions: This study suggests that short sleep duration and irregular sleep schedules are common in children born preterm. Cultural differences in the association between parental perception of child sleep need and actual sleep behaviors provide important targets for future sleep health education. Citation: Biggs SN, Meltzer LJ, Tapia IE, Traylor J, Nixon GM, Horne RS, Doyle LW, Asztalos E, Mindell JA, Marcus CL. Sleep/wake patterns and parental perceptions of sleep in children born preterm. J Clin Sleep Med 2016;12(5):711–717

  17. Feasibility and Emotional Impact of Experimentally Extending Sleep in Short-Sleeping Adolescents.

    Science.gov (United States)

    Van Dyk, Tori R; Zhang, Nanhua; Catlin, Perry A; Cornist, Kaylin; McAlister, Shealan; Whitacre, Catharine; Beebe, Dean W

    2017-09-01

    Published experimental sleep manipulation protocols for adolescents have been limited to the summer, limiting causal conclusions about how short sleep affects them on school nights, when they are most likely to restrict their sleep. This study assesses the feasibility and emotional impact of a school-night sleep manipulation protocol to test the effects of lengthening sleep in habitually short-sleeping adolescents. High school students aged 14-18 years who habitually slept 5-7 hours on school nights participated in a 5-week experimental sleep manipulation protocol. Participants completed a baseline week followed in randomized counterbalanced order by two experimental conditions lasting 2 weeks each: prescribed habitual sleep (HAB; sleep time set to match baseline) and sleep extension (EXT; 1.5-hour increase in time in bed from HAB). All sleep was obtained at home, monitored with actigraphy. Data on adherence, protocol acceptability, mood and behavior were collected at the end of each condition. Seventy-six adolescents enrolled in the study, with 54 retained through all 5 weeks. Compared to HAB, during EXT, participants averaged an additional 72.6 minutes/night of sleep (p sleep manipulation protocol can be feasibly implemented which directly tests the potential protective effects of lengthening sleep. Many short-sleeping adolescents would benefit emotionally from sleeping longer, supporting public health efforts to promote adolescent sleep on school nights. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  18. Sleep/Wake Patterns and Parental Perceptions of Sleep in Children Born Preterm.

    Science.gov (United States)

    Biggs, Sarah N; Meltzer, Lisa J; Tapia, Ignacio E; Traylor, Joel; Nixon, Gillian M; Horne, Rosemary S C; Doyle, Lex W; Asztalos, Elizabeth; Mindell, Jodi A; Marcus, Carole L

    2016-05-15

    To compare sleep/wake patterns in children born preterm in Australia vs Canada and determine cultural differences in the relationship between parental perception of sleep and actual sleep behaviors. Australian and Canadian children born preterm were recruited from the Caffeine for Apnea of Prematurity trial (n = 188, 5-12 y) and underwent 14 days actigraphy monitoring. Parents completed the National Sleep Foundation 2004 Sleep in America questionnaire. Cross-cultural differences in sleep characteristics assessed by actigraphy and parent-reported questionnaire were examined. Correlational analyses determined the associations between parental perceptions of child sleep need and sleep behavior. Actigraphy showed preterm children obtained, on average, 8 h sleep/night, one hour less than population recommendations for their age. There was no difference in total sleep time (TST) between Australian and Canadian cohorts; however, bed and wake times were earlier in Australian children. Bedtimes and TST varied by 60 minutes from night to night in both cohorts. Parent-reported child TST on the National Sleep Foundation questionnaire was 90 minutes longer than recorded by actigraphy. Both bedtime and TST on weekdays and weekends were related to parental perception of child sleep need in the Australian cohort. Only TST on weekdays was related to parental perception of child sleep need in the Canadian cohort. This study suggests that short sleep duration and irregular sleep schedules are common in children born preterm. Cultural differences in the association between parental perception of child sleep need and actual sleep behaviors provide important targets for future sleep health education. © 2016 American Academy of Sleep Medicine.

  19. Creatine supplementation reduces sleep need and homeostatic sleep pressure in rats.

    Science.gov (United States)

    Dworak, Markus; Kim, Tae; Mccarley, Robert W; Basheer, Radhika

    2017-06-01

    Sleep has been postulated to promote brain energy restoration. It is as yet unknown if increasing the energy availability within the brain reduces sleep need. The guanidine amino acid creatine (Cr) is a well-known energy booster in cellular energy homeostasis. Oral Cr-monohydrate supplementation (CS) increases exercise performance and has been shown to have substantial effects on cognitive performance, neuroprotection and circadian rhythms. The effect of CS on cellular high-energy molecules and sleep-wake behaviour is unclear. Here, we examined the sleep-wake behaviour and brain energy metabolism before and after 4-week-long oral administration of CS in the rat. CS decreased total sleep time and non-rapid eye movement (NREM) sleep significantly during the light (inactive) but not during the dark (active) period. NREM sleep and NREM delta activity were decreased significantly in CS rats after 6 h of sleep deprivation. Biochemical analysis of brain energy metabolites showed a tendency to increase in phosphocreatine after CS, while cellular adenosine triphosphate (ATP) level decreased. Microdialysis analysis showed that the sleep deprivation-induced increase in extracellular adenosine was attenuated after CS. These results suggest that CS reduces sleep need and homeostatic sleep pressure in rats, thereby indicating its potential in the treatment of sleep-related disorders. © 2017 European Sleep Research Society.

  20. The effects of sleep extension on sleep and cognitive performance in adolescents with chronic sleep reduction: an experimental study

    NARCIS (Netherlands)

    Dewald-Kaufmann, J.F.; Oort, F.J.; Meijer, A.M.

    2013-01-01

    Objective: To investigate the effects of gradual sleep extension in adolescents with chronic sleep reduction. Outcome variables were objectively measured sleep and cognitive performance. Methods: Participants were randomly assigned to either a sleep extension group (gradual sleep extension by

  1. The effects of sleep extension on sleep and cognitive performance in adolescents with chronic sleep reduction: an experimental study

    NARCIS (Netherlands)

    Dewald-Kaufmann, J. F.; Oort, F. J.; Meijer, A. M.

    2013-01-01

    To investigate the effects of gradual sleep extension in adolescents with chronic sleep reduction. Outcome variables were objectively measured sleep and cognitive performance. Participants were randomly assigned to either a sleep extension group (gradual sleep extension by advancing bedtimes in the

  2. [Sleeping habits and sleep disorders during adolescence: relation to school performance].

    Science.gov (United States)

    Salcedo Aguilar, F; Rodríguez Almonacid, F M; Monterde Aznar, M L; García Jiménez, M A; Redondo Martínez, P; Marcos Navarro, A I

    2005-05-15

    To determine the prevalence of sleep disorders in adolescence. To describe sleeping habits of adolescents in relation to sleep disorders and associated factors. To determine the relation between sleep disorders/inappropiate sleeping habits and school performance. Observational, descriptive, cross-sectional study. Secondary school of Cuenca (city in Spain). 1293 school children of first and fourth curses of secondary education. Structured questionnaire with opened and closed questions on sleeping habits during weekdays and at weekends and sleep disorders to be answered by the adolescents anonymously and on their own. Student's school performance with relation with to sleeping habits and sleep disorders were determined. 1155 students out of 1293 (response rate 89.33%) answered the questionnaire, 537 (45.9%) boys and 618 (54.1%) girls, 14 years old on average (between 11-18 years). On weekdays students went to bed at 23.17 h and got up at 7.46 h (average sleeping time =8 hours and 18 minutes). At weekends they went to bed at 1.02 h and got up at 10.42 h (average sleeping time =9 hours and 40 minutes). 45.4% of students said to sleep badly on Sunday night's. On average the number of subjects failed in class is higher with adolescents who complain about sleep (2.28 vs 1.91; P=.04), who are tired at waking up time (2.17 vs 1.97; P=.048) and who have morning sleepiness (2.17 vs 1.75; P=.004). Schools hours cause deficit sleeping time during weekdays which is partly made up for at weekend. At weekends there is an interruption of the adolescent's sleeping habits. School performance of adolescents with sleep disorders is lower.

  3. Sleep-related declarative memory consolidation and verbal replay during sleep talking in patients with REM sleep behavior disorder.

    Directory of Open Access Journals (Sweden)

    Ginevra Uguccioni

    Full Text Available OBJECTIVE: To determine if sleep talkers with REM sleep behavior disorder (RBD would utter during REM sleep sentences learned before sleep, and to evaluate their verbal memory consolidation during sleep. METHODS: Eighteen patients with RBD and 10 controls performed two verbal memory tasks (16 words from the Free and Cued Selective Reminding Test and a 220-263 word long modified Story Recall Test in the evening, followed by nocturnal video-polysomnography and morning recall (night-time consolidation. In 9 patients with RBD, daytime consolidation (morning learning/recall, evening recall was also evaluated with the modified Story Recall Test in a cross-over order. Two RBD patients with dementia were studied separately. Sleep talking was recorded using video-polysomnography, and the utterances were compared to the studied texts by two external judges. RESULTS: Sleep-related verbal memory consolidation was maintained in patients with RBD (+24±36% words as in controls (+9±18%, p=0.3. The two demented patients with RBD also exhibited excellent nighttime consolidation. The post-sleep performance was unrelated to the sleep measures (including continuity, stages, fragmentation and apnea-hypopnea index. Daytime consolidation (-9±19% was worse than night-time consolidation (+29±45%, p=0.03 in the subgroup of 9 patients with RBD. Eleven patients with RBD spoke during REM sleep and pronounced a median of 20 words, which represented 0.0003% of sleep with spoken language. A single patient uttered a sentence that was judged to be semantically (but not literally related to the text learned before sleep. CONCLUSION: Verbal declarative memory normally consolidates during sleep in patients with RBD. The incorporation of learned material within REM sleep-associated sleep talking in one patient (unbeknownst to himself at the semantic level suggests a replay at a highly cognitive creative level.

  4. Hit-to-lead development of the chamigrane endoperoxide merulin A for the treatment of African sleeping sickness.

    Science.gov (United States)

    Navarro, Gabriel; Chokpaiboon, Supchar; De Muylder, Geraldine; Bray, Walter M; Nisam, Sean C; McKerrow, James H; Pudhom, Khanitha; Linington, Roger G

    2012-01-01

    Human African trypanosomiasis (HAT) is an infectious disease with a large global health burden occurring primarily in Central and Eastern Africa. Most current treatments have poor blood brain barrier (BBB) penetration, which prevent them from targeting the most lethal stage of the infection. In addition, current therapeutics suffer from a variety of limitations ranging from serious side effects to difficulties with treatment administration. Therefore it is of crucial importance to find new treatments that are safe, affordable, and effective against both sub-species of Trypanosoma brucei. Semi-synthetic derivatization of the fungally-derived natural product merulin A (1) has led to the discovery of new development candidates for the protozoan parasite T. brucei, the causative agent of HAT. Creation of an initial SAR library based around the merulin scaffold revealed several key features required for activity, including the endoperoxide bridge, as well as one position suitable for further derivatization. Subsequent synthesis of a 20-membered analogue library, guided by the addition of acyl groups that improve the drug-like properties of the merulin A core, resulted in the development of compound 12 with an IC(50) of 60 nM against T. brucei, and a selectivity index greater than 300-fold against HeLa and immortalized glial cells. We report the semi-synthetic optimization of the merulin class of endoperoxide natural products as development candidates against T. brucei. We have identified compounds with low nM antiparasitic activities and high selectivity indices against HeLa cells. These compounds can be produced economically in large quantities via a one step derivatization from the microbial fermentation broth isolate, making them encouraging lead candidates for further development.

  5. Hit-to-lead development of the chamigrane endoperoxide merulin A for the treatment of African sleeping sickness.

    Directory of Open Access Journals (Sweden)

    Gabriel Navarro

    Full Text Available Human African trypanosomiasis (HAT is an infectious disease with a large global health burden occurring primarily in Central and Eastern Africa. Most current treatments have poor blood brain barrier (BBB penetration, which prevent them from targeting the most lethal stage of the infection. In addition, current therapeutics suffer from a variety of limitations ranging from serious side effects to difficulties with treatment administration. Therefore it is of crucial importance to find new treatments that are safe, affordable, and effective against both sub-species of Trypanosoma brucei.Semi-synthetic derivatization of the fungally-derived natural product merulin A (1 has led to the discovery of new development candidates for the protozoan parasite T. brucei, the causative agent of HAT. Creation of an initial SAR library based around the merulin scaffold revealed several key features required for activity, including the endoperoxide bridge, as well as one position suitable for further derivatization. Subsequent synthesis of a 20-membered analogue library, guided by the addition of acyl groups that improve the drug-like properties of the merulin A core, resulted in the development of compound 12 with an IC(50 of 60 nM against T. brucei, and a selectivity index greater than 300-fold against HeLa and immortalized glial cells.We report the semi-synthetic optimization of the merulin class of endoperoxide natural products as development candidates against T. brucei. We have identified compounds with low nM antiparasitic activities and high selectivity indices against HeLa cells. These compounds can be produced economically in large quantities via a one step derivatization from the microbial fermentation broth isolate, making them encouraging lead candidates for further development.

  6. Why Sleep Matters—The Economic Costs of Insufficient Sleep

    Science.gov (United States)

    Hafner, Marco; Stepanek, Martin; Taylor, Jirka; Troxel, Wendy M.; van Stolk, Christian

    2017-01-01

    Abstract The Centers for Disease Control and Prevention (CDC) in the United States has declared insufficient sleep a “public health problem.” Indeed, according to a recent CDC study, more than a third of American adults are not getting enough sleep on a regular basis. However, insufficient sleep is not exclusively a US problem, and equally concerns other industrialised countries such as the United Kingdom, Japan, Germany, or Canada. According to some evidence, the proportion of people sleeping less than the recommended hours of sleep is rising and associated with lifestyle factors related to a modern 24/7 society, such as psychosocial stress, alcohol consumption, smoking, lack of physical activity and excessive electronic media use, among others. This is alarming as insufficient sleep has been found to be associated with a range of negative health and social outcomes, including success at school and in the labour market. Over the last few decades, for example, there has been growing evidence suggesting a strong association between short sleep duration and elevated mortality risks. Given the potential adverse effects of insufficient sleep on health, well-being and productivity, the consequences of sleep-deprivation have far-reaching economic consequences. Hence, in order to raise awareness of the scale of insufficient sleep as a public-health issue, comparative quantitative figures need to be provided for policy- and decision-makers, as well as recommendations and potential solutions that can help tackling the problem. PMID:28983434

  7. Stability of Loop-Mediated Isothermal Amplification (LAMP) reagents and its amplification efficiency on crude trypanosome DNA templates.

    Science.gov (United States)

    Thekisoe, Oriel M M; Bazie, Raoul S B; Coronel-Servian, Andrea M; Sugimoto, Chihiro; Kawazu, Shin-Ichiro; Inoue, Noboru

    2009-04-01

    This study evaluated the stability of LAMP reagents when stored at 25 degrees C and 37 degrees C, and also assessed its detection efficiency on different DNA template preparations. Accordingly, LAMP using reagents stored at 25 degrees C and 37 degrees C amplified DNA of in vitro cultured T. b. brucei (GUTat 3.1) from day 1 to day 15 of reagent storage. There were no significant differences (P>0.05) in detection sensitivity of LAMP among the reagents stored at 25 degrees C, 37 degrees C and -20 degrees C (recommended storage temperature). LAMP using the reagents stored at above-mentioned temperatures amplified serially diluted DNAs (genomic DNA extracted by phenol-chloroform method, FTA card and hemolysed blood) of T. b. gambiense (IL2343) with high sensitivity. Reactions were conducted on the reagents stored from 1 day to 30 days. LAMP detection sensitivity was poor when fresh blood as DNA template was added directly into reactive solution. Results of this study demonstrated that LAMP has the potential to be used in field conditions for diagnosis of trypanosome infections without being affected by ambient temperatures of tropical and sub-tropical countries where trypanosomosis is endemic.

  8. Sleep in elite athletes and nutritional interventions to enhance sleep.

    Science.gov (United States)

    Halson, Shona L

    2014-05-01

    Sleep has numerous important physiological and cognitive functions that may be particularly important to elite athletes. Recent evidence, as well as anecdotal information, suggests that athletes may experience a reduced quality and/or quantity of sleep. Sleep deprivation can have significant effects on athletic performance, especially submaximal, prolonged exercise. Compromised sleep may also influence learning, memory, cognition, pain perception, immunity and inflammation. Furthermore, changes in glucose metabolism and neuroendocrine function as a result of chronic, partial sleep deprivation may result in alterations in carbohydrate metabolism, appetite, food intake and protein synthesis. These factors can ultimately have a negative influence on an athlete's nutritional, metabolic and endocrine status and hence potentially reduce athletic performance. Research has identified a number of neurotransmitters associated with the sleep-wake cycle. These include serotonin, gamma-aminobutyric acid, orexin, melanin-concentrating hormone, cholinergic, galanin, noradrenaline, and histamine. Therefore, nutritional interventions that may act on these neurotransmitters in the brain may also influence sleep. Carbohydrate, tryptophan, valerian, melatonin and other nutritional interventions have been investigated as possible sleep inducers and represent promising potential interventions. In this review, the factors influencing sleep quality and quantity in athletic populations are examined and the potential impact of nutritional interventions is considered. While there is some research investigating the effects of nutritional interventions on sleep, future research may highlight the importance of nutritional and dietary interventions to enhance sleep.

  9. Sleep and Mental Health in Undergraduate Students with Generally Healthy Sleep Habits.

    Science.gov (United States)

    Milojevich, Helen M; Lukowski, Angela F

    2016-01-01

    Whereas previous research has indicated that sleep problems tend to co-occur with increased mental health issues in university students, relatively little is known about relations between sleep quality and mental health in university students with generally healthy sleep habits. Understanding relations between sleep and mental health in individuals with generally healthy sleep habits is important because (a) student sleep habits tend to worsen over time and (b) even time-limited experience of sleep problems may have significant implications for the onset of mental health problems. In the present research, 69 university students with generally healthy sleep habits completed questionnaires about sleep quality and mental health. Although participants did not report clinically concerning mental health issues as a group, global sleep quality was associated with mental health. Regression analyses revealed that nighttime sleep duration and the frequency of nighttime sleep disruptions were differentially related to total problems and clinically-relevant symptoms of psychological distress. These results indicate that understanding relations between sleep and mental health in university students with generally healthy sleep habits is important not only due to the large number of undergraduates who experience sleep problems and mental health issues over time but also due to the potential to intervene and improve mental health outcomes before they become clinically concerning.

  10. Effects of Sleep Hygiene Education on Subjective Sleep Quality and Academic Performance

    Directory of Open Access Journals (Sweden)

    Erkan Sahin

    2014-12-01

    Full Text Available Aim: Sleep problems are common in students with one third of university students reporting insufficient sleep. It is known that sleep quality and daytime sleepiness cause decrasing academic performans. For this reason we aimed to investigate the effects of a sleep hygiene education on sleep quality and academic performance of first year medical students. Material and Method: Self-reported sleep data and academic performance of 131 first grade medical students were collected. To all students enrolled Pittsburg Sleep Quality Scale in the assessment of sleep quality and Epworth Sleepiness Scale for assessment of daytime sleepiness in the evaluation.The students were divided into two subgroups and the intervention group received a 30 minute structured sleep hygiene education. Global academic performance was assessed by grade point average at the end of the year. Results: Mean Pittsburgh sleep quality index score of the students was 7.9±3.5 and 106 (82.8% of then had a score %u22655.After intervention, .the worse the initial sleep quality, the more improvement by the sleep hygiene education on sleep quality and academic performance. Discussion: An education on sleep hygiene might improve subjective sleep quality and academic performance of medical students.

  11. Sleep duration, subjective sleep need, and sleep habits of 40- to 45-year-olds in the Hordaland Health Study.

    Science.gov (United States)

    Ursin, Reidun; Bjorvatn, Bjørn; Holsten, Fred

    2005-10-01

    To report the distribution of various sleep parameters in a population-based study. Population-based cross-sectional study with self-administered questionnaires. Conducted as part of the Hordaland Health Study '97-'99 in collaboration with the Norwegian National Health Screening Service. 8860 subjects, aged 40 to 45 years, answered the sleep questionnaire part of the study. N/A. Reports on habitual bedtimes, rise times, subjective sleep need, and various sleep characteristics were used in this study. Mean (+/- SD) nocturnal sleep duration during weekdays in men was 6 hours 52 minutes (+/- 55 minutes); in women 7 hours 11 minutes (+/- 57 minutes). Mean subjective sleep need was 7 hours 16 minutes (+/- 52 minutes) in men; 7 hours 45 minutes (+/- 52 minutes) in women. Sleep duration was shorter in shift workers and longer in married subjects and in those living in rural areas. Subjective sleep need was higher in subjects reporting poor subjective health and in subjects living in rural areas. In total, these variables accounted for only around 3% of the variance in sleep duration and sleep need. Ten percent of the men and 12.2% of the women reported frequent insomnia. The wide distribution of sleep duration and subjective sleep need indicate large interindividual variations in these parameters. There were pronounced sex differences in these variables and in most of the sleep characteristics studied. Shift work, urban-rural living, marital status, and education in men were sources of significant, but small, variations in sleep duration.

  12. Mobile Phone Interventions for Sleep Disorders and Sleep Quality: Systematic Review.

    Science.gov (United States)

    Shin, Jong Cheol; Kim, Julia; Grigsby-Toussaint, Diana

    2017-09-07

    Although mobile health technologies have been developed for interventions to improve sleep disorders and sleep quality, evidence of their effectiveness remains limited. A systematic literature review was performed to determine the effectiveness of mobile technology interventions for improving sleep disorders and sleep quality. Four electronic databases (EBSCOhost, PubMed/Medline, Scopus, and Web of Science) were searched for articles on mobile technology and sleep interventions published between January 1983 and December 2016. Studies were eligible for inclusion if they met the following criteria: (1) written in English, (2) adequate details on study design, (3) focus on sleep intervention research, (4) sleep index measurement outcome provided, and (5) publication in peer-reviewed journals. An initial sample of 2679 English-language papers were retrieved from five electronic databases. After screening and review, 16 eligible studies were evaluated to examine the impact of mobile phone interventions on sleep disorders and sleep quality. These included one case study, three pre-post studies, and 12 randomized controlled trials. The studies were categorized as (1) conventional mobile phone support and (2) utilizing mobile phone apps. Based on the results of sleep outcome measurements, 88% (14/16) studies showed that mobile phone interventions have the capability to attenuate sleep disorders and to enhance sleep quality, regardless of intervention type. In addition, mobile phone intervention methods (either alternatively or as an auxiliary) provide better sleep solutions in comparison with other recognized treatments (eg, cognitive behavioral therapy for insomnia). We found evidence to support the use of mobile phone interventions to address sleep disorders and to improve sleep quality. Our findings suggest that mobile phone technologies can be effective for future sleep intervention research. ©Jong Cheol Shin, Julia Kim, Diana Grigsby-Toussaint. Originally published

  13. Effect of obstructive sleep apnea on the sleep architecture in cirrhosis.

    Science.gov (United States)

    Kappus, Matthew R; Leszczyszyn, David J; Moses, Leonard; Raman, Shekar; Heuman, Douglas M; Bajaj, Jasmohan S

    2013-03-15

    Sleep disturbances in cirrhosis are assumed to be due to hepatic encephalopathy (HE). The interaction between cirrhosis, prior HE, and obstructive sleep apnea (OSA) has not been evaluated. We aimed to evaluate the additional effect of cirrhosis with and without prior HE on the sleep architecture and perceived sleep disturbances of OSA patients. A case-control review of OSA patients who underwent polysomnography (PSG) in a liver-transplant center was performed. OSA patients with cirrhosis (with/without prior HE) were age-matched 1:1 with OSA patients without cirrhosis. Sleep quality, daytime sleepiness, sleep quality, and sleep architecture was compared between groups. Forty-nine OSA cirrhotic patients (age 57.4 ± 8.3 years, model for end-stage liver disease (MELD) 8.3 ± 5.4, 51% HCV, 20% prior HE) were age-matched 1:1 to OSA patients without cirrhosis. Apnea-hypopnea index, arousal index, sleep efficiency, daytime sleepiness, and effect of sleepiness on daily activities were similar between OSA patients with/ without cirrhosis. Sleep architecture, including %slow wave sleep (SWS), was also not different between the groups. MELD was positively correlated with time in early (N1) stage (r = 0.4, p = 0.03). All prior HE patients (n = 10) had a shift of the architecture towards early, non-restorative sleep (higher % [N2] stage [66 vs 52%, p = 0.005], lower % SWS [0 vs 29%, p = 0.02], lower REM latency [95 vs 151 minutes, p = 0.04]) compared to the rest. Alcoholic etiology was associated with higher latency to N1/N2 sleep, but no other effect on sleep architecture was seen. OSA can contribute to sleep disturbance in cirrhosis and should be considered in the differential of sleep disturbances in cirrhosis. Prior HE may synergize with OSA in worsening the sleep architecture.

  14. Pediatric sleep apnea

    Science.gov (United States)

    Sleep apnea - pediatric; Apnea - pediatric sleep apnea syndrome; Sleep-disordered breathing - pediatric ... Untreated pediatric sleep apnea may lead to: High blood pressure Heart or lung problems Slow growth and development

  15. [The NHG guideline 'Sleep problems and sleeping pills'].

    Science.gov (United States)

    Damen-van Beek, Zamire; Lucassen, Peter L B J; Gorgels, Wim; Smelt, Antonette F H; Knuistingh Neven, Arie; Bouma, Margriet

    2015-01-01

    The Dutch College of General Practitioners' (NHG) guideline 'Sleep problems and sleeping pills' provides recommendations for the diagnosis and treatment of the most prevalent sleep problems and for the management of chronic users of sleeping pills. The preferred approach for sleeplessness is not to prescribe medication but to give information and behavioural advice. Practice assistants of the Dutch Association of Mental Health and Addiction Care are also expected to be able to undertake this management. The GP may consider prescribing sleeping pills for a short period only in cases of severe insomnia with considerable distress. Chronic users of sleeping pills should be advised by the GP to stop using them or to reduce the dose gradually (controlled dose reduction). The GP may refer patients with suspected obstructive sleep apnoea (OSA) to a pulmonary or ear, nose and throat specialist or neurologist for further diagnosis depending on the regional arrangements. The GP may then consider the cardiovascular risk factors commonly present with OSA. In patients with restless legs syndrome (RLS) who continue to experience major distress despite being given advice without the prescription of medication, the GP may consider prescribing a dopamine agonist.

  16. Sleeping brain, learning brain. The role of sleep for memory systems.

    Science.gov (United States)

    Peigneux, P; Laureys, S; Delbeuck, X; Maquet, P

    2001-12-21

    The hypothesis that sleep participates in the consolidation of recent memory traces has been investigated using four main paradigms: (1) effects of post-training sleep deprivation on memory consolidation, (2) effects of learning on post-training sleep, (3) effects of within sleep stimulation on the sleep pattern and on overnight memories, and (4) re-expression of behavior-specific neural patterns during post-training sleep. These studies convincingly support the idea that sleep is deeply involved in memory functions in humans and animals. However, the available data still remain too scarce to confirm or reject unequivocally the recently upheld hypothesis that consolidations of non-declarative and declarative memories are respectively dependent upon REM and NREM sleep processes.

  17. Effectiveness of sleep education programs to improve sleep hygiene and/or sleep quality in college students: a systematic review.

    Science.gov (United States)

    Dietrich, Shellene K; Francis-Jimenez, Coleen M; Knibbs, Melida Delcina; Umali, Ismael L; Truglio-Londrigan, Marie

    2016-09-01

    Sleep health is essential for overall health, quality of life and safety. Researchers have found a reduction in the average hours of sleep among college students. Poor sleep has been associated with deficits in attention, reduction in academic performance, impaired driving, risk-taking behaviors, depression, impaired social relationships and poorer health. College students may have limited knowledge about sleep hygiene and the behaviors that supports sleep health, which may lead to poor sleep hygiene behavior. To identify, appraise and synthesize the best available evidence on the effectiveness of sleep education programs in improving sleep hygiene knowledge, sleep hygiene behavior and/or sleep quality versus traditional strategies. All undergraduate or graduate college students, male or female, 18 years and older and of any culture or ethnicity. Formal sleep education programs that included a curriculum on sleep hygiene behavior. Educational delivery methods that took place throughout the participants' college experience and included a variety of delivery methods. Randomized controlled trials (RCTs) and quasi-experimental studies. Sleep hygiene knowledge, sleep hygiene behavior and/or sleep quality. Literature including published and unpublished studies in the English language from January 1, 1980 through August 17, 2015. A search of CINAHL, CENTRAL, EMBASE, Academic Search Complete, PsychINFO, Healthsource: Nursing/Academic edition, ProQuest Central, PubMed and ERIC were conducted using identified keywords and indexed terms. A gray literature search was also performed. Quantitative papers were assessed by two reviewers using critical appraisal instruments from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI). Data were extracted using the JBI-MAStARI data extraction tool. Data extracted included interventions, populations, study methods and outcomes of significance to the review question and objectives. Meta

  18. Sleep Quiz

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Sleep Quiz Past Issues / Summer 2007 Table of Contents ... on. Photo: iStock Take the National Center on Sleep Disorders Research Sleep Quiz TRUE OR FALSE ? _____1. ...

  19. Subjective sleep quality and sleep duration of patients in a psychiatric hospital

    Directory of Open Access Journals (Sweden)

    Matthias J. Müller

    2016-07-01

    Full Text Available Sleep complaints and sleep disturbances are highly prevalent in patients with psychiatric disorders. During hospitalization the patients’ condition may be even worse but little is known about the subjective sleep quality in psychiatric hospitals. Thus, we have investigated subjective sleep quality and mean sleep duration in patients with different psychiatric disorders at the end of hospitalization. For a period of one year, inpatients of a psychiatric hospital with diagnosis of substance use disorder (SUD, schizophrenia (SCZ, or anxiety/depressive disorders (AND were routinely asked to fill in an easily comprehensible sleep quality questionnaire at the end of their hospitalization. Age, gender, subjective sleep quality, and sleep duration were analyzed; sleep duration was classified according to age-specific recommendations. Data of n=309 patients (age 52.1±17.9y, 56.1% women were analyzed (n=63 SUD, n=50 SCZ, n=196 AND. Mean sleep duration was 7.0±2.0 h; 20.7% of patients had sleep durations below and 4.5% above age-specific recommendations. Non-restorative sleep during hospitalization was reported “almost always” in 38.2% (n=118, and “occasionally” in 30.1% (n=93. Subjective sleep quality was significantly associated with sleep duration (rs=−0.31, P<0.0005, but not with age, gender or diagnostic subgroup. The study showed that a great proportion of patients reported poor subjective sleep quality during hospitalization, regardless of age, gender and psychiatric diagnosis. As sleep quality was significantly associated with short sleep duration, a first step could be to take care to achieve recommended age-specific sleep durations in psychiatric hospitals.

  20. A Sleep Position Trainer for positional sleep apnea

    DEFF Research Database (Denmark)

    Laub, Rasmus R; Tønnesen, Philip; Jennum, Poul J

    2017-01-01

    We tested the effect of the Sleep Position Trainer, a vibrational device, for positional sleep apnea in an open, randomized controlled trial with 101 patients, where 52 patients were allocated to Sleep Position Trainer and 49 patients to a non-treatment control group for 2 months (Part 1). All...... patients were then followed as a cohort for a period of 6 months with use of the Sleep Position Trainer (Part 2). The participants were assessed with polygraphy at entry, and after 2 and 6 months. The mean apnea-hypopnea index supine was 35 per h (SD, 18) in the Sleep Position Trainer group and 38 per h...... (SD, 15) in the control group at entry. In a per protocol analysis, the mean total apnea-hypopnea index at entry and after 2 months in the Sleep Position Trainer group was 18 per h (SD, 10) and 10 per h (SD, 9; P

  1. Sleep Insufficiency, Sleep Health Problems and Performance in High School Students

    OpenAIRE

    Ming, Xue; Koransky, Rebecca; Kang, Victor; Buchman, Sarah; Sarris, Christina E.; Wagner, George C.

    2011-01-01

    A survey on sleep schedule, sleep health, school performance and school start times was conducted in 1,941 adolescents. A high level of early and circadian-disadvantaged sleep/wake schedules during weekdays was observed. Shorter sleep duration on weekdays was reported, especially in upper classmen. Complaints of inadequate sleep and sleepiness during weekdays, alarm clock use, and napping were prevalent. Night awakening and prolonged sleep onset were common and associated with poor school per...

  2. Relationships between parental sleep quality, fatigue, cognitions about infant sleep, and parental depression pre and post-intervention for infant behavioral sleep problems.

    Science.gov (United States)

    Hall, Wendy A; Moynihan, Melissa; Bhagat, Radhika; Wooldridge, Joanne

    2017-04-04

    Maternal and paternal depression has been associated with infants' behavioral sleep problems. Behavioral sleep interventions, which alter parental cognitions about infant sleep, have improved infant sleep problems. This study reports relationships between parental depression, fatigue, sleep quality, and cognitions about infant sleep pre and post-intervention for a behavioral sleep problem. This secondary analysis of data from Canadian parents (n = 455), with healthy infants aged 6-to-8-months exposed to a behavioral sleep intervention, examined baseline data and follow-up data from 18 or 24 weeks post intervention (group teaching or printed material) exposure. Parents reported on sleep quality, fatigue, depression, and cognitions about infant sleep. Data were analyzed using Pearson's r and stepwise regression analysis. Parents' fatigue, sleep quality, sleep cognitions, and depression scores were correlated at baseline and follow-up. At baseline, sleep quality (b = .52, 95% CI .19-.85), fatigue (b = .48, 95% CI .33-.63), doubt about managing infant sleep (b = .44, 95% CI .19-.69), and anger about infant sleep (b = .69, 95% CI .44-.94) were associated with mothers' depression. At baseline, fathers' depression related to sleep quality (b = .42, 95% CI .01-.83), fatigue (b = .47, 95% CI .32-.63), and doubt about managing infant sleep (b = .50, 95% CI .24-.76). At follow-up, mothers' depression was associated with sleep quality (b = .76, 95% CI .41-1.12), fatigue (b = .25, 95% CI .14-.37), doubt about managing infant sleep (b = .44, 95% CI .16-.73), sleep anger (b = .31, 95% CI .02-.59), and setting sleep limits (b = -.22, 95% CI -.41-[-.03]). At follow-up, fathers' depression related to sleep quality (b = .84, 95% CI .46-1.22), fatigue (b = .31, 95% CI .17-.45), sleep doubt (b = .34, 95% CI .05-.62), and setting sleep limits (b = .25, 95% CI .01-.49). Mothers' and fathers' cognitions about infant

  3. [Sleep habits, sleep quality and sleep medicine use of the Swiss population result].

    Science.gov (United States)

    Tinguely, Gilberte; Landolt, Hans-Peter; Cajochen, Christian

    2014-11-01

    A survey in a representative sample of the Swiss population revealed an average sleep duration of 7.5 hours on workdays and of 8.5 hours on free days, which reflected a more than half an hour (38 min) shorter sleep duration than 28 years ago. The mean time in bed was between 22:41 and 06:37 on workdays and between 23:29 and 08:27 on free days. On workdays as well as on free days the bedtime was delayed by 47 minutes in comparison to a similar survey 28 years ago. By contrast, the mean rise times on workdays and free days did not change. The sleep duration required to feel refreshed was indicated with 7 hours, which was 41 minutes less than 28 years ago. Roughly 90 % of the interviewees answered that they felt healthy, and 75 % described their sleep as good or very good compared to 79 % 28 years ago. The most frequent reasons stated for bad sleep were personal problems and strain at the workplace. The effect of bad quality sleep on every day functioning was considered as essential by 65 % of the respondents compared to 69 % 28 years ago. The use of medication to improve sleep was declared by 2.8 % (2.7 % 28 years ago), most often benzodiazepines, but also Valerian products and so-called z-drugs. In comparison with similar surveys in other countries (France, Great Britain and USA), Swiss residents slept roughly half an hour longer, but these other countries alike showed a sizable shortening of their habitual sleep duration over the last decades.

  4. Secondhand Smoke Exposure, Restless Sleep, and Sleep Duration in Adolescents

    Directory of Open Access Journals (Sweden)

    Jennifer Schwartz

    2014-01-01

    Full Text Available Purpose. To examine whether secondhand smoke (SHS exposure is associated with restless sleep and/or nighttime sleep duration among adolescents. Methods. Data were analyzed from 1,592 adolescents who completed an internet-delivered survey as part of the British Columbia Adolescent Substance Use Survey cohort study. Ordinal logistic and linear regression models were used to examine associations between frequency of SHS exposure in the past month and frequency of restless sleep and nighttime sleep duration, respectively. Results. SHS exposure was significantly positively associated with restless sleep and significantly negatively associated with sleep duration. In fully adjusted models, compared with students who reported never being exposed to SHS in the past month, students who reported a low, medium, or high frequency of SHS exposure were 1.53, 1.76, and 2.51 times as likely, respectively, to report more frequent restless sleep (OR=1.53, 95% CI 1.08–2.16; OR=1.76, 95% CI 1.22–2.53; OR=2.51, 95% CI 1.59–3.98. With regard to sleep duration, as frequency of SHS exposure increased by one category, nighttime sleep duration during the week and weekend decreased by 4 minutes (B=-0.06, 95% CI=-0.01–-0.11 and 6 minutes (B=-0.09, 95% CI=-0.03–-0.14, respectively. Conclusions. This study suggests that frequency of SHS exposure has a significant dose-response relationship with restless sleep and sleep duration in adolescents.

  5. Study of Sleep Habits and Sleep Problems Among Medical Students ...

    African Journals Online (AJOL)

    Background: Good quality sleep and adequate amount of sleep are important in order to have better cognitive performance and avoid health problems and psychiatric disorders. Aim: The aim of this study was to describe sleep habits and sleep problems in a population of undergraduates, interns and postgraduate students ...

  6. The Sleep-Time Cost of Parenting: Sleep Duration and Sleepiness Among Employed Parents in the Wisconsin Sleep Cohort Study

    Science.gov (United States)

    Hagen, Erika W.; Mirer, Anna G.; Palta, Mari; Peppard, Paul E.

    2013-01-01

    Insufficient sleep is associated with poor health and increased mortality. Studies on whether parenthood (including consideration of number and ages of children) is associated with sleep duration or sleep problems are scant and inconclusive. Using data collected in the Wisconsin Sleep Cohort Study (n = 4,809) between 1989 and 2008, we examined cross-sectional associations of number and ages of children with self-reported parental sleep duration, daytime sleepiness, and dozing among employed adults. Longitudinal change in sleep duration over 19 years was examined to evaluate changes in parental sleep associated with children transitioning into adulthood (n = 833). Each child under age 2 years was associated with 13 fewer minutes of parental sleep per day (95% confidence interval (CI): 5, 21); each child aged 2–5 years was associated with 9 fewer minutes of sleep (95% CI: 5, 13); and each child aged 6–18 years was associated with 4 fewer minutes (95% CI: 2, 6). Adult children were not associated with shorter parental sleep duration. Parents of children over age 2 years were significantly more likely to experience daytime sleepiness and dozing during daytime activities. Parents of minor children at baseline had significantly greater increases in sleep duration over 19 years of follow-up. Parenting minor children is associated with shorter sleep duration. As children age into adulthood, the sleep duration of parents with more children approaches that of parents with fewer children. PMID:23378502

  7. Comparisons of Portable Sleep Monitors of Different Modalities: Potential as Naturalistic Sleep Recorders

    Directory of Open Access Journals (Sweden)

    Masahiro Matsuo

    2016-07-01

    Full Text Available Background: Humans spend more than a fourth of their life sleeping, and sleep quality has been significantly linked to health. However, the objective examination of ambulatory sleep quality remains a challenge, since sleep is a state of unconsciousness, which limits the reliability of self-reports. Therefore, a non-invasive, continuous, and objective method for the recording and analysis of naturalistic sleep is required.Objective: Portable sleep recording devices provide a suitable solution for the ambulatory analysis of sleep quality. In this study, the performance of two activity-based sleep monitors (Actiwatch and MTN-210 and a single-channel EEG-based sleep monitor (SleepScope were compared in order to examine their reliability for the assessment of sleep quality.Methods: Twenty healthy adults were recruited for this study. First, data from daily activity recorded by Actiwatch and MTN-210 were compared to determine whether MTN-210, a more affordable device, could yield data similar to Actiwatch, the de-facto standard. In addition, sleep detection ability was examined using data obtained by polysomnography as reference. One simple analysis included comparing the sleep/wake detection ability of Actiwatch, MTN-210, and SleepScope. Furthermore, the fidelity of sleep stage determination was examined using SleepScope in finer time resolution. Results: The results indicate that MTN-210 demonstrates an activity pattern comparable to that of Actiwatch, although their sensitivity preferences were not identical. Moreover, MTN-210 provides assessment of sleep duration comparable to that of the wrist-worn Actiwatch when MTN-210 was attached to the body. SleepScope featured superior overall sleep detection performance among the three methods tested. Furthermore, SleepScope was able to provide information regarding sleep architecture, although systemic bias was found. Conclusion: The present results suggest that single-channel EEG-based sleep monitors are

  8. The orthologue of Sjögren's syndrome nuclear autoantigen 1 (SSNA1 in Trypanosoma brucei is an immunogenic self-assembling molecule.

    Directory of Open Access Journals (Sweden)

    Helen P Price

    Full Text Available Primary Sjögren's Syndrome (PSS is a highly prevalent autoimmune disease, typically manifesting as lymphocytic infiltration of the exocrine glands leading to chronically impaired lacrimal and salivary secretion. Sjögren's Syndrome nuclear autoantigen 1 (SSNA1 or NA14 is a major specific target for autoantibodies in PSS but the precise function and clinical relevance of this protein are largely unknown. Orthologues of the gene are absent from many of the commonly used model organisms but are present in Chlamyodomonas reinhardtii (in which it has been termed DIP13 and most protozoa. We report the functional characterisation of the orthologue of SSNA1 in the kinetoplastid parasite, Trypanosoma brucei. Both TbDIP13 and human SSNA1 are small coiled-coil proteins which are predicted to be remote homologues of the actin-binding protein tropomyosin. We use comparative proteomic methods to identify potential interacting partners of TbDIP13. We also show evidence that TbDIP13 is able to self-assemble into fibril-like structures both in vitro and in vivo, a property which may contribute to its immunogenicity. Endogenous TbDIP13 partially co-localises with acetylated α-tubulin in the insect procyclic stage of the parasite. However, deletion of the DIP13 gene in cultured bloodstream and procyclic stages of T. brucei has little effect on parasite growth or morphology, indicating either a degree of functional redundancy or a function in an alternative stage of the parasite life cycle.

  9. The impact of an online prematriculation sleep course (sleep 101 on sleep knowledge and behaviors in college freshmen: a pilot study

    Directory of Open Access Journals (Sweden)

    Quan SF

    2017-04-01

    Full Text Available College students have a high prevalence of poor sleep quality and sleep deficiency which negatively impacts their academic, mental and physical performance. A prematriculation course focused on improving sleep knowledge and behaviors may reduce sleep problems. “Sleep 101” is an online prematriculation course developed to educate incoming college freshmen about the importance of sleep in their lives and to recommend behaviors that will improve their sleep health. In a pilot program, “Sleep 101” was administered to freshman at four universities. The results of a voluntary survey after completion of the course indicated that there was an improvement in knowledge about sleep and the effects of caffeine use, and that students were less likely to drive drowsy and pull “all-nighters,” These pilot data suggest that an internet administered prematriculation course on the importance of sleep and the adoption of healthy sleep behaviors will be effective in reducing sleep problems among college students.

  10. Poor sleep quality and insufficient sleep of a collegiate student-athlete population.

    Science.gov (United States)

    Mah, Cheri D; Kezirian, Eric J; Marcello, Brandon M; Dement, William C

    2018-06-01

    Poor and inadequate sleep negatively impact cognitive and physical functioning and may also affect sports performance. The study aim is to examine sleep quality, sleep duration, and daytime sleepiness in collegiate student-athletes across a wide range of sports. Questionnaire. University setting. 628 athletes across 29 varsity teams at Stanford University. Athletes completed a questionnaire inquiring about sleep quality via a modified Pittsburgh Sleep Quality Index (PSQI), sleep duration, and daytime sleepiness via Epworth Sleepiness Scale. Sleep quality on campus and while traveling for competition was rated on a 10-point scale. Collegiate athletes were classified as poor sleepers (PSQI 5.38 ± 2.45), and 42.4% of athletes experience poor sleep quality (reporting PSQI global scores >5). Athletes reported lower sleep quality on campus than when traveling for competition (7.1 vs 7.6, Pquality, regularly obtain insufficient sleep, and commonly exhibit daytime sleepiness. Copyright © 2018 National Sleep Foundation. All rights reserved.

  11. [Sleep and sleep disorders in the elderly. Part 2: therapy].

    Science.gov (United States)

    Schlitzer, J; Heubaum, S; Frohnhofen, H

    2014-11-01

    Sleep disorders need to be treated if they affect the quality of life, lead to functional problems in daily life or unfavorably affect self-sufficiency. The large number of sleep disorders is reflected in the number of different and varied available therapeutic procedures. The basic therapeutic procedure for any sleep disorder is the use of sleep hygiene. Sleeplessness (insomnia) is most effectively treated through behavioral therapy, with stimulus control and sleep restriction as the most effective measures, whereas pharmacotherapy is considerably less effective and has side effects. Sleep-disordered breathing is also the most common cause of hypersomnia in the elderly and is most effectively treated by nocturnal positive pressure breathing.

  12. Sleep extension improves neurocognitive functions in chronically sleep-deprived obese individuals.

    Science.gov (United States)

    Lucassen, Eliane A; Piaggi, Paolo; Dsurney, John; de Jonge, Lilian; Zhao, Xiong-ce; Mattingly, Megan S; Ramer, Angela; Gershengorn, Janet; Csako, Gyorgy; Cizza, Giovanni

    2014-01-01

    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. To characterize neurocognitive functions and assess its reversibility. Prospective cohort study. Tertiary Referral Research Clinical Center. A cohort of 121 short-sleeping (Sleep extension (468±88 days) with life-style modifications. Neurocognitive functions, sleep quality and sleep duration. 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% (psleep duration increased by 11% by questionnaires (pattention 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. Drop-out rate. 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. www.ClinicalTrials.gov NCT00261898. NIDDK protocol 06-DK-0036.

  13. Obstructive Sleep Apnoea

    African Journals Online (AJOL)

    Cheyne-Stokes respiration), obstructive sleep apnoea and mixed or complex sleep apnoea.1. Obstructive sleep apnoea (OSA) is the most common of these three disorders and is defined as airway obstruction during sleep, accompanied by at least ...

  14. Sleep and psychiatry

    Science.gov (United States)

    Abad, Vivien C.; Guilleminault, Christian

    2005-01-01

    Psychiatric disorders constitute 15.4% of the disease burden in established market economies. Many psychiatric disorders are associated with sleep disturbances, and the relationship is often bidirectional. This paper reviews the prevalence of various psychiatric disorders, their clinical presentation, and their association with sleep disorders. Among the psychiatric disorders reviewed are affective disorders, psychosis, anxiety disorders (including post-traumatic stress disorder), substance abuse disorders, eating disorders, and attention deficit/hyperactivity disorders. The spectrum of associated sleep disorders includes insomnia, hypersomnia, nocturnal panic, sleep paralysis, hypnagogic hallucinations, restless legs/periodic limb movements of sleep, obstructive sleep apnea, and parasomnias. The effects on sleep of various psychotropic medications utilized to treat the above psychiatric disorders are summarized. PMID:16416705

  15. The role of sleep and sleep deprivation in consolidating fear memories.

    Science.gov (United States)

    Menz, M M; Rihm, J S; Salari, N; Born, J; Kalisch, R; Pape, H C; Marshall, L; Büchel, C

    2013-07-15

    Sleep, in particular REM sleep, has been shown to improve the consolidation of emotional memories. Here, we investigated the role of sleep and sleep deprivation on the consolidation of fear memories and underlying neuronal mechanisms. We employed a Pavlovian fear conditioning paradigm either followed by a night of polysomnographically monitored sleep, or wakefulness in forty healthy participants. Recall of learned fear was better after sleep, as indicated by stronger explicitly perceived anxiety and autonomous nervous responses. These effects were positively correlated with the preceding time spent in REM sleep and paralleled by activation of the basolateral amygdala. These findings suggest REM sleep-associated consolidation of fear memory in the human amygdala. In view of the critical participation of fear learning mechanisms in the etiology of anxiety and post-traumatic stress disorder, deprivation of REM sleep after exposure to distressing events is an interesting target for further investigation. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Ostriches sleep like platypuses.

    Directory of Open Access Journals (Sweden)

    John A Lesku

    Full Text Available Mammals and birds engage in two distinct states of sleep, slow wave sleep (SWS and rapid eye movement (REM sleep. SWS is characterized by slow, high amplitude brain waves, while REM sleep is characterized by fast, low amplitude waves, known as activation, occurring with rapid eye movements and reduced muscle tone. However, monotremes (platypuses and echidnas, the most basal (or 'ancient' group of living mammals, show only a single sleep state that combines elements of SWS and REM sleep, suggesting that these states became temporally segregated in the common ancestor to marsupial and eutherian mammals. Whether sleep in basal birds resembles that of monotremes or other mammals and birds is unknown. Here, we provide the first description of brain activity during sleep in ostriches (Struthio camelus, a member of the most basal group of living birds. We found that the brain activity of sleeping ostriches is unique. Episodes of REM sleep were delineated by rapid eye movements, reduced muscle tone, and head movements, similar to those observed in other birds and mammals engaged in REM sleep; however, during REM sleep in ostriches, forebrain activity would flip between REM sleep-like activation and SWS-like slow waves, the latter reminiscent of sleep in the platypus. Moreover, the amount of REM sleep in ostriches is greater than in any other bird, just as in platypuses, which have more REM sleep than other mammals. These findings reveal a recurring sequence of steps in the evolution of sleep in which SWS and REM sleep arose from a single heterogeneous state that became temporally segregated into two distinct states. This common trajectory suggests that forebrain activation during REM sleep is an evolutionarily new feature, presumably involved in performing new sleep functions not found in more basal animals.

  17. Prevalence and impact of sleep disorders and sleep habits in the United States.

    Science.gov (United States)

    Ram, Saravanan; Seirawan, Hazem; Kumar, Satish K S; Clark, Glenn T

    2010-02-01

    Epidemiologic studies on sleep disorders in the USA have mostly focused on specific disorders in specific groups of individuals. Most studies on sleep habits and sleep-related difficulties have focused on children and adolescents. The authors describe the prevalence of the three common physician-diagnosed sleep disorders (insomnia, sleep apnea, and restless legs syndrome (RLS)) by age, gender, and race in the US population. In addition, the authors describe the sleep habits and sleep-related difficulties in carrying routine daily activities. The authors also investigate the impact of the sleep disorders on performing routine daily activities. Data from the 2005-2006 National Health and Nutrition Examination Survey for 6,139 individuals over the age of 16 was analyzed for sleep-related parameters. The prevalence was highest for sleep apnea (4.2%), followed by insomnia (1.2%) and RLS (0.4%). Hispanics and Whites reported longer sleep duration than Blacks by 24 to 30 min. The predominant sleep habits were snoring while sleeping (48%), feeling unrested during the day (26.5%), and not getting enough sleep (26%). Difficulty concentrating (25%) or remembering (18%) were the main sleep-related difficulties in our sample. Insomnia, sleep apnea, and RLS had the highest impact on concentration and memory. Our findings suggest that the prevalence of sleep disorders in the USA is much lower than previously reported in the literature suggesting under diagnosis of sleep disorders by primary care physicians.

  18. Do Older Adults Need Sleep? A Review of Neuroimaging, Sleep, and Aging Studies.

    Science.gov (United States)

    Scullin, Michael K

    2017-09-01

    Sleep habits, sleep physiology, and sleep disorders change with increasing age. However, there is a longstanding debate regarding whether older adults need sleep to maintain health and daily functioning (reduced-sleep-need view). An alternative possibility is that all older adults need sleep, but that many older adults have lost the ability to obtain restorative sleep (reduced-sleep-ability view). Prior research using behavioral and polysomnography outcomes has not definitively disentangled the reduced-sleep-need and reduced-sleep-ability views. Therefore, this review examines the neuroimaging literature to determine whether age-related changes in sleep cause-or are caused by-age-related changes in brain structure, function, and pathology. In middle-aged and older adults, poorer sleep quality, greater nighttime hypoxia, and shorter sleep duration related to cortical thinning in frontal regions implicated in slow wave generation, in frontoparietal networks implicated in cognitive control, and in hippocampal regions implicated in memory consolidation. Furthermore, poor sleep quality was associated with higher amyloid burden and decreased connectivity in the default mode network, a network that is disrupted in the pathway to Alzheimer's disease. All adults need sleep, but cortical thinning and amyloidal deposition with advancing age may weaken the brain's ability to produce restorative sleep. Therefore, sleep in older adults may not always support identical functions for physical, mental, and cognitive health as in young adults.

  19. Pre-Sleep Arousal and Sleep Problems of Anxiety-Disordered Youth

    Science.gov (United States)

    Alfano, Candice A.; Pina, Armando A.; Zerr, Argero A.; Villalta, Ian K.

    2010-01-01

    The current study examined sleep problems and pre-sleep arousal among 52 anxious children and adolescents, aged 7-14 years, in relation to age, sex, ethnicity, and primary anxiety disorder. Assessment included structured diagnostic interviews and parent and child completed measures of sleep problems and pre-sleep arousal. Overall, 85% of parents…

  20. Sleep-wake patterns and sleep disturbance among Hong Kong Chinese adolescents.

    Science.gov (United States)

    Chung, Ka-Fai; Cheung, Miao-Miao

    2008-02-01

    To determine sleep-wake patterns and evaluate sleep disturbance in Hong Kong adolescents; to identify factors that are associated with sleep disturbance; and to examine the relationship of sleep-wake variables and academic performance. A school-based cross-sectional survey. Sample included 1629 adolescents aged 12 to 19 years. Self-report questionnaires, including sleep-wake habit questionnaire, Sleep Quality Index, Morningness/ Eveningness scale, Epworth Sleepiness Scale, Perceived Stress Scale, academic performance, and personal data were administered. The average school-night bedtime was 23:24, and total sleep time was 7.3 hr. During weekends, the average bedtime and rise time was delayed by 64 min and 195 min, respectively. The prevalence of sleep disturbances occurring > or = 3 days per week in the preceding 3 months were: difficulty falling asleep (5.6%), waking up during the night (7.2%), and waking up too early in the morning (10.4%). The prevalence of > or = 1 of these three symptoms was 19.1%. Stepwise regression analyses revealed that circadian phase preference was the most significant predictor for school night bedtime, weekend oversleep, and daytime sleepiness. Perceived stress was the most significant risk factor for sleep disturbance. Students with marginal academic performance reported later bedtimes and shorter sleep during school nights, greater weekend delays in bedtime, and more daytime sleepiness than those with better grades. The prevalence of sleep deprivation and sleep disturbance among Hong Kong adolescents is comparable to those found in other countries. An intervention program for sleep problems in adolescents should be considered.

  1. Vascular compliance limits during sleep deprivation and recovery sleep.

    Science.gov (United States)

    Phillips, Derrick J; Schei, Jennifer L; Rector, David M

    2013-10-01

    Our previous studies showed that evoked hemodynamic responses are smaller during wake compared to sleep; suggesting neural activity is associated with vascular expansion and decreased compliance. We explored whether prolonged activity during sleep deprivation may exacerbate vascular expansion and blunt hemodynamic responses. Evoked auditory responses were generated with periodic 65 dB speaker clicks over a 72-h period and measured with cortical electrodes. Evoked hemodynamic responses were measured simultaneously with optical techniques using three light-emitting diodes, and a photodiode. Animals were housed in separate 30×30×80 cm enclosures, tethered to a commutator system and maintained on a 12-h light/dark cycle. Food and water were available ad libitum. Seven adult female Sprague-Dawley rats. Following a 24-h baseline recording, sleep deprivation was initiated for 0 to 10 h by gentle handling, followed by a 24-h recovery sleep recording. Evoked electrical and hemodynamic responses were measured before, during, and after sleep deprivation. Following deprivation, evoked hemodynamic amplitudes were blunted. Steady-state oxyhemoglobin concentration increased during deprivation and remained high during the initial recovery period before returning to baseline levels after approximately 9-h. Sleep deprivation resulted in blood vessel expansion and decreased compliance while lower basal neural activity during recovery sleep may allow blood vessel compliance to recover. Chronic sleep restriction or sleep deprivation could push the vasculature to critical levels, limiting blood delivery, and leading to metabolic deficits with the potential for neural trauma.

  2. How Many Sleep Diary Entries Are Needed to Reliably Estimate Adolescent Sleep?

    Science.gov (United States)

    Arora, Teresa; Gradisar, Michael; Taheri, Shahrad; Carskadon, Mary A.

    2017-01-01

    Abstract Study Objectives: To investigate (1) how many nights of sleep diary entries are required for reliable estimates of five sleep-related outcomes (bedtime, wake time, sleep onset latency [SOL], sleep duration, and wake after sleep onset [WASO]) and (2) the test–retest reliability of sleep diary estimates of school night sleep across 12 weeks. Methods: Data were drawn from four adolescent samples (Australia [n = 385], Qatar [n = 245], United Kingdom [n = 770], and United States [n = 366]), who provided 1766 eligible sleep diary weeks for reliability analyses. We performed reliability analyses for each cohort using complete data (7 days), one to five school nights, and one to two weekend nights. We also performed test–retest reliability analyses on 12-week sleep diary data available from a subgroup of 55 US adolescents. Results: Intraclass correlation coefficients for bedtime, SOL, and sleep duration indicated good-to-excellent reliability from five weekday nights of sleep diary entries across all adolescent cohorts. Four school nights was sufficient for wake times in the Australian and UK samples, but not the US or Qatari samples. Only Australian adolescents showed good reliability for two weekend nights of bedtime reports; estimates of SOL were adequate for UK adolescents based on two weekend nights. WASO was not reliably estimated using 1 week of sleep diaries. We observed excellent test–rest reliability across 12 weeks of sleep diary data in a subsample of US adolescents. Conclusion: We recommend at least five weekday nights of sleep dairy entries to be made when studying adolescent bedtimes, SOL, and sleep duration. Adolescent sleep patterns were stable across 12 consecutive school weeks. PMID:28199718

  3. On-call work: To sleep or not to sleep? It depends.

    Science.gov (United States)

    Ferguson, Sally A; Paterson, Jessica L; Hall, Sarah J; Jay, Sarah M; Aisbett, Brad

    On-call working time arrangements are increasingly common, involve work only in the event of an unpredictable incident and exist primarily outside of standard hours. Like other non-standard working time arrangements, on-call work disrupts sleep and can therefore have negative effects on health, safety and performance. Unlike other non-standard working time arrangements, on-call work often allows sleep opportunities between calls. Any sleep obtained during on-call periods will be beneficial for waking performance. However, there is evidence that sleep while on call may be of substantially reduced restorative value because of the expectation of receiving the call and apprehension about missing the call. In turn, waking from sleep to respond to a call may be associated with temporary increases in performance impairment. This is dependent on characteristics of both the preceding sleep, the tasks required upon waking and the availability and utility of any countermeasures to support the transition from sleep to wake. In this paper, we critically evaluate the evidence both for and against sleeping during on-call periods and conclude that some sleep, even if it is of reduced quality and broken by repeated calls, is a good strategy. We also note, however, that organisations utilising on-call working time arrangements need to systematically manage the likelihood that on-call sleep can be associated with temporary performance impairments upon waking. Given that the majority of work in this area has been laboratory-based, there is a significant need for field-based investigations of the magnitude of sleep inertia, in addition to the utility of sleep inertia countermeasures. Field studies should include working with subject matter experts to identify the real-world impacts of changes in performance associated with sleeping, or not sleeping, whilst on call.

  4. Sleep in the Cape Mole Rat: A Short-Sleeping Subterranean Rodent.

    Science.gov (United States)

    Kruger, Jean-Leigh; Gravett, Nadine; Bhagwandin, Adhil; Bennett, Nigel C; Archer, Elizabeth K; Manger, Paul R

    2016-01-01

    The Cape mole rat Georychus capensis is a solitary subterranean rodent found in the western and southern Cape of South Africa. This approximately 200-gram bathyergid rodent shows a nocturnal circadian rhythm, but sleep in this species is yet to be investigated. Using telemetric recordings of the electroencephalogram (EEG) and electromyogram (EMG) in conjunction with video recordings, we were able to show that the Cape mole rat, like all other rodents, has sleep periods composed of both rapid eye movement (REM) and slow-wave (non-REM) sleep. These mole rats spent on average 15.4 h awake, 7.1 h in non-REM sleep and 1.5 h in REM sleep each day. Cape mole rats sleep substantially less than other similarly sized terrestrial rodents but have a similar percentage of total sleep time occupied by REM sleep. In addition, the duration of both non-REM and REM sleep episodes was markedly shorter in the Cape mole rat than has been observed in terrestrial rodents. Interestingly, these features (total sleep time and episode duration) are similar to those observed in another subterranean bathyergid mole rat, i.e. Fukomys mechowii. Thus, there appears to be a bathyergid type of sleep amongst the rodents that may be related to their environment and the effect of this on their circadian rhythm. Investigating further species of bathyergid mole rats may fully define the emerging picture of sleep in these subterranean African rodents. © 2016 S. Karger AG, Basel.

  5. Habitual Sleep Duration, Unmet Sleep Need, and Excessive Daytime Sleepiness in Korean Adults.

    Science.gov (United States)

    Hwangbo, Young; Kim, Won Joo; Chu, Min Kyung; Yun, Chang Ho; Yang, Kwang Ik

    2016-04-01

    Sleep need differs between individuals, and so the same duration of sleep will lead to sleep insufficiency in some individuals but not others. The aim of this study was to determine the separate and combined associations of both sleep duration and unmet sleep need with excessive daytime sleepiness (EDS) in Korean adults. The participants comprised 2,769 Korean adults aged 19 years or older. They completed questionnaires about their sleep habits over the previous month. The question regarding sleep need was "How much sleep do you need to be at your best during the day?" Unmet sleep need was calculated as sleep need minus habitual sleep duration. Participants with a score of >10 on the Epworth Sleepiness Scale were considered to have EDS. The overall prevalence of EDS was 11.9%. Approximately one-third of the participants (31.9%) reported not getting at least 7 hours of sleep. An unmet sleep need of >0 hours was present in 30.2% of the participants. An adjusted multivariate logistic regression analysis revealed a significant excess risk of EDS in the groups with unmet sleep needs of ≥2 hours [odds ratio (OR), 1.80; 95% confidence interval (CI), 1.27-2.54] and 0.01-2 hours (OR, 1.42; 95% CI, 1.02-1.98). However, habitual sleep duration was not significantly related to EDS. EDS was found to be associated with unmet sleep need but not with habitual sleep duration when both factors were examined together. We suggest that individual unmet sleep need is more important than habitual sleep duration in terms of the relation to EDS.

  6. Sleep-Wake Patterns and Sleep Disturbance among Hong Kong Chinese Adolescents

    OpenAIRE

    Chung, Ka-Fai; Cheung, Miao-Miao

    2008-01-01

    STUDY OBJECTIVES: To determine sleep-wake patterns and evaluate sleep disturbance in Hong Kong adolescents; to identify factors that are associated with sleep disturbance; and to examine the relationship of sleep-wake variables and academic performance. DESIGN AND SETTING: A school-based cross-sectional survey. PARTICIPANTS: Sample included 1629 adolescents aged 12 to 19 years. MEASUREMENTS AND RESULTS: Self-report questionnaires, including sleep-wake habit questionnaire,...

  7. Sleep for cognitive enhancement

    Directory of Open Access Journals (Sweden)

    Susanne eDiekelmann

    2014-04-01

    Full Text Available Sleep is essential for effective cognitive functioning. Loosing even a few hours of sleep can have detrimental effects on a wide variety of cognitive processes such as attention, language, reasoning, decision making, learning and memory. While sleep is necessary to ensure normal healthy cognitive functioning, it can also enhance performance beyond the boundaries of the normal condition. This article discusses the enhancing potential of sleep, mainly focusing on the domain of learning and memory. Sleep is known to facilitate the consolidation of memories learned before sleep as well as the acquisition of new memories to be learned after sleep. According to a widely held model this beneficial effect of sleep relies on the neuronal reactivation of memories during sleep that is associated with sleep-specific brain oscillations (slow oscillations, spindles, ripples as well as a characteristic neurotransmitter milieu. Recent research indicates that memory processing during sleep can be boosted by (i cueing memory reactivation during sleep, (ii stimulating sleep-specific brain oscillations, and (iii targeting specific neurotransmitter systems pharmacologically. Olfactory and auditory cues can be used, for example, to increase reactivation of associated memories during post-learning sleep. Intensifying neocortical slow oscillations (the hallmark of slow wave sleep by electrical or auditory stimulation and modulating specific neurotransmitters such as noradrenaline and glutamate likewise facilitates memory processing during sleep. With this evidence in mind, this article concludes by discussing different methodological caveats and ethical issues that should be considered when thinking about using sleep for cognitive enhancement in everyday applications.

  8. Sleep extension improves neurocognitive functions in chronically sleep-deprived obese individuals.

    Directory of Open Access Journals (Sweden)

    Eliane A Lucassen

    Full Text Available 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.To characterize neurocognitive functions and assess its reversibility.Prospective cohort study.Tertiary Referral Research Clinical Center.A cohort of 121 short-sleeping (<6.5 h/night obese (BMI 30-55 kg/m(2 men and pre-menopausal women.Sleep extension (468±88 days with life-style modifications.Neurocognitive functions, sleep quality and sleep duration.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.Drop-out rate.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.www.ClinicalTrials.gov NCT00261898

  9. Sleep and Physiological Dysregulation: A Closer Look at Sleep Intraindividual Variability.

    Science.gov (United States)

    Bei, Bei; Seeman, Teresa E; Carroll, Judith E; Wiley, Joshua F

    2017-09-01

    Variable daily sleep (ie, higher intraindividual variability; IIV) is associated with negative health consequences, but potential physiological mechanisms are poorly understood. This study examined how the IIV of sleep timing, duration, and quality is associated with physiological dysregulation, with diurnal cortisol trajectories as a proximal outcome and allostatic load (AL) as a multisystem distal outcome. Participants are 436 adults (Mage ± standard deviation = 54.1 ± 11.7, 60.3% women) from the Midlife in the United States study. Sleep was objectively assessed using 7-day actigraphy. Diurnal cortisol was measured via saliva samples (four/day for 4 consecutive days). AL was measured using 23 biomarkers from seven systems (inflammatory, hypothalamic-pituitary-adrenal axis, metabolic glucose and lipid, cardiovascular, parasympathetic, sympathetic) using a validated bifactor model. Linear and quadratic effects of sleep IIV were estimated using a validated Bayesian model. Controlling for covariates, more variable sleep timing (p = .04 for risetime, p = .097 for bedtime) and total sleep time (TST; p = .02), but not mean sleep variables, were associated with flatter cortisol diurnal slope. More variable sleep onset latency and wake after sleep onset, later average bedtime, and shorter TST were associated with higher AL adjusting for age and sex (p-values sleep patterns were associated with blunted diurnal cortisol trajectories but not with higher multisystem physiological dysregulation. The associations between sleep IIV and overall health are likely complex, including multiple biopsychosocial determinants and require further investigation. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  10. Information processing during NREM sleep and sleep quality in insomnia.

    Science.gov (United States)

    Ceklic, Tijana; Bastien, Célyne H

    2015-12-01

    Insomnia sufferers (INS) are cortically hyperaroused during sleep, which seems to translate into altered information processing during nighttime. While information processing, as measured by event-related potentials (ERPs), during wake appears to be associated with sleep quality of the preceding night, the existence of such an association during nighttime has never been investigated. This study aims to investigate nighttime information processing among good sleepers (GS) and INS while considering concomitant sleep quality. Following a multistep clinical evaluation, INS and GS participants underwent 4 consecutive nights of PSG recordings in the sleep laboratory. Thirty nine GS (mean age 34.56±9.02) and twenty nine INS (mean age 43.03±9.12) were included in the study. ERPs (N1, P2, N350) were recorded all night on Night 4 (oddball paradigm) during NREM sleep. Regardless of sleep quality, INS presented a larger N350 amplitude during SWS (p=0.042) while GS showed a larger N350 amplitude during late-night stage 2 sleep (p=0.004). Regardless of diagnosis, those who slept objectively well showed a smaller N350 amplitude (p=0.020) while those who slept subjectively well showed a smaller P2 (pInformation processing seems to be associated with concomitant subjective and objective sleep quality for both GS and INS. However, INS show an alteration in information processing during sleep, especially for inhibition processes, regardless of their sleep quality. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Otolaryngology sleep medicine curriculum objectives as determined by sleep experts.

    Science.gov (United States)

    Cass, Nathan; Kominsky, Alan; Cabrera-Muffly, Cristina

    (1) Ascertain the most important concepts and topics for otolaryngology resident education in sleep medicine and surgery, as determined by faculty who teach sleep medicine to otolaryngology residents. (2) Create learning objectives within the area of otolaryngologic sleep medicine in order to design a sleep medicine curriculum for otolaryngology residents. Two web-based surveys were sent to 163 academic otolaryngologists who teach sleep medicine. The first survey determined the topics, and their relative importance, considered most vital to learn during otolaryngology training. Using the Delphi method, the second clarified questions regarding topics determined by the first survey. Sleep medicine learning objectives for residents were ascertained from responses. The response rate of first and second surveys were 24.5% and 19%, respectively. Topics ranked most important for resident education included upper airway anatomy, polysomnogram interpretation, and understanding the range of medical and surgical therapies used to treat sleep disorders. Respondents listed surgical therapy as the most critical topic that most residents do not understand well. The second survey clarified the specific anatomic features, surgical techniques, and polysomnography data points deemed most critical for resident learning. Academic otolaryngology sleep experts hold opinions regarding relative value of different topics for teaching sleep medicine, which is useful in creating a curriculum for otolaryngology residents. Otolaryngology learning objectives related to sleep medicine identified during this study are being used to create an online curriculum to supplement resident education. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Enhanced succinic acid production in Aspergillus saccharolyticus by heterologous expression of fumarate reductase from Trypanosoma brucei

    DEFF Research Database (Denmark)

    Yang, Lei; Lübeck, Mette; Ahring, Birgitte K.

    2015-01-01

    production medium as well as the complete medium, but the measured enzyme activities were different depending on the media. Furthermore, a soluble NADH-dependent fumarate reductase gene (frd) from Trypanosoma brucei was inserted and expressed in A. saccharolyticus. The expression of the frd gene led......Aspergillus saccharolyticus exhibits great potential as a cell factory for industrial production of dicarboxylic acids. In the analysis of the organic acid profile, A. saccharolyticus was cultivated in an acid production medium using two different pH conditions. The specific activities...... of the enzymes, pyruvate carboxylase (PYC), malate dehydrogenase (MDH), and fumarase (FUM), involved in the reductive tricarboxylic acid (rTCA) branch, were examined and compared in cells harvested from the acid production medium and a complete medium. The results showed that ambient pH had a significant impact...

  13. The Sleeping Cerebellum

    NARCIS (Netherlands)

    Canto, Cathrin B; Onuki, Yoshiyuki; Bruinsma, Bastiaan; van der Werf, Ysbrand D; De Zeeuw, Chris I

    2017-01-01

    We sleep almost one-third of our lives and sleep plays an important role in critical brain functions like memory formation and consolidation. The role of sleep in cerebellar processing, however, constitutes an enigma in the field of neuroscience; we know little about cerebellar sleep-physiology,

  14. The Functions of Sleep

    Directory of Open Access Journals (Sweden)

    Samson Z Assefa

    2015-08-01

    Full Text Available Sleep is a ubiquitous component of animal life including birds and mammals. The exact function of sleep has been one of the mysteries of biology. A considerable number of theories have been put forward to explain the reason(s for the necessity of sleep. To date, while a great deal is known about what happens when animals sleep, there is no definitive comprehensive explanation as to the reason that sleep is an inevitable part of animal functioning. It is well known that sleep is a homeostatically regulated body process, and that prolonged sleep deprivation is fatal in animals. In this paper, we present some of the theories as to the functions of sleep and provide a review of some hypotheses as to the overall physiologic function of sleep. To better understand the purpose for sleeping, we review the effects of sleep deprivation on physical, neurocognitive and psychic function. A better understanding of the purpose for sleeping will be a great advance in our understanding of the nature of the animal kingdom, including our own.

  15. Repeated sleep restriction in rats leads to homeostatic and allostatic responses during recovery sleep.

    Science.gov (United States)

    Kim, Youngsoo; Laposky, Aaron D; Bergmann, Bernard M; Turek, Fred W

    2007-06-19

    Recent studies indicate that chronic sleep restriction can have negative consequences for brain function and peripheral physiology and can contribute to the allostatic load throughout the body. Interestingly, few studies have examined how the sleep-wake system itself responds to repeated sleep restriction. In this study, rats were subjected to a sleep-restriction protocol consisting of 20 h of sleep deprivation (SD) followed by a 4-h sleep opportunity each day for 5 consecutive days. In response to the first 20-h SD block on day 1, animals responded during the 4-h sleep opportunity with enhanced sleep intensity [i.e., nonrapid eye movement (NREM) delta power] and increased rapid eye movement sleep time compared with baseline. This sleep pattern is indicative of a homeostatic response to acute sleep loss. Remarkably, after the 20-h SD blocks on days 2-5, animals failed to exhibit a compensatory NREM delta power response during the 4-h sleep opportunities and failed to increase NREM and rapid eye movement sleep times, despite accumulating a sleep debt each consecutive day. After losing approximately 35 h of sleep over 5 days of sleep restriction, animals regained virtually none of their lost sleep, even during a full 3-day recovery period. These data demonstrate that the compensatory/homeostatic sleep response to acute SD does not generalize to conditions of chronic partial sleep loss. We propose that the change in sleep-wake regulation in the context of repeated sleep restriction reflects an allostatic process, and that the allostatic load produced by SD has direct effects on the sleep-wake regulatory system.

  16. Sleep: A Health Imperative

    Science.gov (United States)

    Luyster, Faith S.; Strollo, Patrick J.; Zee, Phyllis C.; Walsh, James K.

    2012-01-01

    Chronic sleep deficiency, defined as a state of inadequate or mistimed sleep, is a growing and underappreciated determinant of health status. Sleep deprivation contributes to a number of molecular, immune, and neural changes that play a role in disease development, independent of primary sleep disorders. These changes in biological processes in response to chronic sleep deficiency may serve as etiological factors for the development and exacerbation of cardiovascular and metabolic diseases and, ultimately, a shortened lifespan. Sleep deprivation also results in significant impairments in cognitive and motor performance which increase the risk of motor vehicle crashes and work-related injuries and fatal accidents. The American Academy of Sleep Medicine and the Sleep Research Society have developed this statement to communicate to national health stakeholders the current knowledge which ties sufficient sleep and circadian alignment in adults to health. Citation: Luyster FS; Strollo PJ; Zee PC; Walsh JK. Sleep: a health imperative. SLEEP 2012;35(6):727-734. PMID:22654183

  17. Sleep inertia, sleep homeostatic and circadian influences on higher-order cognitive functions.

    Science.gov (United States)

    Burke, Tina M; Scheer, Frank A J L; Ronda, Joseph M; Czeisler, Charles A; Wright, Kenneth P

    2015-08-01

    Sleep inertia, sleep homeostatic and circadian processes modulate cognition, including reaction time, memory, mood and alertness. How these processes influence higher-order cognitive functions is not well known. Six participants completed a 73-day-long study that included two 14-day-long 28-h forced desynchrony protocols to examine separate and interacting influences of sleep inertia, sleep homeostasis and circadian phase on higher-order cognitive functions of inhibitory control and selective visual attention. Cognitive performance for most measures was impaired immediately after scheduled awakening and improved during the first ~2-4 h of wakefulness (decreasing sleep inertia); worsened thereafter until scheduled bedtime (increasing sleep homeostasis); and was worst at ~60° and best at ~240° (circadian modulation, with worst and best phases corresponding to ~09:00 and ~21:00 hours, respectively, in individuals with a habitual wake time of 07:00 hours). The relative influences of sleep inertia, sleep homeostasis and circadian phase depended on the specific higher-order cognitive function task examined. Inhibitory control appeared to be modulated most strongly by circadian phase, whereas selective visual attention for a spatial-configuration search task was modulated most strongly by sleep inertia. These findings demonstrate that some higher-order cognitive processes are differentially sensitive to different sleep-wake regulatory processes. Differential modulation of cognitive functions by different sleep-wake regulatory processes has important implications for understanding mechanisms contributing to performance impairments during adverse circadian phases, sleep deprivation and/or upon awakening from sleep. © 2015 European Sleep Research Society.

  18. Sleep Apnea (For Parents)

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Obstructive Sleep Apnea KidsHealth / For Parents / Obstructive Sleep Apnea What's ... How Is Sleep Apnea Treated? Print What Is Sleep Apnea? Brief pauses in breathing during sleep are ...

  19. Understanding the role of sleep quality and sleep duration in commercial driving safety.

    Science.gov (United States)

    Lemke, Michael K; Apostolopoulos, Yorghos; Hege, Adam; Sönmez, Sevil; Wideman, Laurie

    2016-12-01

    Long-haul truck drivers in the United States suffer disproportionately high injury rates. Sleep is a critical factor in these outcomes, contributing to fatigue and degrading multiple aspects of safety-relevant performance. Both sleep duration and sleep quality are often compromised among truck drivers; however, much of the efforts to combat fatigue focus on sleep duration rather than sleep quality. Thus, the current study has two objectives: (1) to determine the degree to which sleep impacts safety-relevant performance among long-haul truck drivers; and (2) to evaluate workday and non-workday sleep quality and duration as predictors of drivers' safety-relevant performance. A non-experimental, descriptive, cross-sectional design was employed to collect survey and biometric data from 260 long-haul truck drivers. The Trucker Sleep Disorders Survey was developed to assess sleep duration and quality, the impact of sleep on job performance and accident risk, and other relevant work organization characteristics. Descriptive statistics assessed work organization variables, sleep duration and quality, and frequency of engaging in safety-relevant performance while sleepy. Linear regression analyses were conducted to evaluate relationships between sleep duration, sleep quality, and work organization variables with safety composite variables. Drivers reported long work hours, with over 70% of drivers working more than 11h daily. Drivers also reported a large number of miles driven per week, with an average of 2,812.61 miles per week, and frequent violations of hours-of-service rules, with 43.8% of drivers "sometimes to always" violating the "14-h rule." Sleep duration was longer, and sleep quality was better, on non-workdays compared on workdays. Drivers frequently operated motor vehicles while sleepy, and sleepiness impacted several aspects of safety-relevant performance. Sleep quality was better associated with driving while sleepy and with job performance and concentration

  20. Sleep Disturbances in Newborns

    OpenAIRE

    Yasova Barbeau, Daphna; Weiss, Michael D.

    2017-01-01

    The purpose of this review is to serve as an introduction to understanding sleep in the fetus, the preterm neonate and the term neonate. Sleep appears to have numerous important roles, particularly in the consolidation of new information. The sleep cycle changes over time, neonates spend the most time in active sleep and have a progressive shortening of active sleep and lengthening of quiet sleep. Additionally, the sleep cycle is disrupted by many things including disease state and environmen...

  1. Sleeping to fuel the immune system: mammalian sleep and resistance to parasites

    Directory of Open Access Journals (Sweden)

    Opp Mark R

    2009-01-01

    Full Text Available Abstract Sleep is an enigma. Why animals forgo eating and reproducing, while potentially increasing their risk of predation remains unknown. Although some may question whether all animals sleep, it is clear that all living organisms possess defenses against attack by pathogens. Immune responses of humans and animals are impaired by sleep loss, and responses to immune challenge include altered sleep. Thus, sleep is hypothesized to be a component of the acute phase response to infection and to function in host defense. Examining phylogenetic relationships among sleep parameters, components of the mammalian immune system and resistance to infection may provide insight into the evolution of sleep and lead to a greater appreciation for the role of sleep in host defense.

  2. Sleep problems and obstructive sleep apnea in children with down syndrome, an overwiew.

    Science.gov (United States)

    Maris, Mieke; Verhulst, Stijn; Wojciechowski, Marek; Van de Heyning, Paul; Boudewyns, An

    2016-03-01

    Children with Down syndrome (DS) have a high prevalence of sleep problems, including behavioural sleep disturbances and obstructive sleep apnea. Sleep problems are associated with a wide range of adverse health effects. Since children with DS are already known to have many comorbidities, they are particularly susceptible for the negative impact of sleep problems. Aim of this study is (1) to evaluate the prevalence of sleep problems in children with DS, (2) compare the prevalence of sleep problems in children with DS with a community sample of typical developing school-aged children, and (3) to correlate the existence of sleep problems in children with DS and OSA. Children enrolled at the multidisciplinary Down team of the University Hospital Antwerp and seen at the ENT department were eligible for this study. The prevalence of sleep problems was evaluated by the use of the Child Sleep Habits Questionnaire (CSHQ) and a full overnight polysomnography was performed to screen for obstructive sleep apnea. Parents of fifty-four children with DS, aged 7.5 years (5.4-11.6), completed the CSHQ and an overall prevalence of sleep problems was found in 74.1%. In 57.1% of the children OSA was diagnosed with a median obstructive apnea-hypopnea index (oAHI) 7.25/h (5.7-9.8). Overall sleep problems were not age-or gender related, however boys suffer more from daytime sleepiness. Symptoms of sleep disordered breathing correlate with parasomnias, a longer sleep duration and more daytime sleepiness. No correlation was found between sleep problems and underlying OSA. Children with Down syndrome have a significantly higher prevalence of sleep problems, compared to normal developing healthy school-aged children. We didn't find any correlation between the parental report of sleep problems and underlying OSA, or OSA severity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Effects of Sleep Hygiene Education on Subjective Sleep Quality and Academic Performance

    OpenAIRE

    Erkan Sahin

    2014-01-01

    Aim: Sleep problems are common in students with one third of university students reporting insufficient sleep. It is known that sleep quality and daytime sleepiness cause decrasing academic performans. For this reason we aimed to investigate the effects of a sleep hygiene education on sleep quality and academic performance of first year medical students. Material and Method: Self-reported sleep data and academic performance of 131 first grade medical students were collected. To all students e...

  4. Sleep in Elite Athletes and Nutritional Interventions to Enhance Sleep

    OpenAIRE

    Halson, Shona L.

    2014-01-01

    Sleep has numerous important physiological and cognitive functions that may be particularly important to elite athletes. Recent evidence, as well as anecdotal information, suggests that athletes may experience a reduced quality and/or quantity of sleep. Sleep deprivation can have significant effects on athletic performance, especially submaximal, prolonged exercise. Compromised sleep may also influence learning, memory, cognition, pain perception, immunity and inflammation. Furthermore, chang...

  5. Sleep quality and sleep associated problems in female pharmacy students

    Directory of Open Access Journals (Sweden)

    Vivek Jain

    2013-01-01

    Full Text Available Background: Sleep is an essential element for adolescent mental and physical growth and development, but today′s young adolescents are deprived of this. Earlier studies in Europe and America showed pitiable sleep quality of young college students, which affect their academic growth. However, as per our literature search there is a lack of such studies in Indian context especially, within pharmacy education. Objective: The present study was designed to investigate the interrelation between the demographic characteristics, life-style, and academic progress with sleep quality and sleep problems along with daytime and nighttime habits in young female pharmacy students of India. Materials and Methods: Questionnaire on sleep and daytime habits (QS and DH was prepared. Our sample survey consists of 226 female pharmacy students of Banasthali University. QS and DH of multiple choice type, covered demographic characteristic (3 questions sleep and daytime habits (25 questions, life-style and academic progress (3 questions, and one question of course curriculum. Parameters were co-related by point scale method using the SPSS 16.0 software. Results: Data derived and analyze from survey illustrated that quality of sleep was as: Excellent - 20.4%, good - 38.5%, satisfactory - 35.8%, poor - 4%, and very poor - 1.3% of participants. Living condition (ρ=0.168, P =0.011, academic progress (ρ=0.151, P=0.023, leisure activity (ρ=0.133, P<0.05, and daytime naps (ρ=0.160, P=0.016 were significantly correlated with sleep quality. In addition, daytime sleepiness caused a significant problem for students and created a number of sleep disorders. Nevertheless, Sleep quality was not associated with age, body mass index, and coffee in the late evening. Conclusion: Study reported that sleep associated problems were common complaints in female pharmacy students.

  6. Late Sleeping Affects Sleep Duration and Body Mass Index in Adolescents

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    Rajesh G.Kathrotia1,

    2010-03-01

    Full Text Available During adolescence, there is a tendency to sleep late andsleep less because of altered psychosocial and life-stylechanges. Recent studies have demonstrated the link betweensleeping less and gaining weight in children, adolescents, andadults. We studied the effect of late sleeping and sleepingless on body mass index (BMI in medical college freshmen.All participants were adolescents (104 male and 38 femaleadolescents, mean age 17.77±0.79 years. After obtaininginformed consent, they filled out a questionnaire about theirsleeping habits. Height and weight were measured after abrief history taking and clinical examination. BMI increasedsignificantly with decrease in total sleep duration and withdelayed bedtime. Late sleeping individuals (after midnighthad significantly less sleep duration (6.78 hours v 7.74 hours,P<0.001, more day time sleepiness (85.2% v 69.3%,P=0.033 and more gap between dinner time and going tosleep (234.16 min v 155.45 min, P<0.001. Increased BMI inlate sleepers may be explained by low physical activity duringthe day caused by excess sleepiness and increased calorieintake with a gap of 5-6 hours between dinner and sleep.Sleep habits of late sleeping and sleeping less contribute toincrease BMI in adolescents.

  7. Sleep disturbances in Parkinsonism.

    Science.gov (United States)

    Askenasy, J J M

    2003-02-01

    The present article is meant to suggest an approach to the guidelines for the therapy of sleep disturbances in Parkinson's Disease (PD) patients.The factors affecting the quality of life in PD patients are depression, sleep disturbances and dependence. A large review of the literature on sleep disturbances in PD patients, provided the basis for the following classification of the sleep-arousal disturbances in PD patients. We suggest a model based on 3 steps in the treatment of sleep disturbances in PD patients. This model allowing the patient, the spouse or the caregiver a quiet sleep at night, may postpone the retirement and the institutionalization of the PD patient. I. Correct diagnosis of sleep disorders based on detailed anamnesis of the patient and of the spouse or of the caregiver. One week recording on a symptom diary (log) by the patient or the caregiver. Correct diagnosis of sleep disorders co morbidities. Selection of the most appropriate sleep test among: polysomnography (PSG), multiple sleep latency test (MSLT), multiple wake latency test (MWLT), Epworth Sleepiness Scale, actigraphy or video-PSG. II. The nonspecific therapeutic approach consists in: a) Checking the sleep effect on motor performance, is it beneficial, worse or neutral. b) Psycho-physical assistance. c) Dopaminergic adjustment is necessary owing to the progression of the nigrostriatal degeneration and the increased sensitivity of the terminals, which alter the normal modulator mechanisms of the motor centers in PD patients. Among the many neurotransmitters of the nigro-striatal pathway one can distinguish two with a major influence on REM and NonREM sleep. REM sleep corresponds to an increased cholinergic receptor activity and a decreased dopaminergic activity. This is the reason why REM sleep deprivation by suppressing cholinergic receptor activity ameliorates PD motor symptoms. L-Dopa and its agonists by suppressing cholinergic receptors suppress REM sleep. The permanent adjustment

  8. Adenosine and sleep

    International Nuclear Information System (INIS)

    Yanik, G.M. Jr.

    1987-01-01

    Behavioral and biochemical approaches have been used to determine the relative contribution of endogenous adenosine and adenosine receptors to the sleep-wake cycle in the rat. Adenosine concentrations in specific areas of the rat brain were not affected by 24 hours of total sleep deprivation, or by 24 or 48 hours of REM sleep deprivation. In order to assess the effect of REM sleep deprivation on adenosine A 1 receptors, 3 H-L-PIA binding was measured. The Bmax values for 3 H-L-PIA binding to membrane preparations of the cortices and corpus striata from 48 hour REM sleep-deprived animals were increased 14.8% and 23%, respectively. These increases were not maintained following the cessation of sleep deprivation and recovered within 2 hours. The results of a 96 hour REM deprivation experiment were similar to those of the 48 hour REM sleep deprivation experiment. However, these increases were not evident in similar structures taken from stress control animals, and conclusively demonstrated that the changes in 3 H-L-PIA binding resulted from REM sleep deprivation and not from stress

  9. RNA interference analyses suggest a transcript-specific regulatory role for mitochondrial RNA-binding proteins MRP1 and MRP2 in RNA editing and other RNA processing in Trypanosoma brucei

    NARCIS (Netherlands)

    Vondrusková, Eva; van den Burg, Janny; Zíková, Alena; Ernst, Nancy Lewis; Stuart, Kenneth; Benne, Rob; Lukes, Julius

    2005-01-01

    Mitochondrial RNA-binding proteins MRP1 and MRP2 occur in a heteromeric complex that appears to play a role in U-insertion/deletion editing in trypanosomes. Reduction in the levels of MRP1 (gBP21) and/or MRP2 (gBP25) mRNA by RNA interference in procyclic Trypanosoma brucei resulted in severe growth

  10. Medicines for sleep

    Science.gov (United States)

    Benzodiazepines; Sedatives; Hypnotics; Sleeping pills; Insomnia - medicines; Sleep disorder - medicines ... are commonly used to treat allergies. While these sleep aids are not addictive, your body becomes used ...

  11. Astrocytic modulation of sleep homeostasis and cognitive consequences of sleep loss.

    Science.gov (United States)

    Halassa, Michael M; Florian, Cedrick; Fellin, Tommaso; Munoz, James R; Lee, So-Young; Abel, Ted; Haydon, Philip G; Frank, Marcos G

    2009-01-29

    Astrocytes modulate neuronal activity by releasing chemical transmitters via a process termed gliotransmission. The role of this process in the control of behavior is unknown. Since one outcome of SNARE-dependent gliotransmission is the regulation of extracellular adenosine and because adenosine promotes sleep, we genetically inhibited the release of gliotransmitters and asked if astrocytes play an unsuspected role in sleep regulation. Inhibiting gliotransmission attenuated the accumulation of sleep pressure, assessed by measuring the slow wave activity of the EEG during NREM sleep, and prevented cognitive deficits associated with sleep loss. Since the sleep-suppressing effects of the A1 receptor antagonist CPT were prevented following inhibition of gliotransmission and because intracerebroventricular delivery of CPT to wild-type mice mimicked the transgenic phenotype, we conclude that astrocytes modulate the accumulation of sleep pressure and its cognitive consequences through a pathway involving A1 receptors.

  12. Modulation of Sleep Homeostasis by Corticotropin Releasing Hormone in REM Sleep-Deprived Rats

    Directory of Open Access Journals (Sweden)

    Ricardo Borges Machado

    2010-01-01

    Full Text Available Studies have shown that sleep recovery following different protocols of forced waking varies according to the level of stress inherent to each method. Sleep deprivation activates the hypothalamic-pituitary-adrenal axis and increased corticotropin-releasing hormone (CRH impairs sleep. The purpose of the present study was to evaluate how manipulations of the CRH system during the sleep deprivation period interferes with subsequent sleep rebound. Throughout 96 hours of sleep deprivation, separate groups of rats were treated i.c.v. with vehicle, CRH or with alphahelical CRH9−41, a CRH receptor blocker, twice/day, at 07:00 h and 19:00 h. Both treatments impaired sleep homeostasis, especially in regards to length of rapid eye movement sleep (REM and theta/delta ratio and induced a later decrease in NREM and REM sleep and increased waking bouts. These changes suggest that activation of the CRH system impact negatively on the homeostatic sleep response to prolonged forced waking. These results indicate that indeed, activation of the HPA axis—at least at the hypothalamic level—is capable to reduce the sleep rebound induced by sleep deprivation.

  13. Neural Plasticity Is Involved in Physiological Sleep, Depressive Sleep Disturbances, and Antidepressant Treatments

    Directory of Open Access Journals (Sweden)

    Meng-Qi Zhang

    2017-01-01

    Full Text Available Depression, which is characterized by a pervasive and persistent low mood and anhedonia, greatly impacts patients, their families, and society. The associated and recurring sleep disturbances further reduce patient’s quality of life. However, therapeutic sleep deprivation has been regarded as a rapid and robust antidepressant treatment for several decades, which suggests a complicated role of sleep in development of depression. Changes in neural plasticity are observed during physiological sleep, therapeutic sleep deprivation, and depression. This correlation might help us to understand better the mechanism underlying development of depression and the role of sleep. In this review, we first introduce the structure of sleep and the facilitated neural plasticity caused by physiological sleep. Then, we introduce sleep disturbances and changes in plasticity in patients with depression. Finally, the effects and mechanisms of antidepressants and therapeutic sleep deprivation on neural plasticity are discussed.

  14. Sleep from an Islamic perspective.

    Science.gov (United States)

    Bahammam, Ahmed S

    2011-10-01

    Sleep medicine is a relatively new scientific specialty. Sleep is an important topic in Islamic literature, and the Quran and Hadith discuss types of sleep, the importance of sleep, and good sleep practices. Islam considers sleep as one of the signs of the greatness of Allνh (God) and encourages followers to explore this important sign. The Quran describes different types of sleep, and these correspond with sleep stages identified by modern science. The Quran discusses the beneficial effects of sleep and emphasizes the importance of maintaining a pattern of light and darkness. A mid-day nap is an important practice for Muslims, and the Prophet Muhammad peace be upon him (pbuh) promoted naps as beneficial. In accordance with the practice and instructions of Muhammad (pbuh), Muslims have certain sleep habits and these sleep habits correspond to some of the sleep hygiene rules identified by modern science. Details during sleep include sleep position, like encouraging sleep on the right side and discouraging sleep in the prone position. Dream interpretation is an established science in the Islamic literature and Islamic scholars have made significant contributions to theories of dream interpretation. We suggest that sleep scientists examine religious literature in general and Islamic literature in particular, to understand the views, behaviors, and practices of ancient people about the sleep and sleep disorders. Such studies may help to answer some unresolved questions in sleep science or lead to new areas of inquiry.

  15. Sleep from an islamic perspective

    Directory of Open Access Journals (Sweden)

    Ahmed S BaHammam

    2011-01-01

    Full Text Available Sleep medicine is a relatively new scientific specialty. Sleep is an important topic in Islamic literature, and the Quran and Hadith discuss types of sleep, the importance of sleep, and good sleep practices. Islam considers sleep as one of the signs of the greatness of Allβh (God and encourages followers to explore this important sign. The Quran describes different types of sleep, and these correspond with sleep stages identified by modern science. The Quran discusses the beneficial effects of sleep and emphasizes the importance of maintaining a pattern of light and darkness. A mid-day nap is an important practice for Muslims, and the Prophet Muhammad peace be upon him (pbuh promoted naps as beneficial. In accordance with the practice and instructions of Muhammad (pbuh, Muslims have certain sleep habits and these sleep habits correspond to some of the sleep hygiene rules identified by modern science. Details during sleep include sleep position, like encouraging sleep on the right side and discouraging sleep in the prone position. Dream interpretation is an established science in the Islamic literature and Islamic scholars have made significant contributions to theories of dream interpretation. We suggest that sleep scientists examine religious literature in general and Islamic literature in particular, to understand the views, behaviors, and practices of ancient people about the sleep and sleep disorders. Such studies may help to answer some unresolved questions in sleep science or lead to new areas of inquiry.

  16. The role of sleep duration and sleep disordered breathing in gestational diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Joshua J. Gooley

    2018-01-01

    Full Text Available Many women experience sleep problems during pregnancy. This includes difficulty initiating and maintaining sleep due to physiologic changes that occur as pregnancy progresses, as well as increased symptoms of sleep-disordered breathing (SDB. Growing evidence indicates that sleep deficiency alters glucose metabolism and increases risk of diabetes. Poor sleep may exacerbate the progressive increase in insulin resistance that normally occurs during pregnancy, thus contributing to the development of maternal hyperglycemia. Here, we critically review evidence that exposure to short sleep duration or SDB during pregnancy is associated with gestational diabetes mellitus (GDM. Several studies have found that the frequency of GDM is higher in women exposed to short sleep compared with longer sleep durations. Despite mixed evidence regarding whether symptoms of SDB (e.g., frequent snoring are associated with GDM after adjusting for BMI or obesity, it has been shown that clinically-diagnosed SDB is prospectively associated with GDM. There are multiple mechanisms that may link sleep deprivation and SDB with insulin resistance, including increased levels of oxidative stress, inflammation, sympathetic activity, and cortisol. Despite emerging evidence that sleep deficiency and SDB are associated with increased risk of GDM, it has yet to be demonstrated that improving sleep in pregnant women (e.g., by extending sleep duration or treating SDB protects against the development of hyperglycemia. If a causal relationship can be established, behavioral therapies for improving sleep can potentially be used to reduce the risk and burden of GDM. Keywords: Pregnancy, Sleep duration, Sleep disordered breathing, Gestational diabetes, Women, Metabolism

  17. Rapid Eye Movement Sleep, Sleep Continuity and Slow Wave Sleep as Predictors of Cognition, Mood, and Subjective Sleep Quality in Healthy Men and Women, Aged 20–84 Years

    Directory of Open Access Journals (Sweden)

    Ciro della Monica

    2018-06-01

    Full Text Available Sleep and its sub-states are assumed to be important for brain function across the lifespan but which aspects of sleep associate with various aspects of cognition, mood and self-reported sleep quality has not yet been established in detail. Sleep was quantified by polysomnography, quantitative Electroencephalogram (EEG analysis and self-report in 206 healthy men and women, aged 20–84 years, without sleep complaints. Waking brain function was quantified by five assessments scheduled across the day covering objectively assessed performance across cognitive domains including sustained attention and arousal, decision and response time, motor and sequence control, working memory, and executive function as well as self-reports of alertness, mood and affect. Controlled for age and sex, self-reported sleep quality was negatively associated with number of awakenings and positively associated with the duration of Rapid Eye Movement (REM sleep, but no significant associations with Slow Wave Sleep (SWS measures were observed. Controlling only for age showed that associations between objective and subjective sleep quality were much stronger in women than in men. Analysis of 51 performance measures demonstrated that, after controlling for age and sex, fewer awakenings and more REM sleep were associated significantly with better performance on the Goal Neglect task, which is a test of executive function. Factor analysis of the individual performance measures identified four latent variables labeled Mood/Arousal, Response Time, Accuracy, and Visual Perceptual Sensitivity. Whereas Mood/Arousal improved with age, Response Times became slower, while Accuracy and Visual perceptual sensitivity showed little change with age. After controlling for sex and age, nominally significant association between sleep and factor scores were observed such that Response Times were faster with more SWS, and Accuracy was reduced where individuals woke more often or had less REM

  18. Sleep board review questions: sleep disordered breathing that improves in REM

    Directory of Open Access Journals (Sweden)

    Budhiraja R

    2012-08-01

    Full Text Available No abstract available. Article truncated at end of question. Which of the following breathing disorders is usually less severe in rapid eye movement (REM sleep compared to non-rapid eye movement (NREM sleep?1.Sleep-related hypoxemia in COPD2.Obstructive Sleep Apnea3.Cheyne Stokes Breathing4.Hypoxemia in Pulmonary Hypertension

  19. Sleep and Metabolism: An Overview

    Directory of Open Access Journals (Sweden)

    Sunil Sharma

    2010-01-01

    Full Text Available Sleep and its disorders are increasingly becoming important in our sleep deprived society. Sleep is intricately connected to various hormonal and metabolic processes in the body and is important in maintaining metabolic homeostasis. Research shows that sleep deprivation and sleep disorders may have profound metabolic and cardiovascular implications. Sleep deprivation, sleep disordered breathing, and circadian misalignment are believed to cause metabolic dysregulation through myriad pathways involving sympathetic overstimulation, hormonal imbalance, and subclinical inflammation. This paper reviews sleep and metabolism, and how sleep deprivation and sleep disorders may be altering human metabolism.

  20. Sleep loss and accidents--work hours, life style, and sleep pathology.

    Science.gov (United States)

    Akerstedt, Torbjörn; Philip, Pierre; Capelli, Aurore; Kecklund, Göran

    2011-01-01

    A very important outcome of reduced sleep is accidents. The present chapter will attempt to bring together some of the present knowledge in this area. We will focus on the driving situation, for which the evidence of the link between sleep loss and accidents is quite well established, but we will also bring up working life in general where evidence is more sparse. It should be emphasized that reduced sleep as a cause of accidents implies that the mediating factor is sleepiness (or fatigue). This link is discussed elsewhere in this volume, but here we will bring in sleepiness (subjective or physiological) as an explanatory factor of accidents. Another central observation is that many real life accident studies do not link accidents to reduced sleep, but infer reduced sleep and/or sleepiness from the context, like, for example, from work schedules, life styles, or sleep pathology. Reduced sleep is mainly due to suboptimal work schedules (or to a suboptimal life style) or to sleep pathology. We have divided the present chapter into two areas. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Sleep spindles predict stress-related increases in sleep disturbances

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    Thien Thanh eDang-Vu

    2015-02-01

    Full Text Available Background and Aim: Predisposing factors place certain individuals at higher risk for insomnia, especially in the presence of precipitating conditions such as stressful life events. Sleep spindles have been shown to play an important role in the preservation of sleep continuity. Lower spindle density might thus constitute an objective predisposing factor for sleep reactivity to stress. The aim of this study was therefore to evaluate the relationship between baseline sleep spindle density and the prospective change in insomnia symptoms in response to a standardized academic stressor. Methods: 12 healthy students had a polysomnography (PSG recording during a period of lower stress at the beginning of the academic semester, along with an assessment of insomnia complaints using the Insomnia Severity Index (ISI. They completed a second ISI assessment at the end of the semester, a period coinciding with the week prior to final examinations and thus higher stress. Spindle density, amplitude, duration and frequency, as well as sigma power were computed from C4-O2 electroencephalography (EEG derivation during stages N2-N3 of non-rapid-eye-movement (NREM sleep, across the whole night and for each NREM sleep period. To test for the relationship between spindle density and changes in insomnia symptoms in response to academic stress, spindle measurements at baseline were correlated with changes in ISI across the academic semester.Results: Spindle density (as well as spindle amplitude and sigma power, particularly during the first NREM sleep period, negatively correlated with changes in ISI (p < 0.05. Conclusion: Lower spindle activity, especially at the beginning of the night, prospectively predicted larger increases in insomnia symptoms in response to stress. This result indicates that individual differences in sleep spindle activity contribute to the differential vulnerability to sleep disturbances in the face of precipitating factors.

  2. Sleep disturbances in patients with major depressive disorder: incongruence between sleep log and actigraphy.

    Science.gov (United States)

    Kung, Pei-Ying; Chou, Kuei-Ru; Lin, Kuan-Chia; Hsu, Hsin-Wei; Chung, Min-Huey

    2015-02-01

    Depression has become a severe global health problem, and sleeping difficulties are typically associated with depression. The purpose of this study was to investigate the relationships among subjective sleep quality, objective sleep quality, and the sleep hygiene practices of hospitalized patients with major depressive disorder. Daily sleep logs and actigraphy were used to obtain subjective and objective sleep data. Thirty patients were recruited from a regional teaching hospital in Taipei and completed the Hamilton Rating Scale for Depression and the Sleep Hygiene Practice Scale. Significant differences were found between subjective and objective sleep data in patients with major depressive disorder (MDD). For patients with more severe depression, subjective measurements obtained using sleep logs, such as total sleep time and sleep efficiency, were significantly lower than those obtained using actigraphy by controlling for demographics. The results regarding the differences between subjective and objective sleep data can be a reference for care providers when comforting depression patients who complain of sleep disturbance. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Topical review: sleep bruxism, headaches, and sleep-disordered breathing in children and adolescents.

    Science.gov (United States)

    Carra, Maria Clotilde; Bruni, Olivero; Huynh, Nelly

    2012-01-01

    Sleep bruxism, a well-known burden for dentists, is commonly observed in pediatric populations. Dentists are responsible for the detection and prevention of the detrimental consequences on the stomatognathic system that may occur in some patients with sleep bruxism. However, sleep bruxism is much more than tooth wear, since it is frequently associated with orofacial pain, headaches, and other more severe sleep disorders, such as sleep-disordered breathing. Although the mechanisms underlying the possible interactions among sleep bruxism, headaches, and sleep-disordered breathing need further research, these conditions are often concomitant. A literature search was performed to identify relevant publications related to the topic, which have been integrated in this topical review. The aim of this article was to provide a brief overview on sleep bruxism, headaches, and sleep-disordered breathing in pediatric patients and to promote a multispecialist approach (including dentists, sleep specialist physicians, and psychologists) in the diagnosis and management of these frequently associated disorders.

  4. Sleep is not just for the brain: transcriptional responses to sleep in peripheral tissues

    Science.gov (United States)

    2013-01-01

    Background Many have assumed that the primary function of sleep is for the brain. We evaluated the molecular consequences of sleep and sleep deprivation outside the brain, in heart and lung. Using microarrays we compared gene expression in tissue from sleeping and sleep deprived mice euthanized at the same diurnal times. Results In each tissue, nearly two thousand genes demonstrated statistically significant differential expression as a function of sleep/wake behavioral state. To mitigate the influence of an artificial deprivation protocol, we identified a subset of these transcripts as specifically sleep-enhanced or sleep-repressed by requiring that their expression also change over the course of unperturbed sleep. 3% and 6% of the assayed transcripts showed “sleep specific” changes in the lung and heart respectively. Sleep specific transcripts in these tissues demonstrated highly significant overlap and shared temporal dynamics. Markers of cellular stress and the unfolded protein response were reduced during sleep in both tissues. These results mirror previous findings in brain. Sleep-enhanced pathways reflected the unique metabolic functions of each tissue. Transcripts related to carbohydrate and sulfur metabolic processes were enhanced by sleep in the lung, and collectively favor buffering from oxidative stress. DNA repair and protein metabolism annotations were significantly enriched among the sleep-enhanced transcripts in the heart. Our results also suggest that sleep may provide a Zeitgeber, or synchronizing cue, in the lung as a large cluster of transcripts demonstrated systematic changes in inter-animal variability as a function of both sleep duration and circadian time. Conclusion Our data support the notion that the molecular consequences of sleep/wake behavioral state extend beyond the brain to include peripheral tissues. Sleep state induces a highly overlapping response in both heart and lung. We conclude that sleep enhances organ specific

  5. Sleep is not just for the brain: transcriptional responses to sleep in peripheral tissues.

    Science.gov (United States)

    Anafi, Ron C; Pellegrino, Renata; Shockley, Keith R; Romer, Micah; Tufik, Sergio; Pack, Allan I

    2013-05-30

    Many have assumed that the primary function of sleep is for the brain. We evaluated the molecular consequences of sleep and sleep deprivation outside the brain, in heart and lung. Using microarrays we compared gene expression in tissue from sleeping and sleep deprived mice euthanized at the same diurnal times. In each tissue, nearly two thousand genes demonstrated statistically significant differential expression as a function of sleep/wake behavioral state. To mitigate the influence of an artificial deprivation protocol, we identified a subset of these transcripts as specifically sleep-enhanced or sleep-repressed by requiring that their expression also change over the course of unperturbed sleep. 3% and 6% of the assayed transcripts showed "sleep specific" changes in the lung and heart respectively. Sleep specific transcripts in these tissues demonstrated highly significant overlap and shared temporal dynamics. Markers of cellular stress and the unfolded protein response were reduced during sleep in both tissues. These results mirror previous findings in brain. Sleep-enhanced pathways reflected the unique metabolic functions of each tissue. Transcripts related to carbohydrate and sulfur metabolic processes were enhanced by sleep in the lung, and collectively favor buffering from oxidative stress. DNA repair and protein metabolism annotations were significantly enriched among the sleep-enhanced transcripts in the heart. Our results also suggest that sleep may provide a Zeitgeber, or synchronizing cue, in the lung as a large cluster of transcripts demonstrated systematic changes in inter-animal variability as a function of both sleep duration and circadian time. Our data support the notion that the molecular consequences of sleep/wake behavioral state extend beyond the brain to include peripheral tissues. Sleep state induces a highly overlapping response in both heart and lung. We conclude that sleep enhances organ specific molecular functions and that it has a

  6. Sleep and inflammatory bowel disease: exploring the relationship between sleep disturbances and inflammation.

    Science.gov (United States)

    Kinnucan, Jami A; Rubin, David T; Ali, Tauseef

    2013-11-01

    Sleep disturbances are associated with a greater risk of serious adverse health events, economic consequences, and, most importantly, increased all-cause mortality. Several studies support the associations among sleep, immune function, and inflammation. The relationship between sleep disturbances and inflammatory conditions is complex and not completely understood. Sleep deprivation can lead to increased levels of inflammatory cytokines, including interleukin (IL)-1β IL-6, tumor necrosis factor-α and C-reactive protein, which can lead to further activation of the inflammatory cascade. The relevance of sleep in inflammatory bowel disease (IBD), a chronic immune-mediated inflammatory disease of the gastrointestinal tract, has recently received more attention. Several studies have shown that patients with both inactive and active IBD have self-reported sleep disturbances. Here, we present a concise review of sleep and its association with the immune system and the process of inflammation. We discuss the studies that have evaluated sleep in patients with IBD as well as possible treatment options for those patients with sleep disturbances. An algorithm for evaluating sleep disturbances in the IBD population is also proposed. Further research is still needed to better characterize sleep disturbances in the IBD population as well as to assess the effects of various therapeutic interventions to improve sleep quality. It is possible that the diagnosis and treatment of sleep disturbances in this population may provide an opportunity to alter disease outcomes.

  7. Development of Home-Based Sleep Monitoring System for Obstructive Sleep Apnea.

    Science.gov (United States)

    Wu, Peirong; Chen, Guan-Ting; Cui, Yanyan; Li, Jin-Wei; Kuo, Terry B J; Chang, Polun

    2017-01-01

    Obstructive Sleep Apnea (OSA) has been proven to increase the risk of high blood pressure, heart attack, stroke, obesity, and diabetes. If people would like to know whether they are suffering from this sleep disorder, they need to go to particular hospital with which a sleep center that could perform polysomnography (PSG); however, for most people, this is not convenient. Consequently, the goal of this study is to develop a convenient, lower priced, and easy-to-use home-based sleep monitoring system. The researchers have developed the "Sleep Healthcare Management System" for OSA patients and healthcare providers. It combines smartphone and wearable devices that can perform real-time sleep monitoring. Healthcare providers could apply their professional knowledge to provide customized feedback via a web application. When the patient is diagnosed with an abnormal sleep health condition, healthcare providers may be able to provide appropriate and timely care.

  8. Children's sleep needs: is there sufficient evidence to recommend optimal sleep for children?

    Science.gov (United States)

    Matricciani, Lisa; Blunden, Sarah; Rigney, Gabrielle; Williams, Marie T; Olds, Tim S

    2013-04-01

    It is widely recognized that sleep is important for children's health and well-being and that short sleep duration is associated with a wide range of negative health outcomes. Recently, there has been much interest in whether or not there are sufficient data to support the specific recommendations made for how much sleep children need. In this article we explore concepts related to children's sleep need, discuss the theory, rationale, and empirical evidence for contemporary sleep recommendations, and outline future research directions for sleep recommendations. If sleep is to be treated as a therapeutic intervention, then consensus guidelines, statements, and evidence-based best-practice documents are needed to underpin sleep recommendations for children.

  9. Sleep education improves the sleep duration of adolescents: a randomized controlled pilot study.

    Science.gov (United States)

    Kira, Geoff; Maddison, Ralph; Hull, Michelle; Blunden, Sarah; Olds, Timothy

    2014-07-15

    To determine the feasibility and pilot a sleep education program in New Zealand high school students. A parallel, two-arm randomized controlled pilot trial was conducted. High school students (13 to 16 years) were randomly allocated to either a classroom-based sleep education program intervention (n = 15) or to a usual curriculum control group (n = 14). The sleep education program involved four 50-minute classroom-based education sessions with interactive groups. Students completed a 7-day sleep diary, a sleep questionnaire (including sleep hygiene, knowledge and problems) at baseline, post-intervention (4 weeks) and 10 weeks follow-up. An overall treatment effect was observed for weekend sleep duration (F 1,24 = 5.21, p = 0.03). Participants in the intervention group slept longer during weekend nights at 5 weeks (1:37 h:min, p = 0.01) and 10 weeks: (1:32 h:min, p = 0.03) compared to those in the control group. No differences were found between groups for sleep duration on weekday nights. No significant differences were observed between groups for any of the secondary outcomes (sleep hygiene, sleep problems, or sleep knowledge). A sleep education program appears to increase weekend sleep duration in the short term. Although this program was feasible, most schools are under time and resource pressure, thus alternative methods of delivery should be assessed for feasibility and efficacy. Larger trials of longer duration are needed to confirm these findings and determine the sustained effect of sleep education on sleep behavior and its impact on health and psychosocial outcomes. A commentary on this article appears in this issue on page 793.

  10. Impact of Sleep Telemedicine Protocol in Management of Sleep Apnea: A 5-Year VA Experience.

    Science.gov (United States)

    Baig, Mirza M; Antonescu-Turcu, Andrea; Ratarasarn, Kavita

    2016-05-01

    There is growing evidence that demonstrates an important role for telemedicine technologies in enhancing healthcare delivery. A comprehensive sleep telemedicine protocol was implemented at the Veterans Administration Medical Center (VAMC), Milwaukee, WI, in 2008 in an effort to improve access to sleep specialty care. The telemedicine protocol relied heavily on sleep specialist interventions based on chart review (electronic consult [e-consult]). This was done in response to long wait time for sleep clinic visits as well as delayed sleep study appointments. Since 2008 all consults are screened by sleep service to determine the next step in intervention. Based on chart review, the following steps are undertaken: (1) eligibility for portable versus in-lab sleep study is determined, and a sleep study order is placed accordingly, (2) positive airway pressure (PAP) therapy is prescribed for confirmed sleep apnea, and (3) need for in-person evaluation in the sleep clinic is determined, and the visit is scheduled. This study summarizes the 5-year trend in various aspects of access to sleep care after implementation of sleep telemedicine protocol at the Milwaukee VAMC. This is a retrospective system efficiency study. The electronic medical record was interrogated 5 years after starting the sleep telemedicine protocol to study annual trends in the following outcomes: (1) interval between sleep consult and prescription of PAP equipment, (2) total sleep consults, and (3) sleep clinic wait time. Two part-time sleep physicians provided sleep-related care at the Milwaukee VAMC between 2008 and 2012. During this period, the interval between sleep consult and PAP prescription decreased from ≥60 days to ≤7 days. This occurred in spite of an increase in total sleep consults and sleep studies. There was also a significant increase in data downloads, indicating overall improved follow-up. There was no change in clinic wait time of ≥60 days. Implementation of a sleep telemedicine

  11. Sleep patterns of Japanese preschool children and their parents: implications for co-sleeping.

    Science.gov (United States)

    Iwata, Sachiko; Iwata, Osuke; Matsuishi, Toyojiro

    2013-06-01

    The aim of this study was to investigate the direct relationship of sleep schedule and sleep quality variables between healthy preschool children and their parents, focusing on the influence of the difference in bedtime between each other. Forty-seven Japanese 5-year-old children and their primary parent were studied. The parents completed questionnaires including the Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index. The children wore an actigraph for one week. Although sleep patterns of children were generally independent of their parents, late sleep end time and bedtime of children were associated with parents' late sleep end time on weekends. For 87% of children and parents who shared a bedroom, sleep quality was negatively affected by a shorter difference in bedtimes between child and parent, but not by co-sleeping. Sleep behaviours of parents can influence those of their children. For parents and children who share a bedroom, the timing of bedtime rather than co-sleeping may be a key factor in modulating sleep patterns. Trying to get children asleep and subsequently falling asleep at a similar time may disturb parents' sleep quality, which may subsequently affect that of their children. ©2013 Foundation Acta Paediatrica. Published by Blackwell Publishing Ltd.

  12. Automatic REM sleep detection associated with idiopathic rem sleep Behavior Disorder

    DEFF Research Database (Denmark)

    Kempfner, J; Sørensen, Gertrud Laura; Sorensen, H B D

    2011-01-01

    Rapid eye movement sleep Behavior Disorder (RBD) is a strong early marker of later development of Parkinsonism. Currently there are no objective methods to identify and discriminate abnormal from normal motor activity during REM sleep. Therefore, a REM sleep detection without the use of chin...... electromyography (EMG) is useful. This is addressed by analyzing the classification performance when implementing two automatic REM sleep detectors. The first detector uses the electroencephalography (EEG), electrooculography (EOG) and EMG to detect REM sleep, while the second detector only uses the EEG and EOG....

  13. Sleep Disorders: Insomnia.

    Science.gov (United States)

    Burman, Deepa

    2017-09-01

    Insomnia is the most common type of sleep disorder in the family medicine population. It is defined as a persistent difficulty initiating or maintaining sleep, or a report of nonrestorative sleep, accompanied by related daytime impairment. Insomnia is a significant public health problem because of its high prevalence and management challenges. There is increasing evidence of a strong association between insomnia and various medical and psychiatric comorbidities. Diagnosis of insomnia and treatment planning rely on a thorough sleep history to address contributing and precipitating factors as well as maladaptive behaviors resulting in poor sleep. Using a sleep diary or sleep log is more accurate than patient recall to determine sleep patterns. A sleep study is not routinely indicated for evaluation of insomnia. Cognitive behavioral therapy for insomnia (CBT-I) is the mainstay of treatment and is a safe and effective approach. The key challenge of CBT-I is the lack of clinicians to implement it. The newer generation nonbenzodiazepines (eg, zolpidem, zaleplon) are used as first-line pharmacotherapy for chronic insomnia. Newer drugs active on targets other than the gamma-aminobutyric acid receptor are now available, but clear treatment guidelines are needed. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  14. Sleep disorders in psychiatry.

    Science.gov (United States)

    Costa e Silva, Jorge Alberto

    2006-10-01

    Sleep is an active state that is critical for our physical, mental, and emotional well-being. Sleep is also important for optimal cognitive functioning, and sleep disruption results in functional impairment. Insomnia is the most common sleep disorder in psychiatry. At any given time, 50% of adults are affected with 1 or more sleep problems such as difficulty in falling or staying asleep, in staying awake, or in adhering to a consistent sleep/wake schedule. Narcolepsy affects as many individuals as does multiple sclerosis or Parkinson disease. Sleep problems are especially prevalent in schizophrenia, depression, and other mental illnesses, and every year, sleep disorders, sleep deprivation, and sleepiness add billions to the national health care bill in industrialized countries. Although psychiatrists often treat patients with insomnia secondary to depression, most patients discuss their insomnia with general care physicians, making it important to provide this group with clear guidelines for the diagnosis and management of insomnia. Once the specific medical, behavioral, or psychiatric causes of the sleep problem have been identified, appropriate treatment can be undertaken. Chronic insomnia has multiple causes arising from medical disorders, psychiatric disorders, primary sleep disorders, circadian rhythm disorders, social or therapeutic use of drugs, or maladaptive behaviors. The emerging concepts of sleep neurophysiology are consistent with the cholinergic-aminergic imbalance hypothesis of mood disorders, which proposes that depression is associated with an increased ratio of central cholinergic to aminergic neurotransmission. The characteristic sleep abnormalities of depression may reflect a relative predominance of cholinergic activity. Antidepressant medications presumably reduce rapid eye movement (REM) sleep either by their anticholinergic properties or by enhancing aminergic neurotransmission. Intense and prolonged dreams often accompany abrupt withdrawal

  15. Alba-domain proteins of Trypanosoma brucei are cytoplasmic RNA-binding proteins that interact with the translation machinery.

    Directory of Open Access Journals (Sweden)

    Jan Mani

    Full Text Available Trypanosoma brucei and related pathogens transcribe most genes as polycistronic arrays that are subsequently processed into monocistronic mRNAs. Expression is frequently regulated post-transcriptionally by cis-acting elements in the untranslated regions (UTRs. GPEET and EP procyclins are the major surface proteins of procyclic (insect midgut forms of T. brucei. Three regulatory elements common to the 3' UTRs of both mRNAs regulate mRNA turnover and translation. The glycerol-responsive element (GRE is unique to the GPEET 3' UTR and regulates its expression independently from EP. A synthetic RNA encompassing the GRE showed robust sequence-specific interactions with cytoplasmic proteins in electromobility shift assays. This, combined with column chromatography, led to the identification of 3 Alba-domain proteins. RNAi against Alba3 caused a growth phenotype and reduced the levels of Alba1 and Alba2 proteins, indicative of interactions between family members. Tandem-affinity purification and co-immunoprecipitation verified these interactions and also identified Alba4 in sub-stoichiometric amounts. Alba proteins are cytoplasmic and are recruited to starvation granules together with poly(A RNA. Concomitant depletion of all four Alba proteins by RNAi specifically reduced translation of a reporter transcript flanked by the GPEET 3' UTR. Pulldown of tagged Alba proteins confirmed interactions with poly(A binding proteins, ribosomal protein P0 and, in the case of Alba3, the cap-binding protein eIF4E4. In addition, Alba2 and Alba3 partially cosediment with polyribosomes in sucrose gradients. Alba-domain proteins seem to have exhibited great functional plasticity in the course of evolution. First identified as DNA-binding proteins in Archaea, then in association with nuclear RNase MRP/P in yeast and mammalian cells, they were recently described as components of a translationally silent complex containing stage-regulated mRNAs in Plasmodium. Our results are

  16. The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation

    Science.gov (United States)

    Van Dongen, Hans P A.; Maislin, Greg; Mullington, Janet M.; Dinges, David F.

    2003-01-01

    OBJECTIVES: To inform the debate over whether human sleep can be chronically reduced without consequences, we conducted a dose-response chronic sleep restriction experiment in which waking neurobehavioral and sleep physiological functions were monitored and compared to those for total sleep deprivation. DESIGN: The chronic sleep restriction experiment involved randomization to one of three sleep doses (4 h, 6 h, or 8 h time in bed per night), which were maintained for 14 consecutive days. The total sleep deprivation experiment involved 3 nights without sleep (0 h time in bed). Each study also involved 3 baseline (pre-deprivation) days and 3 recovery days. SETTING: Both experiments were conducted under standardized laboratory conditions with continuous behavioral, physiological and medical monitoring. PARTICIPANTS: A total of n = 48 healthy adults (ages 21-38) participated in the experiments. INTERVENTIONS: Noctumal sleep periods were restricted to 8 h, 6 h or 4 h per day for 14 days, or to 0 h for 3 days. All other sleep was prohibited. RESULTS: Chronic restriction of sleep periods to 4 h or 6 h per night over 14 consecutive days resulted in significant cumulative, dose-dependent deficits in cognitive performance on all tasks. Subjective sleepiness ratings showed an acute response to sleep restriction but only small further increases on subsequent days, and did not significantly differentiate the 6 h and 4 h conditions. Polysomnographic variables and delta power in the non-REM sleep EEG-a putative marker of sleep homeostasis--displayed an acute response to sleep restriction with negligible further changes across the 14 restricted nights. Comparison of chronic sleep restriction to total sleep deprivation showed that the latter resulted in disproportionately large waking neurobehavioral and sleep delta power responses relative to how much sleep was lost. A statistical model revealed that, regardless of the mode of sleep deprivation, lapses in behavioral alertness

  17. Sleep and protein synthesis-dependent synaptic plasticity: impacts of sleep loss and stress

    Science.gov (United States)

    Grønli, Janne; Soulé, Jonathan; Bramham, Clive R.

    2014-01-01

    Sleep has been ascribed a critical role in cognitive functioning. Several lines of evidence implicate sleep in the consolidation of synaptic plasticity and long-term memory. Stress disrupts sleep while impairing synaptic plasticity and cognitive performance. Here, we discuss evidence linking sleep to mechanisms of protein synthesis-dependent synaptic plasticity and synaptic scaling. We then consider how disruption of sleep by acute and chronic stress may impair these mechanisms and degrade sleep function. PMID:24478645

  18. Knowledge of childhood sleep: a possible variable in under or misdiagnosis of childhood sleep problems.

    Science.gov (United States)

    Schreck, Kimberly A; Richdale, Amanda L

    2011-12-01

    Evidence demonstrates that health professionals have limited knowledge about childhood sleep, frequently do not screen for these problems and often rely on parents to raise sleep issues at clinic visits. However, little is known about parents' sleep knowledge. The goal of this study was to assess parents' knowledge of sleep and specifically: (i) sleep aspects related to the age of children; (ii) developmentally normal sleep; and (iii) sleep problems that may lead to parents' ability to raise sleep issues at clinic visits. This study evaluated the knowledge of 170 parents of children aged 2-17 years about infant, child and adolescent sleep patterns and problems. The majority of parents could not answer correctly questions about developmental sleep patterns or sleep problems, but were more likely to answer correctly questions about normal infant sleep patterns and about sleep problems during waking hours. Parents also were more likely to answer 'don't know' to questions about: (i) older children and adolescents; (ii) sleep apnea; and (iii) dreams and nightmares. The implications of these findings for the identification, intervention and prevention of childhood sleep problems are discussed. 2011 European Sleep Research Society.

  19. Sleep Disorders (PDQ)

    Science.gov (United States)

    ... Types of Cancer Treatment Surgery Radiation Therapy External Beam Radiation Internal Radiation Therapy Side Effects Chemotherapy Immunotherapy ... asleep, sleeping, or waking from sleep, such as walking, talking, or eating. Sleep disorders keep you from ...

  20. Subjective sleep complaints indicate objective sleep problems in psychosomatic patients: a prospective polysomnographic study

    Directory of Open Access Journals (Sweden)

    Linden M

    2016-08-01

    Full Text Available Michael Linden,1,2 Marie Dietz,1 Christian Veauthier,3 Ingo Fietze3 1Research Group Psychosomatic Rehabilitation, Charité University Medicine Berlin, 2Department of Psychosomatic Medicine, Rehabilitation Centre Seehof, Teltow, 3Interdisciplinary Center of Sleep Medicine, Charité University Medicine Berlin, Berlin, Germany Objective: To elucidate the relationship between subjective complaints and polysomnographical parameters in psychosomatic patients.Method: A convenience sample of patients from a psychosomatic inpatient unit were classified according to the Pittsburgh Sleep Quality Index (PSQI as very poor sleepers (PSQI >10, n=80 and good sleepers (PSQI <6, n=19. They then underwent a polysomnography and in the morning rated their previous night’s sleep using a published protocol (Deutschen Gesellschaft für Schlafforschung und Schlafmedizin morning protocol [MP].Results: In the polysomnography, significant differences were found between very poor and good sleepers according to the PSQI with respect to sleep efficiency and time awake after sleep onset. When comparing objective PSG and subjective MP, the polysomnographical sleep onset latency was significantly positively correlated with the corresponding parameters of the MP: the subjective sleep onset latency in minutes and the subjective evaluation of sleep onset latency (very short, short, normal, long, very long were positively correlated with the sleep latency measured by polysomnography. The polysomnographical time awake after sleep onset (in minutes was positively correlated with the subjective time awake after sleep onset (in minutes, evaluation of time awake after sleep onset (seldom, normal often, and subjective restfulness. The polysomnographical total sleep time (TST was positively correlated with the subjective TST. Conversely, the polysomnographical TST was negatively correlated with the evaluation of TST (high polysomnographical TST was correlated with the subjective

  1. Consumer Sleep Technology: An American Academy of Sleep Medicine Position Statement.

    Science.gov (United States)

    Khosla, Seema; Deak, Maryann C; Gault, Dominic; Goldstein, Cathy A; Hwang, Dennis; Kwon, Younghoon; O'Hearn, Daniel; Schutte-Rodin, Sharon; Yurcheshen, Michael; Rosen, Ilene M; Kirsch, Douglas B; Chervin, Ronald D; Carden, Kelly A; Ramar, Kannan; Aurora, R Nisha; Kristo, David A; Malhotra, Raman K; Martin, Jennifer L; Olson, Eric J; Rosen, Carol L; Rowley, James A

    2018-05-15

    Consumer sleep technologies (CSTs) are widespread applications and devices that purport to measure and even improve sleep. Sleep clinicians may frequently encounter CST in practice and, despite lack of validation against gold standard polysomnography, familiarity with these devices has become a patient expectation. This American Academy of Sleep Medicine position statement details the disadvantages and potential benefits of CSTs and provides guidance when approaching patient-generated health data from CSTs in a clinical setting. Given the lack of validation and United States Food and Drug Administration (FDA) clearance, CSTs cannot be utilized for the diagnosis and/or treatment of sleep disorders at this time. However, CSTs may be utilized to enhance the patient-clinician interaction when presented in the context of an appropriate clinical evaluation. The ubiquitous nature of CSTs may further sleep research and practice. However, future validation, access to raw data and algorithms, and FDA oversight are needed. © 2018 American Academy of Sleep Medicine.

  2. Snoring and Sleep Apnea

    Science.gov (United States)

    ... Find an ENT Doctor Near You Snoring and Sleep Apnea Snoring and Sleep Apnea Patient Health Information ... newsroom@entnet.org . Insight into sleeping disorders and sleep apnea Forty-five percent of normal adults snore ...

  3. [Natural factors influencing sleep].

    Science.gov (United States)

    Jurkowski, Marek K; Bobek-Billewicz, Barbara

    2007-01-01

    Sleep is a universal phenomenon of human and animal lives, although the importance of sleep for homeo-stasis is still unknown. Sleep disturbances influence many behavioral and physiologic processes, leading to health complications including death. On the other hand, sleep improvement can beneficially influence the course of healing of many disorders and can be a prognostic of health recovery. The factors influencing sleep have different biological and chemical origins. They are classical hormones, hypothalamic releasing and inhibitory hormones, neuropeptides, peptides and others as cytokines, prostaglandins, oleamid, adenosine, nitric oxide. These factors regulate most physiologic processes and are likely elements integrating sleep with physiology and physiology with sleep in health and disorders.

  4. Sleep-related movement disorders.

    Science.gov (United States)

    Merlino, Giovanni; Gigli, Gian Luigi

    2012-06-01

    Several movement disorders may occur during nocturnal rest disrupting sleep. A part of these complaints is characterized by relatively simple, non-purposeful and usually stereotyped movements. The last version of the International Classification of Sleep Disorders includes these clinical conditions (i.e. restless legs syndrome, periodic limb movement disorder, sleep-related leg cramps, sleep-related bruxism and sleep-related rhythmic movement disorder) under the category entitled sleep-related movement disorders. Moreover, apparently physiological movements (e.g. alternating leg muscle activation and excessive hypnic fragmentary myoclonus) can show a high frequency and severity impairing sleep quality. Clinical and, in specific cases, neurophysiological assessments are required to detect the presence of nocturnal movement complaints. Patients reporting poor sleep due to these abnormal movements should undergo non-pharmacological or pharmacological treatments.

  5. Sleep habits and sleep disturbances in Dutch children: a population-based study

    NARCIS (Netherlands)

    van Litsenburg, R.R.L.; Waumans, R.C.; van den Berg, G.; Gemke, R.J.B.J.

    2010-01-01

    Sleep disorders can lead to significant morbidity. Information on sleep in healthy children is necessary to evaluate sleep disorders in clinical practice, but data from different societies cannot be simply generalized. The aims of this study were to (1) assess the prevalence of sleep disturbances in

  6. Habitual Sleep Duration, Unmet Sleep Need, and Excessive Daytime Sleepiness in Korean Adults

    OpenAIRE

    Hwangbo, Young; Kim, Won-Joo; Chu, Min Kyung; Yun, Chang-Ho; Yang, Kwang Ik

    2016-01-01

    Background and Purpose Sleep need differs between individuals, and so the same duration of sleep will lead to sleep insufficiency in some individuals but not others. The aim of this study was to determine the separate and combined associations of both sleep duration and unmet sleep need with excessive daytime sleepiness (EDS) in Korean adults. Methods The participants comprised 2,769 Korean adults aged 19 years or older. They completed questionnaires about their sleep habits over the previous...

  7. Neurobiology of Sleep and Sleep Treatment Response in PTSD

    Science.gov (United States)

    2009-10-01

    conducted in PTSD samples, these sleep measurement methods do not allow the identification of neurobio - logical underpinnings of trauma-related...vided valuable insights into the potential neurobio - logical underpinnings of altered REM and NREM sleep mechanisms following stress exposure PTSD...nightmare patients often report improvements In sleep quality, feeling more rested upon awakening and having more davtime energy , and reduction in

  8. Sleep and Athletic Performance.

    Science.gov (United States)

    Watson, Andrew M

    Sleep is an essential component of health and well-being, with significant impacts on physical development, emotional regulation, cognitive performance, and quality of life. Along with being an integral part of the recovery and adaptive process between bouts of exercise, accumulating evidence suggests that increased sleep duration and improved sleep quality in athletes are associated with improved performance and competitive success. In addition, better sleep may reduce the risk of both injury and illness in athletes, not only optimizing health but also potentially enhancing performance through increased participation in training. Despite this, most studies have found that athletes fail to obtain the recommended amount of sleep, threatening both performance and health. Athletes face a number of obstacles that can reduce the likelihood of obtaining proper sleep, such as training and competition schedules, travel, stress, academic demands, and overtraining. In addition, athletes have been found to demonstrate poor self-assessment of their sleep duration and quality. In light of this, athletes may require more careful monitoring and intervention to identify individuals at risk and promote proper sleep to improve both performance and overall health. This review attempts to highlight the recent literature regarding sleep issues in athletes, the effects of sleep on athletic performance, and interventions to enhance proper sleep in athletes.

  9. Feeding methods, sleep arrangement, and infant sleep patterns: a Chinese population-based study.

    Science.gov (United States)

    Huang, Xiao-Na; Wang, Hui-Shan; Chang, Jen-Jen; Wang, Lin-Hong; Liu, Xi-Cheng; Jiang, Jing-Xiong; An, Lin

    2016-02-01

    Findings from prior research into the effect of feeding methods on infant sleep are inconsistent. The objectives of this study were to examine infants' sleep patterns by feeding methods and sleep arrangement from birth to eight months old. This longitudinal cohort study enrolled 524 pregnant women at 34-41 weeks of gestation and their infants after delivery in 2006 and followed up until eight months postpartum. The study subjects were recruited from nine women and children hospitals in nine cities in China (Beijing, Chongqing, Wuhan, Changsha, Nanning, Xiamen, Xi'an, Jinan, and Hailin). Participating infants were followed up weekly during the first month and monthly from the second to the eighth month after birth. Twenty-four hour sleep diaries recording infants' sleeping and feeding methods were administered based on caregiver's self-report. Multivariable mixed growth curve models were fitted to estimate the effects of feeding methods and sleep arrangement on infants' sleep patterns over time, controlling for maternal and paternal age, maternal and paternal education level, household income, supplementation of complementary food, and infant birth weight and length. Exclusively formula fed infants had the greatest sleep percentage/24 h, followed by exclusively breast milk fed infants and partially breast milk fed infants (Psleep percentage and night waking frequency between exclusively formula and exclusively breast milk fed infants weakened over time as infants developed. In addition, compared to infants with bed-sharing sleep arrangement, those with room sharing sleep arrangement had greater daytime and 24-hour infant sleep percentage, whereas those with sleeping alone sleep arrangement had greater nighttime sleep percentage. Our data based on caregiver's self-report suggested that partial breastfeeding and bed-sharing may be associated with less sleep in infants. Health care professionals need to work with parents of newborns to develop coping strategies that

  10. Sleep alterations in mammals: did aquatic conditions inhibit rapid eye movement sleep?

    Science.gov (United States)

    Madan, Vibha; Jha, Sushil K

    2012-12-01

    Sleep has been studied widely in mammals and to some extent in other vertebrates. Higher vertebrates such as birds and mammals have evolved an inimitable rapid eye movement (REM) sleep state. During REM sleep, postural muscles become atonic and the temperature regulating machinery remains suspended. Although REM sleep is present in almost all the terrestrial mammals, the aquatic mammals have either radically reduced or completely eliminated REM sleep. Further, we found a significant negative correlation between REM sleep and the adaptation of the organism to live on land or in water. The amount of REM sleep is highest in terrestrial mammals, significantly reduced in semi-aquatic mammals and completely absent or negligible in aquatic mammals. The aquatic mammals are obligate swimmers and have to surface at regular intervals for air. Also, these animals live in thermally challenging environments, where the conductive heat loss is approximately ~90 times greater than air. Therefore, they have to be moving most of the time. As an adaptation, they have evolved unihemispheric sleep, during which they can rove as well as rest. A condition that immobilizes muscle activity and suspends the thermoregulatory machinery, as happens during REM sleep, is not suitable for these animals. It is possible that, in accord with Darwin's theory, aquatic mammals might have abolished REM sleep with time. In this review, we discuss the possibility of the intrinsic role of aquatic conditions in the elimination of REM sleep in the aquatic mammals.

  11. Sleep from an islamic perspective

    OpenAIRE

    Ahmed S BaHammam

    2011-01-01

    Sleep medicine is a relatively new scientific specialty. Sleep is an important topic in Islamic literature, and the Quran and Hadith discuss types of sleep, the importance of sleep, and good sleep practices. Islam considers sleep as one of the signs of the greatness of All?h (God) and encourages followers to explore this important sign. The Quran describes different types of sleep, and these correspond with sleep stages identified by modern science. The Quran discusses the beneficial effects ...

  12. Sleep and Newborns

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Sleep and Newborns KidsHealth / For Parents / Sleep and Newborns ... night it is. How Long Will My Newborn Sleep? Newborns should get 14 to 17 hours of ...

  13. Sleep deprivation and injuries in part-time Kentucky farmers: impact of self reported sleep habits and sleep problems on injury risk.

    Science.gov (United States)

    Spengler, Susan E; Browning, Steven R; Reed, Deborah B

    2004-09-01

    Part-time farmers who hold off-farm jobs may be at risk for injuries because of impaired performance resulting from inadequate sleep. For this study, 1004 part-time male Kentucky farmers completed a telephone interview for the 1994 to 1995 National Institute for Occupational Safety and Health-funded Farm Family Health and Hazard Surveillance Project. Questions were included about demographics, sleep habits, and injury occurrence. Twelve percent of the farmers reported an injury requiring medical intervention in the previous year. Farmers reported sleeping an average of 7.6 hours daily. Approximately 6.7% of the sample had three symptoms of sleep apnea. Although hours of sleep were not related to injury incidence, sleep medication use (odds ratio [OR] = 2.11, 95% confidence interval [CI] = 1.01 to 4.40) and presence of three sleep apnea symptoms (OR = 2.48, 95% CI = 1.13 to 5.41) were related to injury incidence. These data support the need for further research to examine sleep habits and promote strategies that reduce the risk for injuries caused by lack of sleep.

  14. Alcohol and the sleeping brain.

    Science.gov (United States)

    Colrain, Ian M; Nicholas, Christian L; Baker, Fiona C

    2014-01-01

    Alcohol acts as a sedative that interacts with several neurotransmitter systems important in the regulation of sleep. Acute administration of large amounts of alcohol prior to sleep leads to decreased sleep-onset latency and changes in sleep architecture early in the night, when blood alcohol levels are high, with subsequent disrupted, poor-quality sleep later in the night. Alcohol abuse and dependence are associated with chronic sleep disturbance, lower slow-wave sleep, and more rapid-eye-movement sleep than normal, that last long into periods of abstinence and may play a role in relapse. This chapter outlines the evidence for acute and chronic alcohol effects on sleep architecture and sleep electroencephalogram, evidence for tolerance with repeated administration, and possible underlying neurochemical mechanisms for alcohol's effects on sleep. Also discussed are sex differences as well as effects of alcohol on sleep homeostasis and circadian regulation. Evidence for the role of sleep disruption as a risk factor for developing alcohol dependence is discussed in the context of research conducted in adolescents. The utility of sleep-evoked potentials in the assessment of the effects of alcoholism on sleep and the brain and in abstinence-mediated recovery is also outlined. The chapter concludes with a series of questions that need to be answered to determine the role of sleep and sleep disturbance in the development and maintenance of problem drinking and the potential beneficial effects of the treatment of sleep disorders for maintenance of abstinence in alcoholism. © 2014 Elsevier B.V. All rights reserved.

  15. Fiber and Saturated Fat Are Associated with Sleep Arousals and Slow Wave Sleep.

    Science.gov (United States)

    St-Onge, Marie-Pierre; Roberts, Amy; Shechter, Ari; Choudhury, Arindam Roy

    2016-01-01

    Sleep restriction alters food intake, but less is known about how dietary patterns affect sleep. Current goals were to determine whether: (1) sleep is different after consumption of a controlled diet vs. an ad libitum diet, and (2) dietary intake during ad libitum feeding is related to nocturnal sleep. Twenty-six normal weight adults (30-45 y), habitually sleeping 7-9 h/night, participated in a randomized-crossover inpatient study with 2 phases of 5 nights: short (4 h in bed) or habitual (9 h in bed) sleep. Only data from the habitual sleep phase were used for the present analyses. During the first 4 days, participants consumed a controlled diet; on day 5, food intake was self-selected. Linear regression was used to determine relations between daytime food intake and nighttime sleep on day 5. Sleep duration did not differ after 3 days of controlled feeding vs. a day of ad libitum intake. However, sleep after ad libitum eating had less slow wave sleep (SWS, P = 0.0430) and longer onset latency (P = 0.0085). Greater fiber intake predicted less stage 1 (P = 0.0198) and more SWS (P = 0.0286). Percent of energy from saturated fat predicted less SWS (P = 0.0422). Higher percent of energy from sugar and other carbohydrates not considered sugar or fiber was associated with arousals (P = 0.0320 and 0.0481, respectively). Low fiber and high saturated fat and sugar intake is associated with lighter, less restorative sleep with more arousals. Diet could be useful in the management of sleep disorders but this needs to be tested. http://www.clinicaltrials.gov, #NCT00935402. © 2016 American Academy of Sleep Medicine.

  16. The Effect of Dogs on Human Sleep in the Home Sleep Environment.

    Science.gov (United States)

    Patel, Salma I; Miller, Bernie W; Kosiorek, Heidi E; Parish, James M; Lyng, Philip J; Krahn, Lois E

    2017-09-01

    To objectively assess whether a dog in the bedroom or bed disturbs sleep. From August 1, 2015, through December 31, 2015, we evaluated the sleep of humans and dogs occupying the same bedroom to determine whether this arrangement was conducive to sleep. The study included 40 healthy adults without sleep disorders and their dogs (no dogs dog a validated dog accelerometer for 7 nights. The mean ± SD age of the participants (88% women) was 44±14 years and body mass index was 25±6. The mean ± SD age of the dogs was 5±3 years and weight was 15±13 kg. Mean ± SD actigraphy data showed 475±101 minutes in bed, 404±99 minutes total sleep time, 81%±7% sleep efficiency, and 71±35 minutes wake time after sleep onset. The dogs' accelerometer activity during the corresponding human sleep period was characterized as mean ± SD minutes at rest, active, and at play of 413±102, 62±43, and 2±4. The dogs had mean ± SD 85%±15% sleep efficiency. Human sleep efficiency was lower if the dog was on the bed as opposed to simply in the room (P=.003). Humans with a single dog in their bedroom maintained good sleep efficiency; however, the dog's position on/off the bed made a difference. A dog's presence in the bedroom may not be disruptive to human sleep, as was previously suspected. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  17. Overnight improvements in two REM sleep-sensitive tasks are associated with both REM and NREM sleep changes, sleep spindle features, and awakenings for dream recall.

    Science.gov (United States)

    Nielsen, T; O'Reilly, C; Carr, M; Dumel, G; Godin, I; Solomonova, E; Lara-Carrasco, J; Blanchette-Carrière, C; Paquette, T

    2015-07-01

    Memory consolidation is associated with sleep physiology but the contribution of specific sleep stages remains controversial. To clarify the contribution of REM sleep, participants were administered two REM sleep-sensitive tasks to determine if associated changes occurred only in REM sleep. Twenty-two participants (7 men) were administered the Corsi Block Tapping and Tower of Hanoi tasks prior to and again after a night of sleep. Task improvers and non-improvers were compared for sleep structure, sleep spindles, and dream recall. Control participants (N = 15) completed the tasks twice during the day without intervening sleep. Overnight Corsi Block improvement was associated with more REM sleep whereas Tower of Hanoi improvement was associated with more N2 sleep. Corsi Block improvement correlated positively with %REM sleep and Tower of Hanoi improvement with %N2 sleep. Post-hoc analyses suggest Tower of Hanoi effects-but not Corsi Block effects-are due to trait differences. Sleep spindle density was associated with Tower of Hanoi improvement whereas spindle amplitude correlated with Corsi Block improvement. Number of REM awakenings for dream reporting (but not dream recall per se) was associated with Corsi Block, but not Tower of Hanoi, improvement but was confounded with REM sleep time. This non-replication of one of 2 REM-sensitive task effects challenges both 'dual-process' and 'sequential' or 'sleep organization' models of sleep-dependent learning and points rather to capacity limitations on REM sleep. Experimental awakenings for sampling dream mentation may not perturb sleep-dependent learning effects; they may even enhance them. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Sleep and Obesity

    Directory of Open Access Journals (Sweden)

    Chenzhao Ding

    2018-03-01

    Full Text Available Rising global prevalence and incidence of obesity lead to increased cardiovascular-renal complications and cancers. Epidemiological studies reported a worldwide trend towards suboptimal sleep duration and poor sleep quality in parallel with this obesity epidemic. From rodents and human models, it is highly plausible that abnormalities in sleep, both quantity and quality, impact negatively on energy metabolism. While excess dietary intake and physical inactivity are the known drivers of the obesity epidemic, promotion of healthy sleep habits has emerged as a new target to combat obesity. In this light, present review focuses on the existing literature examining the relationship between sleep physiology and energy homeostasis. Notably, sleep dysregulation perturbs the metabolic milieu via alterations in hormones such as leptin and ghrelin, eating behavior, neuroendocrine and autonomic nervous systems. In addition, shift work and trans-meridian air travel may exert a negative influence on the hypothalamic-pituitary-adrenal axis and trigger circadian misalignment, leading to impaired glucose tolerance and increased fat accumulation. Amassing evidence has also suggested that uncoupling of the circadian clock can increase the risk of adverse metabolic health. Given the importance of sleep in maintaining energy homeostasis and that it is potentially modifiable, promoting good sleep hygiene may create new avenues for obesity prevention and treatment.

  19. Changing your sleep habits

    Science.gov (United States)

    ... falling asleep; Sleep hygiene References American Academy of Sleep Medicine. Insomnia. Updated March 4, 2015. SleepEducation.org. sleepeducation. ... T, Dement WC, eds. Principles and Practice of Sleep Medicine . 6th ed. Philadelphia, PA: Elsevier; 2017:chap 86. ...

  20. Exercise Effects on Sleep Physiology

    Directory of Open Access Journals (Sweden)

    Sunao eUchida

    2012-04-01

    Full Text Available This mini-review focuses on the effects of exercise on sleep. In its early days, sleep research largely focused on central nervous system (CNS physiology using standardized tabulations of several sleep-specific landmark electroencephalogram (EEG waveforms. Though coarse, this method has enabled the observation and inspection of numerous uninterrupted sleep phenomena. Thus, research on the effects of exercise on sleep began, in the 1960’s, with a focus primarily on sleep EEG (CNS sleep changes. Those early studies found only small effects of exercise on sleep. More recent sleep research has explored not only CNS functioning, but somatic physiology as well. As physical exercise mostly affects somatic functions, endocrine and autonomic nervous system (ANS changes that occur during sleep should be affected by daytime exercise. Since endocrinological, metabolic and autonomic changes can be measured during sleep, it should be possible to assess exercise effects on somatic physiology in addition to CNS sleep quality, building from standard polysomnographic (PSG techniques. Incorporating measures of somatic physiology in the quantitative assessment of sleep could further our understanding of sleep's function as an auto-regulatory, global phenomenon.

  1. Are You Sleep Deprived?

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Sleep Disorders Are You Sleep Deprived? Past Issues / Summer 2015 Table of Contents ... even if you think you've had enough sleep? You might have a sleep disorder. There are ...

  2. Sleep and Metabolism: An Overview

    OpenAIRE

    Sharma, Sunil; Kavuru, Mani

    2010-01-01

    Sleep and its disorders are increasingly becoming important in our sleep deprived society. Sleep is intricately connected to various hormonal and metabolic processes in the body and is important in maintaining metabolic homeostasis. Research shows that sleep deprivation and sleep disorders may have profound metabolic and cardiovascular implications. Sleep deprivation, sleep disordered breathing, and circadian misalignment are believed to cause metabolic dysregulation through myriad pathways i...

  3. Sleep disorders in children

    OpenAIRE

    Montgomery, Paul; Dunne, Danielle

    2007-01-01

    Sleep disorders may affect 20-30% of young children, and include excessive daytime sleepiness, problems getting to sleep (dysomnias), or undesirable phenomena during sleep (parasomnias), such as sleep terrors, and sleepwalking. Children with physical or learning disabilities are at increased risk of sleep disorders. Other risk factors include the child being the first born, having a difficult temperament or having had colic, and increased maternal responsiveness.

  4. Sleep disorders in children

    OpenAIRE

    Bruni, Oliveiero; Novelli, Luana

    2010-01-01

    Sleep disorders may affect between 20% and 30% of young children, and include problems getting to sleep (dyssomnias) or undesirable phenomena during sleep (parasomnias), such as sleep terrors and sleepwalking. Children with physical or learning disabilities are at increased risk of sleep disorders. Other risk factors include the child being the first born, having a difficult temperament or having had colic, and increased maternal responsiveness.

  5. Interaction of Sleep Duration and Sleep Quality on Hypertension Prevalence in Adult Chinese Males.

    Science.gov (United States)

    Lu, Kai; Chen, Jia; Wu, Shouling; Chen, Ji; Hu, Dayi

    2015-01-01

    Previous studies demonstrated conflicting results about the association of sleep duration and hypertension. Given the potential relationship between sleep quality and hypertension, this study aimed to investigate the interaction of self-reported sleep duration and sleep quality on hypertension prevalence in adult Chinese males. We undertook a cross-sectional analysis of 4144 male subjects. Sleep duration were measured by self-reported average sleep time during the past month. Sleep quality was evaluated using the standard Pittsburgh Sleep Quality Index. Hypertension was defined as blood pressure level ≥140/90 mm Hg or current antihypertensive treatment. The association between hypertension prevalence, sleep duration, and sleep quality was analyzed using logistic regression after adjusting for basic cardiovascular characteristics. Sleep duration shorter than 8 hours was found to be associated with increased hypertension, with odds ratios and 95% confidence intervals (CIs) of 1.25 (95% CI, 1.03-1.52) for 7 hours, 1.41 (95% CI, 1.14-1.73) for 6 hours, and 2.38 (95% CI, 1.81-3.11) for quality as the reference, good, poor, and very poor sleep quality were associated with hypertension, with odds ratios of 1.20 (95% CI, 1.01-1.42), 1.67 (95% CI, 1.32-2.11), and 2.32 (95% CI, 1.67-3.21), respectively. More importantly, further investigation of the association of different combinations of sleep duration and quality in relation to hypertension indicated an additive interaction. There is an additive interaction of poor sleep quality and short sleep duration on hypertension prevalence. More comprehensive measurement of sleep should be performed in future studies.

  6. Sleep patterns and predictors of disturbed sleep in a large population of college students.

    Science.gov (United States)

    Lund, Hannah G; Reider, Brian D; Whiting, Annie B; Prichard, J Roxanne

    2010-02-01

    To characterize sleep patterns and predictors of poor sleep quality in a large population of college students. This study extends the 2006 National Sleep Foundation examination of sleep in early adolescence by examining sleep in older adolescents. One thousand one hundred twenty-five students aged 17 to 24 years from an urban Midwestern university completed a cross-sectional online survey about sleep habits that included the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale, the Horne-Ostberg Morningness-Eveningness Scale, the Profile of Mood States, the Subjective Units of Distress Scale, and questions about academic performance, physical health, and psychoactive drug use. Students reported disturbed sleep; over 60% were categorized as poor-quality sleepers by the PSQI, bedtimes and risetimes were delayed during weekends, and students reported frequently taking prescription, over the counter, and recreational psychoactive drugs to alter sleep/wakefulness. Students classified as poor-quality sleepers reported significantly more problems with physical and psychological health than did good-quality sleepers. Students overwhelmingly stated that emotional and academic stress negatively impacted sleep. Multiple regression analyses revealed that tension and stress accounted for 24% of the variance in the PSQI score, whereas exercise, alcohol and caffeine consumption, and consistency of sleep schedule were not significant predictors of sleep quality. These results demonstrate that insufficient sleep and irregular sleep-wake patterns, which have been extensively documented in younger adolescents, are also present at alarming levels in the college student population. Given the close relationships between sleep quality and physical and mental health, intervention programs for sleep disturbance in this population should be considered. Copyright 2010 Society for Adolescent Medicine. Published by Elsevier Inc. All rights reserved.

  7. Quantitative Structure ‒ Antiprotozoal Activity Relationships of Sesquiterpene Lactones

    Directory of Open Access Journals (Sweden)

    Reto Brun

    2009-06-01

    Full Text Available Prompted by results of our previous studies where we found high activity of some sesquiterpene lactones (STLs against Trypanosoma brucei rhodesiense (which causes East African sleeping sickness, we have now conducted a structure-(in-vitro-activity study on a set of 40 STLs against T. brucei rhodesiense, T. cruzi, Leishmania donovani and Plasmodium falciparum. Furthermore, cytotoxic activity against L6 rat skeletal myoblast cells was assessed. Some of the compounds possess high activity, especially against T. brucei (e.g. helenalin and some of its esters with IC50-values of 0.05-0.1 µM, which is about 10 times lower than their cytotoxic activity. It was found that all investigated antiprotozoal activities are significantly correlated with cytotoxicity and the major determinants for activity are a,b-unsaturated structural elements, also known to be essential for other biological activities of STLs. It was observed, however, that certain compounds are considerably more toxic against protozoa than against mammalian cells while others are more cytotoxic than active against the protozoa. A comparative QSAR analysis was therefore undertaken, in order to discern the antiparasitic activity of STLs against T. brucei and cytotoxicity. Both activities were found to depend to a large extent on the same structural elements and molecular properties. The observed variance in the biological data can be explained in terms of subtle variations in the relative influences of various molecular descriptors.

  8. Altered sleep composition after traumatic brain injury does not affect declarative sleep-dependent memory consolidation

    Directory of Open Access Journals (Sweden)

    Janna eMantua

    2015-06-01

    Full Text Available Individuals with a history of traumatic brain injury (TBI often report sleep disturbances, which may be caused by changes in sleep architecture or reduced sleep quality (greater time awake after sleep onset, poorer sleep efficiency, and sleep stage proportion alterations. Sleep is beneficial for memory formation, and herein we examine whether altered sleep physiology following TBI has deleterious effects on sleep-dependent declarative memory consolidation. Participants learned a list of word pairs in the morning or evening, and recall was assessed 12-hrs later, following an interval awake or with overnight sleep. Young adult participants (18-22 yrs were assigned to one of four experimental groups: TBI Sleep (n=14, TBI Wake (n=12, non-TBI Sleep (n=15, non-TBI Wake (n=15. Each TBI participant was >1 yr post-injury. Sleep physiology was measured with polysomnography. Memory consolidation was assessed by comparing change in word-pair recall over 12-hr intersession intervals. The TBI group spent a significantly greater proportion of the night in SWS than the non-TBI group at the expense of NREM1. The TBI group also had marginally lower EEG delta power during SWS in the central region. Intersession changes in recall were greater for intervals with sleep than without sleep in both groups. However, despite abnormal sleep stage proportions for individuals with a TBI history, there was no difference in the intersession change in recall following sleep for the TBI and non-TBI groups. In both Sleep groups combined, there was a positive correlation between Intersession Change and the proportion of the night in NREM2 + SWS. Overall, sleep composition is altered following TBI but such deficits do not yield insufficiencies in sleep-dependent memory consolidation.

  9. Key indicators for the monitoring and evaluation of control programmes of human African trypanosomiasis due to Trypanosoma brucei gambiense.

    Science.gov (United States)

    Bouchet, B; Legros, D; Lee, E

    1998-06-01

    Very little research has been devoted to the design of epidemiological tools for the monitoring and evaluation of National Human African Trypanosomiasis (HAT) Control Programmes and daily management decisions are made in the absence of accurate knowledge of the situation. This paper identifies key indicators necessary to make decisions in the field and constantly adjust control activities to changing situations. Examples are derived from the Médecins Sans Frontières (MSF) HAT Control Programme in Adjumani, Uganda. Based on the principles of quality assurance, the focus is placed on process indicators. A conceptual framework derived from a system view/planning cycle perspective is also described for the construction of indicators. Finally, some specific challenging aspects of the epidemiology of HAT are presented and the limitations of the interpretation of the indicators discussed.

  10. Recommended Amount of Sleep for a Healthy Adult: A Joint Consensus Statement of the American Academy of Sleep Medicine and Sleep Research Society

    OpenAIRE

    Watson, Nathaniel F.; Badr, M. Safwan; Belenky, Gregory; Bliwise, Donald L.; Buxton, Orfeu M.; Buysse, Daniel; Dinges, David F.; Gangwisch, James; Grandner, Michael A.; Kushida, Clete; Malhotra, Raman K.; Martin, Jennifer L.; Patel, Sanjay R.; Quan, Stuart F.; Tasali, Esra

    2015-01-01

    Sleep is essential for optimal health. The American Academy of Sleep Medicine (AASM) and Sleep Research Society (SRS) developed a consensus recommendation for the amount of sleep needed to promote optimal health in adults, using a modified RAND Appropriateness Method process. The recommendation is summarized here. A manuscript detailing the conference proceedings and evidence supporting the final recommendation statement will be published in SLEEP and the Journal of Clinical Sleep Medicine.

  11. REM Sleep Phase Preference in the Crepuscular Octodon degus Assessed by Selective REM Sleep Deprivation

    Science.gov (United States)

    Ocampo-Garcés, Adrián; Hernández, Felipe; Palacios, Adrian G.

    2013-01-01

    Study Objectives: To determine rapid eye movement (REM) sleep phase preference in a crepuscular mammal (Octodon degus) by challenging the specific REM sleep homeostatic response during the diurnal and nocturnal anticrepuscular rest phases. Design: We have investigated REM sleep rebound, recovery, and documented REM sleep propensity measures during and after diurnal and nocturnal selective REM sleep deprivations. Subjects: Nine male wild-captured O. degus prepared for polysomnographic recordings Interventions: Animals were recorded during four consecutive baseline and two separate diurnal or nocturnal deprivation days, under a 12:12 light-dark schedule. Three-h selective REM sleep deprivations were performed, starting at midday (zeitgeber time 6) or midnight (zeitgeber time 18). Measurements and Results: Diurnal and nocturnal REM sleep deprivations provoked equivalent amounts of REM sleep debt, but a consistent REM sleep rebound was found only after nocturnal deprivation. The nocturnal rebound was characterized by a complete recovery of REM sleep associated with an augment in REM/total sleep time ratio and enhancement in REM sleep episode consolidation. Conclusions: Our results support the notion that the circadian system actively promotes REM sleep. We propose that the sleep-wake cycle of O. degus is modulated by a chorus of circadian oscillators with a bimodal crepuscular modulation of arousal and a unimodal promotion of nocturnal REM sleep. Citation: Ocampo-Garcés A; Hernández F; Palacios AG. REM sleep phase preference in the crepuscular Octodon degus assessed by selective REM sleep deprivation. SLEEP 2013;36(8):1247-1256. PMID:23904685

  12. The great sleep recession: changes in sleep duration among US adolescents, 1991-2012.

    Science.gov (United States)

    Keyes, Katherine M; Maslowsky, Julie; Hamilton, Ava; Schulenberg, John

    2015-03-01

    Average nightly sleep times precipitously decline from childhood through adolescence. There is increasing concern that historical shifts also occur in overall adolescent sleep time. Data were drawn from Monitoring the Future, a yearly, nationally representative cross-sectional survey of adolescents in the United States from 1991 to 2012 (N = 272 077) representing birth cohorts from 1973 to 2000. Adolescents were asked how often they get ≥7 hours of sleep and how often they get less sleep than they should. Age-period-cohort models were estimated. Adolescent sleep generally declined over 20 years; the largest change occurred between 1991-1995 and 1996-2000. Age-period-cohort analyses indicate adolescent sleep is best described across demographic subgroups by an age effect, with sleep decreasing across adolescence, and a period effect, indicating that sleep is consistently decreasing, especially in the late 1990s and early 2000s. There was also a cohort effect among some subgroups, including male subjects, white subjects, and those in urban areas, with the earliest cohorts obtaining more sleep. Girls were less likely to report getting ≥7 hours of sleep compared with boys, as were racial/ethnic minorities, students living in urban areas, and those of low socioeconomic status (SES). However, racial/ethnic minorities and adolescents of low SES were more likely to self-report adequate sleep, compared with white subjects and those of higher SES. Declines in self-reported adolescent sleep across the last 20 years are concerning. Mismatch between perceptions of adequate sleep and actual reported sleep times for racial/ethnic minorities and adolescents of low SES are additionally concerning and suggest that health education and literacy approaches may be warranted. Copyright © 2015 by the American Academy of Pediatrics.

  13. Ventilatory control sensitivity in patients with obstructive sleep apnea is sleep stage dependent.

    Science.gov (United States)

    Landry, Shane A; Andara, Christopher; Terrill, Philip I; Joosten, Simon A; Leong, Paul; Mann, Dwayne L; Sands, Scott A; Hamilton, Garun S; Edwards, Bradley A

    2018-05-01

    The severity of obstructive sleep apnea (OSA) is known to vary according to sleep stage; however, the pathophysiology responsible for this robust observation is incompletely understood. The objective of the present work was to examine how ventilatory control system sensitivity (i.e. loop gain) varies during sleep in patients with OSA. Loop gain was estimated using signals collected from standard diagnostic polysomnographic recordings performed in 44 patients with OSA. Loop gain measurements associated with nonrapid eye movement (NREM) stage 2 (N2), stage 3 (N3), and REM sleep were calculated and compared. The sleep period was also split into three equal duration tertiles to investigate how loop gain changes over the course of sleep. Loop gain was significantly lower (i.e. ventilatory control more stable) in REM (Mean ± SEM: 0.51 ± 0.04) compared with N2 sleep (0.63 ± 0.04; p = 0.001). Differences in loop gain between REM and N3 (p = 0.095), and N2 and N3 (p = 0.247) sleep were not significant. Furthermore, N2 loop gain was significantly lower in the first third (0.57 ± 0.03) of the sleep period compared with later second (0.64 ± 0.03, p = 0.012) and third (0.64 ± 0.03, p = 0.015) tertiles. REM loop gain also tended to increase across the night; however, this trend was not statistically significant [F(2, 12) = 3.49, p = 0.09]. These data suggest that loop gain varies between REM and NREM sleep and modestly increases over the course of sleep. Lower loop gain in REM is unlikely to contribute to the worsened OSA severity typically observed in REM sleep, but may explain the reduced propensity for central sleep apnea in this sleep stage.

  14. Associations of sleep bruxism with age, sleep apnea, and daytime problematic behaviors in children.

    Science.gov (United States)

    Tachibana, M; Kato, T; Kato-Nishimura, K; Matsuzawa, S; Mohri, I; Taniike, M

    2016-09-01

    The aims of this study were to investigate the prevalence of sleep bruxism in children in Japan, and its relationships with sleep-related factors and daytime problematic behavior. Guardians of 6023 children aged 2-12 years completed the Japanese Sleep Questionnaire. Multiple regression analysis and structural equation modeling were performed. Sleep bruxism was reported in 21.0% children (n = 1263): the prevalence was highest in the age group of 5-7 years (27.4%). Multiple regression analysis showed that sleep bruxism had significant correlations with age 5-7 years (OR: 1.72; P bruxism had a significant but weak direct effect on daytime problematic behavior, while sleep bruxism significantly correlated with obstructive sleep apnea, which had a higher direct effect on daytime problematic behavior. Sleep bruxism was reported in 21.0% of Japanese children and had independent relationships with age, movements during sleep, and snoring. A comorbidity of sleep-disordered breathing might be related to daytime problematic behavior in children with sleep bruxism. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Delayed Sleep and Sleep Loss in University Students.

    Science.gov (United States)

    Lack, Leon C.

    1986-01-01

    A sample of 211 first-year psychology students completed a questionnaire of sleep habits and difficulities. It was discovered that Delayed Sleep Phase Syndrome may be a significant problem in university student populations. (Author/JD)

  16. Sleep and Eating Disorders.

    Science.gov (United States)

    Allison, Kelly C; Spaeth, Andrea; Hopkins, Christina M

    2016-10-01

    Insomnia is related to an increased risk of eating disorders, while eating disorders are related to more disrupted sleep. Insomnia is also linked to poorer treatment outcomes for eating disorders. However, over the last decade, studies examining sleep and eating disorders have relied on surveys, with no objective measures of sleep for anorexia nervosa or bulimia nervosa, and only actigraphy data for binge eating disorder. Sleep disturbance is better defined for night eating syndrome, where sleep efficiency is reduced and melatonin release is delayed. Studies that include objectively measured sleep and metabolic parameters combined with psychiatric comorbidity data would help identify under what circumstances eating disorders and sleep disturbance produce an additive effect for symptom severity and for whom poor sleep would increase risk for an eating disorder. Cognitive behavior therapy for insomnia may be a helpful addition to treatment of those with both eating disorder and insomnia.

  17. Automatic REM Sleep Detection Associated with Idiopathic REM Sleep Behavior Disorder

    DEFF Research Database (Denmark)

    Kempfner, Jacob; Sørensen, Gertrud Laura; Sørensen, Helge Bjarup Dissing

    2011-01-01

    Rapid eye movement sleep Behavior Disorder (RBD) is a strong early marker of later development of Parkinsonism. Currently there are no objective methods to identify and discriminate abnormal from normal motor activity during REM sleep. Therefore, a REM sleep detection without the use of chin...... electromyography (EMG) is useful. This is addressed by analyzing the classification performance when implementing two automatic REM sleep detectors. The first detector uses the electroencephalography (EEG), electrooculography (EOG) and EMG to detect REM sleep, while the second detector only uses the EEG and EOG......, an automatic computerized REM detection algorithm has been implemented, using wavelet packet combined with artificial neural network. Results: When using the EEG, EOG and EMG modalities, it was possible to correctly classify REM sleep with an average Area Under Curve (AUC) equal to 0:900:03 for normal subjects...

  18. [Sleep disorders in Parkinson's disease: insomnia and sleep fragmentation, daytime hypersomnia, alterations to the circadian rhythm and sleep apnea syndrome].

    Science.gov (United States)

    Mondragón-Rezola, E; Arratíbel-Echarren, I; Ruiz-Martínez, J; Martí-Massó, J F

    2010-02-08

    Sleep disorders in Parkinson's disease are present in 60-98% of patients and reduce their quality of life. To review the pathophysiology, diagnostic approach and management of the different sleep disorders. We describe the pathophysiology associated with neurodegeneration, due to symptoms (motor and nonmotor) and drug therapies. This article reviews insomnia, excessive daytime sleepiness, circadian sleep disorders and sleep apnea. Subjective or objective sleepiness assessment should routinely be performed by physicians looking after Parkinson's disease patients. Management is difficult and should be targeted to the specific sleep disorder and its likely cause.

  19. Sleep hygiene awareness: its relation to sleep quality and diurnal preference

    OpenAIRE

    Voinescu, Bogdan Ioan; Szentagotai-Tatar, Aurora

    2015-01-01

    Background Sleep hygiene is a core component for psychological treatments of insomnia and essential for maintaining a satisfactory sleep. Our study aimed to measure the sleep hygiene awareness and the self-reported quality of sleep among three age groups (young adults, adults and middle-aged adults) and to determine their relation. We also measured their relation with diurnal preference. Methods Using an online questionnaire, we surveyed six hundred fifty two participants, recruited nationwid...

  20. Degeneration of rapid eye movement sleep circuitry underlies rapid eye movement sleep behavior disorder.

    Science.gov (United States)

    McKenna, Dillon; Peever, John

    2017-05-01

    During healthy rapid eye movement sleep, skeletal muscles are actively forced into a state of motor paralysis. However, in rapid eye movement sleep behavior disorder-a relatively common neurological disorder-this natural process is lost. A lack of motor paralysis (atonia) in rapid eye movement sleep behavior disorder allows individuals to actively move, which at times can be excessive and violent. At first glance this may sound harmless, but it is not because rapid eye movement sleep behavior disorder patients frequently injure themselves or the person they sleep with. It is hypothesized that the degeneration or dysfunction of the brain stem circuits that control rapid eye movement sleep paralysis is an underlying cause of rapid eye movement sleep behavior disorder. The link between brain stem degeneration and rapid eye movement sleep behavior disorder stems from the fact that rapid eye movement sleep behavior disorder precedes, in the majority (∼80%) of cases, the development of synucleinopathies such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, which are known to initially cause degeneration in the caudal brain stem structures where rapid eye movement sleep circuits are located. Furthermore, basic science and clinical evidence demonstrate that lesions within the rapid eye movement sleep circuits can induce rapid eye movement sleep-specific motor deficits that are virtually identical to those observed in rapid eye movement sleep behavior disorder. This review examines the evidence that rapid eye movement sleep behavior disorder is caused by synucleinopathic neurodegeneration of the core brain stem circuits that control healthy rapid eye movement sleep and concludes that rapid eye movement sleep behavior disorder is not a separate clinical entity from synucleinopathies but, rather, it is the earliest symptom of these disorders. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and

  1. Cell Injury and Repair Resulting from Sleep Loss and Sleep Recovery in Laboratory Rats

    Science.gov (United States)

    Everson, Carol A.; Henchen, Christopher J.; Szabo, Aniko; Hogg, Neil

    2014-01-01

    Study Objectives: Increased cell injury would provide the type of change in constitution that would underlie sleep disruption as a risk factor for multiple diseases. The current study was undertaken to investigate cell injury and altered cell fate as consequences of sleep deprivation, which were predicted from systemic clues. Design: Partial (35% sleep reduction) and total sleep deprivation were produced in rats for 10 days, which was tolerated and without overtly deteriorated health. Recovery rats were similarly sleep deprived for 10 days, then allowed undisturbed sleep for 2 days. The plasma, liver, lung, intestine, heart, and spleen were analyzed and compared to control values for damage to DNA, proteins, and lipids; apoptotic cell signaling and death; cell proliferation; and concentrations of glutathione peroxidase and catalase. Measurements and Results: Oxidative DNA damage in totally sleep deprived rats was 139% of control values, with organ-specific effects in the liver (247%), lung (166%), and small intestine (145%). Overall and organ-specific DNA damage was also increased in partially sleep deprived rats. In the intestinal epithelium, total sleep deprivation resulted in 5.3-fold increases in dying cells and 1.5-fold increases in proliferating cells, compared with control. Two days of recovery sleep restored the balance between DNA damage and repair, and resulted in normal or below-normal metabolic burdens and oxidative damage. Conclusions: These findings provide physical evidence that sleep loss causes cell damage, and in a manner expected to predispose to replication errors and metabolic abnormalities; thereby providing linkage between sleep loss and disease risk observed in epidemiological findings. Properties of recovery sleep include biochemical and molecular events that restore balance and decrease cell injury. Citation: Everson CA, Henchen CJ, Szabo A, Hogg N. Cell injury and repair resulting from sleep loss and sleep recovery in laboratory rats

  2. No Compromise of Competition Sleep Compared With Habitual Sleep in Elite Australian Footballers.

    Science.gov (United States)

    Lalor, Benita J; Halson, Shona L; Tran, Jacqueline; Kemp, Justin G; Cormack, Stuart J

    2018-01-01

    To assess the impact of match-start time and days relative to match compared with the habitual sleep characteristics of elite Australian Football (AF) players. 45 elite male AF players were assessed during the preseason (habitual) and across 4 home matches during the season. Players wore an activity monitor the night before (-1), night of (0), 1 night after (+1), and 2 nights (+2) after each match and completed a self-reported rating of sleep quality. A 2-way ANOVA with Tukey post hoc was used to determine differences in sleep characteristics between match-start times and days relative to the match. Two-way nested ANOVA was conducted to examine differences between competition and habitual phases. Effect size ± 90% confidence interval (ES ± 90% CI) was calculated to quantify the magnitude of pairwise differences. Differences observed in sleep-onset latency (ES = 0.11 ± 0.16), sleep rating (ES = 0.08 ± 0.14), and sleep duration (ES = 0.08 ± 0.01) between competition and habitual periods were trivial. Sleep efficiency was almost certainly higher during competition than habitual, but this was not reflected in the subjective rating of sleep quality. Elite AF competition does not cause substantial disruption to sleep characteristics compared with habitual sleep. While match-start time has some impact on sleep variables, it appears that the match itself is more of a disruption than the start time. Subjective ratings of sleep from well-being questionnaires appear limited in their ability to accurately provide an indication of sleep quality.

  3. Effects of three hypnotics on the sleep-wakefulness cycle in sleep-disturbed rats.

    Science.gov (United States)

    Shinomiya, Kazuaki; Shigemoto, Yuki; Omichi, Junji; Utsu, Yoshiaki; Mio, Mitsunobu; Kamei, Chiaki

    2004-04-01

    New sleep disturbance model in rats is useful for estimating the characteristics of some hypnotics. The present study was undertaken to investigate the utility of a sleep disturbance model by placing rats on a grid suspended over water using three kinds of hypnotics, that is, short-acting benzodiazepine (triazolam), intermediate-acting benzodiazepine (flunitrazepam) and long-acting barbiturate (phenobarbital). Electrodes for measurement of EEG and EMG were implanted into the frontal cortex and the dorsal neck muscle of rats. EEG and EMG were recorded with an electroencephalogram. SleepSign ver.2.0 was used for EEG and EMG analysis. Total times of wakefulness, non-REM and REM sleep were measured from 0900 to 1500 hours. In rats placed on the grid suspended over water up to 1 cm under the grid surface, not only triazolam but also flunitrazepam and phenobarbital caused a shortening of sleep latency. Both flunitrazepam and phenobarbital were effective in increasing of total non-REM sleep time in rats placed on sawdust or the grid, and the effects of both drugs in rats placed on the grid were larger than those in rats placed on sawdust. Measurement of the hourly non-REM sleep time was useful for investigating the peak time and duration of effect of the three hypnotics. Phenobarbital showed a decrease in total REM sleep time in rats placed on the grid, although both triazolam and flunitrazepam were without effect. The present insomnia model can be used as a sleep disturbance model for testing not only the sleep-inducing effects but also the sleep-maintaining effects including non-REM sleep and REM sleep of hypnotics.

  4. Aging induced ER stress alters sleep and sleep homeostasis

    OpenAIRE

    Brown, Marishka K.; Chan, May T.; Zimmerman, John E.; Pack, Allan I.; Jackson, Nicholas E.; Naidoo, Nirinjini

    2013-01-01

    Alterations in the quality, quantity and architecture of baseline and recovery sleep have been shown to occur during aging. Sleep deprivation induces endoplasmic reticular (ER) stress and upregulates a protective signaling pathway termed the unfolded protein response (UPR). The effectiveness of the adaptive UPR is diminished by age. Previously, we showed that endogenous chaperone levels altered recovery sleep in Drosophila melanogaster. We now report that acute administration of the chemical ...

  5. Sleep characteristics, sleep problems, and associations of self-efficacy among German university students

    Directory of Open Access Journals (Sweden)

    Gulewitsch MD

    2012-02-01

    Full Text Available Angelika A Schlarb1,2, Dominika Kulessa1,*, Marco D Gulewitsch1,*1Faculty of Science, Department of Psychology, University of Tübingen, 2Faculty of Psychology, University of Koblenz-Landau, Germany*These authors contributed equally to this workBackground: Sleep problems, especially insomnia, are a common complaint among adults. International studies on university students have shown prevalence rates between 4.7% and 36.2% for sleep difficulties, and 13.1% and 28.1% for insomnia. Sleep problems are associated with lower social and academic performance and can have a severe impact on psychological and physical health.Objective: The goal of this study was to outline sleep characteristics, prevalence of sleep problems, insomnia, and associations with self-efficacy among German university students.Methods: A total of 2196 university students (70.9% women; mean age 24.16 years participated in the study. Sleep characteristics, sleep problems, insomnia, and self-efficacy were assessed using a questionnaire.Results and conclusion: Analyses revealed that more than 16% of surveyed students needed more than 30 minutes to fall asleep. About 7.7% of the students suffered from insomnia. Short sleep was significantly associated with a considerably increased rate of insomnia (20%. Insomniacs showed lower self-efficacy than students without sleep problems.Keywords: university students, sleep characteristics, sleep problems, insomnia, self-efficacy

  6. Sleep duration and cancer risk: time to use a "sleep-years" index?

    Science.gov (United States)

    Erren, Thomas C

    2012-09-01

    With a focus on melatonin, a recent paper in the Journal investigated the hypothesis that endometrial cancer might be associated with the duration, and ultimately, amount of sleep. The authors found that "[s]elf-reported sleep duration may not adequately represent melatonin levels." The authors also concluded that there was "weak evidence of an association between sleep duration and endometrial cancer risk." Overall, these are interesting observations because primarily experimental and mechanistic research from many angles supports the study's notion that inappropriate sleep may be a determinant of cancer risk. To find out whether this is so in man, rather than assigning study individuals to fixed or average "baseline sleep categories" i.e., ≤5, 6, 7, 8, ≥9 h of habitual sleep in the present study, the accumulated amount of sleep over decades should be reconstructed in retrospective or constructed in prospective studies. To achieve this end, future epidemiological studies may want to use a sleep-years index [SYI]. This simple exposure parameter promises to be a sensible, feasible, and affordable way to approximate cumulative time spent at sleep in critical time windows over many years which we should expect to be relevant for the development of cancer. The SYI could be tested and used in observational studies which promise to be comparable and can be merged. This commentary provides roots of the index and explains why and how it should be used and how it could be interpreted in rigorous studies of biologically plausible links between sleep, on the one hand, and the development of internal cancers, on the other. This commentary also points out limitations of interpreting the SYI. It is emphasized that, where possible, the SYI should be assessed independently of (a) other sleep facets--such as quality--and of (b) known or suspected cancer risk factors. The respective contribution of (a) and (b) to risk must then be assessed during the analyses. Overall, the

  7. Sleep Talking (Somniloquy)

    Science.gov (United States)

    ... radius (in miles): 10 25 50 Share: Essentials in Sleep Insomnia Overview & Facts Symptoms & Causes Diagnosis & Self Tests Treatment ... Sleep talking is very common. It is reported in 50% of young children. About 5% of adults are reported to talk in their sleep. It ...

  8. Dream Content in Patients With Sleep Apnea: A Prospective Sleep Laboratory Study.

    Science.gov (United States)

    Di Pauli, Franziska; Stefani, Ambra; Holzknecht, Evi; Brandauer, Elisabeth; Mitterling, Thomas; Holzinger, Brigitte; Högl, Birgit

    2018-01-15

    Few studies have addressed dreaming in patients with sleep apnea. We hypothesized that respiratory events and subsequent oxygen desaturation act as an important physiological trigger and may thus influence dream content in patients with a sleep-related breathing disorder. Seventy-six patients (28 women, mean age 54 years, range 20-82) who underwent polysomnography because of suspected sleep apnea participated in this study. Dream reports and dream questionnaires were collected immediately after first morning awakening, at 5:30 AM, at the sleep laboratory. Dream content analysis with respect to possible respiratory-related content was performed. Patients were stratified into primary snoring, mild, moderate, and severe sleep apnea groups. In 63 patients sleep apnea was diagnosed (mild n = 31, 49.2%, moderate n = 13, 20.6%, severe n = 19, 30.2%), and 13 subjects in whom a sleep-related breathing disorder was not confirmed were included as a control group with primary snoring. There was no significant difference in respiratory-related dream topics between patients and controls. Also, no influence of respiratory parameters measured during polysomnography on dream content was detectable. We failed to detect a difference in dream content between patients with sleep apnea and controls. Further studies are required to determine whether these results indicate that the incorporation of respiratory events into dreams is absent in patients with sleep apnea or represents a bias due to the collection of dream content in the early morning hours. © 2018 American Academy of Sleep Medicine

  9. Does self-perceived sleep reflect sleep estimated via activity monitors in professional rugby league athletes?

    Science.gov (United States)

    Caia, Johnpaul; Thornton, Heidi R; Kelly, Vincent G; Scott, Tannath J; Halson, Shona L; Cupples, Balin; Driller, Matthew W

    2018-07-01

    This study examined agreement between self-perceived sleep and sleep estimated via activity monitors in professional rugby league athletes. 63 athletes, from three separate teams wore actigraphy monitors for 10.3 ± 3.9 days. During the monitoring period, ratings of perceived sleep quality (on a 1-5 and 1-10 Likert scale), and an estimate of sleep duration were recorded daily. Agreement between sleep estimated via activity monitors and self-perceived sleep was examined using mean bias, Pearson correlation (r) and typical error of the estimate (TEE). 641 nights of sleep were recorded, with a very large, positive correlation observed between sleep duration estimated via activity monitors and subjective sleep duration (r = 0.85), and a TEE of 48 minutes. Mean bias revealed subjective sleep duration overestimated sleep by an average of 19.8 minutes. The relationship between sleep efficiency estimated via activity monitors and self-perceived sleep quality on a 1-5 (r = 0.22) and 1-10 Likert scale (r = 0.28) was limited. The outcomes of this investigation support the use of subjective measures to monitor sleep duration in rugby league athletes when objective means are unavailable. However, practitioners should be aware of the tendency of athletes to overestimate sleep duration.

  10. The Biology of REM Sleep

    Science.gov (United States)

    Peever, John; Fuller, Patrick M.

    2018-01-01

    Considerable advances in our understanding of the mechanisms and functions of rapid-eye-movement (REM) sleep have occurred over the past decade. Much of this progress can be attributed to the development of new neuroscience tools that have enabled high-precision interrogation of brain circuitry linked with REM sleep control, in turn revealing how REM sleep mechanisms themselves impact processes such as sensorimotor function. This review is intended to update the general scientific community about the recent mechanistic, functional and conceptual developments in our current understanding of REM sleep biology and pathobiology. Specifically, this review outlines the historical origins of the discovery of REM sleep, the diversity of REM sleep expression across and within species, the potential functions of REM sleep (e.g., memory consolidation), the neural circuits that control REM sleep, and how dysfunction of REM sleep mechanisms underlie debilitating sleep disorders such as REM sleep behaviour disorder and narcolepsy. PMID:26766231

  11. The Neuroprotective Aspects of Sleep.

    Science.gov (United States)

    Eugene, Andy R; Masiak, Jolanta

    2015-03-01

    Sleep is an important component of human life, yet many people do not understand the relationship between the brain and the process of sleeping. Sleep has been proven to improve memory recall, regulate metabolism, and reduce mental fatigue. A minimum of 7 hours of daily sleep seems to be necessary for proper cognitive and behavioral function. The emotional and mental handicaps associated with chronic sleep loss as well as the highly hazardous situations which can be contributed to the lack of sleep is a serious concern that people need to be aware of. When one sleeps, the brain reorganizes and recharges itself, and removes toxic waste byproducts which have accumulated throughout the day. This evidence demonstrates that sleeping can clear the brain and help maintain its normal functioning. Multiple studies have been done to determine the effects of total sleep deprivation; more recently some have been conducted to show the effects of sleep restriction, which is a much more common occurrence, have the same effects as total sleep deprivation. Each phase of the sleep cycle restores and rejuvenates the brain for optimal function. When sleep is deprived, the active process of the glymphatic system does not have time to perform that function, so toxins can build up, and the effects will become apparent in cognitive abilities, behavior, and judgment. As a background for this paper we have reviewed literature and research of sleep phases, effects of sleep deprivation, and the glymphatic system of the brain and its restorative effect during the sleep cycle.

  12. Sleep is not just for the brain: transcriptional responses to sleep in peripheral tissues

    OpenAIRE

    Anafi, Ron C; Pellegrino, Renata; Shockley, Keith R; Romer, Micah; Tufik, Sergio; Pack, Allan I

    2013-01-01

    Background Many have assumed that the primary function of sleep is for the brain. We evaluated the molecular consequences of sleep and sleep deprivation outside the brain, in heart and lung. Using microarrays we compared gene expression in tissue from sleeping and sleep deprived mice euthanized at the same diurnal times. Results In each tissue, nearly two thousand genes demonstrated statistically significant differential expression as a function of sleep/wake behavioral state. To mitigate the...

  13. Who are Sleeping in Sleep Laboratory? A Retrospective Study

    Directory of Open Access Journals (Sweden)

    Mine Ayşe Altun Emirza

    2012-03-01

    Full Text Available OBJECTIVE: Aim of this study is to compare the results of gold standard in diagnosing sleep disorders polysomnography (PSG with the physician’s preliminary diagnosis and complaints of patients in our data of sleep laboratory. METHODS: 656 patients who made PSG were included in the study. All of the patients age, gender, comorbid chronic disease, complaints, preliminary diagnosis and PSG diagnosis were evaluated retrospectively. RESULTS: In our study, the average age of patients was 56 and 43% women 57% were male. Complaints of patients were snoring, fatigue, stopped breath during sleep, insomnia, headache, daytime sleepiness, restless legs and abnormal behaviors during sleep. According to preliminary diagnoses and PSG diagnoses; Obstructive Sleep Apnea Syndrome (OSAS, narcolepsy, REM behavior disorder (RBD reduced (p 0.05. Sleep disorders in patients was accompanied by chronic diseases, hypertension (34.3%, diabetes (12.8%, Chronic Obstructive Pulmonary Disease (COPD (1.2%, epilepsy (1.8%, Parkinson's disease (3.5%, dementia (3.2%, depression (18.4%, cardiovascular disease (13.3% and cerebrovascular disease (4.9%. 9%. CONCLUSION: We are offering a good clinical history and physical examination with the correct interpretation of PSG for the differential diagnosis can be made true, accurate diagnoses and appropriate treatment modalities in our patients

  14. Sleep habits in adolescents of Saudi Arabia; distinct patterns and extreme sleep schedules.

    Science.gov (United States)

    Merdad, Roah A; Merdad, Leena A; Nassif, Rawan A; El-Derwi, Douaa; Wali, Siraj O

    2014-11-01

    There is a need for comprehensive studies on adolescents' sleep habits in the Middle Eastern region. The aim of this study was to investigate the sleep-wake patterns, prevalence of excessive daytime sleepiness (EDS), and disturbed sleep among adolescents in Saudi Arabia and to identify the associated factors. The study was a cross-sectional survey done on a random sample of 1035 high school students, ages 14-23 years, in Jeddah, Saudi Arabia. The response rate was 91%. Students filled a self-reported questionnaire that included sleep-wake questions, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Perceived Stress Scale, academic performance, and personal data. Students slept an average of 7.0 hours on school nights, with an average delay of 2.8 and 6.0 hours in weekend sleep and rise times, respectively. Around 1 in 10 students stayed up all night and slept after returning from school (exhibiting a reversed sleep cycle) on weeknights. This pattern was more prevalent among boys and students with lower grade point averages. The prevalence of sleep disturbance was 65%, and EDS was found in 37% of the students. Predictors of EDS were school type, stress, napping and caffeine use, while gender was a predictor of disturbed sleep. Adolescents in Saudi Arabia showed a high percentage of poor sleep quality. Compared with adolescents from other countries, they had a larger delay in weekend sleep and rise times. An alarming reversed sleep cycle on weekdays is present and highlights the need for further assessment. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Sickness absenteeism is associated with sleep problems independent of sleep disorders: results of the 2016 Sleep Health Foundation national survey.

    Science.gov (United States)

    Reynolds, Amy C; Appleton, Sarah L; Gill, Tiffany K; Taylor, Anne W; McEvoy, R Douglas; Ferguson, Sally A; Adams, Robert J

    2017-10-01

    Sleep disorders are associated with sickness absenteeism (SA), at significant economic cost. Correlates of absenteeism are less well described in nonclinical samples. We determined the relationship between markers of inadequate sleep and SA in a sample of 551 working adults aged ≥18 years across Australia. We considered diagnosed obstructive sleep apnea (OSA) and insomnia symptoms, daytime symptoms, and sleepiness with respect to sickness absenteeism (missing ≥1 day of work in the past 28 days because of problems with physical or mental health). Sickness absenteeism was reported by 27.0% of participants and was more frequent in younger participants, university graduates, and those experiencing financial stress. Sickness absenteeism was independently associated with insomnia (odds ratio [OR]=2.5, confidence interval [CI]=1.5-4.0], OSA (OR=9.8, CI=4.7-20.7), sleep aid use (OR=3.0, CI=1.9-4.7), and daytime symptoms (OR=3.0, CI=2.0-4.6) and inversely associated with perception of getting adequate sleep (OR=0.6, CI=0.4-0.9). Associations persisted in the population free of insomnia and/or OSA. In adults without clinical sleep disorders, sleep behaviors are contributing to sickness absenteeism. An increased focus at an organizational level on improvement of sleep hygiene is important to reduce lost work performance. Copyright © 2017 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.

  16. The Joint Effect of Sleep Duration and Disturbed Sleep on Cause-Specific Mortality

    DEFF Research Database (Denmark)

    Rod, Naja Hulvej; Kumari, Meena; Lange, Theis

    2014-01-01

    Both sleep duration and sleep quality are related to future health, but their combined effects on mortality are unsettled. We aimed to examine the individual and joint effects of sleep duration and sleep disturbances on cause-specific mortality in a large prospective cohort study....

  17. Sleep extension normalizes ERP of waking auditory sensory gating in healthy habitually short sleeping individuals.

    Science.gov (United States)

    Gumenyuk, Valentina; Korzyukov, Oleg; Roth, Thomas; Bowyer, Susan M; Drake, Christopher L

    2013-01-01

    Chronic sleep loss has been associated with increased daytime sleepiness, as well as impairments in memory and attentional processes. In the present study, we evaluated the neuronal changes of a pre-attentive process of wake auditory sensory gating, measured by brain event-related potential (ERP)--P50 in eight normal sleepers (NS) (habitual total sleep time (TST) 7 h 32 m) vs. eight chronic short sleeping individuals (SS) (habitual TST ≤6 h). To evaluate the effect of sleep extension on sensory gating, the extended sleep condition was performed in chronic short sleeping individuals. Thus, one week of time in bed (6 h 11 m) corresponding to habitual short sleep (hSS), and one week of extended time (∼ 8 h 25 m) in bed corresponding to extended sleep (eSS), were counterbalanced in the SS group. The gating ERP assessment was performed on the last day after each sleep condition week (normal sleep and habitual short and extended sleep), and was separated by one week with habitual total sleep time and monitored by a sleep diary. We found that amplitude of gating was lower in SS group compared to that in NS group (0.3 µV vs. 1.2 µV, at Cz electrode respectively). The results of the group × laterality interaction showed that the reduction of gating amplitude in the SS group was due to lower amplitude over the left hemisphere and central-midline sites relative to that in the NS group. After sleep extension the amplitude of gating increased in chronic short sleeping individuals relative to their habitual short sleep condition. The sleep condition × frontality interaction analysis confirmed that sleep extension significantly increased the amplitude of gating over frontal and central brain areas compared to parietal brain areas.

  18. Sleep extension normalizes ERP of waking auditory sensory gating in healthy habitually short sleeping individuals.

    Directory of Open Access Journals (Sweden)

    Valentina Gumenyuk

    Full Text Available Chronic sleep loss has been associated with increased daytime sleepiness, as well as impairments in memory and attentional processes. In the present study, we evaluated the neuronal changes of a pre-attentive process of wake auditory sensory gating, measured by brain event-related potential (ERP--P50 in eight normal sleepers (NS (habitual total sleep time (TST 7 h 32 m vs. eight chronic short sleeping individuals (SS (habitual TST ≤6 h. To evaluate the effect of sleep extension on sensory gating, the extended sleep condition was performed in chronic short sleeping individuals. Thus, one week of time in bed (6 h 11 m corresponding to habitual short sleep (hSS, and one week of extended time (∼ 8 h 25 m in bed corresponding to extended sleep (eSS, were counterbalanced in the SS group. The gating ERP assessment was performed on the last day after each sleep condition week (normal sleep and habitual short and extended sleep, and was separated by one week with habitual total sleep time and monitored by a sleep diary. We found that amplitude of gating was lower in SS group compared to that in NS group (0.3 µV vs. 1.2 µV, at Cz electrode respectively. The results of the group × laterality interaction showed that the reduction of gating amplitude in the SS group was due to lower amplitude over the left hemisphere and central-midline sites relative to that in the NS group. After sleep extension the amplitude of gating increased in chronic short sleeping individuals relative to their habitual short sleep condition. The sleep condition × frontality interaction analysis confirmed that sleep extension significantly increased the amplitude of gating over frontal and central brain areas compared to parietal brain areas.

  19. Sleep in Children and Adolescents with Angelman Syndrome: Association with Parent Sleep and Stress

    Science.gov (United States)

    Goldman, S. E.; Bichell, T. J.; Surdyka, K.; Malow, B. A.

    2012-01-01

    Background: Sleep concerns are common in children with Angelman syndrome, with 20-80% of individuals having a decreased sleep need and/or abnormal sleep-wake cycles. The impact of these sleep behaviours on parental sleep and stress is not known. Method: Through the use of standardised questionnaires, wrist actigraphy and polysomnography, we…

  20. Differential Editosome Protein Function between Life Cycle Stages of Trypanosoma brucei.

    Science.gov (United States)

    McDermott, Suzanne M; Guo, Xuemin; Carnes, Jason; Stuart, Kenneth

    2015-10-09

    Uridine insertion and deletion RNA editing generates functional mitochondrial mRNAs in Trypanosoma brucei. The mRNAs are differentially edited in bloodstream form (BF) and procyclic form (PF) life cycle stages, and this correlates with the differential utilization of glycolysis and oxidative phosphorylation between the stages. The mechanism that controls this differential editing is unknown. Editing is catalyzed by multiprotein ∼20S editosomes that contain endonuclease, 3'-terminal uridylyltransferase, exonuclease, and ligase activities. These editosomes also contain KREPB5 and KREPA3 proteins, which have no functional catalytic motifs, but they are essential for parasite viability, editing, and editosome integrity in BF cells. We show here that repression of KREPB5 or KREPA3 is also lethal in PF, but the effects on editosome structure differ from those in BF. In addition, we found that point mutations in KREPB5 or KREPA3 differentially affect cell growth, editosome integrity, and RNA editing between BF and PF stages. These results indicate that the functions of KREPB5 and KREPA3 editosome proteins are adjusted between the life cycle stages. This implies that these proteins are involved in the processes that control differential editing and that the 20S editosomes differ between the life cycle stages. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Sleep, Memory & Brain Rhythms.

    Science.gov (United States)

    Watson, Brendon O; Buzsáki, György

    2015-01-01

    Sleep occupies roughly one-third of our lives, yet the scientific community is still not entirely clear on its purpose or function. Existing data point most strongly to its role in memory and homeostasis: that sleep helps maintain basic brain functioning via a homeostatic mechanism that loosens connections between overworked synapses, and that sleep helps consolidate and re-form important memories. In this review, we will summarize these theories, but also focus on substantial new information regarding the relation of electrical brain rhythms to sleep. In particular, while REM sleep may contribute to the homeostatic weakening of overactive synapses, a prominent and transient oscillatory rhythm called "sharp-wave ripple" seems to allow for consolidation of behaviorally relevant memories across many structures of the brain. We propose that a theory of sleep involving the division of labor between two states of sleep-REM and non-REM, the latter of which has an abundance of ripple electrical activity-might allow for a fusion of the two main sleep theories. This theory then postulates that sleep performs a combination of consolidation and homeostasis that promotes optimal knowledge retention as well as optimal waking brain function.

  2. Effects of daytime food intake on memory consolidation during sleep or sleep deprivation.

    Directory of Open Access Journals (Sweden)

    Nina Herzog

    Full Text Available Sleep enhances memory consolidation. Bearing in mind that food intake produces many metabolic signals that can influence memory processing in humans (e.g., insulin, the present study addressed the question as to whether the enhancing effect of sleep on memory consolidation is affected by the amount of energy consumed during the preceding daytime. Compared to sleep, nocturnal wakefulness has been shown to impair memory consolidation in humans. Thus, a second question was to examine whether the impaired memory consolidation associated with sleep deprivation (SD could be compensated by increased daytime energy consumption. To these aims, 14 healthy normal-weight men learned a finger tapping sequence (procedural memory and a list of semantically associated word pairs (declarative memory. After the learning period, standardized meals were administered, equaling either ∼50% or ∼150% of the estimated daily energy expenditure. In the morning, after sleep or wakefulness, memory consolidation was tested. Plasma glucose was measured both before learning and retrieval. Polysomnographic sleep recordings were performed by electroencephalography (EEG. Independent of energy intake, subjects recalled significantly more word pairs after sleep than they did after SD. When subjects stayed awake and received an energy oversupply, the number of correctly recalled finger sequences was equal to those seen after sleep. Plasma glucose did not differ among conditions, and sleep time in the sleep conditions was not influenced by the energy intake interventions. These data indicate that the daytime energy intake level affects neither sleep's capacity to boost the consolidation of declarative and procedural memories, nor sleep's quality. However, high energy intake was followed by an improved procedural but not declarative memory consolidation under conditions of SD. This suggests that the formation of procedural memory is not only triggered by sleep but is also

  3. Effects of daytime food intake on memory consolidation during sleep or sleep deprivation.

    Science.gov (United States)

    Herzog, Nina; Friedrich, Alexia; Fujita, Naoko; Gais, Steffen; Jauch-Chara, Kamila; Oltmanns, Kerstin M; Benedict, Christian

    2012-01-01

    Sleep enhances memory consolidation. Bearing in mind that food intake produces many metabolic signals that can influence memory processing in humans (e.g., insulin), the present study addressed the question as to whether the enhancing effect of sleep on memory consolidation is affected by the amount of energy consumed during the preceding daytime. Compared to sleep, nocturnal wakefulness has been shown to impair memory consolidation in humans. Thus, a second question was to examine whether the impaired memory consolidation associated with sleep deprivation (SD) could be compensated by increased daytime energy consumption. To these aims, 14 healthy normal-weight men learned a finger tapping sequence (procedural memory) and a list of semantically associated word pairs (declarative memory). After the learning period, standardized meals were administered, equaling either ∼50% or ∼150% of the estimated daily energy expenditure. In the morning, after sleep or wakefulness, memory consolidation was tested. Plasma glucose was measured both before learning and retrieval. Polysomnographic sleep recordings were performed by electroencephalography (EEG). Independent of energy intake, subjects recalled significantly more word pairs after sleep than they did after SD. When subjects stayed awake and received an energy oversupply, the number of correctly recalled finger sequences was equal to those seen after sleep. Plasma glucose did not differ among conditions, and sleep time in the sleep conditions was not influenced by the energy intake interventions. These data indicate that the daytime energy intake level affects neither sleep's capacity to boost the consolidation of declarative and procedural memories, nor sleep's quality. However, high energy intake was followed by an improved procedural but not declarative memory consolidation under conditions of SD. This suggests that the formation of procedural memory is not only triggered by sleep but is also sensitive to the

  4. Sleep duration and sleep quality are associated differently with alterations of glucose homeostasis.

    Science.gov (United States)

    Byberg, S; Hansen, A-L S; Christensen, D L; Vistisen, D; Aadahl, M; Linneberg, A; Witte, D R

    2012-09-01

    Studies suggest that inadequate sleep duration and poor sleep quality increase the risk of impaired glucose regulation and diabetes. However, associations with specific markers of glucose homeostasis are less well explained. The objective of this study was to explore possible associations of sleep duration and sleep quality with markers of glucose homeostasis and glucose tolerance status in a healthy population-based study sample. The study comprised 771 participants from the Danish, population-based cross-sectional 'Health2008' study. Sleep duration and sleep quality were measured by self-report. Markers of glucose homeostasis were derived from a 3-point oral glucose tolerance test and included fasting plasma glucose, 2-h plasma glucose, HbA(1c), two measures of insulin sensitivity (the insulin sensitivity index(0,120) and homeostasis model assessment of insulin sensitivity), the homeostasis model assessment of β-cell function and glucose tolerance status. Associations of sleep duration and sleep quality with markers of glucose homeostasis and tolerance were analysed by multiple linear and logistic regression. A 1-h increment in sleep duration was associated with a 0.3 mmol/mol (0.3%) decrement in HbA(1c) and a 25% reduction in the risk of having impaired glucose regulation. Further, a 1-point increment in sleep quality was associated with a 2% increase in both the insulin sensitivity index(0,120) and homeostasis model assessment of insulin sensitivity, as well as a 1% decrease in homeostasis model assessment of β-cell function. In the present study, shorter sleep duration was mainly associated with later alterations in glucose homeostasis, whereas poorer sleep quality was mainly associated with earlier alterations in glucose homeostasis. Thus, adopting healthy sleep habits may benefit glucose metabolism in healthy populations. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

  5. [Sleep, work, and study: sleep duration in working and non-working students].

    Science.gov (United States)

    Pereira, Erico Felden; Bernardo, Maria Perpeto Socorro Leite; D'Almeida, Vânia; Louzada, Fernando Mazzilli

    2011-05-01

    The aim of this study was to investigate the duration of sleep and associated factors in working and non-working students. Data were analyzed on the sleep-wake cycle in 863 teenage students in São Paulo, Brazil. Adjusted analyses were performed to compare sleep duration in working and non-working students. 18.4% of the group worked, and 52% of the working students slept eight hours or less per night. Prevalence of short sleep duration was higher in working students of both sexes (males, p = 0.017; females, p Working students showed short sleep duration in the analysis adjusted for socioeconomic status, but short sleep was more frequent in older adolescents (p = 0.004) and in lower (p = 0.001) and middle (p = 0.011) socioeconomic classes. Although more working students were in night school, in the model adjusted for gender and socioeconomic status, working students in afternoon courses showed higher prevalence of short sleep duration (PR = 2.53; 95%CI: 1.68-4.12).

  6. Effect of Inhaled Lavender and Sleep Hygiene on Self-Reported Sleep Issues: A Randomized Controlled Trial

    Science.gov (United States)

    Lillehei, Angela Smith; Savik, Kay; Reis, Reilly

    2015-01-01

    Abstract Objectives: To compare the effectiveness of lavender (Lavandula angustifolia) and sleep hygiene versus sleep hygiene alone on sleep quantity and sleep quality and to determine sustained effect at two-week follow-up. Design: A randomized controlled trial with investigator blinding and steps taken to blind the participants. Setting: Participants' usual sleep setting. Subjects: Seventy-nine college students with self-reported sleep issues. Interventions: The intervention took place over five nights with baseline, postintervention, and two-week follow-up assessments. Both groups practiced good sleep hygiene and wore an inhalation patch on their chest at night. One group wore a patch with 55 μl of lavender essential oil and the other group wore a blank patch. Outcome measures: Sleep quantity was measured using a Fitbit® tracker and a sleep diary, and sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI) and the NIH Patient-Reported Outcomes Measurement Information System (PROMIS) sleep disturbance short form. Results: The lavender and sleep hygiene group demonstrated better sleep quality at postintervention and two-week follow-up (PSQI p=0 .01, <0.001 and PROMIS p=0.04, 0.007, respectively). The sleep-hygiene-only group also demonstrated better sleep quality but to a lesser extent (PSQI p=0.02, 0.06 and PROMIS p=0.03, 0.03, respectively). Additionally, a clinical effect was found for the lavender group at postintervention, along with a significant finding for waking feeling refreshed (p=0.01). Sleep quantity did not differ between groups. Conclusions: Lavender and sleep hygiene together, and sleep hygiene alone to a lesser degree, improved sleep quality for college students with self-reported sleep issues, with an effect remaining at follow-up. PMID:26133206

  7. Sleep During Pregnancy: The nuMoM2b Pregnancy and Sleep Duration and Continuity Study.

    Science.gov (United States)

    Reid, Kathryn J; Facco, Francesca L; Grobman, William A; Parker, Corette B; Herbas, Marcos; Hunter, Shannon; Silver, Robert M; Basner, Robert C; Saade, George R; Pien, Grace W; Manchanda, Shalini; Louis, Judette M; Nhan-Chang, Chia-Lang; Chung, Judith H; Wing, Deborah A; Simhan, Hyagriv N; Haas, David M; Iams, Jay; Parry, Samuel; Zee, Phyllis C

    2017-05-01

    To characterize sleep duration, timing and continuity measures in pregnancy and their association with key demographic variables. Multisite prospective cohort study. Women enrolled in the nuMoM2b study (nulliparous women with a singleton gestation) were recruited at the second study visit (16-21 weeks of gestation) to participate in the Sleep Duration and Continuity substudy. Women sleep log for 7 consecutive days. Time in bed, sleep duration, fragmentation index, sleep efficiency, wake after sleep onset, and sleep midpoint were averaged across valid primary sleep periods for each participant. Valid data were available from 782 women with mean age of 27.3 (5.5) years. Median sleep duration was 7.4 hours. Approximately 27.9% of women had a sleep duration of sleep duration of >9 hours. In multivariable models including age, race/ethnicity, body mass index, insurance status, and recent smoking history, sleep duration was significantly associated with race/ethnicity and insurance status, while time in bed was only associated with insurance status. Sleep continuity measures and sleep midpoint were significantly associated with all covariates in the model, with the exception of age for fragmentation index and smoking for wake after sleep onset. Our results demonstrate the relationship between sleep and important demographic characteristics during pregnancy. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  8. Cynaropicrin targets the trypanothione redox system in Trypanosoma brucei.

    Science.gov (United States)

    Zimmermann, Stefanie; Oufir, Mouhssin; Leroux, Alejandro; Krauth-Siegel, R Luise; Becker, Katja; Kaiser, Marcel; Brun, Reto; Hamburger, Matthias; Adams, Michael

    2013-11-15

    In mice cynaropicrin (CYN) potently inhibits the proliferation of Trypanosoma brucei-the causative agent of Human African Trypanosomiasis-by a so far unknown mechanism. We hypothesized that CYNs α,β-unsaturated methylene moieties act as Michael acceptors for glutathione (GSH) and trypanothione (T(SH)2), the main low molecular mass thiols essential for unique redox metabolism of these parasites. The analysis of this putative mechanism and the effects of CYN on enzymes of the T(SH)2 redox metabolism including trypanothione reductase, trypanothione synthetase, glutathione-S-transferase, and ornithine decarboxylase are shown. A two step extraction protocol with subsequent UPLC-MS/MS analysis was established to quantify intra-cellular CYN, T(SH)2, GSH, as well as GS-CYN and T(S-CYN)2 adducts in intact T. b. rhodesiense cells. Within minutes of exposure to CYN, the cellular GSH and T(SH)2 pools were entirely depleted, and the parasites entered an apoptotic stage and died. CYN also showed inhibition of the ornithine decarboxylase similar to the positive control eflornithine. Significant interactions with the other enzymes involved in the T(SH)2 redox metabolism were not observed. Alongside many other biological activities sesquiterpene lactones including CYN have shown antitrypanosomal effects, which have been postulated to be linked to formation of Michael adducts with cellular nucleophiles. Here the interaction of CYN with biological thiols in a cellular system in general, and with trypanosomal T(SH)2 redox metabolism in particular, thus offering a molecular explanation for the antitrypanosomal activity is demonstrated. At the same time, the study provides a novel extraction and analysis protocol for components of the trypanosomal thiol metabolism. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Sleep Characteristics, Sleep Problems, and Associations to Quality of Life among Psychotherapists.

    Science.gov (United States)

    Schlarb, Angelika A; Reis, Dorota; Schröder, Annette

    2012-01-01

    Sleep problems, especially insomnia, are a common complaint among adults. International studies have shown prevalence rates between 4.7 and 36.2% for sleep difficulties in general, whereas 13.1-28.1% report insomnia symptoms. Sleep problems are associated with lower social and academic performance and can have a severe impact on psychological and physical health. Psychotherapists are suppliers within the public health system. The goal of this study was to outline sleep characteristics, prevalence of sleep problems, insomnia, and associations of quality of life among psychotherapists. A total of 774 psychotherapists (74.7% women; mean age 46 years) participated in the study. Sleep characteristics, sleep problems, well-being, life satisfaction and workload, as well as specific job demands, were assessed via a questionnaire. Analyses revealed that more than 4.2% of the surveyed psychotherapists have difficulties falling asleep, 12.7% often wake up in the night, and 26.6% feel tired, and 3.4% think that their interrupted sleep affects work performance. About 44.1% of them suffer from symptoms of insomnia. Path models showed that insomnia is significantly related to well-being and life satisfaction.

  10. Sleep Characteristics, Sleep Problems, and Associations to Quality of Life among Psychotherapists

    Directory of Open Access Journals (Sweden)

    Angelika A. Schlarb

    2012-01-01

    Full Text Available Sleep problems, especially insomnia, are a common complaint among adults. International studies have shown prevalence rates between 4.7 and 36.2% for sleep difficulties in general, whereas 13.1–28.1% report insomnia symptoms. Sleep problems are associated with lower social and academic performance and can have a severe impact on psychological and physical health. Psychotherapists are suppliers within the public health system. The goal of this study was to outline sleep characteristics, prevalence of sleep problems, insomnia, and associations of quality of life among psychotherapists. A total of 774 psychotherapists (74.7% women; mean age 46 years participated in the study. Sleep characteristics, sleep problems, well-being, life satisfaction and workload, as well as specific job demands, were assessed via a questionnaire. Analyses revealed that more than 4.2% of the surveyed psychotherapists have difficulties falling asleep, 12.7% often wake up in the night, and 26.6% feel tired, and 3.4% think that their interrupted sleep affects work performance. About 44.1% of them suffer from symptoms of insomnia. Path models showed that insomnia is significantly related to well-being and life satisfaction.

  11. Cell injury and repair resulting from sleep loss and sleep recovery in laboratory rats.

    Science.gov (United States)

    Everson, Carol A; Henchen, Christopher J; Szabo, Aniko; Hogg, Neil

    2014-12-01

    Increased cell injury would provide the type of change in constitution that would underlie sleep disruption as a risk factor for multiple diseases. The current study was undertaken to investigate cell injury and altered cell fate as consequences of sleep deprivation, which were predicted from systemic clues. Partial (35% sleep reduction) and total sleep deprivation were produced in rats for 10 days, which was tolerated and without overtly deteriorated health. Recovery rats were similarly sleep deprived for 10 days, then allowed undisturbed sleep for 2 days. The plasma, liver, lung, intestine, heart, and spleen were analyzed and compared to control values for damage to DNA, proteins, and lipids; apoptotic cell signaling and death; cell proliferation; and concentrations of glutathione peroxidase and catalase. Oxidative DNA damage in totally sleep deprived rats was 139% of control values, with organ-specific effects in the liver (247%), lung (166%), and small intestine (145%). Overall and organ-specific DNA damage was also increased in partially sleep deprived rats. In the intestinal epithelium, total sleep deprivation resulted in 5.3-fold increases in dying cells and 1.5-fold increases in proliferating cells, compared with control. Recovery sleep restored the balance between DNA damage and repair, and resulted in normal or below-normal metabolic burdens and oxidative damage. These findings provide physical evidence that sleep loss causes cell damage, and in a manner expected to predispose to replication errors and metabolic abnormalities; thereby providing linkage between sleep loss and disease risk observed in epidemiological findings. Properties of recovery sleep include biochemical and molecular events that restore balance and decrease cell injury. © 2014 Associated Professional Sleep Societies, LLC.

  12. Sleep quality but not sleep quantity effects on cortisol responses to acute psychosocial stress.

    Science.gov (United States)

    Bassett, Sarah M; Lupis, Sarah B; Gianferante, Danielle; Rohleder, Nicolas; Wolf, Jutta M

    2015-01-01

    Given the well-documented deleterious health effects, poor sleep has become a serious public health concern and increasing efforts are directed toward understanding underlying pathways. One potential mechanism may be stress and its biological correlates; however, studies investigating the effects of poor sleep on a body's capacity to deal with challenges are lacking. The current study thus aimed at testing the effects of sleep quality and quantity on cortisol responses to acute psychosocial stress. A total of 73 college-aged adults (44 females) were investigated. Self-reported sleep behavior was assessed via the Pittsburgh Sleep Quality Index and salivary cortisol responses to the Trier Social Stress Test were measured. In terms of sleep quality, we found a significant three-way interaction, such that relative to bad sleep quality, men who reported fairly good or very good sleep quality showed blunted or exaggerated cortisol responses, respectively, while women's stress responses were less dependent on their self-reported sleep quality. Contrarily, average sleep duration did not appear to impact cortisol stress responses. Lastly, participants who reported daytime dysfunctions (i.e. having trouble staying awake or keeping up enthusiasm) also showed a trend to blunted cortisol stress responses compared to participants who did not experience these types of daytime dysfunctions. Overall, the current study suggests gender-specific stress reactivity dysfunctions as one mechanism linking poor sleep with detrimental physical health outcomes. Furthermore, the observed differential sleep effects may indicate that while the body may be unable to maintain normal hypothalamic-pituitary-adrenal functioning in an acute psychosocial stress situation after falling prey to low sleep quality, it may retain capacities to deal with challenges during extended times of sleep deprivation.

  13. Parkinsonian syndromes presenting with circadian rhythm sleep disorder- advanced sleep-phase type.

    Science.gov (United States)

    Shukla, Garima; Kaul, Bhavna; Gupta, Anupama; Goyal, Vinay; Behari, Madhuri

    2015-01-01

    Circadian rhythm sleep disorder-advanced sleep-phase type is a relatively uncommon disorder, mostly seen among the elderly population. Impaired circadian rhythms have been reported in neurodegenerative conditions; however, there are no reports of any circadian rhythm sleep disorder among patients with Parkinsonian syndromes. We report two patients who presented with this circadian rhythm disorder, and were then diagnosed with a Parkinsonian syndrome. The cases. A 65-year-old retired man presented with history of abrupt change in sleep schedules, sleeping around 6.30-7 p.m. and waking up around 3-4 a.m. for the last 2 months. On detailed examination, the patient was observed to have symmetrical bradykinesia and cogwheel rigidity of limbs. A diagnosis of multiple system atrophy was made, supported by MRI findings and evidence of autonomic dysfunction. Symptoms of change in sleep-wake cycles resolved over the next 1 year, while the patient was treated with dopaminergic therapy. A 47-year-old man, who was being evaluated for presurgical investigation for refractory temporal lobe epilepsy, presented with complaints suggestive of dysarthria, bradykinesia of limbs and frequent falls for 5 months. Simultaneously, he began to sleep around 7 p.m. and wake up at about 2-3 a.m. Examination revealed severe axial rigidity, restricted vertical gaze and bradykinesia of limbs. A diagnosis of progressive supranuclear palsy was made. This is the first report of Parkinson's plus syndromes presenting with a circadian rhythm sleep disorder-advanced sleep-phase type. More prospective assessment for circadian sleep disorders may introduce useful insights into similar associations. Copyright 2015, NMJI.

  14. Chronic sleep reduction in adolescents

    NARCIS (Netherlands)

    Dewald-Kaufmann, J.F.

    2012-01-01

    Based on the results of this thesis, it can be concluded that sleep problems and chronic sleep reduction have a high impact on adolescents’ daytime functioning. Additionally, this research shows that gradual sleep extension can improve adolescents’ sleep and especially their chronic sleep reduction.

  15. Sleep and Sleep-wake Rhythm in Older Adults with Intellectual Disabilities

    NARCIS (Netherlands)

    E. van de Wouw-Van Dijk (Ellen)

    2013-01-01

    textabstractEveryone who has experienced poor sleep knows how it affects daytime functioning and wellbeing. A good night’s rest and a stable sleep-wake rhythm are therefore very important. The sleep-wake rhythm is regulated by several brain structures. People with an intellectual disability (ID) all

  16. Sleep and Salivary Cortisol

    DEFF Research Database (Denmark)

    Garde, Anne Helene; Karlson, Bernt; Hansen, Åse Marie

    2011-01-01

    The aim of the present chapter was to analyze whether measures of cortisol in saliva were associated with measures of sleep and to explore if divergent results were related to underlying differences in theoretic assumptions and methods. Measures of sleep quality included sleep duration, overall...... sleep quality, difficulty falling asleep, disturbed sleep, and sleep deprivation. Twenty-three papers were found to fulfill the inclusion criteria. Cortisol measures were grouped into single time points at different times during the day, deviations at different time periods during the day, reactivity...... and recovery after a standardized laboratory test, area under the curve and response to dexamethasone test. A large proportion of the studies included showed non-significant findings, which, in several cases, may be a result of low power. The most consistent results were a positive association between sleep...

  17. Relationship of symptoms with sleep-stage abnormalities in obstructive sleep apnea-hypopnea syndrome

    Directory of Open Access Journals (Sweden)

    Md Basunia

    2016-09-01

    Full Text Available Background: Patients with obstructive sleep apnea-hypopnea syndrome (OSAHS present with a variety of sleep-related symptoms. In polysomnography, sleep architecture is almost always abnormal, but it is not known which of the sleep-stage abnormalities are related to symptoms. Finding key sleep-stage abnormality that cause symptoms may be of therapeutic importance to alleviate symptoms. So far the mainstay of treatment is continuous positive airway pressure (CPAP/bi-level positive airway pressure (BIPAP therapy, but many patients are non-compliant to it. Correcting the sleep-stage abnormality that cause symptoms by pharmacotherapy may become an important adjunct to CPAP/BIPAP therapy. Methods: A cross-sectional study. Adult subjects who attended a sleep laboratory for diagnostic polysomnography for a period of 1 month were recruited consecutively. OSAHS was diagnosed using American Academy of Sleep Medicine criteria. Subjects filled a questionnaire for symptoms prior to polysomnography. Results: Thirty subjects, of whom 83.3% were obese, met diagnostic criteria, with males constituting 46.7% and females constituting 53%. Mean age was 53.40±11.60 years. Sleep architecture comprised N1 19.50±19.00%, N2 53.93±13.39%, N3 3.90±19.50%, and rapid eye movement 8.92±6.21%. Excessive fatigue or sleepiness, waking up tired, falling asleep during the day, trouble paying attention, snoring and insomnia were significantly related to decreased N3 sleep. Conclusions: Most of the symptoms in OSAHS in adults are related to decreased stage N3 sleep. If confirmed by larger controlled studies, correcting N3 sleep deficiency by pharmacotherapy may become an important adjunct to CPAP/BIPAP therapy to alleviate symptoms.

  18. Pinellia ternata (Thunb.) Makino Preparation promotes sleep by increasing REM sleep.

    Science.gov (United States)

    Lin, Sisi; Nie, Bo; Yao, Guihong; Yang, Hui; Ye, Ren; Yuan, Zhengzhong

    2018-05-15

    Pinellia ternata (Thunb.) Makino Preparation (PTP) is widely used to treat insomnia in traditional Chinese medicine; however, its specific role is not clear. In this study, PTP was prepared at three concentrations. For locomotor activity tests, mice were treated with PTP and evaluated for 14 days. For polygraph recordings, mice were treated for 14 days and recorded after treatment. The main chemical constituents in PTP were identified by Ultra performance liquid chromatography/quadrupole time spectrometry (UPLC/Q-TOF-MS). The results showed that 0.9 g/mL PTP significantly reduced locomotor activity. The effect was related to the time of treatment. PTP reduced wakefulness and increased sleep in mice. Furthermore, PTP promoted sleep by increasing the number of REM sleep episodes with a duration of 64-128s and increasing the number of transitions from NREM sleep to REM sleep and from REM sleep to wakefulness. A total of 17 compounds were identified.

  19. Effects of Sleep Deprivation on Brain Bioenergetics, Sleep, and Cognitive Performance in Cocaine-Dependent Individuals

    Science.gov (United States)

    Trksak, George H.; Bracken, Bethany K.; Jensen, J. Eric; Plante, David T.; Penetar, David M.; Tartarini, Wendy L.; Maywalt, Melissa A.; Dorsey, Cynthia M.; Renshaw, Perry F.; Lukas, Scott E.

    2013-01-01

    In cocaine-dependent individuals, sleep is disturbed during cocaine use and abstinence, highlighting the importance of examining the behavioral and homeostatic response to acute sleep loss in these individuals. The current study was designed to identify a differential effect of sleep deprivation on brain bioenergetics, cognitive performance, and sleep between cocaine-dependent and healthy control participants. 14 healthy control and 8 cocaine-dependent participants experienced consecutive nights of baseline, total sleep deprivation, and recovery sleep in the research laboratory. Participants underwent [31]P magnetic resonance spectroscopy (MRS) brain imaging, polysomnography, Continuous Performance Task, and Digit Symbol Substitution Task. Following recovery sleep, [31]P MRS scans revealed that cocaine-dependent participants exhibited elevated global brain β-NTP (direct measure of adenosine triphosphate), α-NTP, and total NTP levels compared to those of healthy controls. Cocaine-dependent participants performed worse on the Continuous Performance Task and Digit Symbol Substitution Task at baseline compared to healthy control participants, but sleep deprivation did not worsen cognitive performance in either group. Enhancements of brain ATP levels in cocaine dependent participants following recovery sleep may reflect a greater impact of sleep deprivation on sleep homeostasis, which may highlight the importance of monitoring sleep during abstinence and the potential influence of sleep loss in drug relapse. PMID:24250276

  20. Repeated Sleep Restriction in Adolescent Rats Altered Sleep Patterns and Impaired Spatial Learning/Memory Ability

    Science.gov (United States)

    Yang, Su-Rong; Sun, Hui; Huang, Zhi-Li; Yao, Ming-Hui; Qu, Wei-Min

    2012-01-01

    Study Objectives: To investigate possible differences in the effect of repeated sleep restriction (RSR) during adolescence and adulthood on sleep homeostasis and spatial learning and memory ability. Design: The authors examined electroencephalograms of rats as they were subjected to 4-h daily sleep deprivation that continued for 7 consecutive days and assessed the spatial learning and memory by Morris water maze test (WMT). Participants: Adolescent and adult rats. Measurements and Results: Adolescent rats exhibited a similar amount of rapid eye movement (REM) and nonrapid eye movement (NREM) sleep with higher slow wave activity (SWA, 0.5-4 Hz) and fewer episodes and conversions with prolonged durations, indicating they have better sleep quality than adult rats. After RSR, adult rats showed strong rebound of REM sleep by 31% on sleep deprivation day 1; this value was 37% on sleep deprivation day 7 in adolescents compared with 20-h baseline level. On sleep deprivation day 7, SWA in adult and adolescent rats increased by 47% and 33%, and such elevation lasted for 5 h and 7 h, respectively. Furthermore, the authors investigated the effects of 4-h daily sleep deprivation immediately after the water maze training sessions on spatial cognitive performance. Adolescent rats sleep-restricted for 7 days traveled a longer distance to find the hidden platform during the acquisition training and had fewer numbers of platform crossings in the probe trial than those in the control group, something that did not occur in the sleep-deprived adult rats. Conclusions: Repeated sleep restriction (RSR) altered sleep profiles and mildly impaired spatial learning and memory capability in adolescent rats. Citation: Yang SR; Sun H; Huang ZL; Yao MH; Qu WM. Repeated sleep restriction in adolescent rats altered sleep patterns and impaired spatial learning/memory ability. SLEEP 2012;35(6):849-859. PMID:22654204

  1. Children's Sleep Needs: Is There Sufficient Evidence to Recommend Optimal Sleep for Children?

    OpenAIRE

    Matricciani, Lisa; Blunden, Sarah; Rigney, Gabrielle; Williams, Marie T.; Olds, Tim S.

    2013-01-01

    It is widely recognized that sleep is important for children's health and well-being and that short sleep duration is associated with a wide range of negative health outcomes. Recently, there has been much interest in whether or not there are sufficient data to support the specific recommendations made for how much sleep children need. In this article we explore concepts related to children's sleep need, discuss the theory, rationale, and empirical evidence for contemporary sleep recommendati...

  2. Assessing the sleeping habits of patients in a sleep disorder centre: a review of sleep diary accuracy

    Science.gov (United States)

    Lawrence, Geoffrey

    2018-01-01

    Background Excessive daytime sleepiness (EDS) is a complaint common to many aspects of medicine. There are primary and secondary causes for EDS, with secondary causes including a large number of common conditions. Primary causes, such as narcolepsy, are much rarer. When assessing for primary hypersomnia, restricted or fragmented sleep must be ruled out. This process involves assessment of sleeping habits using a sleep diary and/or actigraphy. Clinicians are suspicious of the accuracy with which patients use the former. This review aims to evaluate the accuracy of a sleep diary study against the ‘objective gold standard’ actigraphy report. Methods Data from 35 patients at a Sleep Disorder Centre who underwent both a sleep diary and actigraphy study for suspected primary hypersomnia in 2016 was collected. Mean values of four variables were calculated: ‘time of lights out’, ‘time to fall asleep’, ‘time of waking’ and ‘sleep time’. The ‘similarity’ was assessed. This was a term defined in three different ways: if sleep diary values are accurate to within 20, 30 and 60 min respectively. Percentage ‘similarity’, mean time differences and standard deviations (SDs) were calculated for each variable. A paired t-test was also performed to assess the significance of the time differences between the two modalities. Results Least accurate was ‘sleep time’, with 14.7%, 23.5% and 58.8% of patients within 20, 30 and 60 min of the actigraphy respectively. Mean time difference for this variable was 66 min (versus 33, 15 and 22). ‘Time to fall asleep’ was most accurate, with 76.5%, 82.4% and 100% ‘similarity’ respectively. Conclusions The clinically acceptable accuracy has no universal definition, so clinicians must use experience and reasoning to determine this level to interpret this data. The review suggests that some variables are entered with high accuracy, and the diary is low cost and adds subjective information that cannot be gathered

  3. Sleep Apnea

    Science.gov (United States)

    Sleep apnea is a common disorder that causes your breathing to stop or get very shallow. Breathing ... an hour. The most common type is obstructive sleep apnea. It causes your airway to collapse or ...

  4. Slow wave and REM sleep deprivation effects on explicit and implicit memory during sleep.

    Science.gov (United States)

    Casey, Sarah J; Solomons, Luke C; Steier, Joerg; Kabra, Neeraj; Burnside, Anna; Pengo, Martino F; Moxham, John; Goldstein, Laura H; Kopelman, Michael D

    2016-11-01

    It has been debated whether different stages in the human sleep cycle preferentially mediate the consolidation of explicit and implicit memories, or whether all of the stages in succession are necessary for optimal consolidation. Here we investigated whether the selective deprivation of slow wave sleep (SWS) or rapid eye movement (REM) sleep over an entire night would have a specific effect on consolidation in explicit and implicit memory tasks. Participants completed a set of explicit and implicit memory tasks at night, prior to sleep. They had 1 control night of undisturbed sleep and 2 experimental nights, during which either SWS or REM sleep was selectively deprived across the entire night (sleep conditions counterbalanced across participants). Polysomnography recordings quantified precisely the amount of SWS and REM sleep that occurred during each of the sleep conditions, and spindle counts were recorded. In the morning, participants completed the experimental tasks in the same sequence as the night before. SWS deprivation disrupted the consolidation of explicit memories for visuospatial information (ηp2 = .23), and both SWS (ηp2 = .53) and REM sleep (ηp2 = .52) deprivation adversely affected explicit verbal recall. Neither SWS nor REM sleep deprivation affected aspects of short-term or working memory, and did not affect measures of verbal implicit memory. Spindle counts did not correlate significantly with memory performance. These findings demonstrate the importance of measuring the sleep cycles throughout the entire night, and the contribution of both SWS and REM sleep to memory consolidation. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  5. Chronic Stress is Prospectively Associated with Sleep in Midlife Women: The SWAN Sleep Study.

    Science.gov (United States)

    Hall, Martica H; Casement, Melynda D; Troxel, Wendy M; Matthews, Karen A; Bromberger, Joyce T; Kravitz, Howard M; Krafty, Robert T; Buysse, Daniel J

    2015-10-01

    Evaluate whether levels of upsetting life events measured over a 9-y period prospectively predict subjective and objective sleep outcomes in midlife women. Prospective cohort study. Four sites across the United States. 330 women (46-57 y of age) enrolled in the Study of Women's Health Across the Nation (SWAN) Sleep Study. N/A. Upsetting life events were assessed annually for up to 9 y. Trajectory analysis applied to life events data quantitatively identified three distinct chronic stress groups: low stress, moderate stress, and high stress. Sleep was assessed by self-report and in-home polysomnography (PSG) during the ninth year of the study. Multivariate analyses tested the prospective association between chronic stress group and sleep, adjusting for race, baseline sleep complaints, marital status, body mass index, symptoms of depression, and acute life events at the time of the Sleep Study. Women characterized by high chronic stress had lower subjective sleep quality, were more likely to report insomnia, and exhibited increased PSG-assessed wake after sleep onset (WASO) relative to women with low to moderate chronic stress profiles. The effect of chronic stress group on WASO persisted in the subsample of participants without baseline sleep complaints. Chronic stress is prospectively associated with sleep disturbance in midlife women, even after adjusting for acute stressors at the time of the sleep study and other factors known to disrupt sleep. These results are consistent with current models of stress that emphasize the cumulative effect of stressors on health over time. © 2015 Associated Professional Sleep Societies, LLC.

  6. Waking up is the hardest thing I do all day: Sleep inertia and sleep drunkenness.

    Science.gov (United States)

    Trotti, Lynn M

    2017-10-01

    The transition from sleep to wake is marked by sleep inertia, a distinct state that is measurably different from wakefulness and manifests as performance impairments and sleepiness. Although the precise substrate of sleep inertia is unknown, electroencephalographic, evoked potential, and neuroimaging studies suggest the persistence of some features of sleep beyond the point of awakening. Forced desynchrony studies have demonstrated that sleep inertia impacts cognition differently than do homeostatic and circadian drives and that sleep inertia is most intense during awakenings from the biological night. Recovery sleep after sleep deprivation also amplifies sleep inertia, although the effects of deep sleep vary based on task and timing. In patients with hypersomnolence disorders, especially but not exclusively idiopathic hypersomnia, a more pronounced period of confusion and sleepiness upon awakening, known as "sleep drunkenness", is common and problematic. Optimal treatment of sleep drunkenness is unknown, although several medications have been used with benefit in small case series. Difficulty with awakening is also commonly endorsed by individuals with mood disorders, disproportionately to the general population. This may represent an important treatment target, but evidence-based treatment guidance is not yet available. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Pediatric Sleep Disorders: Validation of the Sleep Disorders Inventory for Students

    Science.gov (United States)

    Luginbuehl, Marsha; Bradley-Klug, Kathy L.; Ferron, John; Anderson, W. McDowell; Benbadis, Selim R.

    2008-01-01

    Approximately 20%-25% of the pediatric population will likely develop a sleep disorder sometime during childhood or adolescence. Studies have shown that untreated sleep disorders can negatively affect cognitive abilities, and academic and behavior performance. The Sleep Disorders Inventory for Students (SDIS) is a screening instrument designed to…

  8. [Sleep disorders and epilepsy].

    Science.gov (United States)

    Aoki, Ryo; Ito, Hiroshi

    2014-05-01

    It has been reported that patients with epilepsy often have insomnia and/or daytime sleepiness; the symptomatologic features differ in seizure types. Not only the administration of anti-epileptics, but also inappropriate sleep hygiene cause daytime sleepiness. In subjective assessment of sleepiness, we need to pay attention if it can correctly assess or not. The prevalence of obstructive sleep apnea in patients with epilepsy is approximately 10-30%. Sleep apnea deteriorates the seizure control because of worsen sleep condition by sleep apnea, especially in elderly patients. Some researchers report that continuous positive airway pressure was effective for seizure control. Patients with epilepsy occasionally have REM sleep behavior disorder as comorbidity. Examination using polysomnography is required for differential diagnosis.

  9. Infant sleep development from 3 to 6 months postpartum: links with maternal sleep and paternal involvement.

    Science.gov (United States)

    Tikotzky, Liat; Sadeh, Avi; Volkovich, Ella; Manber, Rachel; Meiri, Gal; Shahar, Golan

    2015-03-01

    The aims of this longitudinal study were to examine (a) development of infant sleep and maternal sleep from 3 to 6 months postpartum; (b) concomitant and prospective links between maternal sleep and infant sleep; and (c) triadic links between paternal involvement in infant caregiving and maternal and infant sleep. The study included 57 families that were recruited during pregnancy. Maternal and infant sleep was assessed using actigraphy and sleep diaries for 5 nights. Both fathers and mothers completed a questionnaire assessing the involvement of fathers relative to mothers in infant caregiving. The results demonstrated moderate improvement in infant and maternal sleep percent between 3 and 6 months. Maternal sleep percent at 3 months significantly predicted infant sleep percent at 6 months. Greater paternal involvement in infant daytime and nighttime caregiving at 3 months significantly predicted more consolidated maternal and infant sleep at 6 months. These findings suggest that maternal sleep is an important predictor of infant sleep and that increased involvement of fathers in infant caregiving responsibilities may contribute to improvements in both maternal and infant sleep during the first 6 months postpartum. © 2015 The Society for Research in Child Development, Inc.

  10. Sleep and Recovery in Team Sport: Current Sleep-Related Issues Facing Professional Team-Sport Athletes.

    Science.gov (United States)

    Fullagar, Hugh H K; Duffield, Rob; Skorski, Sabrina; Coutts, Aaron J; Julian, Ross; Meyer, Tim

    2015-11-01

    While the effects of sleep loss on performance have previously been reviewed, the effects of disturbed sleep on recovery after exercise are less reported. Specifically, the interaction between sleep and physiological and psychological recovery in team-sport athletes is not well understood. Accordingly, the aim of the current review was to examine the current evidence on the potential role sleep may play in postexercise recovery, with a tailored focus on professional team-sport athletes. Recent studies show that team-sport athletes are at high risk of poor sleep during and after competition. Although limited published data are available, these athletes also appear particularly susceptible to reductions in both sleep quality and sleep duration after night competition and periods of heavy training. However, studies examining the relationship between sleep and recovery in such situations are lacking. Indeed, further observational sleep studies in team-sport athletes are required to confirm these concerns. Naps, sleep extension, and sleep-hygiene practices appear advantageous to performance; however, future proof-of-concept studies are now required to determine the efficacy of these interventions on postexercise recovery. Moreover, more research is required to understand how sleep interacts with numerous recovery responses in team-sport environments. This is pertinent given the regularity with which these teams encounter challenging scenarios during the course of a season. Therefore, this review examines the factors that compromise sleep during a season and after competition and discusses strategies that may help improve sleep in team-sport athletes.

  11. Functions and Mechanisms of Sleep

    Directory of Open Access Journals (Sweden)

    Mark R. Zielinski

    2016-04-01

    Full Text Available Sleep is a complex physiological process that is regulated globally, regionally, and locally by both cellular and molecular mechanisms. It occurs to some extent in all animals, although sleep expression in lower animals may be co-extensive with rest. Sleep regulation plays an intrinsic part in many behavioral and physiological functions. Currently, all researchers agree there is no single physiological role sleep serves. Nevertheless, it is quite evident that sleep is essential for many vital functions including development, energy conservation, brain waste clearance, modulation of immune responses, cognition, performance, vigilance, disease, and psychological state. This review details the physiological processes involved in sleep regulation and the possible functions that sleep may serve. This description of the brain circuitry, cell types, and molecules involved in sleep regulation is intended to further the reader’s understanding of the functions of sleep.

  12. Impaired sleep and allostatic load

    DEFF Research Database (Denmark)

    Clark, Alice Jessie; Dich, Nadya; Lange, Theis

    2014-01-01

    Objective: Understanding the mechanisms linking sleep impairment to morbidity and mortality is important for future prevention, but these mechanisms are far from elucidated. We aimed to determine the relation between impaired sleep, both in terms of duration and disturbed sleep, and allostatic load...... Biobank with comprehensive information on sleep duration, disturbed sleep, objective measures of an extensive range of biological risk markers, and physical conditions. Results: Long sleep (mean difference 0.23; 95% confidence interval, 0.13, 0.32) and disturbed sleep (0.14; 0.06, 0.22) were associated...... with higher AL as well as with high-risk levels of risk markers from the anthropometric, metabolic, and immune system. Sub-analyses suggested that the association between disturbed sleep and AL might be explained by underlying disorders. Whereas there was no association between short sleep and AL...

  13. Sleep in trigeminal autonomic cephalagias

    DEFF Research Database (Denmark)

    Barløse, Mads; Lund, Nunu; Jensen, Rigmor Højland

    2014-01-01

    and eventually to more effective therapeutic regimens. This review aims to evaluate the existing literature on the subject of TACs and sleep. An association between episodic CH and distinct macrostructural sleep phases, especially the relation to rapid eye movement (REM) sleep, has been described in some older...... studies but could not be confirmed in other, more recent studies. Investigations into the microstructure of sleep in these patients are lacking. Only a few case reports exist on the relation between sleep and other TACs. SUMMARY: Recent studies do not find an association between CH and REM sleep. One...... older study suggests chronic paroxysmal hemicranias may be locked to REM sleep but otherwise the relation is unknown. Reports indicate that CH and obstructive sleep apnoea are associated in some individuals but results are diverging. Single cases show improvement of CH upon treatment of sleep apnoea...

  14. EEG Changes across Multiple Nights of Sleep Restriction and Recovery in Adolescents: The Need for Sleep Study.

    Science.gov (United States)

    Ong, Ju Lynn; Lo, June C; Gooley, Joshua J; Chee, Michael W L

    2016-06-01

    To investigate sleep EEG changes in adolescents across 7 nights of sleep restriction to 5 h time in bed [TIB]) and 3 recovery nights of 9 h TIB. A parallel-group design, quasi-laboratory study was conducted in a boarding school. Fifty-five healthy adolescents (25 males, age = 15-19 y) who reported habitual TIBs of approximately 6 h on week nights (group average) but extended their sleep on weekends were randomly assigned to Sleep Restriction (SR) or Control groups. Participants underwent a 2-week protocol comprising 3 baseline nights (TIB = 9 h), 7 nights of sleep opportunity manipulation (TIB = 5 h for the SR and 9 h for the Control group), and 3 nights of recovery sleep (TIB = 9 h). Polysomnography was obtained on two baseline, three manipulation, and two recovery nights. Across the sleep restriction nights, total SWS duration was preserved relative to the 9 h baseline sleep opportunity, while other sleep stages were reduced. Considering only the first 5 h of sleep opportunity, SR participants had reduced N1 duration and wake after sleep onset (WASO), and increased total sleep time (TST), rapid eye movement (REM) sleep, and slow wave sleep (SWS) relative to baseline. Total REM sleep, N2, and TST duration remained above baseline levels by the third recovery sleep episode. In spite of preservation of SWS duration over multiple nights of sleep restriction, adolescents accustomed to curtailing nocturnal sleep on school day nights evidence residual effects on sleep macro-structure, even after three nights of recovery sleep. Older teenagers may not be as resilient to successive nights of sleep restriction as is commonly believed. © 2016 Associated Professional Sleep Societies, LLC.

  15. Obstructive Sleep Apnea during REM Sleep and Cardiovascular Disease.

    Science.gov (United States)

    Aurora, R Nisha; Crainiceanu, Ciprian; Gottlieb, Daniel J; Kim, Ji Soo; Punjabi, Naresh M

    2018-03-01

    Obstructive sleep apnea (OSA) during REM sleep is a common disorder. Data on whether OSA that occurs predominantly during REM sleep is associated with health outcomes are limited. The present study examined the association between OSA during REM sleep and a composite cardiovascular endpoint in a community sample with and without prevalent cardiovascular disease. Full-montage home polysomnography was conducted as part of the Sleep Heart Health Study. The study cohort was followed for an average of 9.5 years, during which time cardiovascular events were assessed. Only participants with a non-REM apnea-hypopnea index (AHI) of less than 5 events/h were included. A composite cardiovascular endpoint was determined as the occurrence of nonfatal or fatal events, including myocardial infarction, coronary artery revascularization, congestive heart failure, and stroke. Proportional hazards regression was used to derive the adjusted hazards ratios for the composite cardiovascular endpoint. The sample consisted of 3,265 subjects with a non-REM AHI of less than 5.0 events/h. Using a REM AHI of less than 5.0 events/h as the reference group (n = 1,758), the adjusted hazards ratios for the composite cardiovascular endpoint in those with severe REM OSA (≥30 events/h; n = 180) was 1.35 (95% confidence interval, 0.98-1.85). Stratified analyses demonstrated that the association was most notable in those with prevalent cardiovascular disease and severe OSA during REM sleep with an adjusted hazards ratio of 2.56 (95% confidence interval, 1.46-4.47). Severe OSA that occurs primarily during REM sleep is associated with higher incidence of a composite cardiovascular endpoint, but in only those with prevalent cardiovascular disease.

  16. Age-related Changes In Sleep Spindles Characteristics During Daytime Recovery Following a 25-Hour Sleep Deprivation

    Directory of Open Access Journals (Sweden)

    Thaïna eRosinvil

    2015-06-01

    Full Text Available Objectives: The mechanisms underlying sleep spindles (~11-15Hz; >0.5s help to protect sleep. With age, it becomes increasingly difficult to maintain sleep at a challenging time (e.g. daytime, even after sleep loss. This study compared spindle characteristics during daytime recovery and nocturnal sleep in young and middle-aged adults. In addition, we explored whether spindles characteristics in baseline nocturnal sleep were associated with the ability to maintain sleep during daytime recovery periods in both age groups.Methods: Twenty-nine young (15 women and 14 men; 27.3 ± 5.0 and 31 middle-aged (19 women and 13 men; 51.6 y ± 5.1 healthy subjects participated in a baseline nocturnal sleep and a daytime recovery sleep after 25 hours of sleep deprivation. Spindles were detected on artefact-free NREM sleep epochs. Spindle density (nb/min, amplitude (μV, frequency (Hz and duration (s were analyzed on parasagittal (linked-ears derivations. Results: In young subjects, spindle frequency increased during daytime recovery sleep as compared to baseline nocturnal sleep in all derivations, whereas middle-aged subjects showed spindle frequency enhancement only in the prefrontal derivation. No other significant interaction between age group and sleep condition was observed. Spindle density for all derivations and centro-occipital spindle amplitude decreased whereas prefrontal spindle amplitude increased from baseline to daytime recovery sleep in both age groups. Finally, no significant correlation was found between spindle characteristics during baseline nocturnal sleep and the marked reduction in sleep efficiency during daytime recovery sleep in both young and middle-aged subjects.Conclusion: These results suggest that the interaction between homeostatic and circadian pressure module spindle frequency differently in aging. Spindle characteristics do not seem to be linked with the ability to maintain daytime recovery sleep.

  17. Sleep and Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Dongwoo Kang

    2015-06-01

    Full Text Available Sleep architecture and sleep patterns normally change with aging. In preclinical Alzheimer’s disease (AD, the accumulation of amyloid plaques begins 10 to 20 years before any cognitive symptoms progress. Soluble amyloid-β (Aβ is secreted during physiological synaptic activity. Since synaptic activity is correlated with sleep and awake state, a degree of Aβ fluctuates in a diurnal sleep pattern. In animal and human studies, a degree of sleep quality showed a significant correlation with brain levels of Aβ and a risk of AD. Conversely, Aβ aggregation would debilitate neuronal function in brain regions critical to sleep and wake promotion. This bidirectional relationship can be explained as positive feedback loop and associated factors that influence this relationship. In AD, the degree of sleep disturbances is much more severe compared with in the normal elderly. Further, Sundowning syndrome and a reduction of melatonin level cause a stressful neuropsychiatric symptoms and a disruption of physiological sleep rhythm, respectively. In AD patients, a correlation between sleep architectural modifications and learning performances has been reported. Moreover, executive function and emotional reactivity might be attenuated by sleep disturbances, too. However, sleep disturbance does not impact cognitive functions of all patients with AD. This could support an individual and potentially genetically determined susceptibility. Sleep disturbances have an important effect on patients and caregivers. It has a critical value to confirm and treat individuals with sleep disorders and to explore whether good quality of sleep in humans can decrease the progression of preclinical to symptomatic AD.

  18. Sitting and television viewing: novel risk factors for sleep disturbance and apnea risk? results from the 2013 National Sleep Foundation Sleep in America Poll.

    Science.gov (United States)

    Buman, Matthew P; Kline, Christopher E; Youngstedt, Shawn D; Phillips, Barbara; Tulio de Mello, Marco; Hirshkowitz, Max

    2015-03-01

    Excess sitting is emerging as a novel risk factor for cardiovascular disease, diabetes, mental illness, and all-cause mortality. Physical activity, distinct from sitting, is associated with better sleep and lower risk for OSA, yet relationships among sitting behaviors and sleep/OSA remain unknown. We examined whether total sitting time and sitting while viewing television were associated with sleep duration and quality, OSA risk, and sleepiness. The 2013 National Sleep Foundation Sleep in America Poll was a cross-sectional study of 1,000 adults aged 23 to 60 years. Total sitting time, time watching television while sitting, sleep duration and quality, OSA risk, and daytime sleepiness were assessed. After adjusting for confounding factors (including BMI and physical activity), each additional hour per day of total sitting was associated with greater odds of poor sleep quality (OR [95% CI] = 1.06 [1.01, 1.11]) but not with other sleep metrics (including sleep duration), OSA risk, or daytime sleepiness. For television viewing while sitting, each additional hour per day was associated with greater odds of long sleep onset latency (≥ 30 min) (OR = 1.15 [1.04, 1.27]), waking up too early in the morning (OR = 1.12 [1.03, 1.23]), poor sleep quality (OR = 1.12 [1.02, 1.24]), and "high risk" for OSA (OR = 1.15 [1.04, 1.28]). Based upon an interaction analysis, regular physical activity was protective against OSA risk associated with television viewing (P = .04). Excess sitting was associated with relatively poor sleep quality. Sitting while watching television was associated with relatively poor sleep quality and OSA risk and may be an important risk factor for sleep disturbance and apnea risk.

  19. Sleep to implement an intention.

    Science.gov (United States)

    Diekelmann, Susanne; Wilhelm, Ines; Wagner, Ullrich; Born, Jan

    2013-01-01

    Sleep supports the consolidation of new memories. However, this effect has mainly been shown for memories of past events. Here we investigated the role of sleep for the implementation of intentions for the future. Subjects were instructed on a plan that had to be executed after a delay of 2 days. After plan instruction, subjects were either allowed to sleep or stayed awake for one night (Exp. 1) or had a 3-h sleep period either during the early night (SWS-rich sleep) or late night (REM-rich sleep; Exp. 2). In both experiments, retesting took place 2 days later after one recovery night. Sleep laboratory. A total of 56 healthy young adults participated in the study. N/A. All of the subjects who were allowed to sleep after plan instruction executed the intention 2 days later, whereas only 61% of wake subjects did so (P = 0.004; Exp. 1). Also after early SWS-rich sleep all of the subjects remembered to execute the intention, but only 55% did so after late REM-rich sleep (P = 0.015; Exp. 2). Sleep, especially SWS, plays an important role for the successful implementation of delayed intentions.

  20. Rheumatoid arthritis and sleep quality.

    Science.gov (United States)

    Goes, Ana Claudia Janiszewski; Reis, Larissa Aparecida Busatto; Silva, Marilia Barreto G; Kahlow, Barbara Stadler; Skare, Thelma L

    Sleep disturbances are common in rheumatoid arthritis (RA) patients and contribute to loss of life quality. To study associations of sleep quality with pain, depression and disease activity in RA. This is a transversal observational study of 112 RA patients submitted to measurement of DAS-28, Epworth scale for daily sleepiness, index of sleep quality by Pittsburg index, risk of sleep apnea by the Berlin questionnaire and degree of depression by the CES-D (Center for Epidemiologic Studies Depression scale) questionnaire. We also collected epidemiological, clinical, serological and treatment data. Only 18.5% of RA patients had sleep of good quality. In univariate analysis a bad sleep measured by Pittsburg index was associated with daily doses of prednisone (p=0.03), DAS-28 (p=0.01), CES-D (p=0.0005) and showed a tendency to be associated with Berlin sleep apnea questionnaire (p=0.06). In multivariate analysis only depression (p=0.008) and Berlin sleep apnea questionnaire (p=0.004) kept this association. Most of RA patients do not have a good sleep quality. Depression and risk of sleep apnea are independently associated with sleep impairment. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

  1. Habitual sleep durations and subjective sleep quality predict white matter differences in the human brain

    Directory of Open Access Journals (Sweden)

    Sakh Khalsa

    2017-06-01

    Full Text Available Self-imposed short sleep durations are increasingly commonplace in society, and have considerable health and performance implications for individuals. Reduced sleep duration over multiple nights has similar behavioural effects to those observed following acute total sleep deprivation, suggesting that lack of sleep affects brain function cumulatively. A link between habitual sleep patterns and functional connectivity has previously been observed, and the effect of sleep duration on the brain's intrinsic functional architecture may provide a link between sleep status and cognition. However, it is currently not known whether differences in habitual sleep patterns across individuals are related to changes in the brain's white matter, which underlies structural connectivity. In the present study we use diffusion–weighted imaging and a group comparison application of tract based spatial statistics (TBSS to investigate changes to fractional anisotropy (FA and mean diffusivity (MD in relation to sleep duration and quality, hypothesising that white matter metrics would be positively associated with sleep duration and quality. Diffusion weighted imaging data was acquired from a final cohort of 33 (23–29 years, 10 female, mean 25.4 years participants. Sleep patterns were assessed for a 14 day period using wrist actigraphs and sleep diaries, and subjective sleep quality with the Pittsburgh Sleep Quality Index (PSQI. Median splits based on total sleep time and PSQI were used to create groups of shorter/longer and poorer/better sleepers, whose imaging data was compared using TBSS followed by post-hoc correlation analysis in regions identified as significantly different between the groups. There were significant positive correlations between sleep duration and FA in the left orbito-frontal region and the right superior corona radiata, and significant negative correlations between sleep duration and MD in right orbito-frontal white matter and the right

  2. BDNF in sleep, insomnia, and sleep deprivation.

    Science.gov (United States)

    Schmitt, Karen; Holsboer-Trachsler, Edith; Eckert, Anne

    2016-01-01

    The protein brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors involved in plasticity of neurons in several brain regions. There are numerous evidence that BDNF expression is decreased by experiencing psychological stress and that, accordingly, a lack of neurotrophic support causes major depression. Furthermore, disruption in sleep homeostatic processes results in higher stress vulnerability and is often associated with stress-related mental disorders. Recently, we reported, for the first time, a relationship between BDNF and insomnia and sleep deprivation (SD). Using a biphasic stress model as explanation approach, we discuss here the hypothesis that chronic stress might induce a deregulation of the hypothalamic-pituitary-adrenal system. In the long-term it leads to sleep disturbance and depression as well as decreased BDNF levels, whereas acute stress like SD can be used as therapeutic intervention in some insomniac or depressed patients as compensatory process to normalize BDNF levels. Indeed, partial SD (PSD) induced a fast increase in BDNF serum levels within hours after PSD which is similar to effects seen after ketamine infusion, another fast-acting antidepressant intervention, while traditional antidepressants are characterized by a major delay until treatment response as well as delayed BDNF level increase. Key messages Brain-derived neurotrophic factor (BDNF) plays a key role in the pathophysiology of stress-related mood disorders. The interplay of stress and sleep impacts on BDNF level. Partial sleep deprivation (PSD) shows a fast action on BDNF level increase.

  3. Sleep Hygiene Behaviors Among Midlife Women with Insomnia or Sleep-Disordered Breathing: The SWAN Sleep Study

    Science.gov (United States)

    Kline, Christopher E.; Irish, Leah A.; Buysse, Daniel J.; Kravitz, Howard M.; Okun, Michele L.; Owens, Jane F.

    2014-01-01

    Abstract Background: Insomnia and sleep-disordered breathing (SDB) are the most common sleep disorders among midlife women. Although promoting sleep hygiene behaviors may be a useful behavioral approach for the management of insomnia or SDB, the frequency with which women engage in these behaviors is unclear. Methods: Participants were from the Study of Women's Health Across the Nation (SWAN) Sleep Study (N=321; age range=48–58 years). Out of the full sample, 10.3% (n=33) met Diagnostic and Statistical Manual of Mental Disorders—Fourth Edition diagnostic criteria for insomnia, 15.3% (n=49) had clinically significant SDB (apnea–hypopnea index ≥15), and 4.7% (n=15) met criteria for both insomnia and SDB, resulting in an overall prevalence of 15.0% (n=48) for insomnia and 19.9% (n=64) for SDB. Participants provided diary-based assessments of sleep hygiene behaviors for 14–35 days. Two positive behaviors (sufficient exercise, regular morning out-of-bed time) and four negative behaviors (taking long daytime naps, caffeine consumption near bedtime, alcohol consumption near bedtime, smoking) were examined. These behaviors were compared between women with and without insomnia or SDB following adjustment for sociodemographic factors and mental and physical health indices. Results: Women with insomnia engaged in significantly fewer negative sleep hygiene behaviors than women without insomnia (1.61±0.15 vs. 2.09±0.09 behaviors; phygiene behaviors were observed. Conclusions: These data suggest that insomnia in midlife women is not associated with poor sleep hygiene. Increasing physical activity may be a valuable recommendation for midlife women with SDB. PMID:25353709

  4. Sleep quality and correlates of poor sleep in patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Løppenthin, Katrine Bjerre; Esbensen, Bente Appel; Jennum, Poul

    2015-01-01

    The objective of this study is to examine sleep quality and correlates of poor sleep in patients with rheumatoid arthritis (RA). Five hundred patients with RA were recruited from a rheumatology outpatient clinic and included in this cross-sectional study. Sleep quality and disturbances were...... assessed using the Pittsburgh Sleep Quality Index (PSQI). Other instruments included the Multidimensional Fatigue Inventory, the Epworth Sleepiness Scale, and the Health Assessment Questionnaire. Disease activity was assessed according to disease activity score DAS28-CRP-based. Complete scores on PSQI were...... obtained from 384 patients (77 %). In those, the prevalence of poor sleep (PSQI >5) was 61 %, and the mean global PSQI score was 7.54 (SD 4.17). A linear association was found between poor sleep and mental fatigue, reduced activity related to fatigue, physical fatigue, and general fatigue. Mental fatigue...

  5. SensibleSleep: A Bayesian Model for Learning Sleep Patterns from Smartphone Events

    DEFF Research Database (Denmark)

    Cuttone, Andrea; Bækgaard, Per; Sekara, Vedran

    2017-01-01

    We propose a Bayesian model for extracting sleep patterns from smartphone events. Our method is able to identify individuals' daily sleep periods and their evolution over time, and provides an estimation of the probability of sleep and wake transitions. The model is fitted to more than 400...... to quantify uncertainty and encode prior knowledge about sleep patterns. Compared with existing smartphone-based systems, our method requires only screen on/off events, and is therefore much less intrusive in terms of privacy and more battery-efficient....... participants from two different datasets, and we verify the results against ground truth from dedicated armband sleep trackers. We show that the model is able to produce reliable sleep estimates with an accuracy of 0.89, both at the individual and at the collective level. Moreover the Bayesian model is able...

  6. SensibleSleep: A Bayesian Model for Learning Sleep Patterns from Smartphone Events.

    Science.gov (United States)

    Cuttone, Andrea; Bækgaard, Per; Sekara, Vedran; Jonsson, Håkan; Larsen, Jakob Eg; Lehmann, Sune

    2017-01-01

    We propose a Bayesian model for extracting sleep patterns from smartphone events. Our method is able to identify individuals' daily sleep periods and their evolution over time, and provides an estimation of the probability of sleep and wake transitions. The model is fitted to more than 400 participants from two different datasets, and we verify the results against ground truth from dedicated armband sleep trackers. We show that the model is able to produce reliable sleep estimates with an accuracy of 0.89, both at the individual and at the collective level. Moreover the Bayesian model is able to quantify uncertainty and encode prior knowledge about sleep patterns. Compared with existing smartphone-based systems, our method requires only screen on/off events, and is therefore much less intrusive in terms of privacy and more battery-efficient.

  7. SensibleSleep: A Bayesian Model for Learning Sleep Patterns from Smartphone Events.

    Directory of Open Access Journals (Sweden)

    Andrea Cuttone

    Full Text Available We propose a Bayesian model for extracting sleep patterns from smartphone events. Our method is able to identify individuals' daily sleep periods and their evolution over time, and provides an estimation of the probability of sleep and wake transitions. The model is fitted to more than 400 participants from two different datasets, and we verify the results against ground truth from dedicated armband sleep trackers. We show that the model is able to produce reliable sleep estimates with an accuracy of 0.89, both at the individual and at the collective level. Moreover the Bayesian model is able to quantify uncertainty and encode prior knowledge about sleep patterns. Compared with existing smartphone-based systems, our method requires only screen on/off events, and is therefore much less intrusive in terms of privacy and more battery-efficient.

  8. Sleep quality, sleep duration and physical activity in obese adolescents: effects of exercise training.

    Science.gov (United States)

    Mendelson, M; Borowik, A; Michallet, A-S; Perrin, C; Monneret, D; Faure, P; Levy, P; Pépin, J-L; Wuyam, B; Flore, P

    2016-02-01

    Decreased sleep duration and altered sleep quality are risk factors for obesity in youth. Structured exercise training has been shown to increase sleep duration and improve sleep quality. This study aimed at evaluating the impact of exercise training for improving sleep duration, sleep quality and physical activity in obese adolescents (OB). Twenty OB (age: 14.5 ± 1.5 years; body mass index: 34.0 ± 4.7 kg m(-2) ) and 20 healthy-weight adolescents (HW) completed an overnight polysomnography and wore an accelerometer (SenseWear Bodymedia) for 7 days. OB participated in a 12-week supervised exercise-training programme consisting of 180 min of exercise weekly. Exercise training was a combination of aerobic exercise and resistance training. Sleep duration was greater in HW compared with OB (P < 0.05). OB presented higher apnoea-hypopnoea index than HW (P < 0.05). Physical activity (average daily metabolic equivalent of tasks [METs]) by accelerometer was lower in OB (P < 0.05). After exercise training, obese adolescents increased their sleep duration (+64.4 min; effect size: 0.88; P = 0.025) and sleep efficiency (+7.6%; effect size: 0.76; P = 0.028). Physical activity levels were increased in OB as evidenced by increased steps per day and average daily METs (P < 0.05). Improved sleep duration was associated with improved average daily METs (r = 0.48, P = 0.04). The present study confirms altered sleep duration and quality in OB. Exercise training improves sleep duration, sleep quality and physical activity. © 2015 World Obesity.

  9. Moderate Exercise Plus Sleep Education Improves Self-Reported Sleep Quality, Daytime Mood, and Vitality in Adults with Chronic Sleep Complaints: A Waiting List-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Carmen Gebhart

    2011-01-01

    Full Text Available Research indicates that physical exercise can contribute to better sleep quality. This study investigates the six-week influence of a combined intervention on self-rated sleep quality, daytime mood, and quality of life. A nonclinical sample of 114 adults with chronic initiating and the maintaining of sleep complaints participated in the study. The intervention group of 70 adults underwent moderate physical exercise, conducted weekly, plus sleep education sessions. Improvements among participants assigned to the intervention group relative to the waiting-list control group (n=44 were noted for subjective sleep quality, daytime mood, depressive symptoms and vitality. Derived from PSQI subscores, the intervention group reported increased sleep duration, shortened sleep latency, fewer awakenings after sleep onset, and overall better sleep efficiency compared to controls. The attained scores were well sustained and enhanced over a time that lasted through to the follow-up 18 weeks later. These findings have implications in treatment programs concerning healthy lifestyle approaches for adults with chronic sleep complaints.

  10. Moderate Exercise Plus Sleep Education Improves Self-Reported Sleep Quality, Daytime Mood, and Vitality in Adults with Chronic Sleep Complaints: A Waiting List-Controlled Trial

    Science.gov (United States)

    Gebhart, Carmen; Erlacher, Daniel; Schredl, Michael

    2011-01-01

    Research indicates that physical exercise can contribute to better sleep quality. This study investigates the six-week influence of a combined intervention on self-rated sleep quality, daytime mood, and quality of life. A nonclinical sample of 114 adults with chronic initiating and the maintaining of sleep complaints participated in the study. The intervention group of 70 adults underwent moderate physical exercise, conducted weekly, plus sleep education sessions. Improvements among participants assigned to the intervention group relative to the waiting-list control group (n = 44) were noted for subjective sleep quality, daytime mood, depressive symptoms and vitality. Derived from PSQI subscores, the intervention group reported increased sleep duration, shortened sleep latency, fewer awakenings after sleep onset, and overall better sleep efficiency compared to controls. The attained scores were well sustained and enhanced over a time that lasted through to the follow-up 18 weeks later. These findings have implications in treatment programs concerning healthy lifestyle approaches for adults with chronic sleep complaints. PMID:23471095

  11. Moderate exercise plus sleep education improves self-reported sleep quality, daytime mood, and vitality in adults with chronic sleep complaints: a waiting list-controlled trial.

    Science.gov (United States)

    Gebhart, Carmen; Erlacher, Daniel; Schredl, Michael

    2011-01-01

    Research indicates that physical exercise can contribute to better sleep quality. This study investigates the six-week influence of a combined intervention on self-rated sleep quality, daytime mood, and quality of life. A nonclinical sample of 114 adults with chronic initiating and the maintaining of sleep complaints participated in the study. The intervention group of 70 adults underwent moderate physical exercise, conducted weekly, plus sleep education sessions. Improvements among participants assigned to the intervention group relative to the waiting-list control group (n = 44) were noted for subjective sleep quality, daytime mood, depressive symptoms and vitality. Derived from PSQI subscores, the intervention group reported increased sleep duration, shortened sleep latency, fewer awakenings after sleep onset, and overall better sleep efficiency compared to controls. The attained scores were well sustained and enhanced over a time that lasted through to the follow-up 18 weeks later. These findings have implications in treatment programs concerning healthy lifestyle approaches for adults with chronic sleep complaints.

  12. Functional neuroimaging of sleep disorders

    International Nuclear Information System (INIS)

    Qiu Chun; Zhao Jun; Guan Yihui

    2013-01-01

    Sleep disorders may affect the health and normal life of human badly. However, the pathophysiology underlying adult sleep disorders is still unclear. Functional neuroimaging can be used to investigate whether sleep disorders are associated with specific changes in brain structure or regional activity. This paper reviews functional brain imaging findings in major intrinsic sleep disorders (i.e., idiopathic insomnia, narcolepsy, and obstructive sleep apnea) and in abnormal motor behavior during sleep (i.e., periodic limb movement disorder and REM sleep behavior disorder). Metabolic/functional investigations (positron emission tomography, single photon emission computed tomography, functional magnetic resonance imaging) are mainly reviewed, as well as neuroanatomical assessments (voxel-based morphometry, magnetic resonance spectroscopy). Meanwhile, here are some brief introduction of different kinds of sleep disorders. (authors)

  13. Human genetics and sleep behavior.

    Science.gov (United States)

    Shi, Guangsen; Wu, David; Ptáček, Louis J; Fu, Ying-Hui

    2017-06-01

    Why we sleep remains one of the greatest mysteries in science. In the past few years, great advances have been made to better understand this phenomenon. Human genetics has contributed significantly to this movement, as many features of sleep have been found to be heritable. Discoveries about these genetic variations that affect human sleep will aid us in understanding the underlying mechanism of sleep. Here we summarize recent discoveries about the genetic variations affecting the timing of sleep, duration of sleep and EEG patterns. To conclude, we also discuss some of the sleep-related neurological disorders such as Autism Spectrum Disorder (ASD) and Alzheimer's Disease (AD) and the potential challenges and future directions of human genetics in sleep research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Sleep and Women’s Health

    Directory of Open Access Journals (Sweden)

    Sara Nowakowski

    2013-06-01

    Full Text Available Sex differences in sleep begin at a very early age and women report poorer sleep quality and have higher risk for insomnia than do men. Sleep may be affected by variation in reproductive hormones, stress, depression, aging, life/role transitions, and other factors. The menstrual cycle is associated with changes in circadian rhythms and sleep architecture. Menstruating women (even without significant menstrual-related complaints often report poorer sleep quality and greater sleep disturbance during the premenstrual week compared to other times of her menstrual cycle. In addition to these sleep disturbances, women with severe premenstrual syndrome often report more disturbing dreams, sleepiness, fatigue, decreased alertness and concentration during the premenstrual phase. Sleep disturbances are also commonly reported during pregnancy and increase in frequency and duration as the pregnancy progresses. The precipitous decline in hormones and unpredictable sleep patterns of the newborn contribute to and/or exacerbate poor sleep and daytime sleepiness during the early postpartum period. Insomnia is also among the most common health complaints that are reported by perimenopausal women. Women are particularly vulnerable to developing insomnia disorder during these times of reproductive hormonal change. In this review, we present a discussion on the most relevant and recent publications on sleep across the woman’s lifespan, including changes in sleep related to menstruation, pregnancy, postpartum, and the menopausal transition. Treatment for sleep disturbances and insomnia disorder and special considerations for treating women will also be discussed.

  15. Validation of the PROMIS Sleep Disturbance and Sleep-Related Impairment item banks in Dutch adolescents.

    Science.gov (United States)

    van Kooten, Jojanneke A M C; van Litsenburg, Raphaёle R L; Yoder, Whitney R; Kaspers, Gertjan J L; Terwee, Caroline B

    2018-04-16

    Sleep problems are common in adolescents and have a negative impact on daytime functioning. However, there is a lack of well-validated adolescent sleep questionnaires. The Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance and Sleep-Related Impairment item banks are well-validated instruments developed for and tested in adults. The aim of this study was to evaluate their structural validity in adolescents. Test and retest data were collected for the Dutch-Flemish V1.0 PROMIS Sleep Disturbance (27) and Sleep-Related Impairment (16 items) item banks from 1046 adolescents (11-19 years). Cross-validation methods, Confirmatory (CFA), and Exploratory Factor Analyses (EFA) were used. Fit indices and factor loadings were used to improve the models. The final models were assessed for model fit using retest data. The one-factor Sleep Disturbance (CFI = 0.795, TLI = 0.778, RMSEA = 0.117) and Sleep-Related Impairment (CFI = 0.897, TLI = 0.882, RMSEA = 0.156) models could not be replicated in adolescents. Cross-validation resulted in a final Sleep Disturbance model of 23 and a Sleep-Related Impairment model of 11 items. Retest data CFA showed adequate fit for the Sleep-Related Impairment-11 (CFI = 0.981, TLI = 0.976, RMSEA = 0.116). The Sleep Disturbance-23 model fit indices stayed below the recommended values (CFI = 0.895, TLI = 0.885, RMSEA = 0.105). While the PROMIS Sleep Disturbance-23 for adolescents and PROMIS Sleep-Related Impairment-11 for adolescents provide a framework to assess adolescent sleep, additional research is needed to replicate these findings in a larger and more diverse sample.

  16. [Healthy sleep: evidence and guidelines for action. Official document of the Spanish Sleep Society].

    Science.gov (United States)

    Merino-Andreu, M; Alvarez-Ruiz de Larrinaga, A; Madrid-Perez, J A; Martinez-Martinez, M A; Puertas-Cuesta, F J; Asencio-Guerra, A J; Romero Santo-Tomas, O; Jurado-Luque, M J; Segarra-Isern, F J; Canet-Sanz, T; Gimenez-Rodriguez, P; Teran-Santos, J; Alonso-Alvarez, M L; Garcia-Borreguero Diaz-Varela, D; Barriuso-Esteban, B

    2016-10-03

    One of the main objectives of the Spanish Sleep Society is to promote healthy sleep in both the general population and in health professionals. This document aims to conduct a review of the current scientific literature on sleep habits that can serve as the basis on which to establish a set of general recommendations, regarding healthy sleep, for use by the general population in Spain as well as to identify the main challenges faced by research into sleep habits. The document has been developed by a multidisciplinary team made up of members of the Spanish Sleep Society who are experts in paediatric sleep medicine, clinical neurophysiology, pulmonology, neurology, chronobiology, physiology and psychology. The existing scientific literature dealing with sleep habits in the general population was reviewed, and the following aspects were addressed: the current state of sleep habits in the Spanish population; a generic review of the optimum number of hours of sleep; the impact of the environmental setting (noise, temperature, illumination, etc.), hours of sleep, diet and sport, together with several specific sections for children and teenagers, shift-workers and drivers of different vehicles. The conclusions from all the aspects addressed in this document have resulted in a set of final general recommendations that will serve as a guide for the general population and health professionals. Likewise, the principal environmental challenges and future lines of research are also discussed.

  17. Sleep Characteristics, Sleep Problems, and Associations to Quality of Life among Psychotherapists

    OpenAIRE

    Schlarb, Angelika A.; Reis, Dorota; Schröder, Annette

    2012-01-01

    Sleep problems, especially insomnia, are a common complaint among adults. International studies have shown prevalence rates between 4.7 and 36.2% for sleep difficulties in general, whereas 13.1?28.1% report insomnia symptoms. Sleep problems are associated with lower social and academic performance and can have a severe impact on psychological and physical health. Psychotherapists are suppliers within the public health system. The goal of this study was to outline sleep characteristics, preval...

  18. AASM standards of practice compliant validation of actigraphic sleep analysis from SOMNOwatch(TM) versus polysomnographic sleep diagnostics shows high conformity also among subjects with sleep disordered breathing

    International Nuclear Information System (INIS)

    Dick, R; Schulz, J; Penzel, T; Fietze, I; Partinen, M; Hein, H

    2010-01-01

    In recent AASM practice, parameter actimetry is cited to measure total sleep time in obstructive sleep apnoea patients, when polysomnography is not available. An actigraph was therefore compared to polysomnographic data in 28 subjects with known sleep disordered breathing. Total sleep time (TST), sleep period time (SPT), sleep efficiency (SE), sustained sleep efficiency (SSE), sleep onset latency (SL) and sleep/wake pattern were compared to gold standard polysomnography. The results of an epoch-by-epoch comparison of sleep/wake from actigraphy to sleep stages from polysomnography gave a sensitivity of 90.2%, a specificity of 95.2% and an overall accuracy of 85.9%. Correlations were moderately strong for SE (0.71, p < 0.001) and SSE (0.65, p < 0.001) and high for TST (0.89, p < 0.001), SPT (0.91, p < 0.001) and SL (0.89, p < 0.001). It was concluded that actigraphy is not identical with PSG recording but gives good results in sleep/wake patterns and predicting TST, SPT, SSE, SE and SL also in sleep apnoea patients not suffering from other sleep disorders. The difficult detection of correct sleep onset causes SSE and SL to be less predictable. Therefore a 15-epoch criterion was introduced and resulted in high correlation of 0.89 for sleep latency, but has to be tested on a bigger population

  19. Beauty sleep: experimental study on the perceived health and attractiveness of sleep deprived people

    NARCIS (Netherlands)

    Axelsson, J.; Ingre, M.; van Someren, E.J.W.; Olsson, A.; Lekander, M.

    2010-01-01

    Objective To investigate whether sleep deprived people are perceived as less healthy, less attractive, and more tired than after a normal night's sleep. Design Experimental study. Setting Sleep laboratory in Stockholm, Sweden. Participants 23 healthy, sleep deprived adults (age 18-31) who were

  20. Sleep, sport, and the brain.

    Science.gov (United States)

    Halson, Shona L; Juliff, Laura E

    2017-01-01

    The recognition that sleep is one of the foundations of athlete performance is increasing both in the elite athlete arena as well as applied performance research. Sleep, as identified through sleep deprivation and sleep extension investigations, has a role in performance, illness, injury, metabolism, cognition, memory, learning, and mood. Elite athletes have been identified as having poorer quality and quantity of sleep in comparison to the general population. This is likely the result on training times, competition stress/anxiety, muscle soreness, caffeine use, and travel. Sleep, in particular slow wave sleep, provides a restorative function to the body to recover from prior wakefulness and fatigue by repairing processes and restoring energy. In addition, research in the general population is highlighting the importance of sleep on neurophysiology, cognitive function, and mood which may have implications for elite athlete performance. It is thus increased understanding of both the effects of sleep deprivation and potential mechanisms of influence on performance that may allow scientists and practitioners to positively influence sleep in athletes and ultimately maximize performances. © 2017 Elsevier B.V. All rights reserved.