A preliminary investigation of sleep quality in functional neurological disorders: Poor sleep appears common, and is associated with functional impairment

Purpose: Functional neurological disorders (FND) are disabling conditions for which there are few empirically-supported treatments. Disturbed sleep appears to be part of the FND context; however, the clinical importance of sleep disturbance (extent, characteristics and impact) remains largely unknown. We described sleep quality in two samples, and investigated the relationship between sleep and FND-related functional impairment. Methods: We included a sample recruited online via patient charities (N = 205) and a consecutive clinical sample (N = 20). Participants completed validated measures of sleep quality and sleep characteristics (e.g. total sleep time, sleep efficiency), mood, and FND-related functional impairment. Results: Poor sleep was common in both samples (89% in the clinical range), which was characterised by low sleep efficiency (M = 65.40%) and low total sleep time (M = 6.05 h). In regression analysis, sleep quality was negatively associated with FND-related functional impairment, accounting for 16% of the variance and remaining significant after the introduction of mood variables. Conclusions: These preliminary analyses suggest that subjective sleep disturbance is common in FND. Sleep quality was negatively associated with the functional impairment attributed to FND, independent of depression. Therefore, sleep disturbance may be a clinically important feature of FND

Взаимосвязь ожирения и нарушений углеводного обмена с синдромом обструктивного апноэ во сне

Представлены литературные данные клинических исследований, в которых синдром обструктивного апноэ во сне (СОАС) рассматривается как фактор риска развития нарушений углеводного обмена, в том числе сахарного диабета 2−го типа. Анализируется взаимосвязь наиболее значимых факторов, влияющих на прогрессирование нарушений углеводного обмена у пациентов с СОАС. Приведен анализ данных о связи СОАС с диабетической автономной нейропатией и инсулинорезистентностью. Рассматривается возможность применения СРАР−терапии для коррекции метаболических нарушений у пациентов с сахарным диабетом.Представлено літературні дані клінічних досліджень, у яких синдром обструктивного апное під час сну (СОАС) розглянуто як фактор ризику розвитку порушень вуглеводного обміну, у тому числі цукрового діабету 2−го типу. Аналізується взаємозв'язок найбільш значущих факторів, що впливають на прогресування порушень вуглеводного обміну у пацієнтів із СОАС. Наведено аналіз даних про зв'язок СОАС із діабетичною автономною нейропатією та інсулінорезистентністю. Розглянуто можливість використання СРАР−терапії для корекції метаболічних порушень у пацієнтів із цукровим діабетом.Literature data about clinical trials, in which sleep apnea syndrome (SAS) is featured as a risk factor of carbohydrate metabolism disorders, including type 2 diabetes mellitus, are presented. Association of the most significant factors influencing the progress carbohydrate metabolism disorders in patients with SAS is analyzed. The data about the association of SAS and diabetic autonomous neuropathy and insulin resistance are featured. Possibility to use CPAP therapy for correction of metabolic disorders in patients with diabetes mellitus is discussed

Small-molecule-induced DNA damage identifies alternative DNA structures in human genes.

Guanine-rich DNA sequences that can adopt non-Watson-Crick structures in vitro are prevalent in the human genome. Whether such structures normally exist in mammalian cells has, however, been the subject of active research for decades. Here we show that the G-quadruplex-interacting drug pyridostatin promotes growth arrest in human cancer cells by inducing replication- and transcription-dependent DNA damage. A chromatin immunoprecipitation sequencing analysis of the DNA damage marker γH2AX provided the genome-wide distribution of pyridostatin-induced sites of damage and revealed that pyridostatin targets gene bodies containing clusters of sequences with a propensity for G-quadruplex formation. As a result, pyridostatin modulated the expression of these genes, including the proto-oncogene SRC. We observed that pyridostatin reduced SRC protein abundance and SRC-dependent cellular motility in human breast cancer cells, validating SRC as a target of this drug. Our unbiased approach to define genomic sites of action for a drug establishes a framework for discovering functional DNA-drug interactions

A cross-sectional survey of the nature and correlates of sleep disturbance in people with psoriasis.

BACKGROUND: Research suggests that sleep disturbance is common in psoriasis. Despite 32 studies conducted in sleep, many demonstrate methodological flaws, often using unvalidated measurement, with no study examining multiple dimensions of sleep-wake functioning. Moreover, research has yet to comprehensively examine the range of physical and psychological factors that may affect sleep in people with psoriasis. OBJECTIVE: To characterise sleep disturbance using validated measures and identify physical and psychological predictors of sleep quality in people with psoriasis. METHODS: An online survey was conducted (n=186;Mage =39.2) comprising validated measures assessing sleep (Pittsburgh Sleep Quality Index [PSQI], Berlin Questionnaire, Pre-Sleep Arousal Scale), chronotype (Morningness-Eveningness Questionnaire), mood (Hospital Anxiety and Depression Scale), itch (5-D Itch Scale) and psoriasis severity (Simplified Psoriasis Index). Group comparisons and regression analyses were used to examine predictors of poor sleep. RESULTS: Mean PSQI score was 9.24 (SD=4.32), with 76.3% scoring above the threshold for poor sleep (≥ 6 on the PSQI) and 32.5% scoring 'positive' for probable obstructive sleep apnoea. Poor sleep and high likelihood of OSA was associated with more severe psoriasis (p<.05; η(2) =.07; η(2) =.005). Cognitive arousal (β=.264, p=.001), itch (β=.260, p<.001) and depression (β=.236, p=.001) were the most robust predictors of poor sleep quality which, together with somatic arousal (β=.168, p=.022), accounted for 43% of variance in PSQI scores. CONCLUSIONS: Poor sleep is common in psoriasis and associated with psychological and physical factors. Rates of probable obstructive sleep apnoea are also high. Given the importance of restorative sleep for health, sleep complaints should receive greater clinical attention in the management of psoriasis. This article is protected by copyright. All rights reserved

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Comparison of Three Commercially Available Dengue NS1 Antigen Capture Assays for Acute Diagnosis of Dengue in Brazil

Dengue is the one of the most prevalent arthropod-borne viral diseases in tropical regions of the world. Manifestations may vary from asymptomatic to potentially fatal complications. Laboratorial diagnosis is essential to diagnose dengue and differentiate it from other diseases. Dengue virus non-structural protein 1 (NS1) may be used as a marker of acute dengue virus infection. Our results, based in the comparison of three NS1 antigen capture assays available, have shown that this approach is reliable for the early diagnosis of dengue infections, especially in the first four days after the onset of the symptoms. A lower sensitivity was observed in DENV-3 cases. Serum positive by virus isolation were more often detected than those positive by RT-PCR by all three assays. Only the Platelia™ NS1 test showed a higher sensitivity in confirming primary infections than secondary ones. In conclusion, NS1 antigen capture commercial kits are useful for diagnosis of acute primary and secondary dengue infections and, in endemic countries where secondary infections are expected to occur, may be used in combination with MAC-ELISA to increase the overall sensitivity of both tests

A Comparison of Administrative and Physiologic Predictive Models in Determining Risk Adjusted Mortality Rates in Critically Ill Patients

Hospitals are increasingly compared based on clinical outcomes adjusted for severity of illness. Multiple methods exist to adjust for differences between patients. The challenge for consumers of this information, both the public and healthcare providers, is interpreting differences in risk adjustment models particularly when models differ in their use of administrative and physiologic data. We set to examine how administrative and physiologic models compare to each when applied to critically ill patients.We prospectively abstracted variables for a physiologic and administrative model of mortality from two intensive care units in the United States. Predicted mortality was compared through the Pearsons Product coefficient and Bland-Altman analysis. A subgroup of patients admitted directly from the emergency department was analyzed to remove potential confounding changes in condition prior to ICU admission.We included 556 patients from two academic medical centers in this analysis. The administrative model and physiologic models predicted mortalities for the combined cohort were 15.3% (95% CI 13.7%, 16.8%) and 24.6% (95% CI 22.7%, 26.5%) (t-test p-value<0.001). The r(2) for these models was 0.297. The Bland-Atlman plot suggests that at low predicted mortality there was good agreement; however, as mortality increased the models diverged. Similar results were found when analyzing a subgroup of patients admitted directly from the emergency department. When comparing the two hospitals, there was a statistical difference when using the administrative model but not the physiologic model. Unexplained mortality, defined as those patients who died who had a predicted mortality less than 10%, was a rare event by either model.In conclusion, while it has been shown that administrative models provide estimates of mortality that are similar to physiologic models in non-critically ill patients with pneumonia, our results suggest this finding can not be applied globally to patients admitted to intensive care units. As patients and providers increasingly use publicly reported information in making health care decisions and referrals, it is critical that the provided information be understood. Our results suggest that severity of illness may influence the mortality index in administrative models. We suggest that when interpreting "report cards" or metrics, health care providers determine how the risk adjustment was made and compares to other risk adjustment models

Fault Tolerance in Protein Interaction Networks: Stable Bipartite Subgraphs and Redundant Pathways

As increasing amounts of high-throughput data for the yeast interactome become available, more system-wide properties are uncovered. One interesting question concerns the fault tolerance of protein interaction networks: whether there exist alternative pathways that can perform some required function if a gene essential to the main mechanism is defective, absent or suppressed. A signature pattern for redundant pathways is the BPM (between-pathway model) motif, introduced by Kelley and Ideker. Past methods proposed to search the yeast interactome for BPM motifs have had several important limitations. First, they have been driven heuristically by local greedy searches, which can lead to the inclusion of extra genes that may not belong in the motif; second, they have been validated solely by functional coherence of the putative pathways using GO enrichment, making it difficult to evaluate putative BPMs in the absence of already known biological annotation. We introduce stable bipartite subgraphs, and show they form a clean and efficient way of generating meaningful BPMs which naturally discard extra genes included by local greedy methods. We show by GO enrichment measures that our BPM set outperforms previous work, covering more known complexes and functional pathways. Perhaps most importantly, since our BPMs are initially generated by examining the genetic-interaction network only, the location of edges in the protein-protein physical interaction network can then be used to statistically validate each candidate BPM, even with sparse GO annotation (or none at all). We uncover some interesting biological examples of previously unknown putative redundant pathways in such areas as vesicle-mediated transport and DNA repair

Clinical and Virological Factors Influencing the Performance of a NS1 Antigen-Capture Assay and Potential Use as a Marker of Dengue Disease Severity

Dengue is the most prevalent arthropod-borne disease in tropical regions. The clinical manifestation may vary from asymptomatic to potentially fatal dengue shock syndrome. Early laboratory confirmation of dengue diagnosis is essential since many symptoms are not specific. Dengue non-structural protein 1 (NS1) may be used in simple antigen-capture ELISA for early detection of dengue virus infection. Our result demonstrated that the Platelia NS1 antigen detection kit had a quite low overall sensitivity. However, sensitivity rises significantly when used in combination with MAC-ELISA. When taking into account the various forms of dengue infection, the NS1 antigen detection was found relatively high in patients sampled during the first 3 days of fever onset, in patients with primary infection, DENV-1 infection, with high level of viremia and in mild form of dengue fever. In asymptomatically infected individuals, RT-PCR assay has proved to be more sensitive than NS1 antigen detection. Moreover, the NS1 antigen level correlated significantly with high viremia and low level of NS1 antigen was associated with more severe disease