Loneliness and sleep: A systematic review and meta-analysis

Despite the mounting evidence linking loneliness with health, the mechanisms underlying this relationship remain obscure. This systematic review and meta-analysis on the association between loneliness and one potential mechanism—sleep—identified 27 relevant articles. Loneliness correlated with self-reported sleep disturbance (r = .28, 95% confidence interval (.24, .33)) but not duration, across a diverse set of samples and measures. There was no evidence supporting age or gender as moderators or suggesting publication bias. The longitudinal relationship between loneliness and sleep remains unclear. Loneliness is related to sleep disturbance, but research is necessary to determine directionality, examine the influence of other factors, and speak to causality

A Database and Evaluation for Classification of RNA Molecules Using Graph Methods

In this paper, we introduce a new graph dataset based on the representation of RNA. The RNA dataset includes 3178 RNA chains which are labelled in 8 classes according to their reported biological functions. The goal of this database is to provide a platform for investigating the classication of RNA using graph-based methods. The molecules are represented by graphs representing the sequence and base-pairs of the RNA, with a number of labelling schemes using base labels and local shape. We report the results of a number of state-of-the-art graph based methods on this dataset as a baseline comparison and investigate how these methods can be used to categorise RNA molecules on their type and functions. The methods applied are Weisfeiler Lehman and optimal assignment kernels, shortest paths kernel and the all paths and cycle methods. We also compare to the standard Needleman-Wunsch algorithm used in bioinformatics for DNA and RNA comparison, and demonstrate the superiority of graph kernels even on a string representation. The highest classication rate is obtained by the WL-OA algorithm using base labels and base-pair connections

Rethinking the patient: using Burden of Treatment Theory to understand the changing dynamics of illness

<b>Background</b> In this article we outline Burden of Treatment Theory, a new model of the relationship between sick people, their social networks, and healthcare services. Health services face the challenge of growing populations with long-term and life-limiting conditions, they have responded to this by delegating to sick people and their networks routine work aimed at managing symptoms, and at retarding - and sometimes preventing - disease progression. This is the new proactive work of patient-hood for which patients are increasingly accountable: founded on ideas about self-care, self-empowerment, and self-actualization, and on new technologies and treatment modalities which can be shifted from the clinic into the community. These place new demands on sick people, which they may experience as burdens of treatment.<p></p> <b>Discussion</b> As the burdens accumulate some patients are overwhelmed, and the consequences are likely to be poor healthcare outcomes for individual patients, increasing strain on caregivers, and rising demand and costs of healthcare services. In the face of these challenges we need to better understand the resources that patients draw upon as they respond to the demands of both burdens of illness and burdens of treatment, and the ways that resources interact with healthcare utilization.<p></p> <b>Summary</b> Burden of Treatment Theory is oriented to understanding how capacity for action interacts with the work that stems from healthcare. Burden of Treatment Theory is a structural model that focuses on the work that patients and their networks do. It thus helps us understand variations in healthcare utilization and adherence in different healthcare settings and clinical contexts

Temperature-dependent polymorphism of N-(4-fluorophenyl)-1,5-dimethyl-1H-imidazole-4-carboxamide 3-oxide: experimental and theoretical studies on intermolecular interactions in the crystal state

X-ray analysis of N-(4-fluorophenyl)-1,5-dimethyl-1H-imidazole-4-carboxamide 3-oxide reveals the temperature-dependent polymorphism associated with the crystallographic symmetry conversion. The observed crystal structure transformation corresponds to a symmetry reduction from I41 /a (I) to P43 (II) space groups. The phase transition mainly concerns the subtle but clearly noticeable reorganization of molecules in the crystal space, with the structure of individual molecules left almost unchanged. The Hirshfeld surface analysis shows that various intermolecular contacts play an important role in the crystal packing, revealing graphically the differences in spatial arrangements of the molecules in both polymorphs. The N-oxide oxygen atom acts as a formally negatively charged hydrogen bonding acceptor in intramolecular hydrogen bond of N–H…O− type. The combined crystallographic and theoretical DFT methods demonstrate that the observed intramolecular N-oxide N–H…O hydrogen bond should be classified as a very strong charge-assisted and closed-shell non-covalent interaction

HIV-1 Envelope Subregion Length Variation during Disease Progression

The V3 loop of the HIV-1 Env protein is the primary determinant of viral coreceptor usage, whereas the V1V2 loop region is thought to influence coreceptor binding and participate in shielding of neutralization-sensitive regions of the Env glycoprotein gp120 from antibody responses. The functional properties and antigenicity of V1V2 are influenced by changes in amino acid sequence, sequence length and patterns of N-linked glycosylation. However, how these polymorphisms relate to HIV pathogenesis is not fully understood. We examined 5185 HIV-1 gp120 nucleotide sequence fragments and clinical data from 154 individuals (152 were infected with HIV-1 Subtype B). Sequences were aligned, translated, manually edited and separated into V1V2, C2, V3, C3, V4, C4 and V5 subregions. V1-V5 and subregion lengths were calculated, and potential N-linked glycosylation sites (PNLGS) counted. Loop lengths and PNLGS were examined as a function of time since infection, CD4 count, viral load, and calendar year in cross-sectional and longitudinal analyses. V1V2 length and PNLGS increased significantly through chronic infection before declining in late-stage infection. In cross-sectional analyses, V1V2 length also increased by calendar year between 1984 and 2004 in subjects with early and mid-stage illness. Our observations suggest that there is little selection for loop length at the time of transmission; following infection, HIV-1 adapts to host immune responses through increased V1V2 length and/or addition of carbohydrate moieties at N-linked glycosylation sites. V1V2 shortening during early and late-stage infection may reflect ineffective host immunity. Transmission from donors with chronic illness may have caused the modest increase in V1V2 length observed during the course of the pandemic

Arterio-venous gradients of IL-6, plasma and serum VEGF and D-dimers in human cancer

The circulating angiogenic factors vascular endothelial growth factor-A, interleukin-6 and the fibrin D-dimer fragment were measured in the mesenteric vein, the uterine vein, as well as in peripheral venous and arterial samples in 21 randomly selected patients with operable colorectal, ovarian and cervical carcinoma. In addition, immunohistochemistry for vascular endothelial growth factor-A and interleukin-6 was performed on colorectal tumours of such patients. Serum and plasma vascular endothelial growth factor-A were not significantly elevated in the vein draining the tumours, despite tumour cell expression of vascular endothelial growth factor-A. Serum vascular endothelial growth factor-A is therefore not all tumour-derived. In contrast, serum interleukin-6 was highly elevated in the draining veins in agreement with expression of interleukin-6 in the cytoplasm of tumour cells. In the megakaryoblastic cell line MEG-01, the expression of vascular endothelial growth factor-A was found to be regulated by interleukin-6. Thus, the higher platelet vascular endothelial growth factor-A load resulting in higher serum vascular endothelial growth factor levels in cancer patients may partly result from an interleukin-6 mediated up-regulation of the expression of vascular endothelial growth factor-A in the precursor of the platelet, i.e. the megakaryocyte. We also confirmed by immunohistochemistry that platelets adhere and aggregate on tumour endothelium. We propose that interleukin-6 indirectly promotes tumour angiogenesis through its up-regulation of the vascular endothelial growth factor-A load in platelets. In addition, the correlations found between peripheral venous interleukin-6 and peripheral venous fibrinogen and D-dimers levels, and the high D-dimer levels found in the draining vein of the tumour, in agreement with fibrin deposits found in the tumour stroma, suggest an important role for interleukin-6 in extra-vascular fibrinogen metabolism. Our results suggest a pivotal role for interleukin-6 in the intrinsic link between haemostasis and angiogenesis. This might be of importance in the development of anti-angiogenic agents based on interference with haemostasis