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Modern Applied Statistics With S

The adverse effects of loneliness and of poor perceived social support on physical health and mortality are established, but no systematic synthesis is available of their relationship with the outcomes of mental health problems over time. In this systematic review, we aim to examine the evidence on whether loneliness and closely related concepts predict poor outcomes among adults with mental health problems. We searched six databases and reference lists for longitudinal quantitative studies that examined the relationship between baseline measures of loneliness and poor perceived social support and outcomes at follow up. Thirty-four eligible papers were retrieved. Due to heterogeneity among included studies in clinical populations, predictor measures and outcomes, a narrative synthesis was conducted. We found substantial evidence from prospective studies that people with depression who perceive their social support as poorer have worse outcomes in terms of symptoms, recovery and social functioning. Loneliness has been investigated much less than perceived social support, but there is some evidence that greater loneliness predicts poorer depression outcome. There is also some preliminary evidence of associations between perceived social support and outcomes in schizophrenia, bipolar disorder and anxiety disorders. Loneliness and quality of social support in depression are potential targets for development and testing of interventions, while for other conditions further evidence is needed regarding relationships with outcomes.

/pdf/associations-between-loneliness-and-perceived-social-support-388z44tyre.pdf

Associations between loneliness and perceived social support and outcomes of mental health problems: a systematic review

Tumor-specific, circulating cell-free DNA in liquid biopsies is a promising source of biomarkers for minimally invasive serial monitoring of treatment responses in cancer management. We will review the current understanding of the origin of circulating cell-free DNA and different forms of DNA release (including various types of cell death and active secretion processes) and clearance routes. The dynamics of extracellular DNA in blood during therapy and the role of circulating DNA in pathophysiological processes (tumor-associated inflammation, NETosis, and pre-metastatic niche development) provide insights into the mechanisms that contribute to tumor development and metastases formation. Better knowledge of circulating tumor-specific cell-free DNA could facilitate the development of new therapeutic and diagnostic options for cancer management.

https://tandfonline.com/doi/pdf/10.1080/15384047.2019.1598759

Life and death of circulating cell-free DNA.

The arginase enzyme developed in early life forms and was maintained during evolution. As the last step in the urea cycle, arginase cleaves l-arginine to form urea and l-ornithine. The urea cycle p...

Arginase: A Multifaceted Enzyme Important in Health and Disease.

Amino acid metabolism is a critical regulator of the immune response, and its modulating becomes a promising approach in various forms of immunotherapy. Insufficient concentrations of essential amino acids restrict T-cells activation and proliferation. However, only arginases, that degrade L-arginine, as well as enzymes that hydrolyze L-tryptophan are substantially increased in cancer. Two arginase isoforms, ARG1 and ARG2, have been found to be present in tumors and their increased activity usually correlates with more advanced disease and worse clinical prognosis. Nearly all types of myeloid cells were reported to produce arginases and the increased numbers of various populations of myeloid-derived suppressor cells and macrophages correlate with inferior clinical outcomes of cancer patients. Here, we describe the role of arginases produced by myeloid cells in regulating various populations of immune cells, discuss molecular mechanisms of immunoregulatory processes involving L-arginine metabolism and outline therapeutic approaches to mitigate the negative effects of arginases on antitumor immune response. Development of potent arginase inhibitors, with improved pharmacokinetic properties, may lead to the elaboration of novel therapeutic strategies based on targeting immunoregulatory pathways controlled by L-arginine degradation.

/pdf/myeloid-cell-derived-arginase-in-cancer-immune-response-4351y0p3t8.pdf

Myeloid Cell-Derived Arginase in Cancer Immune Response

Loneliness is a prevalent and global problem for adult populations and has been linked to multiple chronic conditions in quantitative studies. This paper presents a systematic review of quantitative studies that examined the links between loneliness and common chronic conditions including: heart disease, hypertension, stroke, lung disease, and metabolic disorders. A comprehensive literature search process guided by the PRISMA statement led to the inclusion of 33 articles that measure loneliness in chronic illness populations. Loneliness is a significant biopsychosocial stressor that is prevalent in adults with heart disease, hypertension, stroke, and lung disease. The relationships among loneliness, obesity, and metabolic disorders are understudied but current research indicates that loneliness is associated with obesity and with psychological stress in obese persons. Limited interventions have demonstrated long-term effectiveness for reducing loneliness in adults with these same chronic conditions. Future longitudinal randomized trials that enhance knowledge of how diminishing loneliness can lead to improved health outcomes in persons with common chronic conditions would continue to build evidence to support the translation of findings to recommendations for clinical care.

/pdf/a-systematic-review-of-loneliness-and-common-chronic-1ue733su0v.pdf

A Systematic Review of Loneliness and Common Chronic Physical Conditions in Adults

Although typically associated with maintenance of female reproductive function, estrogens mediate physiological processes in nearly every body tissue, including the central nervous system. Numerous pre-clinical studies have shown that estrogen, specifically 17-beta-estradiol (17β-E2), protects the brain from ischemic injury following stroke. There are multiple mechanisms of 17β-E2's neuroprotection, including activation of several neuroprotective pathways in the brain, but 17β-E2 also mediates the local and systemic immune response to ischemic stroke. This review summarizes the immune response to stroke, sex differences in stroke pathophysiology, and the role of estrogen as an immunomodulator. This review will focus almost entirely on the role of 17β-E2; however, there will be a brief review and comparison to other forms of estrogen. Understanding the immunomodulatory action of estrogens may provide an opportunity for the use of estrogens in treatment of stroke and other inflammatory disease.

17β-estradiol and inflammation: implications for ischemic stroke.

Objective: The objective of this work was to assess the ability of peripheral blood cell-free DNA (cfDNA) levels to identify ischaemic stroke early in the acute phase of care, as well as to examine the relationship between peripheral blood cfDNA levels and stroke-induced innate immune system activation. Methods: Upon emergency department admission, peripheral blood samples were obtained from 43 patients experiencing acute ischaemic stroke and 20 patients identified as stroke mimics. Plasma cfDNA levels were measured using quantitative polymerase chain reaction (qPCR), infarct volume and NIH stroke scale (NIHSS) were used to assess injury severity, and peripheral blood neutrophil count was used as a measure of innate immune system status.Results: Peripheral blood cfDNA levels were significantly elevated in patients suffering stroke relative to those diagnosed as stroke mimics, and could differentiate between groups with 86% (95% CI = 72–95%) sensitivity and 75% (95% CI = 51–91%) specificity. Furthe...

Circulating extracellular DNA levels are acutely elevated in ischaemic stroke and associated with innate immune system activation.

Early and accurate diagnosis of stroke improves the probability of positive outcome. The objective of this study was to identify a pattern of gene expression in peripheral blood that could potentially be optimised to expedite the diagnosis of acute ischaemic stroke (AIS). A discovery cohort was recruited consisting of 39 AIS patients and 24 neurologically asymptomatic controls. Peripheral blood was sampled at emergency department admission, and genome-wide expression profiling was performed via microarray. A machine-learning technique known as genetic algorithm k-nearest neighbours (GA/kNN) was then used to identify a pattern of gene expression that could optimally discriminate between groups. This pattern of expression was then assessed via qRT-PCR in an independent validation cohort, where it was evaluated for its ability to discriminate between an additional 39 AIS patients and 30 neurologically asymptomatic controls, as well as 20 acute stroke mimics. GA/kNN identified 10 genes (ANTXR2, STK3, PDK4, CD163, MAL, GRAP, ID3, CTSZ, KIF1B and PLXDC2) whose coordinate pattern of expression was able to identify 98.4% of discovery cohort subjects correctly (97.4% sensitive, 100% specific). In the validation cohort, the expression levels of the same 10 genes were able to identify 95.6% of subjects correctly when comparing AIS patients to asymptomatic controls (92.3% sensitive, 100% specific), and 94.9% of subjects correctly when comparing AIS patients with stroke mimics (97.4% sensitive, 90.0% specific). The transcriptional pattern identified in this study shows strong diagnostic potential, and warrants further evaluation to determine its true clinical efficacy.

/pdf/machine-learning-approach-identifies-a-pattern-of-gene-4wtn431aw1.pdf

Machine-learning approach identifies a pattern of gene expression in peripheral blood that can accurately detect ischaemic stroke

A balanced immune system response plays an important role in acute ischemic stroke (AIS) recovery. Our laboratory has previously identified several immune-related genes, including arginase 1 (ARG1), with altered expression in human AIS patients. The neutrophil-lymphocyte ratio (NLR) may be a marker of the degree of immune dysregulation following AIS; however, the molecular mechanisms that may mediate the NLR are unknown. The purpose of this study was to (1) examine the relationship between ARG1, NLR, and AIS severity and (2) to utilize principal component analysis (PCA) to statistically model multiple gene expression changes following AIS. AIS patients and stroke-free control subjects were recruited, and blood samples were collected from AIS patients within 24 h of stroke symptom onset. White blood cell differentials were obtained at this time to calculate the NLR. Gene expression was measured using real-time PCR. PCA with varimax rotation was used to develop composite variables consisting of a five-gene profile. ARG1 was positively correlated with NLR (r = 0.57, p = 0.003), neutrophil count (r = 0.526, p = 0.007), NIHSS (r = 0.607, p = 0.001), and infarct volume (r = 0.27, p = 0.051). PCA identified three principal components that explain 84.4 % of variation in the original patient gene dataset comprised of ARG1, LY96, MMP9, s100a12, and PC1 was a significant explanatory variable for NIHSS (p < 0.001) and NLR (p = 0.005). Our study suggests a novel relationship between ARG1, NLR, and stroke severity, and the NLR is an underutilized clinically available biomarker to monitor the post-stroke immune response.

/pdf/the-role-of-arginase-1-in-post-stroke-immunosuppression-and-3ry9ryrf2z.pdf

Ashley B Petrone

Papers

A Systematic Review of Loneliness and Common Chronic Physical Conditions in Adults

17β-estradiol and inflammation: implications for ischemic stroke.

Circulating extracellular DNA levels are acutely elevated in ischaemic stroke and associated with innate immune system activation.

Machine-learning approach identifies a pattern of gene expression in peripheral blood that can accurately detect ischaemic stroke

The Role of Arginase 1 in Post-Stroke Immunosuppression and Ischemic Stroke Severity