Observation of HCN hyperfine line anomalies towards low- and high-mass star-forming cores

HCN is becoming a popular choice of molecule for studying star formation in both low- and high-mass regions and for other astrophysical sources from comets to high-redshift galaxies. However, a major and often overlooked difficulty with HCN is that it can exhibit non-local thermodynamic equilibrium (non-LTE) behaviour in its hyperfine line structure. Individual hyperfine lines can be strongly boosted or suppressed. In low-mass star-forming cloud observations, this could possibly lead to large errors in the calculation of opacity and excitation temperature, while in massive star-forming clouds, where the hyperfine lines are blended due to turbulent broadening, errors will arise in infall measurements that are based on the separation of the peaks in a self-absorbed profile. The underlying line shape cannot be known for certain if hyperfine anomalies are present. We present a first observational investigation of these anomalies across a range of conditions and transitions by carrying out a survey of low-mass starless cores (in Taurus & Ophiuchus) and high-mass protostellar objects (in the G333 giant molecular cloud) using hydrogen cyanide (HCN) J=1-0 and J=3-2 emission lines. We quantify the degree of anomaly in these two rotational levels by considering ratios of individual hyperfine lines compared to LTE values. We find that all the cores observed show some degree of anomaly while many of the lines are severely anomalous. We conclude that HCN hyperfine anomalies are common in both lines in both low-mass and high-mass protostellar objects, and we discuss the differing hypotheses for the generation of the anomalies. In light of the results, we favour a line overlap effect for the origins of the anomalies. We discuss the implications for the use of HCN as a dynamical tracer and suggest in particular that the J=1-0, F=0-1 hyperfine line should be avoided in quantitative calculations.Comment: 17 pages, 8 figure

A review of the pharmacotherapeutic considerations for managing epilepsy in people with autism.

INTRODUCTION: Autism, like other neurodevelopmental disorders (NDDs), has a strong association with epilepsy. There are known common genetic pathways in both autism and epilepsy. There are also specific genetic syndromes associated with both complex epilepsy and the autism phenotype. AREAS COVERED: This review explores the evidence for common genetic etiologies and pathophysiological pathways in relation to both epilepsy and autism. Autism with comorbid epilepsy are associated with a high prevalence of medical and psychiatric comorbidities. This paper discusses how this influences assessment, treatment, and outcomes. The evidence for the treatment of specific seizure types in the context of NDDs is also examined alongside clinical commentary. EXPERT OPINION: Despite the strong association, there is a limited evidence base to support the efficacy and tolerability of anti-seizure medications specifically in autism, with no Level 1 evidence or National Guidance available. Autism and epilepsy should be approached under a NDD model with cautious introduction and titration of anti-seizure medication. Alongside this, there is evidence to support a move toward precision medicine in specific genetic syndromes such as Tuberous Sclerosis Complex and other genetic seizure disorders. The first-line treatments that should be considered for focal seizures include carbamazepine, lamotrigine, and levetiracetam

Thermoelectric efficiency at maximum power in a quantum dot

We identify the operational conditions for maximum power of a nanothermoelectric engine consisting of a single quantum level embedded between two leads at different temperatures and chemical potentials. The corresponding thermodynamic efficiency agrees with the Curzon-Ahlborn expression up to quadratic terms in the gradients, supporting the thesis of universality beyond linear response.Comment: 4 pages, 3 figure

Carriage of Staphylococcus aureus in the elderly

The point prevalence and incidence of Staphylococcus aureus (methicillin-sensitive and -resistant) carriage by inpatients on acute elderly care wards was estimated. The relationship to body site and to previous admissions to hospital or other institutions was determined. Fifty-five patients were included in the point prevalence study and 136 in the incidence study, which was performed over a two-month period. One in three patients carried S. aureus and 1 in 20 was infected. The incidence rate for MRSA was 2.9%. No endemic strain was found. Nostrils were significantly associated with carriage, and skin break isolates were significant in the point prevalence survey. Screening these sites alone would be most cost effective

Post-operative immune suppression is reversible with interferon gamma and independent of IL-6 pathways

Introduction The post-operative period is characterised by increased IL-6 production and clinical features of immune suppression. In vitro anti-inflammatory actions of IL-6 are mediated through suppression of interferon gamma (IFNγ) [1]. The clinical significance of IL-6 in mediating post-operative immune suppression remains unclear. Objectives To evaluate the role of IL-6 pathways in post-operative immune suppression and the reversibility of this phenomenon. Methods Patients over 45 years old undergoing elective surgery involving the gastrointestinal tract and requiring at least an overnight hospital stay were recruited. The primary outcome was hospital-acquired infection. IL-6 and IFNγ levels were assayed using ELISA preoperatively and at 24 and 48 hours. Pooled healthy control peripheral blood mononuclear cells (PBMCs) were cultured in perioperative serum and CD14+HLA-DR (mHLA-DR) geometric mean florescent intensity (MFI) measured in the presence and absence of interferon gamma (IFNγ) and IL-6 neutralising antibody. Data were analysed with non-parametric statistics. Results 119 patients were recruited and 44 (37%) developed a post-operative infection a median of 9 (IQR 5-11) days postoperatively (Figure 1). IL-6 levels increased from baseline to 24 hours postoperatively (P < 0.0001, Figure 1A) but were then unchanged between 24 and 48 hours (P = 0.06, Figure 1B). Postoperative IL-6 levels correlated with the duration of the procedure (P = 0.009). Higher preoperative IL-6 levels were observed in patients with cancer (P = 0.02). IL-6 levels at 24 (P = 0.0002) and 48 hours (P = 0.003) were associated with the later occurrence of infectious complications. This pattern remained similar after adjustment for baseline characteristics. Healthy donor PBMCs incubated with postoperative serum downregulated mHLA-DR MFI when compared with serum from baseline (n = 8, p = 0.008). Culturing in the presence of IFNγ 250IU (n = 4) prevented this decrease whereas culturing in the presence of IL-6 neutralising antibody 15ng/ml (n = 8) did not. Conclusions IL-6 levels increase following major surgery and are associated with an increased susceptibility to post-operative infections. Serum obtained from post-operative patients induces an immunosuppressive response through an IL-6 independent pathways which is reversible with IFNγ treatment

Changes in gene expression following trauma are related to the age of transfused packed red blood cells

BACKGROUND Transfusion of packed red blood cells (PRBCs) is associated with an increased incidence of nosocomial infections and an increased risk of death. The duration of storage before transfusion may influence these outcomes. Here, we explore the association between the age of transfused PRBCs and specific patterns of inflammatory gene expression in severely injured trauma patients. METHODS Severely injured trauma patients requiring intensive care unit treatment and receiving transfusion of PRBCs within 24 hours of the injury were recruited. Blood samples were obtained within 2 hours of the trauma, at 24 hours, and at 72 hours. Messenger RNA was extracted from whole blood, and gene expression was quantified using quantitative polymerase chain reaction. The median age of the units of PRBCs transfused to each patient was recorded. The primary outcome measure was the change in candidate gene expression over the initial 72 hours. RESULTS Sixty-four patients were studied. Fifty-three patients (83%) were male, and the median age was 40.5 years (interquartile range [IQR], 31-59). Median Injury Severity Score (ISS) was 31.5 (IQR, 23-43), and 55 patients (86%) experienced a blunt injury. Forty-one patients (64%) developed a nosocomial infection, and 15 patients (23%) died before hospital discharge. Each patient received a median of 5 U of PRBCs (IQR, 4-9.8 U) during the first 24 hours of hospital admission. The median age of the units of PRBCs transfused in each patient was 20 days (IQR, 17-22 days). Older blood was associated with greater decreases in interleukin 12 (IL-12), IL-23, and RORγt (all p's < 0.05) gene expression over the initial 24 hours, greater decreases in IL-12 gene expression over 72 hours, and a rise in transforming growth factor β gene expression over the first 72 hours. A multivariate analysis confirmed the independence of these associations. CONCLUSION Increasing the duration of storage of PRBCs before transfusion is associated with a pattern of gene expression consistent with more severe immunosuppression. LEVEL OF EVIDENCE Epidemiologic study, level III

Features of postoperative immune suppression are reversible with interferon gamma and independent of interleukin-6 pathways

OBJECTIVE The aim of this study was to evaluate the role of interleukin (IL)-6 pathways in postoperative immune suppression and to assess the reversibility of this phenomenon. BACKGROUND The postoperative period is characterized by increased IL-6 production and features of immune suppression. In vitro, IL-6 mediates anti-inflammatory effects through inhibition of interferon gamma (IFN-γ) pathways. The significance of the immunomodulatory effects of IL-6 in the clinical setting of postoperative immune suppression remains unclear. METHODS Patients over 45 years old undergoing elective surgery, involving the gastrointestinal tract, were recruited. IL-6 levels were assayed using an enzyme linked immunosorbent assay preoperatively, and at 24 and 48 hours. Peripheral blood mononuclear cells from healthy volunteers were cultured in perioperative serum and CD14Human Leukocyte Antigen-DR (HLA-DR) [monocyte HLA-DR (mHLA-DR)] geometric mean florescent intensity was measured in the presence and absence of IL-6 neutralizing antibody and recombinant IFN-γ. RESULTS Of the 108 patients, 41 developed a postoperative infection. The IL-6 levels increased 19-fold from the preoperative sample to 24 hours postoperatively (P < 0.0001). Higher IL-6 levels at 24 (P = 0.0002) and 48 hours (P = 0.003) were associated with subsequent postoperative infectious complications. mHLA-DR mean florescent intensity fell when healthy peripheral blood mononuclear cells were cultured with postoperative serum compared with preoperative serum (P = 0.008). This decrease was prevented by the presence of IFN-γ in the culture media, but not by the presence of IL-6-neutralizing antibody. CONCLUSIONS IL-6 levels increase after a major surgery and are associated with an increased susceptibility to postoperative infections. Serum obtained from postoperative patients induces an immunosuppressive response, reflected in reduced mHLA-DR levels, mediated through IL-6 independent pathways and is reversible with IFN-γ. These data may have therapeutic implications for the prevention of infection in patients undergoing major surgery

Epigenetic regulatory pathways involving microRNAs may modulate the host immune response following major trauma

BACKGROUND Posttraumatic nosocomial pneumonia is a common complication resulting in significant morbidity. Trauma-induced immunocompromise is associated with an enhanced susceptibility to pneumonia. In this study, we explore the hypothesis that posttranscriptional epigenetic regulation of gene expression may be an important factor in determining this immune phenotype. We describe the pattern of production of microRNAss (miRs) and their association with nosocomial pneumonia following severe trauma. METHODS A convenience sample of 30 ventilated polytrauma patients (UKCRN ID: 5637) and 16 healthy controls were recruited. Messenger RNA and protein levels of key cytokines were quantified within 2 hours of the injury and at 24 hours. Three miRs per cytokine were then selected based on miRBase target prediction scores and quantified using polymerase chain reaction. Nosocomial pneumonia was defined using the Centers for Disease Control and Prevention definitions. RESULTS Median Injury Severity Score (ISS) was 29, and 47% of the patients developed nosocomial pneumonia. miR-125a and miR-202 decreased by 34% and 77%, respectively, immediately following injury, whereas their target, IL-10, increased messenger RNA levels 3-fold and protein levels 180 fold. Tumor necrosis factor α (TNF-α) and IL-12 gene expression decreased by 68% and 43%, respectively, following injury, and this was mirrored by a 10-fold increase in miR-181, an miR predicted to target TNF-α transcripts. Lower levels of miR-125a and miR-374b were associated with the later acquisition of hospital-acquired pneumonia. CONCLUSION Alteration in the expression of miRs with highly predicted complementarity to IL-10 and TNF-α may be an important mechanism regulating the posttraumatic immunosuppressive phenotype in intensive care unit patients. LEVEL OF EVIDENCE Retrospective observational study, level III

Post-operative immune suppression is reversible with interferon gamma and independent of IL-6 pathways

Introduction The post-operative period is characterised by increased IL-6 production and clinical features of immune suppression. In vitro anti-inflammatory actions of IL-6 are mediated through suppression of interferon gamma (IFNγ) [1]. The clinical significance of IL-6 in mediating post-operative immune suppression remains unclear. Objectives To evaluate the role of IL-6 pathways in post-operative immune suppression and the reversibility of this phenomenon. Methods Patients over 45 years old undergoing elective surgery involving the gastrointestinal tract and requiring at least an overnight hospital stay were recruited. The primary outcome was hospital-acquired infection. IL-6 and IFNγ levels were assayed using ELISA preoperatively and at 24 and 48 hours. Pooled healthy control peripheral blood mononuclear cells (PBMCs) were cultured in perioperative serum and CD14+HLA-DR (mHLA-DR) geometric mean florescent intensity (MFI) measured in the presence and absence of interferon gamma (IFNγ) and IL-6 neutralising antibody. Data were analysed with non-parametric statistics. Results 119 patients were recruited and 44 (37%) developed a post-operative infection a median of 9 (IQR 5-11) days postoperatively (Figure 1). IL-6 levels increased from baseline to 24 hours postoperatively (P < 0.0001, Figure 1A) but were then unchanged between 24 and 48 hours (P = 0.06, Figure 1B). Postoperative IL-6 levels correlated with the duration of the procedure (P = 0.009). Higher preoperative IL-6 levels were observed in patients with cancer (P = 0.02). IL-6 levels at 24 (P = 0.0002) and 48 hours (P = 0.003) were associated with the later occurrence of infectious complications. This pattern remained similar after adjustment for baseline characteristics. Healthy donor PBMCs incubated with postoperative serum downregulated mHLA-DR MFI when compared with serum from baseline (n = 8, p = 0.008). Culturing in the presence of IFNγ 250IU (n = 4) prevented this decrease whereas culturing in the presence of IL-6 neutralising antibody 15ng/ml (n = 8) did not. Conclusions IL-6 levels increase following major surgery and are associated with an increased susceptibility to post-operative infections. Serum obtained from post-operative patients induces an immunosuppressive response through an IL-6 independent pathways which is reversible with IFNγ treatment