Healthcare-Related Regret among Nurses and Physicians Is Associated with Self-Rated Insomnia Severity: A Cross-Sectional Study

To examine the association between healthcare-related regrets and sleep difficulties among nurses and physicians, we surveyed 240 nurses and 220 physicians at the University Hospitals of Geneva. Regret intensity and regret coping were measured using validated scales. Sleep difficulties were measured using the Insomnia Severity Index (ISI), and an additional question assessed the frequency of sleeping pill use. After controlling for sex, profession, years of experience, rate of employment, and depression as well as for all other regret-related variables, the following variables remained significantly associated with self-rated severity of insomnia: regret intensity (slope = 1.32, p = 0.007, 95%CI: [0.36; 2.29], std. coefficient = 0.16) and maladaptive (e.g., rumination) emotion-focused coping (slope = 1.57, p = 0.002, 95%CI: [0.60; 2.55], std. coefficient = 0.17) remained significant predictors of self-rated insomnia severity. If these cross-sectional associations represent causal effects, the development of regret-management programs may represent a promising approach to mitigating sleep difficulties of healthcare professionals.     

Phylogenetic relationships of the Suidae (Mammalia,Cetartiodactyla): new insights on the relationships within Suoidea

Orliac, M. J., Antoine, P. ‐O., Ducrocq, S. (2010). Phylogenetic relationships of the Suidae (Mammalia, Cetartiodactyla): new insights on the relationships within Suoidea. —Zoologica Scripta, 39, 315–330. In most analyses, both molecular and morphological phylogenies of the Cetartiodactyla support the monophyly of Suoidea. However, the evolutionary history of this superfamily remains poorly known primarily due to long‐lasting debates about the taxonomic content and relationships of the suoid families and subfamilies. Despite their crucial position in the reconstruction of the phylogeny of Cetartiodactyla, Suoidea themselves have received little attention in those phylogenies, and no extensive analysis of the group has been performed so far. We therefore examine the phylogeny of the Suidae through the first phylogenetic analysis of Suoidea, including recent and fossil representatives of all four putative families. The results support the monophyly of the traditional suid subfamilies and indicate the Sanitheriidae as sister taxon to the Suidae clade. The evolutionary history within Suidae reveals its complexity, with major convergences involving important morphological structures such as the auditory region or the upper male canine. Divergent signals gathered from either dental or cranio‐mandibular features are responsible for two long‐lasting unresolved issues within Suoidea: the question of the relationships between ‘Old World’ and ‘New World’ peccaries remaining unsolved, as well as the position and familial status of the mid‐Tertiary tayassuid Perchoerus.     

Myocardial Infarct Size and Mortality Depend on the Time of Day—A Large Multicenter Study

Background

Different studies have shown circadian variation of ischemic burden among patients with ST-Elevation Myocardial Infarction (STEMI), but with controversial results. The aim of this study was to analyze circadian variation of myocardial infarction size and in-hospital mortality in a large multicenter registry.

Methods

This retrospective, registry-based study was based on data from AMIS Plus, a large multicenter Swiss registry of patients who suffered myocardial infarction between 1999 and 2013. Peak creatine kinase (CK) was used as a proxy measure for myocardial infarction size. Associations between peak CK, in-hospital mortality, and the time of day at symptom onset were modelled using polynomial-harmonic regression methods.

Results

6,223 STEMI patients were admitted to 82 acute-care hospitals in Switzerland and treated with primary angioplasty within six hours of symptom onset. Only the 24-hour harmonic was significantly associated with peak CK (p = 0.0001). The maximum average peak CK value (2,315 U/L) was for patients with symptom onset at 23:00, whereas the minimum average (2,017 U/L) was for onset at 11:00. The amplitude of variation was 298 U/L. In addition, no correlation was observed between ischemic time and circadian peak CK variation. Of the 6,223 patients, 223 (3.58%) died during index hospitalization. Remarkably, only the 24-hour harmonic was significantly associated with in-hospital mortality. The risk of death from STEMI was highest for patients with symptom onset at 00:00 and lowest for those with onset at 12:00.

Discussion

As a part of this first large study of STEMI patients treated with primary angioplasty in Swiss hospitals, investigations confirmed a circadian pattern to both peak CK and in-hospital mortality which were independent of total ischemic time. Accordingly, this study proposes that symptom onset time be incorporated as a prognosis factor in patients with myocardial infarction.     

IPS-1 Is Essential for the Control of West Nile Virus Infection and Immunity

The innate immune response is essential for controlling West Nile virus (WNV) infection but how this response is propagated and regulates adaptive immunity in vivo are not defined. Herein, we show that IPS-1, the central adaptor protein to RIG-I-like receptor (RLR) signaling, is essential for triggering of innate immunity and for effective development and regulation of adaptive immunity against pathogenic WNV. IPS-1^−/− mice exhibited increased susceptibility to WNV infection marked by enhanced viral replication and dissemination with early viral entry into the CNS. Infection of cultured bone-marrow (BM) derived dendritic cells (DCs), macrophages (Macs), and primary cortical neurons showed that the IPS-1-dependent RLR signaling was essential for triggering IFN defenses and controlling virus replication in these key target cells of infection. Intriguingly, infected IPS-1^−/− mice displayed uncontrolled inflammation that included elevated systemic type I IFN, proinflammatory cytokine and chemokine responses, increased numbers of inflammatory DCs, enhanced humoral responses marked by complete loss of virus neutralization activity, and increased numbers of virus-specific CD8+ T cells and non-specific immune cell proliferation in the periphery and in the CNS. This uncontrolled inflammatory response was associated with a lack of regulatory T cell expansion that normally occurs during acute WNV infection. Thus, the enhanced inflammatory response in the absence of IPS-1 was coupled with a failure to protect against WNV infection. Our data define an innate/adaptive immune interface mediated through IPS-1-dependent RLR signaling that regulates the quantity, quality, and balance of the immune response to WNV infection.     

Linagliptin prevents left ventricular stiffening by reducing titin cleavage and hypophosphorylation

The metabolic syndrome (MetS) is an escalating problem worldwide, causing left ventricular stiffening, an early characteristic of diastolic dysfunction for which no treatment exists. As diastolic dysfunction and stiffening in MetS patients are associated with increased circulating dipeptidyl peptidase-4 (DPP-4) levels, we investigated whether the clinically approved DPP-4 inhibitor linagliptin reduces left ventricular stiffness in MetS-induced cardiac disease. Sixteen-week-old obese ZSF1 rats, displaying the MetS and left ventricular stiffness, received linagliptin-supplemented or placebo diet for four weeks. Linagliptin significantly reduced obesity, hyperlipidaemia, and hyperglycaemia and improved left ventricular relaxation. This improved relaxation was related to decreased cardiac fibrosis and cardiomyocyte passive stiffness (F_passive). The reduced F_passive was the result of titin isoform switching from the stiff N2B to the more flexible N2BA and increased phosphorylation of total titin and specifically its N2Bus region (S4080 and S3391). Importantly, DPP-4 directly cleaved titin in vitro, resulting in an increased F_passive, which was prevented by simultaneous administration of linagliptin. In conclusion, linagliptin improves left ventricular stiffness in obese ZSF1 rats by preventing direct DPP4-mediated titin cleavage, as well as by modulating both titin isoform levels and phosphorylation. Reducing left ventricular stiffness by administering linagliptin might prevent MetS-induced early diastolic dysfunction in human.     

Green Alternatives in Treatment of Liver Diseases: the Challenges of Traditional Medicine and Green Nanomedicine

Over the last decade, liver diseases have become a global problem, with approximately two million deaths per year. The high increase in the mortality rate of these diseases is mostly related to the limitations in the understanding of the evolutionary clinical cases of liver diseases, the low delivery of drugs in the liver, the non-specific administration of drugs, and the side effects generated at the systemic level by conventional therapeutic agents. Today it is common knowledge that phytochemicals have a high curative potential, even in the prevention and/or reversibility of liver disorders; however, even using these green molecules, researchers continue to deal with the same challenges implemented with conventional therapeutic agents, which limits the pharmacological potential of these friendly molecules. On the other hand, the latest advances in nanotechnology have proven that the use of nanocarriers as a delivery system for green active ingredients, as well as conventional ones, increases the pharmacological potential of these active ingredients due to their physicochemical characteristics (size, Zeta potential, etc.,) moldable depending on the therapeutic objective; in addition to the above, it should be noted that in recent years, nanoparticles have been developed for the specific delivery of drugs towards a specific target (stellar cells, hepatocytes, Kupffer cells), depending on the clinical state of the disease in the patient. The present review addresses the challenges of traditional medicine and green nanomedicine as alternatives in the treatment of liver diseases.     

Simultaneous measurement of changes in red and blue fluorescence in illuminated isolated chloroplasts and leaf pieces: The contribution of NADPH to the blue fluorescence signal

A newly developed nitrogen laser fluorimeter insensitive to actinic illumination was used to follow simultaneously the light induced changes in red and blue fluorescence of intact isolated spinach chloroplasts and leaf pieces. The recorded variable blue fluorescence was linked to a water soluble component of intact isolated chloroplasts, depended on Photosystem I, and was related to changes in carbon metabolism. From the comparison of changes in intact and broken chloroplasts and from fluorescence spectra under different conditions, it was concluded that the variation in NADPH was the major cause for the changes in blue fluorescence. This study opens a path towards continuous and non-destructive monitoring of NADPH redox state in chloroplasts and leaves.Abbreviations Chl chlorophyll - DHAP dihydroxyacetone phosphate - DLGA DL-glyceraldehyde - FNR ferredoxin-NADP reductase - FWHM full width at half maximum - LED light emitting diodes - OAA oxaloacetate - q_N non-photochemical quenching - PGA 3-phosphoglycerate - Pi inorganic orthophosphate - q_P photochemical quenching - PPFD photosynthetic photon flux density - Q_A primary quinone acceptor of Photosystem II Preliminary results of this work were presented at the First Conference on the Physiology and Biochemistry of high Mountain Plants, 2–3 July 1992, Villar d'Arene, France.     

Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels

Novel antiangiogenic strategies with complementary mechanisms are needed to maximize efficacy and minimize resistance to current angiogenesis inhibitors. We explored the therapeutic potential and mechanisms of alphaPlGF, an antibody against placental growth factor (PlGF), a VEGF homolog, which regulates the angiogenic switch in disease, but not in health. alphaPlGF inhibited growth and metastasis of various tumors, including those resistant to VEGF(R) inhibitors (VEGF(R)Is), and enhanced the efficacy of chemotherapy and VEGF(R)Is. alphaPlGF inhibited angiogenesis, lymphangiogenesis, and tumor cell motility. Distinct from VEGF(R)Is, alphaPlGF prevented infiltration of angiogenic macrophages and severe tumor hypoxia, and thus, did not switch on the angiogenic rescue program responsible for resistance to VEGF(R)Is. Moreover, it did not cause or enhance VEGF(R)I-related side effects. The efficacy and safety of alphaPlGF, its pleiotropic and complementary mechanism to VEGF(R)Is, and the negligible induction of an angiogenic rescue program suggest that alphaPlGF may constitute a novel approach for cancer treatment.     

Homozygous mutation in SPATA16 is associated with male infertility in human globozoospermia

Globozoospermia is a rare (incidence <0.1% in male infertile patients) form of teratozoospermia, mainly characterized by round-headed spermatozoa that lack an acrosome. It originates from a disturbed spermiogenesis, which is expected to be induced by a genetic factor. Several family cases and recessive mouse models with the same phenotype support this expectation. In this study, we present a consanguineous family with three affected brothers, in whom we have identified a homozygous mutation in the spermatogenesis-specific gene SPATA16. This is the first example of a nonsyndromic male infertility condition in humans caused by an autosomal gene defect, and it could also mean that the identification of other partners like SPATA16 could elucidate acrosome formation.