Use of intraoperative haemoadsorption in patients undergoing heart transplantation: a proof-of-concept randomized trial.

AIMS: The aim of this trial was to compare the clinical effects of intraoperative haemoadsorption versus standard care in patients undergoing orthotopic heart transplantation (OHT). METHODS AND RESULTS: In a randomized, controlled trial, OHT recipients were randomized to receive intraoperative haemoadsorption or standard care. Outcomes were vasoactive-inotropic score (VIS), frequency of vasoplegic syndrome (VS) in the first 24 h; post-operative change in procalcitonin (PCT) and C-reactive protein (CRP) levels; intraoperative change in mycophenolic acid (MPA) concentration; frequency of post-operative organ dysfunction, major complications, adverse immunological events and length of in-hospital stay and 1-year survival. Sixty patients were randomized (haemoadsorption group N = 30, control group N = 25 plus 5 exclusions). Patients in the haemoadsorption group had a lower median VIS and rate of VS (VIS: 27.2 [14.6-47.7] vs. 41.9 [22.4-63.2], P = 0.046, and VS: 20.0% vs. 48.0%, P = 0.028, respectively), a 6.4-fold decrease in the odds of early VS (OR: 0.156, CI: 0.029-0.830, P = 0.029), lower PCT levels, shorter median mechanical ventilation (MV: 25 [19-68.8] hours vs. 65 [23-287] hours, P = 0.025, respectively) and intensive care unit stay (ICU stay: 8.5 [8.0-10.3] days vs. 12 [8.5-18.0] days, P = 0.022, respectively) than patients in the control group. Patients in the haemoadsorption versus control group experienced lower rates of acute kidney injury (AKI: 36.7% vs. 76.0%, P = 0.004, respectively), renal replacement therapy (RRT: 0% vs. 16.0%, P = 0.037, respectively) and lower median per cent change in bilirubin level (PCB: 2.5 [-24.6 to 71.1] % vs. 72.1 [11.2-191.4] %, P = 0.009, respectively) during the post-operative period. MPA concentrations measured at pre-defined time points were comparable in the haemoadsorption compared to control groups (MPA pre-cardiopulmonary bypass: 2.4 [1.15-3.60] µg/mL vs. 1.6 [1.20-3.20] µg/mL, P = 0.780, and MPA 120 min after cardiopulmonary bypass start: 1.1 [0.58-2.32] µg/mL vs. 0.9 [0.45-2.10] µg/mL, P = 0.786). The rates of cardiac allograft rejection, 30-day mortality and 1-year survival were similar between the groups. CONCLUSIONS: Intraoperative haemoadsorption was associated with better haemodynamic stability, mitigated PCT response, lower rates of post-operative AKI and RRT, more stable hepatic bilirubin excretion, and shorter durations of MV and ICU stay. Intraoperative haemoadsorption did not show any relevant adsorption effect on MPA. There was no increase in the frequency of early cardiac allograft rejection related to intraoperative haemoadsorption use.

Seroconversion after SARS-CoV-2 vaccination is protective against severe COVID-19 disease in heart transplant recipients.

BACKGROUND: Heart transplant (HTX) recipients are prone to develop complications after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Vaccination is often ineffective due to weaker immunogenicity. In this high-volume single-center study, we aimed to determine factors influencing seroconversion after vaccination and predictors of severe SARS-CoV-2 infection. METHODS: Two hundred twenty-nine HTX recipients were enrolled. Type of the first two vaccine doses included messenger RNA (mRNA), vector, and inactivated vaccines. We carried out analyses on seroconversion after the second and third doses of vaccination and on severity of infection. Antispike protein SARS-CoV-2 immunoglobulin G (IgG) was measured after the second and third vaccines and serostatus was defined. Effect of the first two vaccine doses was studied on patients who did not suffer SARS-CoV-2 infection before antibody measurement (n = 175). The effectivity of the third vaccine was evaluated among seronegative recipients after the second vaccine (n = 53). Predictors for severe infection defined as pneumonia, hospitalization or death were assessed in all patients who contracted SARS-CoV-2 infection (n = 92). RESULTS: 62% of the recipients became seropositive after the second vaccination. Longer time between HTX and vaccination (odds ratio [OR]: 2.35) and mRNA vaccine (OR: 4.83) were predictors of seroconversion. 58% of the nonresponsive patients became seropositive after receiving the third vaccine. Male sex increased the chance of IgG production after the third dose (OR: 5.65). Clinical course of SARS-CoV-2 infection was severe in 32%. Of all parameters assessed, only seropositivity before infection was proven to have a protective effect against severe infection (OR: 0.11). CONCLUSIONS: We found that longer time since HTX, mRNA vaccine type, and male sex promoted seroconversion after SARS-CoV-2 vaccination in HTX recipients. Seropositivity-but not the number of vaccine doses-seemed to be protective against severe SARS-CoV-2 infection. Screening of HTX patients for anti-SARS-COV-2 antibodies may help to identify patients at risk for severe infection.

Associations between daily affective experiences, trait and daily rumination on negative and positive affect: a diary study.

BACKGROUND: Rumination has mostly been studied in relation to depression, however, it may also occur in response to positive emotions (i.e., positive rumination) and therefore may be a protective factor related to the maintenance of positive mood. OBJECTIVE: We hypothesized that daily positive and negative affect would be associated with daily positive and negative rumination even after controlling for trait-level rumination. METHOD: We carried out a diary study with university students (n = 178), where participants had to answer short surveys online about their daily affect and daily rumination every evening for 10 days. We analyzed our data with multilevel regression in R. RESULTS: Daily positive and negative affect were significantly associated with daily negative and positive rumination, while trait-level rumination scores were not. Daily and trait-level rumination were moderately correlated (r = 0.333-0.440). CONCLUSIONS: Our findings highlight that daily rumination plays a more significant role in daily emotional experiences than trait rumination across positive and negative valence domains. Daily negative affect appears to be more closely related to higher daily negative rumination than the lack of daily positive rumination, which could be relevant for intervention strategies.

Extracorporeal photopheresis in the treatment of cardiac allograft rejection: A single-centre experience.

Despite novel immunosuppressive (IS) protocols, adverse effects of IS drugs continue to have notable negative impact on patient and cardiac allograft survival after heart transplantation (HTx). Therefore, IS regimens with less toxic side effects are sorely needed. We aimed to evaluate the efficacy of extracorporeal photopheresis (ECP) in combination with tacrolimus-based maintenance IS therapy in the treatment of allograft rejection in adult HTx recipients. Indications for ECP included acute moderate-to-severe or persistent mild cellular rejection, or mixed rejection. Twenty-two patients underwent a median of 22(2-44) ECP treatments after HTx. Median duration of ECP course was 173.5(2-466) days. No relevant adverse effects of ECP were noted. Reduction of methylprednisolone doses was safe throughout the ECP course. ECP, used in conjunction with pharmacological anti-rejection therapy, had a successful reversal of cardiac allograft rejection, decreased the rates of subsequential rejection episodes and normalized the allograft function in patients completing the ECP course. Short- and long-term survivals were excellent (91% at 1 and 5 years post-ECP) and comparable to International Society for Heart and Lung Transplantation registry data on HTx recipient overall survival. In conclusion, ECP can be safely used for the treatment and prevention of cardiac allograft rejection in conjunction with traditional IS regimen.

Perioperative Gelatin Use Is Associated With Increased Complication Rates and Does Not Prevent Postoperative Fluid Overload in Patients Undergoing Elective Cardiac Surgery.

OBJECTIVES: The benefit of using gelatin solution in cardiac surgery is still controversial. Previous data suggested adverse interactions of gelatin infusion with acute kidney injury (AKI) or coagulopathy. The purpose of this study was to evaluate the association between perioperative gelatin use and fluid overload (FO), hemodynamic stability, and outcomes compared to crystalloid-based fluid management. DESIGN: A retrospective study design. SETTING: At a single-center tertiary university setting. PARTICIPANTS: Propensity score-matched cohort study of 191 pairs of patients scheduled for cardiac surgery. INTERVENTIONS: Patients received either gelatin + crystalloid or pure crystalloid-based perioperative fluid management. The primary outcomes were the frequency of FO and hemodynamic stability defined by the vasoactive-inotropic score. Postoperative complications and 3-year survival were analyzed also. MEASUREMENTS AND MAIN RESULTS: Patients who received gelatin experienced more frequent postoperative FO than controls (11.0% v 3.1%, p = 0.006) despite comparable hemodynamic stability in both groups. Gelatin administration was linked with a higher rate of postoperative complications, including blood loss, AKI, and new-onset postoperative atrial fibrillation. Use of gelatin infusion resulted in an adjusted odds ratio of 1.982 (95% CI 1.051-3.736, p = 0.035) for developing early postoperative AKI. This study confirmed a dose-dependent relationship between gelatin infusion and AKI. Thirty-day mortality and 3-year survival were similar in the groups. CONCLUSIONS: Gelatin administration versus crystalloid fluid management showed a significant association with a higher rate of FO and an increased risk for early postoperative AKI in a dose-dependent manner.

Influence of Venoarterial Extracorporeal Membrane Oxygenation Integrated Hemoadsorption on the Early Reversal of Multiorgan and Microcirculatory Dysfunction and Outcome of Refractory Cardiogenic Shock.

Background: The purpose of this investigation was to evaluate the impact of venoarterial extracorporeal membrane oxygenation (VA−ECMO) integrated hemoadsorption on the reversal of multiorgan and microcirculatory dysfunction, and early mortality of refractory cardiogenic shock patients. Methods: Propensity score−matched cohort study of 29 pairs of patients. Subjects received either VA−ECMO supplemented with hemoadsorption or standard VA−ECMO management. Results: There was a lower mean sequential organ failure assessment score (p = 0.04), lactate concentration (p = 0.015), P(v−a)CO2 gap (p < 0.001), vasoactive inotropic score (p = 0.007), and reduced delta C−reactive protein level (p = 0.005) in the hemoadsorption compared to control groups after 72 h. In−hospital mortality was similar to the predictions in the control group (62.1%) and was much lower than the predicted value in the hemoadsorption group (44.8%). There were less ECMO-associated bleeding complications in the hemoadsorption group compared to controls (p = 0.049). Overall, 90-day survival was better in the hemoadsorption group than in controls without statistical significance. Conclusion: VA−ECMO integrated hemoadsorption treatment was associated with accelerated recovery of multiorgan and microcirculatory dysfunction, mitigated inflammatory response, less bleeding complications, and lower risk for early mortality in comparison with controls.

Membrane Permeability and Aqueous Stability Study of Linear and Cyclic Diarylheptanoids from Corylus maxima.

Seven diarylheptanoids were isolated from Corylus maxima by flash chromatography and semipreparative high-performance liquid chromatography (HPLC) and identified by Orbitrap® mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy as linear diarylheptanoids: hirsutanonol-5-O-ß-D-glucopyranoside (1), platyphyllonol-5-O-ß-D-xylopyranoside (4), platyphyllenone (5); and cyclic derivatives: alnusonol-11-O-ß-D-glucopyranoside (6), alnusone (7), giffonin F (8), carpinontriol B (9). Cyclic diarylheptanoids are reported in C. maxima for the first time. The aqueous stability of the isolated compounds and other characteristic constituents of C. maxima, oregonin (2), hirsutenone (3), quercitrin (10) and myricitrin (11) was evaluated at pH 1.2, 6.8 and 7.4. The passive diffusion of the constituents across biological membranes was investigated by parallel artificial membrane permeability assay for the gastrointestinal tract (PAMPA-GI) and the blood-brain barrier (PAMPA-BBB) methods. The cyclic diarylheptanoid aglycones and quercitrin were stable at all investigated pH values, while a pH-dependent degradation of the other compounds was observed. A validated ultrahigh-performance liquid chromatography-diode-array detection (UHPLC-DAD) method was utilized for the determination of compound concentrations. The structures of the degradation products were characterized by UHPLC-Orbitrap® MS. Platyphyllenone and alnusone possessed log Pe values greater than -5.0 and -6.0 in the PAMPA-GI and PAMPA-BBB studies, respectively, indicating their ability to cross the membranes via passive diffusion. However, only alnusone can be considered to have both good aqueous stability and satisfactory membrane penetration ability.

CYP3A-status is associated with blood concentration and dose-requirement of tacrolimus in heart transplant recipients.

High inter-individual variability in tacrolimus clearance is attributed to genetic polymorphisms of CYP3A enzymes. However, due to CYP3A phenoconversion induced by non-genetic factors, continuous changes in tacrolimus-metabolizing capacity entail frequent dose-refinement for optimal immunosuppression. In heart transplant recipients, the contribution of patients' CYP3A-status (CYP3A5 genotype and CYP3A4 expression) to tacrolimus blood concentration and dose-requirement was evaluated in the early and late post-operative period. In low CYP3A4 expressers carrying CYP3A5*3/*3, the dose-corrected tacrolimus level was significantly higher than in normal CYP3A4 expressers or in those with CYP3A5*1. Modification of the initial tacrolimus dose was required for all patients: dose reduction by 20% for low CYP3A4 expressers, a 40% increase for normal expressers and a 2.4-fold increase for CYP3A5*1 carriers. The perioperative high-dose corticosteroid therapy was assumed to ameliorate the low initial tacrolimus-metabolizing capacity during the first month. The fluctuation of CYP3A4 expression and tacrolimus blood concentration (C0/D) was found to be associated with tapering and cessation of corticosteroid in CYP3A5 non-expressers, but not in those carrying CYP3A5*1. Although monitoring of tacrolimus blood concentration cannot be omitted, assaying recipients' CYP3A-status can guide optimization of the initial tacrolimus dose, and can facilitate personalized tacrolimus therapy during steroid withdrawal in the late post-operative period.

Pseudoaneurysm of the ascending aorta: case report of a donor-derived Pseudomonas infection in a heart transplant recipient.

BACKGROUND: Mycotic aortic pseudoaneurysm is a rare complication after heart transplantation (HTX) with remarkable mortality. Intrathoracic infection is a well-documented predisposing factor for this disease. Staphylococcus aureus, Pseudomonas aeruginosa or Candida species are commonly isolated from resected specimens of the pseudoaneurysms. We demonstrate a unique case of mycotic pseudoaneurysm caused by presumably donor-derived Pseudomonas infection in a heart transplant recipient. CASE PRESENTATION: Our 67-year-old male patient treated with diabetes mellitus underwent HTX. The donor suffered from epiglottic abscess and pneumonia with known microorganisms including Pseudomonas, therefore both the donor and recipient received targeted antimicrobial therapy and prophylaxis. Five months after the uneventful HTX, lab test of the asymptomatic patient showed moderate, increasing C-reactive protein level without obviuos source of infection. Chest computed tomography showed a large (90 mm) saccular dilatation of the tubular portion of ascending aorta. Urgent surgical intervention identified a pseudoaneurysm, histological examinations and cultures of the resected aorta verified Pseudomonas aeruginosa aortitis, while all blood cultures remained negative. Retrospective interrogation of other transplanted organs of the donor supported donor-derived infection as the transport fluid of the right kidney grew Pseudomonas. The patient received 3 weeks of ceftazidime followed by 7 months of oral ciprofloxacin therapy. One year after the operation the patient was asymptomatic with normal inflammatory markers. CONCLUSIONS: Donor-derived infection is a rare but potential cause of aortitis. Early diagnosis, surgical intervention and adjuvant antibiotic therapy seem to be the keys to successful management of mycotic pseudoaneurysms after HTX.

The stressed bird in the hand: Influence of sampling design on the physiological stress response in a free-living songbird.

Despite the widely used application of standardized capture-handling protocols to collect blood and assess the physiological stress response, the actual sampling design (e.g., timing and the number of blood samples) often differs between studies, and the potential implications for the measured physiological endpoints remain understudied. We, therefore experimentally tested the effects of repeated handling and multiple blood sampling on the stress response in wintering free-living great tits (Parus major). We modified a well-established sampling protocol of avian studies by adding either an additional blood sample or a "sham-manipulation" (i.e., handling associated with the blood sampling procedure without venepuncture), to disentangle the effects of handling stress and blood loss. We combined three different stress metrics along the endocrine-immune interface to investigate the acute short-term stress response: total corticosterone concentrations (Cort), the heterophil/lymphocyte ratio (H:L), and the Leucocyte Coping Capacity (LCC). Our study provided three key results: i) no relationship between Cort levels, LCC and H:L, confirming that these three parameters represent different physiological endpoints within the stress response; ii) contrasting dynamics in response to stress by the measured parameters and iii) no difference in physiological stress levels 30 min after capture due to one additional blood sampling or handling event. By optimising the sampling design, our results provide implications for animal welfare and planning experimental procedures on stress physiology in passerine species.

Effects of experimental increase in insulin-like growth factor 1 on feather growth rate, moult intensity and feather quality in a passerine bird.

Moulting is a crucial, yet often overlooked life-history stage in many animals, when they renew their integumental structures. This life-history stage is an energetically demanding somatic growth event that has particular importance in birds because feathers play a crucial role in flight, insulation and communication. Somatic growth processes are regulated by the evolutionarily conserved peptide hormone insulin-like growth factor 1 (IGF-1). However, the role of IGF-1 in feather growth remains unknown. In this study, we captured 41 juvenile free-living bearded reedlings (Panurus biarmicus) that had started their first complete moult and brought them into captivity. Then, we manipulated their circulating IGF-1 levels using poly-(lactic-co-glycolid acid) microparticles (microspheres) that provide a sustained release of IGF-1. The treatment increased IGF-1 levels but did not affect the feather growth rate. However, 2 weeks after the treatment, birds in the increased IGF-1 group were moulting more feathers simultaneously than the controls and were at a more advanced stage of moult. Birds with experimentally increased IGF-1 levels had better quality feathers (measured by a lower number of fault bars) than the controls. These results suggest that an increase in IGF-1 does not speed up feather growth, but may alter moult intensity by initiating the renewal of several feathers simultaneously. This may shorten the overall moulting time but may imply costs in terms of IGF-1-induced oxidative stress.

An Interaction Effect Analysis of Thermodilution-Guided Hemodynamic Optimization, Patient Condition, and Mortality after Successful Cardiopulmonary Resuscitation.

Proper hemodynamic management is necessary among post-cardiac arrest patients to improve survival. We aimed to investigate the effects of PiCCO™-guided (pulse index contour cardiac output) hemodynamic management on mortality in post-resuscitation therapy. In this longitudinal analysis of 63 comatose patients after successful cardiopulmonary resuscitation cooled to 32-34 °C, 33 patients received PiCCO™, and 30 were not monitored with PiCCO™. Primary and secondary outcomes were 30 day and 1 year mortality. Kaplan-Meier curves and log-rank tests were used to assess differences in mortality among the groups. Interaction effects to disentangle the relationship between patient's condition, PiCCO™ application, and mortality were assessed by means of Chi-square tests and logistic regression models. A 30 day mortality was significantly higher among PiCCO™ patients, while 1 year mortality was marginally higher. More severe patient condition per se was not the cause of higher mortality rate in the PiCCO™ group. Patients in better health conditions (without ST-elevation myocardial infarction, without cardiogenic shock, without intra-aortic balloon pump device, or without stroke in prior history) had worse outcomes with PiCCO™-guided therapy. Catecholamine administration worsened both 30 day and 1 year mortality among all patients. Our analysis showed that there was a complex interaction relationship between PiCCO™-guided therapy, patients' condition, and 30 day mortality for most conditions.

Acute heart transplantation from mechanical circulatory support in a human immunodeficiency virus-positive patient with fulminant myocarditis.

Since the establishment of highly active antiretroviral therapy, survival rates have improved among patients with human immunodeficiency virus infection giving them the possibility to become transplant candidates. Recent publications revealed that human immunodeficiency virus-positive heart transplant recipients' survival is similar to non-infected patients. We present the case of a 40-year-old human immunodeficiency virus infected patient, who was hospitalized due to severely decreased left ventricular function with a possible aetiology of acute myocarditis, that has later been confirmed by histological investigation of myocardial biopsy. Due to rapid progression to refractory cardiogenic shock, extracorporeal membrane oxygenation implantation had been initiated, which was upgraded to biventricular assist device later. On the 35th day of upgraded support, the patient underwent heart transplantation uneventfully. Our clinical experience confirms that implementation of temporary mechanical circulatory support and subsequent cardiac transplantation might be successful in human immunodeficiency virus-positive patients even in case of new onset, irreversible acute heart failure.

Pilot analysis of the usefulness of mortality risk score systems at resuscitated patients / Halálozásikockázat-becslo pontrendszerek alkalmazhatóságának elozetes vizsgálata újraélesztett betegek körében.

Összefoglaló. Bevezetés: A cardiovascularis halálokok közül világszerte nagy jelentoségu a hirtelen szívhalál. Annak ellenére, hogy a cardiopulmonalis resuscitatio és a postresuscitatiós intenzív osztályos kezelés is komoly metodikai és technikai fejlodésen ment keresztül az elmúlt idoszakban, kevés az olyan validált pontrendszer, amely jól becsülné a beteg intenzív osztályra kerülésekor a mortalitási rizikót. Célkituzés: A sikeres újraélesztést követo intenzív osztályos kezelés kezdetekor felmért, a cardiogen shock rizikóstratifikációjára alkalmazott CardShock Risk Score (CSRS) és az általunk hozzáadott, specifikus súlyozófaktorokkal (iniciális ritmus, inotropigény) módosított CardShock Risk Score (mCSRS) összevetése a mortalitás elorejelzésében post-cardiac arrest szindrómás betegeknél. Módszerek: Retrospektív vizsgálatunk során 172, kórházon kívül sikeresen újraélesztett és klinikánkon ellátott consecutiv betegbol a CSRS- és mCSRS-pontrendszerek segítségével végül 123 beteg adatait elemeztük. A CSRS- és mCSRS-változók és a korai/késoi mortalitás közötti összefüggést Cox-regressziós analízissel vizsgáltuk. A pontszámok alapján 3 csoportba (1-3, 4-6, 7+) soroltuk a betegeket. Az összevont csoportok túlélését log-rank teszttel hasonlítottuk össze. Eredmények: A betegpopuláció átlagéletkora 63,6 év volt (69% férfi), és a hirtelen szívhalál hátterében 80%-ban akut coronaria szindróma állt. A korai/késoi mortalitást leginkább a felvétel utáni neurológiai állapot, a szérumlaktátszint, a vesefunkció, az iniciális ritmus és a beteg katecholaminigénye határozta meg. A mCSRS alkalmazását követoen mind az "1-3" és a "4-6" (p≤0,001), mind a "4-6" és a "7+" (p = 0,006) csoportok között szignifikáns különbséget találtunk a túlélésben. Következtetés: A felvételkori pontok alapján a mCSRS pontosabban definiálja és differenciálja egymástól az általunk beválasztott két extra súlyozófaktorral az enyhe, a közepes és a magas mortalitási rizikóval bíró betegpopulációkat, mint a CSRS. Orv Hetil. 2021; 162(2): 52-60. INTRODUCTION: Sudden cardiac death is one of the most significant cardiovascular causes of death worldwide. Although there have been immense methodological and technical advances in the field of cardiopulmonary resuscitation and following intensive care in the last decade, currently there are only a few validated risk-stratification scoring systems for the quick and reliable estimation of the mortality risk of these patients at the time of admission to the intensive care unit. OBJECTIVE: Our aim was to correlate the mortality prediction risk points calculated by CardShock Risk Score (CSRS) and modified (m) CSRS based on the admission data of the post-cardiac arrest syndrome (PCAS) patients. METHODS: The medical records of 172 out-of-hospital resuscitated cardiac arrest patients, who were admitted at the Heart and Vascular Centre of Semmelweis University, were screened retrospectively. Out of the 172 selected patients, 123 were eligible for inclusion to calculate CSRS and mCSRS. Based on CSRS score, we generated three different groups of patients, with scores 1 to 3, 4 to 6, and 7+, respectively. Mortality data of the groups were compared by log-rank test. RESULTS: Mean age of the patients was 63.6 years (69% male), the cause of sudden cardiac death was acut coronary syndrome in 80% of the cases. The early and late mortality was predicted by neurological status, serum lactate level, renal function, initial rhythm, and the need of catecholamines. Using mCSRS, a significant survival difference was proven in between the groups "1-3" vs "4-6" (p≤0.001), "4-6" vs "7+" (p = 0.006). CONCLUSION: Compared to the CSRS, the mCSRS expanded with the 2 additional weighting points differentiates more specifically the low-moderate and high survival groups in the PCAS patient population treated in our institute. Orv Hetil. 2021; 162(2): 52-60.

The Relationship between Hormones, Glucose, and Oxidative Damage Is Condition and Stress Dependent in a Free-Living Passerine Bird.

AbstractPhysiological state is an emergent property of the interactions among physiological systems within an intricate network. Understanding the connections within this network is one of the goals in physiological ecology. Here, we studied the relationship between body condition, two neuroendocrine hormones (corticosterone and insulin-like growth factor 1 [IGF-1]) as physiological regulators, and two physiological systems related to resource metabolism (glucose) and oxidative balance (malondialdehyde). We measured these traits under baseline and stress-induced conditions in free-living house sparrows (Passer domesticus). We used path analysis to analyze different scenarios about the structure of the physiological network. Our data were most consistent with a model in which corticosterone was the major regulator under baseline conditions. This model shows that individuals in better condition have lower corticosterone levels; corticosterone and IGF-1 levels are positively associated; and oxidative damage is higher when levels of corticosterone, IGF-1, and glucose are elevated. After exposure to acute stress, these relationships were considerably reorganized. In response to acute stress, birds increased their corticosterone and glucose levels and decreased their IGF-1 levels. However, individuals in better condition increased their corticosterone levels more and better maintained their IGF-1 levels in response to acute stress. The acute stress-induced changes in corticosterone and IGF-1 levels were associated with an increase in glucose levels, which in turn was associated with a decrease in oxidative damage. We urge ecophysiologists to focus more on physiological networks, as the relationships between physiological traits are complex and dynamic during the organismal stress response.

Rumination in major depressive and bipolar disorder - a meta-analysis.

BACKGROUND: rumination, defined as repetitive thoughts about emotionally relevant experiences, has been linked extensively with mood disorders, especially major depressive disorder (MDD).1 However, there is a growing body of evidence suggesting the importance of rumination in bipolar disorder (BD)2 as well. METHODS: we searched for studies that investigated rumination in both BD and MDD in four databases. Our systematic search identified 12 studies with an overall sample size of 2071 clinical patients. RESULTS: results demonstrated no significant difference in the ruminative tendencies of the two patient groups when all rumination measures were included. We tested for the effect of rumination subtype, BD subgroups, and the current mood state of BD and MDD patients. There were no significant differences in terms of depressive rumination, however, BD patients reported more rumination on positive affect. This difference remained significant when examining in BD-I3 and BD-II4 patient groups, with similar effect sizes. LIMITATIONS: due to the lack of sufficient data in the literature, only a few self-report studies qualified to be included in our analysis. Thus additional moderating factors, such as the current mood state of the two patient groups could not be analyzed. CONCLUSIONS: this review demonstrates that rumination is a significant process in both MDD and BD, highlighting the importance of interventions to reduce rumination in mood disorders. The two patient groups share several commonalities in terms of rumination, however, rumination subtype was found to be an important moderating variable underlining a difference in rumination on positive affect.

Iron Metabolism, Pseudohypha Production, and Biofilm Formation through a Multicopper Oxidase in the Human-Pathogenic Fungus Candida parapsilosis.

Among all the essential micronutrients, iron plays an important role in mammalian biology. It is also essential for pathogens infecting mammalian hosts, including bacteria, fungi, and protozoans. As the availability of accessible iron is limited within the mammalian host, several human-pathogenic fungal pathogens, such as Candida albicans, Cryptococcus neoformans, Candida glabrata, and Aspergillus fumigatus, have developed various iron uptake mechanisms. Although Candida parapsilosis is the second or third most common non-albicans Candida species associated with systemic and superficial Candida infections in immunocompromised patients, the mechanisms of iron uptake and homoeostasis remain unknown in this fungus. In the current report, we show that a homologue of the multicopper oxidase gene FET3 is present in the genome of C. parapsilosis (CPAR2_603600) and plays a significant role in iron acquisition. We found that homozygous deletion mutants of CPAR2_603600 showed defects under low-iron conditions and were also sensitive to various stressors. Our results also revealed that the levels of pseudohypha formation and biofilm formation were reduced in the null mutants compared to the wild type. This phenotypic defect could be partially rescued by supplementation with excess iron in the growth medium. The expression levels of the orthologues of various iron metabolism-related genes were also altered in the mutants compared to the parental strain. In conclusion, our report describes the role of CPAR2_603600 in iron homoeostasis maintenance as well as morphology and biofilm formation regulation in this pathogenic fungus.IMPORTANCEC. parapsilosis is the second or third most common opportunistic human-pathogenic Candida species, being responsible for severe fungal infections among immunocompromised patients, especially low-birth-weight infants (0 to 2 years of age). Among the major virulence factors that pathogenic fungi possess is the ability to compete with the host for essential micronutrients, including iron. Accessible iron is required for the maintenance of several metabolic processes. In order to obtain accessible iron from the host, pathogenic fungi have developed several iron acquisition and metabolic mechanisms. Although C. parapsilosis is a frequent cause of invasive candidiasis, little is known about what iron metabolic processes this fungus possesses that could contribute to the species' virulent behavior. In this study, we identified the multicopper oxidase FET3 gene that regulates iron homeostasis maintenance and also plays important roles in the morphology of the fungus as well as in biofilm formation, two additional factors in fungal virulence.

Extremely low malaria prevalence in a wetland specialist passerine.

Avian malaria (caused by Plasmodium spp.) and avian malaria-like infections (caused by Haemoproteus spp.) are widespread and can seriously affect the health of their bird hosts, especially of immunologically naïve individuals. Therefore, these parasites have long been in the focus of bird-parasite studies. However, the species richness and diversity of these protozoan species have only been revealed since the use of molecular techniques. Diversity and prevalence of these parasites among different bird species and even between populations of a species show a large variation. Here, we investigated prevalence of avian malaria and avian malaria-like parasites in two distant populations of a non-migratory wetland specialist passerine, the bearded reedling (Panurus biarmicus). While previous studies have shown that reed-dwelling bird species often carry various blood parasite lineages and the presence of the vectors transmitting Plasmodium and Haemoproteus species has been confirmed from our study sites, prevalence of these parasites was extremely low in our populations. This may either suggest that bearded reedlings may avoid or quickly clear these infections, or these parasites cause high mortality in this species. The remarkably low prevalence of infection in this species is consistent with earlier studies and makes bearded reedlings a possible model organism for investigating the genetic or behavioural adaptations of parasite resistance.

Exploring the mechanistic link between corticosterone and insulin-like growth factor-1 in a wild passerine bird.

BACKGROUND: Physiological regulators of life history trade-offs need to be responsive to sudden changes of resource availability. When homeostasis is challenged by unpredictable stressors, vertebrates respond through a set of physiological reactions, which can promote organismal survival. Glucocorticoids have been traditionally recognized as one of the main regulators of the physiological stress response, but the role of an evolutionarily more conserved pathway, the hypothalamic-pituitary-somatotropic (HPS) axis producing insulin-like growth factor-1 (IGF-1) has received much less attention. Although IGF-1 is known to affect several life history traits, little is known about its role in the physiological stress response and it has never been studied directly in adult wild animals. METHODS: In this study, we combined field observations with a controlled experiment to investigate how circulating levels of IGF-1 change in response to stress and whether this change is due to concomitant change in glucocorticoids in a free-living songbird, the bearded reedling Panurus biarmicus. We used a standard capture-restraint protocol in field observation, in which we took first and second (stress induced: 15 minutes later) samples. In a follow-up experiment, we used a minimally invasive oral corticosterone manipulation. RESULTS: We showed that corticosterone levels significantly increased while IGF-1 levels significantly decreased during capture and handling stress. However, change in corticosterone levels were not related to change in IGF-1 levels. We found that experimentally elevated corticosterone levels did not affect IGF-1 levels. DISCUSSION: Our results are the first to highlight that circulating IGF-1 levels are responsive to stress independently from glucocorticoids and suggest that the HPS axis is an autonomous physiological pathway that may play an important role as regulator of life-history decisions.

Expression of a Grapevine NAC Transcription Factor Gene Is Induced in Response to Powdery Mildew Colonization in Salicylic Acid-Independent Manner.

Tissue colonization by grape powdery mildew (PM) pathogen Erysiphe necator (Schw.) Burr triggers a major remodeling of the transcriptome in the susceptible grapevine Vitis vinifera L. While changes in the expression of many genes bear the signature of salicylic acid (SA) mediated regulation, the breadth of PM-induced changes suggests the involvement of additional regulatory networks. To explore PM-associated gene regulation mediated by other SA-independent systems, we designed a microarray experiment to distinguish between transcriptome changes induced by E. necator colonization and those triggered by elevated SA levels. We found that the majority of genes responded to both SA and PM, but certain genes were responsive to PM infection alone. Among them, we identified genes of stilbene synthases, PR-10 proteins, and several transcription factors. The microarray results demonstrated that the regulation of these genes is either independent of SA, or dependent, but SA alone is insufficient to bring about their regulation. We inserted the promoter-reporter fusion of a PM-responsive transcription factor gene into a wild-type and two SA-signaling deficient Arabidopsis lines and challenged the resulting transgenic plants with an Arabidopsis-adapted PM pathogen. Our results provide experimental evidence that this grape gene promoter is activated by the pathogen in a SA-independent manner.