Cognitive Motivation as a Resource for Affective Adjustment and Mental Health.

Background: Depressive symptoms compromise cognitive and self-regulating capacities. Overcoming associated deficits (e.g., attentional bias) demands cognitive effort and motivation. Previous studies on healthy individuals have found cognitive motivation to positively relate to self-regulation and negatively to depressive symptoms. A test of these associations in a clinical sample is lacking. Methods: We assessed cognitive motivation, self-regulation and depressive symptoms by means of well-validated questionnaires in N = 1,060 psychosomatic rehabilitation in-patients before and after treatment. Data were split and analyzed in two steps: We tested previously reported cross-sectional and longitudinal associations of all variables as well as their longitudinal changes in a first sample. Afterward, findings and derived hypotheses were replicated and tested in a second sample. Results: Analyses of both samples confirmed earlier reports on positive associations between cognitive motivation and self-regulation, and negative associations of both with depressive symptoms. While the change in all variables was predicted by their baseline scores, higher baseline cognitive motivation was found to predict stronger improvements in self-regulation, and lower baseline depression scores to predict smaller changes in cognitive motivation and self-regulation. In addition, the change in cognitive motivation partially mediated the association between the changes in depressive symptoms and self-regulation. Conclusion: Based on a large longitudinal data set, the present study expands previous findings and suggests a resource allocation model in which decreasing depressive symptoms lead to a release of capacities benefitting self-regulation directly, and indirectly via cognitive motivation.

Neurofeedback and its possible relevance for the treatment of Tourette syndrome.

Neurofeedback is an increasingly recognized therapeutic option in various neuropsychiatric disorders to treat dysfunctions in cognitive control as well as disorder-specific symptoms. In this review we propose that neurofeedback may also reflect a valuable therapeutic option to treat executive control functions in Gilles-de-la-Tourette syndrome (GTS). Deficits in executive control functions when ADHD symptoms appear in GTS likely reflect pathophysiological processes in cortico-thalamic-striatal circuits and may also underlie the motor symptoms in GTS. Such executive control deficits evident in comorbid GTS/ADHD depend on neurophysiological processes well-known to be modifiable by neurofeedback. However, so far efforts to use neurofeedback to treat cognitive dysfunctions are scarce. We outline why neurofeedback should be considered a promising treatment option, what forms of neurofeedback may prove to be most effective and how neurofeedback may be implemented in existing intervention strategies to treat comorbid GTS/ADHD and associated dysfunctions in cognitive control. As cognitive control deficits in GTS mostly appear in comorbid GTS/ADHD, neurofeedback may be most useful in this frequent combination of disorders.

Sirolimus and everolimus reduce albumin endocytosis in proximal tubule cells via an angiotensin II-dependent pathway.

BACKGROUND: The proliferation signal inhibitors (PSIs) sirolimus (SRL) and everolimus (ERL) often induce proteinuria due to glomerular but also tubular dysfunction in transplant patients. The beneficial effect of angiotensin converting enzyme inhibitors (ACE-I) and angiotensin II (Ang II) type 1 receptor blockers (ARB) has been reported. AIM: This study aimed to investigate: (i) the role of an Ang II-dependent mechanism and Ang II type 1 receptor (AT(1)R) in the regulation of receptor-mediated albumin endocytosis on proximal tubular epithelial cells (PTEC) following PSI treatment; (ii) the specific roles of the albumin receptors cubilin and megalin in albumin binding and uptake in PTEC. METHODS: A human renal PTEC line (HK-2) was used in the study. The binding of Alexa 488 conjugated albumin was measured by flow cytometry. Albumin uptake and the expression of cubilin and megalin were determined by cellular ELISA. RESULTS: The administration of PSIs resulted in decreased albumin binding and uptake and downregulation of cubilin and megalin expression in PTEC. These effects were significantly reversed by the administration of an ACE-I (ramipril) or an ARB (losartan). Combined use of ramipril and losartan demonstrated additive effects on cubilin expression, but not on megalin expression or albumin binding and uptake. CONCLUSIONS: Our findings suggest that decreased albumin endocytosis in PTECs following PSI treatment involve an Ang II-dependent pathway via AT(1)R. The albumin receptor megalin may play a more crucial role than cubulin, since its expression correlated directly with albumin uptake.

Anti-HLA I antibodies induce VEGF production by endothelial cells, which increases proliferation and paracellular permeability.

Anti-human leukocyte antigen class I (HLA I) antibodies were shown to activate several protein kinases in endothelial cells (ECs), which induces proliferation and cell survival. An important phenomenon in antibody-mediated rejection is the occurrence of interstitial edema. We investigated the effect of anti-HLA I antibodies on endothelial proliferation and permeability, as one possible underlying mechanism of edema formation. HLA I antibodies increased the permeability of cultured ECs isolated from umbilical veins. Anti-HLA I antibodies induced the production of vascular endothelial growth factor (VEGF) by ECs, which activated VEGF receptor 2 (VEGFR2) in an autocrine manner. Activated VEGFR2 led to a c-Src-dependent phosphorylation of vascular endothelial (VE)-cadherin and its degradation. Aberrant VE-cadherin expression resulted in impaired adherens junctions, which might lead to increased endothelial permeability. This effect was only observed after cross-linking of HLA I molecules by intact antibodies. Furthermore, our results suggest that increased endothelial proliferation following anti-HLA I treatment occurs via autocrine VEGFR2 activation. Our data indicate the ability of anti-HLA I to induce VEGF production in ECs. Transactivation of VEGFR2 leads to increased EC proliferation and paracellular permeability. The autocrine effect of VEGF on endothelial permeability might be an explanation for the formation of interstitial edema after transplantation.

Proliferation signal inhibitor-induced decrease of vascular endothelial cadherin expression and increase of endothelial permeability in vitro are prevented by an anti-oxidant.

BACKGROUND: Rapamycines, sirolimus (SRL) and everolimus (ERL), are proliferation signal inhibitors (PSIs). PSI therapy often leads to edema. We hypothesized that increased oxidative stress in response to PSIs may modulate the expression of vascular endothelial (VE)-cadherin on endothelial cells (ECs) and, subsequently, vascular permeability, which in turn may be involved in the development of edema. METHODS: Experiments were performed on human umbilical vein ECs (HUVECs). Oxidative stress was measured by dichlorofluorescein-diacetate. Expression of VE-cadherin was evaluated by immunofluorescent staining and western blot analysis. Endothelial "permeability" was assessed using a transwell model. RESULTS: SRL and ERL, at concentrations of 1, 10 and 100 nmol/liter, enhanced oxidative stress (SRL: 24 +/- 12%, 29 +/- 9%, 41 +/- 13% [p < 0.05, in all three cases]; ERL: 13 +/- 10%, 27 +/- 2%, 40 +/- 12% [p < 0.05, in the latter two cases], respectively) on HUVECs, which was inhibited by the anti-oxidant, N-acetyl-cysteine (NAC) and, to a lesser extent, by the specific inhibitor of nitric oxide synthase, N-Omega-nitro-L-arginine methylester. By the use of NAC, VE-cadherin expression remained comparable with control, according to both immunocytochemistry and western blot analysis. Permeability was significantly increased by SRL and ERL at 100 nmol/liter (29.5 +/- 6.4% and 33.8 +/- 4.2%, respectively); however, co-treatment with NAC abrogated the increased permeability. CONCLUSIONS: EC homeostasis, as indicated by VE-cadherin expression, may be damaged by SRL and ERL, but resolved by the anti-oxidant NAC.

[Surveillance results of nosocomial infections of the ICU in Kenézy Hospital, based on two years data]. / Nosocomialis surveillance eredményei a Kenézy Gyula Kórház Intenzív Osztályán, két év adatai alapján.

INTRODUCTION: According to data in the literature, the number of nosocomial infections in the ICU is far higher than in non-ICU patients. As a result of improving lifesaving technologies, the risk of nosocomial infections increases in ICUs. Utilization of epidemiological methods is recommended for the detection and follow up of nosocomial infections. AIMS: Prospective surveillance to assess the epidemiology of nosocomial infections in an ICU. METHODS: Kenézy Hospital is a country hospital with 1637 beds and a 16-bed central ICU. During the investigated period (01. 04. 2004-31. 03. 2006) 1490 patients, with a total 8058 ICU days, were hospitalised in the mixed medical-surgical ICU. The commonest primary diagnosis were respiratory failure, multiple trauma and head injury. Surveillance was performed by a trained infection control nurse and was supervised by an infection control physician and infectious disease physician. CDC definitions were used to define nosocomial infections. RESULTS: A total of 194 nosocomial infections in 134 patients were detected during the study period. The overall incidence and incidence density of nosocomial infections were 13.0 per 100 patients and 24.0 per 1000 patient-days. Respiratory tract infections (44.3%) were the most frequent nosocomial infection, followed by urinary tract (21.1%) and bloodstream infections (20.1%). CONCLUSIONS: Nosocomial surveillance is useful in detecting nosocomial infections in ICU. A multidisciplinary approach and partnership between the physicians and infection control nurses is needed. Patient-to-nurse ratio is an independent risk factor for nosocomial infections in intensive care, this must be kept in mind when planning rationalization of the number of nursing staff.

[Bacterial infections in liver cirrhosis]. / Bakteriális fertozések májcirrhosisban.

Bacterial infections are well described complications of cirrhosis that greatly increase mortality rates. Two factors play important roles in the development of bacterial infections in these patients: the severity of liver disease and gastrointestinal haemorrhage. The most common infections are spontaneous bacterial peritonitis, urinary tract infections, pneumonia and sepsis. Gram-negative and gram-positive bacteria are equal causative organisms. For primary prophylaxis, short-term antibiotic treatment (oral norfloxacin or ciprofloxacin) is indicated in cirrhotic patients (with or without ascites) admitted with gastrointestinal haemorrhage (variceal or non-variceal). Administration of norfloxacin is advisable for hospitalized patients with low ascitic protein even without gastrointestinal haemorrhage. The first choice in empirical treatment of spontaneous bacterial peritonitis is the iv. III. generation cephalosporin; which can be switched for a targeted antibiotic regime based on the result of the culture. The duration of therapy is 5-8 days. Amoxicillin/clavulanic acid and fluoroquinolones--patients not on prior quinolone prophylaxis--were shown to be as effective and safe as cefotaxime. In patients with evidence of improvement, iv. antibiotics can be switched safely to oral antibiotics after 2 days. In case of renal dysfunction, iv albumin should also be administered. Long-term antibiotic prophylaxis is recommended in patients who have recovered from an episode of spontaneous bacterial peritonitis (secondary prevention). For "selective intestinal decontamination", poorly absorbed oral norfloxacin is the preferred schedule. Oral ciprofloxacin or levofloxacin (added gram positive spectrum) all the more are reasonable alternatives. Trimethoprim/sulfamethoxazole is only for patients who are intolerant to quinolones. Prophylaxis is indefinite until disappearance of ascites, transplant or death. Long-term prophylaxis is currently not recommended for patients without previous spontaneous bacterial peritonitis episode, not even when refractory ascites or low ascites protein content is present.