Altered functional connectivity in common resting-state networks in patients with major depressive disorder: A resting-state functional connectivity study.

The neural correlates of major depressive disorder (MDD) remain disputed. In the absence of reliable biological markers, the dysfunction and interaction of neural networks have been proposed as pathophysiological neural mechanisms in depression. Here, we examined the functional connectivity (FC) of brain networks. 51 healthy volunteers (mean age 33.57 ± 7.80) and 55 individuals diagnosed with MDD (mean age 33.89 ± 11.00) participated by performing a resting-state (rs) fMRI scan. Seed to voxel FC analyses were performed. Compared to healthy control (HC), MDD patients showed higher connectivity between the hippocampus and the anterior cingulate cortex (ACC) and lower connectivity between the insula and the ACC. The MDD group displayed lower connectivity between the inferior parietal lobule (IPL) and the superior frontal gyrus (SFG). The current data replicate previous findings regarding the cortico-limbic network (hippocampus - ACC connection) and the salience network (insula - ACC connection) and provide novel insight into altered rsFC in MDD, in particular involving the hippocampus - ACC and the insula - ACC connection. Furthermore, altered connectivity between the IPL and SFG indicates that the processing in higher cognitive processes such as attention and working memory is affected in MDD. These data further support dysfunctional neuronal networks as an interesting pathophysiological marker in depression.

Cardiovascular outcomes after simultaneous pancreas kidney transplantation compared to kidney transplantation alone: a propensity score matching analysis.

BACKGROUND: Coronary heart disease due to arteriosclerosis is the leading cause of death in type 1 diabetic patients with end-stage renal disease (ESRD). The aim of this study was to evaluate the effect of simultaneous pancreas kidney transplantation (SPKT) compared to kidney transplantation alone (KTA) on survival, cardiovascular function and metabolic outcomes. METHODS: A cohort of 127 insulin-dependent diabetes mellitus (IDDM) patients with ESRD who underwent either SPKT (n = 100) or KTA (n = 27) between 1998 and 2019 at the University Hospital of Leipzig were retrospectively evaluated with regard to cardiovascular and metabolic function/outcomes as well as survival rates. An additional focus was placed on the echocardiographic assessment of systolic and diastolic cardiac function pretransplant and during follow-up. To avoid selection bias, a 2:1 propensity score matching analysis (PSM) was performed. RESULTS: After PSM, a total of 63 patients were identified; 42 patients underwent SPKT, and 21 patients received KTA. Compared with the KTA group, SPKT recipients received organs from younger donors (p < 0.05) and donor BMI was higher (p = 0.09). The risk factor-adjusted hazard ratio for mortality in SPKT recipients compared to KTA recipients was 0.63 (CI: 0.49-0.89; P < 0.05). The incidence of pretransplant cardiovascular events was higher in the KTA group (KTA: n = 10, 47% versus SPKT: n = 10, 23%; p = 0.06), but this difference was not significant. However, the occurrence of cardiovascular events in the SPKT group (n = 3, 7%) was significantly diminished after transplantation compared to that in the KTA recipients (n = 6, 28%; p = 0.02). The cardiovascular death rate was higher in KTA recipients (19%) than in SPK recipients with functioning grafts (3.3%) and comparable to that in patients with failed SPKT (16.7%) (p = 0.16). In line with pretransplant values, SPKT recipients showed significant improvements in Hb1ac values (p = 0.001), blood pressure control (p = < 0.005) and low-density lipoprotein/high-density lipoprotein (LDL/HDL) ratio (p = < 0.005) 5 years after transplantation. With regard to echocardiographic assessment, SPKT recipients showed significant improvements in left ventricular systolic parameters during follow-up. CONCLUSIONS: Normoglycaemia and improvement of lipid metabolism and blood pressure control achieved by successful SPKT are associated with beneficial effects on survival, cardiovascular outcomes and systolic left ventricular cardiac function. Future studies with larger samples are needed to make predictions regarding cardiovascular events and graft survival.

[Interhospital transport of patients with ARDS]. / Interhospitaltransport von Patienten mit ARDS.

In patients with severely compromised gas exchange, interhospital transportation is frequently necessary due to the need to provide access to specialized care. Risks are inherent during transport, so the anticipated benefits of transportation must be weighed against the possible negative outcome during the transport. The use of specialized teams during transportation can help to reduce adverse events. Diligent planning of the transportation, monitoring and medical staff during transport can decrease adverse events and reduce risks. This article defines the group of patients that may benefit from referral. This article discusses the risks associated with the transportation of patients with severely impaired gas exchange and the risks related to different means of transportation. The decisions required before transportation are described as well as the practical approach starting at the transferring hospital until arrival at the admitting hospital.

[Prone positioning of patients during venovenous extracorporeal membrane oxygenation is safe and feasible]. / Bauchlagerung von Patienten an der venovenösen ECMO ist möglich und sicher.

BACKGROUND: Prone positioning of patients with acute respiratory distress syndrome (ARDS) has been shown to significantly improve survival rates. Prone positioning reduces collapse of dorsal lung segments with subsequent reduction of alveolar overdistension of ventral lung segments, optimizes lung recruitment and enhances drainage. Patients with ARDS treated by extracorporeal membrane oxygenation (ECMO) can also benefit from prone positioning; however, the procedure is associated with a possible higher risk of serious adverse events. OBJECTIVE: The aim of this study was to evaluate the safety and feasibility of prone positioning for patients with severe ARDS during ECMO therapy. MATERIAL AND METHODS: This study involved a retrospective analysis of all patients placed in a prone position while being treated by venovenous ECMO (vvECMO) for severe hypoxemia in ARDS as bridge to recovery in the interdisciplinary intensive care unit at the University Hospital Leipzig between January 2009 and August 2013. Baseline data, hospital mortality and serious adverse events were documented. Serious adverse events were defined as dislocation or obstruction of endotracheal tube or tracheal cannula, ECMO cannulas and cardiac arrest. Prone positioning was carried out by at least one doctor and three nurses according to a standardized protocol. Results are given as the median (1st and 3rd quartiles). RESULTS: A total of 26 patients were treated with vvECMO as bridge to recovery due to severe ARDS. Causes for ARDS were pneumonia (n = 20) and aspiration (n = 2) and four patients had different rare causes of ARDS. The median time on ECMO was 8 days (6;11) and during this period 134 turning events were documented. Patients were proned for a median of 5 (3;7) periods with a median duration of 12 h (8;12). No serious adverse events were recorded. The hospital mortality was 42% and mortality during the ECMO procedure was 35%. CONCLUSION: Prone positioning significantly reduces the mortality of patients with severe ARDS. In this series of 26 patients with severe ARDS during ECMO therapy no serious adverse events were found during the use of prone positioning.

[Targeted temperature management in critical care : current 2011 recommendations]. / Gezieltes Temperaturmanagement auf der Intensivstation : Aktuelle Empfehlungen 2011.

Since October 2011 new guidelines exist for temperature management in critical care. According to the guidelines the term targeted temperature management (TTM) should replace the term therapeutic hypothermia. There is now a strong recommendation for TTM using 32-34°C as the preferred treatment for out-of-hospital adult cardiac arrest with a first registered electrocardiography rhythm of ventricular fibrillation or pulseless ventricular tachycardia and still unconscious after restoration of spontaneous circulation. A TTM of 32.5-35.5°C is also recommended for the treatment of term newborns who sustain asphyxia and exhibit acidosis and/or encephalopathy.

Synaptic morphology and the influence of auditory experience.

The auditory experience is crucial for the normal development and maturation of brain structure and the maintenance of the auditory pathways. The specific aims of this review are (i) to provide a brief background of the synaptic morphology of the endbulb of Held in hearing and deaf animals; (ii) to argue the importance of this large synaptic ending in linking neural activity along ascending pathways to environmental acoustic events; (iii) to describe how the re-introduction of electrical activity changes this synapse; and (iv) to examine how changes at the endbulb synapse initiate trans-synaptic changes in ascending auditory projections to the superior olivary complex, the inferior complex, and the auditory cortex.

Bilateral effects of unilateral cochlear implantation in congenitally deaf cats.

Congenital deafness results in synaptic abnormalities in auditory nerve endings. These abnormalities are most prominent in terminals called endbulbs of Held, which are large, axosomatic synaptic endings whose size and evolutionary conservation emphasize their importance. Transmission jitter, delay, or failures, which would corrupt the processing of timing information, are possible consequences of the perturbations at this synaptic junction. We sought to determine whether electrical stimulation of the congenitally deaf auditory system via cochlear implants would restore the endbulb synapses to their normal morphology. Three and 6-month-old congenitally deaf cats received unilateral cochlear implants and were stimulated for a period of 10-19 weeks by using human speech processors. Implanted cats exhibited acoustic startle responses and were trained to approach their food dish in response to a specific acoustic stimulus. Endbulb synapses were examined by using serial section electron microscopy from cohorts of cats with normal hearing, congenital deafness, or congenital deafness with a cochlear implant. Synapse restoration was evident in endbulb synapses on the stimulated side of cats implanted at 3 months of age but not at 6 months. In the young implanted cats, postsynaptic densities exhibited normal size, shape, and distribution, and synaptic vesicles had density values typical of hearing cats. Synapses of the contralateral auditory nerve in early implanted cats also exhibited synapses with more normal structural features. These results demonstrate that electrical stimulation with a cochlear implant can help preserve central auditory synapses through direct and indirect pathways in an age-dependent fashion.

Catecholaminergic neuronal loss in locus coeruleus of aged female dtg APP/PS1 mice.

Alzheimer's disease (AD) is the most common type of dementia afflicting the elderly. In addition to the presence of cortical senile plaques and neurofibrillary tangles, AD is characterized at autopsy by extensive degeneration of brainstem locus coeruleus (LC) neurons that provide noradrenergic innervation to cortical neuropil, together with relative stability of dopaminergic neuron number in substantia nigra (SN) and ventral tegmental area (VTA). The present study used design-based stereological methods to assess catecholaminergic neuronal loss in brains of double transgenic female mice that co-express two human mutations associated with familial AD, amyloid precursor protein (APP(swe)) and presenilin-1 (PS1(DeltaE9)). Mice were analyzed at two age groups, 3-6 months and 16-23 months, when deposition of AD-type beta-amyloid (Abeta) plaques occurs in cortical brain regions. Blocks of brain tissue containing the noradrenergic LC nucleus and two nuclei of dopaminergic neurons, the SN and VTA, were sectioned and sampled in a systematic-random manner and immunostained for tyrosine hydroxylase (TH), a specific marker for catecholaminergic neurons. Using the optical fractionator method we found a 24% reduction in the total number of TH-positive neurons in LC with no changes in SN-VTA of aged dtg APP/PS1 mice compared with non-transgenic controls. No significant differences were observed in numbers of TH-positive neurons in LC or SN-VTA in brains of young female dtg APP/PS1 mice compared to their age-matched controls. The findings of selective neurodegeneration of LC neurons in the brains of aged female dtg APP/PS1 mice mimic the neuropathology in the brains of AD patients at autopsy. These findings support the use of murine models of Abeta deposition to develop novel strategies for the therapeutic management of patients afflicted with AD.

Neuropathological quantification of dtg APP/PS1: neuroimaging, stereology, and biochemistry.

Murine models that mimic the neuropathology of Alzheimer's disease (AD) have the potential to provide insight into the pathogenesis of the disease and lead to new strategies for the therapeutic management of afflicted patients. We used magnetic resonance imaging (MRI), design-based stereology, and high performance liquid chromatography (HPLC) to assess the age-related neuropathology in double transgenic mice that overexpress two AD-related proteins--amyloid precursor protein (APP) and presenilin 1 (PS1)--and age- and gender-matched wild-type (WT) controls. In mice ranging in age from 4-28 months, total volumes of the hippocampal formation (V (HF)) and whole brain (V (brain)) were quantified by the Cavalieri-point counting method on a systematic-random sample of coronal T2-weighted MRI images; the same stereological methods were used to quantify V (HF) and V (brain) after perfusion and histological processing. To assess changes in AD-type beta-amyloid (A beta) plaques, sections from the hippocampal formation and amylgdaloid complex of mice aged 5, 12, and 15 months were stained by Congo Red histochemistry. In aged mice with large numbers of amyloid plaques, systematic-random samples of sections were stained by GFAP immunocytochemistry to assess gender and genotype effects on total numbers of astrocytes. In addition, levels of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and 5-HT metabolites were assayed by HPLC in fresh-frozen samples from neocortex, striatum, hippocampus, and brainstem. We confirmed age-related increases in amyloid plaques, beginning with a few plaques at 5 months of age and increasing densities by 12 and 15 months. At 15 months of age, there were robust genotype effects, but no gender effects, on GFAP-immunopositive astrocytes in the amygdaloid complex and hippocampus. There were no effects on monoamine levels in all brain regions examined, and no volume changes in hippocampal formation or whole brain as quantified on either neuroimages or tissue sections. Strong correlations were present between volume estimates from MRI images and histological sections, with about 85% reduction in mean V (HF) or mean V (brain) between MRI and processed histological sections. In summary, these findings show that the double transgenic expression of AD-type mutations is associated with age-related increases in amyloid plaques and astrocytosis; however, this model does not recapitulate the cortical atrophy or neurochemical changes that are characteristic of AD.

[Soluble leukocyte adhesion molecules in vegetarians of various ages]. / Lösliche Leukozytenadhäsionsmoleküle bei Vegetariern unterschiedlichen Alters.

OBJECTIVES: Upregulation of leukocyte adhesion molecules under atherogenic conditions is accompanied by the release of soluble forms of adhesion molecules into the bloodstream. Vegetarians have a favorable cardiovascular risk profile. The aim of the present study was to assess the levels of circulating E-selectin (cE-selectin), circulating intercellular adhesion molecule-1 (cICAM-1), and circulating vascular adhesion molecule-1 (cVCAM-1) in both vegetarians and subjects of the average population and furthermore to evaluate the age dependence of cell adhesion molecules. METHODS: 24 male and 59 female vegetarians (mainly members of the German Society of Vegetarians) and 124 male and 179 female control subjects (volunteers, of the ILSE study Leipzig = Interdisciplinary Long Time Study of Health Adult Age and the Lipid-Study Leipzig), 18-89 years old were included in the study. The serum levels of circulating cell adhesion molecules were determined using monoclonal antibody-based ELISA assays (R & D Systems, Abingdon, Europe Ltd.). RESULTS: Vegetarians were characterized by a favorable lipid profile and a low prevalence of common risk factors for atherosclerosis. This group showed a tendency towards lower cICAM-1 levels in comparison with control subjects. Furthermore, significantly lower cE-selectin levels were found in the group of vegetarians. An age-dependent increase of cVCAM-1 and cICAM-1 levels was found both in the group of vegetarians and control subjects. No significant differences were noted regarding the gender of the subjects included in the study. CONCLUSION: Low cE-selectin levels of vegetarians may reflect the favorable cardiovascular risk profile of this group. Furthermore, the present data indicate that cVCAM-1 and cICAM-1 are age-dependent parameters independent of risk for atherosclerosis.

Somatostatin receptor scintigraphy in the differential diagnosis of meningioma.

The aim of this study was to evaluate somatostatin receptor scintigraphy (SRS) in patients with meningioma proven or suspected on magnetic resonance imaging (MRI). Prior to surgery, 47 patients were investigated up to 24 h following the injection of 200 MBq 111In-octreotide. Tracer uptake was compared with the histological presence of meningioma. Histology revealed 43 meningiomas, 3 neurinomas and 1 ependymoma. A true-positive SRS result was obtained in 36 patients, in 13 of whom a tumour volume of < 10 ml was noted. A false-negative SRS result was obtained in seven patients, all of whom had a tumour volume of < 10 ml. Whereas MRI alone was decisive in 38 of 47 patients, it could only provide a differential diagnosis in the remaining 9 patients. A positive SRS result confirmed meningioma in five of these patients, and a negative SRS result excluded meningioma in the other four. Therefore, cases of SRS-negative meningioma do exist. Nevertheless, significant clinical benefit can be obtained from functional imaging with 111In-octreotide in patients with an inconclusive MRI result, as large meningiomas can be excluded by scintigraphy alone, whereas meningiomas of any size may be confirmed in combination with specific MRI results.

Somatostatin receptor scintigraphy in the staging of small cell lung cancer.

The aim of this study was to evaluate somatostatin receptor scintigraphy (SRS) in the staging of patients with small cell lung cancer. Prior to chemotherapy, 20 patients were investigated up to 24 h following an injection of 200 MBq 111In-octreotide. Following chemotherapy and restaging, four patients were re-evaluated. Primary tumour was detected in 18 of 23 studies, which exhibited increasing target-to-back-ground ratios over time. Lymph node metastases and distant metastases were detected in 7 of 27 and 8 of 31 sites, respectively. Thus, the overall sensitivity for detecting metastases was less than 26%. SRS did not result in any upstaging of patients. We conclude that in patients with small cell lung cancer, functional imaging by SRS has no impact on clinical decision making.

Heterologous expression of a mutated toxin gene from Bacillus thuringiensis subsp. tenebrionis.

Using oligonucleotide probes we have isolated a DNA fragment encoding an insecticidal toxin of the coleopteran specific Bacillus thuringiensis subsp. tenebrionis. The gene was altered by site directed mutagenesis at its 5'-end and adapted for general cloning and expression purposes with a linker including a start codon and new restriction sites. The constructs were inserted into several vector plasmids and expressed in Escherichia coli. Expression E. coli was strongly enhanced by the lac-promoter. A fusion protein with phage MS2-polymerase was produced together with a 67 kDa protein also found for normal expression of the toxin gene. Synthesis of the latter protein indicated a second ribosome binding site at the 5'-terminus of the toxin encoding sequence. Toxin-containing proteins were identified by Western blot analysis. The positive cell extracts from E. coli had insecticidal activity on larvae of the Colorado potato beetle. The cloned gene is not homologous to a gene previously cloned by us whose gene products were also toxic to coleopteran larvae.