Glass-Zirconia Composites as Seals for Solid Oxide Cells: Preparation, Properties, and Stability over Repeated Thermal Cycles.

This study focuses on the preparation and characterization of composite gaskets designed for the sealing of the solid oxide cell stacks operating below 700 °C. The seals were fabricated with the addition of various amounts (10-90 wt.%) of 3 mol.% yttria partially stabilized zirconia to a BaO-Al2O3-CaO-SiO2 glass matrix. The sample gaskets in the form of thin frames were shaped by tape casting. The quality of the junctions between the composites and Crofer 22APU steel commonly used as an SOC interconnect was evaluated after thermal treatment of heating to 710 °C, then cooling to the working temperature of around 620 °C and then leaving them for 10h in an air atmosphere, before cooling to room temperature. The samples were also studied after 3, 5, and 10 thermal cycles to determine the changes in microstructure and to evaluate the porosity and possible crystallization of the glass phase. The compression of the seals was calculated on the basis of differences in thickness before and after thermal treatment. The influence of zirconia additions on the mechanical properties of the seals was studied. The experimental results confirmed that glass-ceramic composites are promising materials for gaskets in SOC stacks. The most beneficial properties were obtained for a composite containing 40 wt.% of YSZ.

Acute kidney injury and diabetic kidney disease in children with acute complications of diabetes.

BACKGROUND: Diabetic ketoacidosis (DKA) and hyperglycaemia without ketoacidosis are common acute complications of diabetes. Their association with acute kidney injury (AKI) and diabetic kidney disease (DKD) was studied. METHODS: The study group consisted of 197 children with type 1 diabetes with average diabetes duration of 8.08 ± 2.32 years. The medical history of the patients was retrospectively reviewed. The number of children with severe hyperglycaemia, DKA and AKI was assessed. The association with the risk of chronic kidney disease (CKD) was analysed. RESULTS: AKI was found in 14% of cases hospitalised for DKA and 8% of cases hospitalised for hyperglycaemia. Patients with AKI showed a significantly increased corrected sodium (141.23 ± 5.09 mmol/L, p = 0.035). Patients with AKI in DKA showed a significant increase in WBC (20.73 ± 8.71 × 103/µL, p = 0.0009). Follow-up analysis after a minimum of 5 years of diabetes revealed that a single episode of DKA was found in 63 patients and a single episode of AKI in 18 patients. Two or more episodes of DKA were found in 18 patients, and nine cases were complicated by AKI. These patients showed a significant increase in urinary albumin excretion (44.20 ± 64.21 mg/24 h), the highest values of eGFR and the worst glycaemic control. CONCLUSIONS: Diabetic children can develop AKI in the course of DKA and hyperglycaemia without ketoacidosis, which is associated with volume depletion and reflected by corrected sodium concentration. AKI in DKA seems to be complicated by stress and inflammation activation. AKI and poor glycaemic control with repeated DKA episodes can magnify the risk of progression to DKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Transient global amnesia - hippocampal lesions in magnetic resonance imaging.

BACKGROUND: Transient global amnesia is a benign syndrome characterized by a sudden onset loss of anterograde amnesia with full recovery. Magnetic resonance of the brain including diffusion-weighted imaging of patients with transient global amnesia revealed the presence of punctate hyperintense signal abnormalities in the hippocampus. OBJECTIVE: Analysis of the presence of hippocampal lesions in brain magnetic resonance imaging in patients with transient global amnesia and the possible influence of additional factors on their appearance. METHODS: In this retrospective, an observational study we assessed brain magnetic resonance imaging in 38 consecutive patients with transient global amnesia. The incidence of brain magnetic resonance imaging lesions was analyzed for the coexisting cardiovascular risk factors and precipitating events. RESULTS: Hippocampal brain magnetic resonance imaging lesions were detected in 47% of patients with transient global amnesia. Of those, 65% had unilateral lesions, 82% were left-sided, and 28% were right-sided. Most lesions were located in the CA1 subfield. The incidence of hypertension in patients with transient global amnesia was higher than in the general population. Stress and exercise preceded the onset of transient global amnesia only in 13% and 16% of patients, respectively. There was no higher incidence of migraine in transient global amnesia patients (13%). CONCLUSIONS: We found that nearly 50% of patients with transient global amnesia had hyperintense hippocampal brain magnetic resonance imaging lesions. In addition to hypertension, individuals with transient global amnesia had similar cardiovascular risk factors as the general population. We did not identify any precipitating events prior to the onset of transient global amnesia.

Animal Foetal Models of Obesity and Diabetes - From Laboratory to Clinical Settings.

The prenatal period, during which a fully formed newborn capable of surviving outside its mother's body is built from a single cell, is critical for human development. It is also the time when the foetus is particularly vulnerable to environmental factors, which may modulate the course of its development. Both epidemiological and animal studies have shown that foetal programming of physiological systems may alter the growth and function of organs and lead to pathology in adulthood. Nutrition is a particularly important environmental factor for the pregnant mother as it affects the condition of offspring. Numerous studies have shown that an unbalanced maternal metabolic status (under- or overnutrition) may cause long-lasting physiological and behavioural alterations, resulting in metabolic disorders, such as obesity and type 2 diabetes (T2DM). Various diets are used in laboratory settings in order to induce maternal obesity and metabolic disorders, and to alter the offspring development. The most popular models are: high-fat, high-sugar, high-fat-high-sugar, and cafeteria diets. Maternal undernutrition models are also used, which results in metabolic problems in offspring. Similarly to animal data, human studies have shown the influence of mothers' diets on the development of children. There is a strong link between the maternal diet and the birth weight, metabolic state, changes in the cardiovascular and central nervous system of the offspring. The mechanisms linking impaired foetal development and adult diseases remain under discussion. Epigenetic mechanisms are believed to play a major role in prenatal programming. Additionally, sexually dimorphic effects on offspring are observed. Therefore, further research on both sexes is necessary.

Novel adipokine associated with OA: retinol binding protein 4 (RBP4) is produced by cartilage and is correlated with MMPs in osteoarthritis patients.

OBJECTIVE: Retinol binding protein 4 (RBP4) is a member of the lipocalin family and a vitamin A carrier in the blood. More recently, RBP4 has been described as an adipokine that is involved in insulin resistance and metabolic syndrome (MetS). As obesity, MetS and some adipokines contribute to the pathogenesis of osteoarthritis (OA), we investigated RBP4 in patients with OA. MATERIALS AND METHODS: Cartilage, synovial fluid and blood samples were collected from 100 OA patients undergoing total knee replacement surgery. Primary chondrocytes and cartilage tissue were cultured to measure the RBP4 expression. The concentrations of RBP4, other adipokines (adipsin, adiponectin, leptin and resistin) and biomarkers of OA (COMP, MMP-1, MMP-3 and YKL-40) were measured by immunoassay, and gene expression was measured by next-generation RNA sequencing. RESULTS: The OA cartilage samples released RBP4 into the culture medium, and the levels correlated positively with the expression of the adipokines adipsin, adiponectin, leptin and resistin. RBP4 was the most prominently expressed of these adipokines in the OA chondrocytes, and the expression of the RBP4 receptors STRA6 (stimulated by retinoic acid gene homologue 6) and TLR4 (Toll-like receptor 4) was also detected. Within the cartilage culture medium, RBP4 showed a positive correlation with MMP-1, MMP-3 and YKL-40. RBP4 was also present in the synovial fluid from the OA patients and correlated positively with the concentrations of RBP4 found in the plasma and the cartilage culture medium. Plasma RBP4 concentrations also showed a positive correlation with MMP-3 and adipsin. CONCLUSIONS: We show here, for the first time, that RBP4 is produced within OA joints and that it is associated with increased levels of adipokines and MMPs. The results suggest a role for RBP4 in the pathogenesis of OA and as a possible target for the disease-modifying drugs for the treatment of OA.

Catabolic and proinflammatory effects of leptin in chondrocytes are regulated by suppressor of cytokine signaling-3.

BACKGROUND: Previous studies provide evidence that adipokine leptin increases production of catabolic and proinflammatory factors in chondrocytes and serves as a link between obesity and osteoarthritis (OA). However, the magnitude of the response to leptin treatment varies greatly between chondrocytes from different donor patients. In the present study, we investigated the regulatory role of suppressor of cytokine signaling-3 (SOCS-3) in the leptin-induced responses in OA cartilage. METHODS: Cartilage and synovial fluid samples from 97 patients with OA undergoing knee replacement surgery were collected. Cartilage samples were cultured with leptin (10 µg/ml), and the levels of proinflammatory and catabolic factors in synovial fluid and in the cartilage culture media, and SOCS-3 expression in the cartilage were measured. The role of SOCS-3 in leptin signaling was further studied in H4 murine chondrocytes by downregulating SOCS-3 with siRNA. RESULTS: Leptin-induced expression of matrix metalloproteinases MMP-1, MMP-3, MMP-13, interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were higher in the cartilage samples with low SOCS-3 expression. Accordingly, downregulation of SOCS-3 by siRNA in H4 chondrocytes led to enhanced leptin-induced expression of MMP-3, MMP-13, IL-6 and iNOS. Synovial fluid leptin was associated positively, and cartilage SOCS-3 negatively with synovial fluid levels of MMPs in a multivariate model in obese (body mass index (BMI) >30 kg/m2) but not in non-obese (BMI <30 kg/m2) patients. CONCLUSIONS: Our results show, for the first time, that SOCS-3 regulates leptin-induced responses in cartilage, and could thus be a future drug target in the treatment or prevention of OA, especially in obese patients.

CAV3 mutation in a patient with transient hyperCKemia and myalgia.

Mutations in caveolin-3 (CAV3) can lead to different clinical phenotypes affecting skeletal or cardiac muscles. Here, we describe a patient with Klinefelter syndrome, ulcerative colitis and Sjögren syndrome, who developed transient hyperCKemia, myalgia and mild muscular weakness. Using whole exome sequencing (WES), a missense mutation G169A was found in the CAV3 gene. In addition, we identified a homozygous frameshift deletion in MS4A12 that may contribute to inflammatory bowel disease, further demonstrating usefulness of WES in dual molecular diagnoses.

Quantitative Single-Cell mRNA Analysis in Hydrogel Beads.

In recent years, technologies capable of analyzing single cells have emerged that are transforming many fields of biological research. Herein we report how DNA-functionalized hydrogel beads can serve as a matrix to capture mRNA from lysed single cells. mRNA quantification free of pre-amplification bias is ensured by using padlock probes and rolling circle amplification followed by hybridization with fluorescent probes. The number of transcripts in individual cells is assessed by simply counting fluorescent dots inside gel beads. The method extends the potential of existing techniques and provides a general platform for capturing molecules of interest from single cells.

Medullary thyroid carcinoma - PET/CT imaging with 68Ga-labelled gastrin and somatostatin analogues.

CASE PRESENTATION: a 75-year-old man with a 10-year history of nodular goitre was referred for clinical evaluation. The ultrasound scan revealed enlarged thyroid right lobe almost fully filled with a heterogeneous nodule with numerous calcifications. Fine-needle aspiration biopsy suggested medullary thyroid carcinoma (MTC). Before the surgery the patient was referred to the nuclear medicine department and somatostatin receptor imaging (SRS; 68Ga-DOTATATE) with PET/CT was performed. The scan demonstrated an increased uptake within the right thyroid mass. Subsequent PET/CT with 68Ga-gastrin analogue (MG48) revealed the same indications as the SRS: an increased alveolar uptake in the right thyroid mass without the signs of lymph node metastases. The patient underwent total thyroidectomy and central lymph nodes dissection. Histopathology examination confirmed the presence of MTC with vascular invasion, but without lymph node metastases (pT3NoMx according to the 7th edition of the AJCC Cancer Staging Manual). Immunohistochemical staining revealed positive reaction to calcitonin and CD56, whereas the reaction to thyroglobulin remained negative. The Ki-67 was 1%. Staining for SSTR2 and CCK2 showed high cytoplasmic expression in both cases. Knowledge of the presence of CCK2 receptor in MTC patients may be an important indication for the choice of diagnostic and therapeutic procedures. The presence of both the receptor types, cholecystokinin-2/gastrin and somatostatin, is possibly an interesting combination as far as the therapeutic target is concerned.

Translocation of 5' mRNA cap analogue--peptide conjugates across the membranes of giant unilamellar vesicles.

Cell-penetrating peptides (CPPs) have been extensively studied because of their ability to deliver various cargo molecules, which are often potential therapeutic agents. However, in most cases, the exact entry mechanism of CPPs is still unknown. In this study, we focused our attention on the membrane permeability sequence (MPS) peptide (AAVALLPAVLLALLAK) conjugated to analogues of a 5' mRNA cap. This unique RNA structure plays a pivotal role in eukaryotic gene expression and has a large therapeutic application potential. We validated the translocation abilities of conjugates across the membranes of giant unilamellar vesicles (GUVs) composed of POPC lipids by application of fluorescence microscopy. Translocation of the MPS peptide itself was observed in contrast to peptide conjugates containing mono- and dinucleotide cap analogues, indicating that even for such small cargos, passive translocation does not occur. However, membrane permeability was observed in the case of conjugated mononucleotides. Fluorescence lifetime microscopy (FLIM) of the C6-NBD-phospholipid revealed changes in lipid packing induced by a penetrating peptide. Our results support the usefulness of artificial membrane systems applied to elucidate membrane crossing mechanisms.

Common carotid artery access for transcatheter aortic valve implantation.

Transcatheter aortic valve implantation (TAVI) is an alternative method of treatment for severe symptomatic aortic stenosis in patients who are at high risk of surgical aortic valve replacement (AVR). In randomised clinical trials TAVI was shown to be superior to standard medical therapy in a cohort of inoperable patients and non-inferior to AVR in high-risk operable patients. Additionally, in a recent trial with self-expandable prosthesis use, TAVI was associated with lower mortality compared with surgery. Usually, femoral arteries are the most common vascular access to deliver the bioprosthesis; however, in some cases (up to 20%) this route may not be applied because of significant peripheral artery disease or tortuosity. In this article, we present the first two TAVI procedures in Poland performed via the left common carotid artery.

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) - a case report and review of literature.

CANVAS (cerebellar ataxia with neuropathy and vestibular areflexia syndrome) is a rare neurological syndrome of unknown etiology. The main clinical features include bilateral vestibulopathy, cerebellar ataxia and sensory neuropathy. An abnormal visually enhanced vestibulo-ocular reflex is the hallmark of the disease. We present a case of 58-year-old male patient who has demonstrated gait disturbance, imbalance and paresthesia of feet for 2 years. On examination ataxia of gait, diminished knee and ankle reflexes, absence of plantar reflexes, fasciculations of thigh muscles, gaze-evoked downbeat nystagmus and abnormal visually enhanced vestibulo-ocular reflex were found. Brain magnetic resonance imaging revealed cerebellar atrophy. Vestibular function testing showed severely reduced horizontal nystagmus in response to bithermal caloric stimulation. Nerve conduction study revealed loss of upper and lower limb sensory nerve action potentials. The course of illness was progressive with ataxic gait and unsteadiness as the most disabling symptoms. We report 4-year follow-up of the patient since the beginning of the disease.

Multiple metastatic intracranial lesions associated with left atrial myxoma.

BACKGROUND: One of the most common cardiac tumors is myxoma. Despite its predominantly benign course, diverse cardiological, systemic as well as neurological complications have been reported. CASE REPORT: We are the first from Poland to present the case of a patient with multiple central nervous system metastases associated with the left atrial myxoma. Various diagnostic, neuroradiological and histopathological procedures were described. The patient underwent cardiac surgery. CONCLUSIONS: Follow-up studies excluded the recurrence of the heart tumor and confirmed partial resolution of brain metastases. Nevertheless, subsequent neurological assessment was advised according to the literature data and possible late relapses mainly due to cerebral emboli.

Radioguided surgery in patient with pancreatic neuroendocrine tumour followed by PET/CT scan as a new approach of complete resection evaluation--case report.

Radioguided surgery using 68-gallium labelled somatostatin analogues is a promising method for detection of small, intra-abdominal, neuroendocrine neoplasm (NEN). However, due to high background activity (physiological uptake in e.g. spleen, adrenal glands and kidneys) tumours of the tail and body of pancreas might be impossible to detect with hand-held gamma probe. Therefore a new concept of intraoperative PET/CT scan of the resected tissue can be helpful in determining whether the tumour has been excised within the margins of healthy tissue. A 71-year-old woman with primary, non-metastatic NEN of the tail of pancreas is described. The tumour was diagnosed using MRI and PET/CT scan. Before operation patient was administered intravenously 80 MBq of 68Ga-DOTATATE. The surgery procedure was performed 60-180 minutes post injection. During the procedure pancreas was visualized, but the tumour could not be localized neither with palpation nor gamma probe. The tail of the pancreas was resected en bloc with spleen and adjacent lymph nodes. PET/CT scan of the tissue specimen was performed immediately followed by pathological examination. PET/CT scan of the resected tissue showed moderate activity in the tail of pancreas, and a small focus of high activity in the tail. Area of high SSTR expression in the tail corresponded with preoperative findings in MRI and whole-body PET/CT. Histopathological examination of the specimen confirmed the presence of neuroendocrine tumour grade 1. Immediate PET/CT scan of the surgical specimen can bring new quality to intraoperative assessment of completeness of resection of neuroendocrine tumours.

A frequency and semiquantitative analysis of pathological 68Ga DOTATATE PET/CT uptake by primary site-dependent neuroendocrine tumor metastasis.

UNLABELLED: The aim of this study was to define the frequency of neuroendocrine neoplasia (NEN) metastasis sites based on the primary lesion and create a database of SUVmax as a marker of human SSTR (somatostatin receptors) expression by semiquantitative analysis in vivo Ga DOTATATE PET/CT. PATIENTS AND METHODS: Two hundred forty-five patients, 89 men and 156 women (mean [SD] age, 56.1 [12.8]), were imaged 60 to 70 minutes after 120 to 200 MBq (3.2-5.4 mCi) Ga DOTATATE injection using a Siemens Medical Solutions Biograph 64 PET/CT TruePoint. Visual assessments were made using a multimodality workstation, and sites of increased uptake were recorded. Pathological Ga DOTATATE uptake was quantified using semiquantitative analysis (SUVmax). RESULTS: In patients with unknown primary tumors, Ga DOTATATE PET/CT revealed primary location in 92% (pancreas, 47%; intestines, 28%; and lung, 17%).Metastases, with respect to the primary sites, were predominantly in the liver (33% vs 49% vs 40%), lymph nodes (24% vs 34% vs 25%), and bone (10% vs 20% vs 30%). The SUVmax of metastases (mean [SD]) was highest in the liver (28.7 [23.5]), followed by the adrenal glands (24.7 [9.7]), bone (24.1 [36.8]), lymph nodes (22.5 [24.5]), pancreas (24.9 [28.1]), peritoneum (21.9 [24]), and the brain (4.6 [2.9]). CONCLUSIONS: Ga DOTATATE PET/CT is very useful in the localization of NEN primary tumors. Ga DOTATATE PET/CT allows for visualizations of bone and lymph node metastases, not detected by any other modalities, which provides better staging and changes the clinical decision in approximately one third of patients.Our study shows that pancreatic NEN presented statistically a significantly lower frequency of bone metastases in comparison to lung and intestinal NEN. No significant frequency of metastases in the liver and lymph nodes based on primary tumors was observed.

[Analysis of solitary pulmonary nodules found in chest radiograms]. / Analiza pojedynczych guzków pluca stwierdzonych w radiogramach klatki piersiowej.

INTRODUCTION: The detection of solitary pulmonary nodules (SPNs) has increased due to widespread use of computed tomography; nevertheless, chest radiographs still remain the basic routine examination. The aim of the study was to estimate the detection of SPNs in routine chest X-rays in hospitalized patients and to assess the incidence of malignancy in newly diagnosed SPNs. MATERIAL AND METHODS: We analyzed 5,726 routine chest radiographs of patients admitted to the Department of Internal Diseases, Pneumology and Allergology in 2004 and 2005. Most of the patients were admitted to hospital due to emergency reasons. The malignant nature of the nodules was confirmed by pathological examination. The nature of benign nodules was confirmed either by pathological examination or based on radiological criteria: no growth within 2 years of radiological follow up, regression in control radiograms or CT scans, benign pattern of calcification. RESULTS: Among the 5,726 radiograms we found 116 newly diagnosed SPNs (2.2%). Twenty-four nodules (21%) were malignant: NSCLC in 21 cases and metastases in 3 cases. Fifty-one nodules (44%) were benign. In 19 patients (16%) SPNs proved to be artefacts or erroneously interpreted extrathoracic lesions. In 22 cases (19%) there was no final diagnosis (lack of data, diagnostic procedure renunciation). CONCLUSION: The incidence of newly detected SPNs in chest X-rays was 2.2%. Most SPNs were benign. About 21% of SPNs were diagnosed as malignant.

Towards the proteome of Brassica napus phloem sap.

The soluble proteins in sieve tube exudate from Brassica napus plants were systematically analyzed by 1-DE and high-resolution 2-DE, partial amino acid sequence determination by MS/MS, followed by database searches. 140 proteins could be identified by their high similarity to database sequences (135 from 2-DE, 5 additional from 1-DE). Most analyzed spots led to successful protein identifications, demonstrating that Brassica napus, a close relative of Arabidopsis thaliana, is a highly suitable model plant for phloem research. None of the identified proteins was formerly known to be present in Brassica napus phloem, but several proteins have been described in phloem sap of other species. The data, which is discussed with respect to possible physiological importance of the proteins in the phloem, further confirms and substantially extends earlier findings and uncovers the presence of new protein functions in the vascular system. For example, we found several formerly unknown phloem proteins that are potentially involved in signal generation and transport, e.g., proteins mediating calcium and G-protein signaling, a set of RNA-binding proteins, and FLOWERING LOCUS T (FT) and its twin sister that might be key components for the regulation of flowering time.

Xylem sap protein composition is conserved among different plant species.

Xylem sap from broccoli (Brassica oleracea L. cv. Calabrais), rape (Brassica napus L. cv. Drakkar), pumpkin (Cucurbita maxima Duch. cv. gelber Zentner) and cucumber (Cucumis sativus L. cv. Hoffmanns Giganta) was collected by root pressure exudation from the surface of cut stems of healthy, adult plants. Total protein concentrations were in the range of 100 microg ml(-1). One-dimensional gel electrophoresis (SDS-PAGE) resulted in 10-20 visible protein bands in a molecular mass range from 10 to 100 kDa. The main bands were cut out, digested with trypsin, and analysed using tandem mass spectrometry. Fifty bands resulted in amino acid sequence information that was used to perform database similarity searches. Sequences from 30 bands showed high homology to proteins present in databases. Among them, we found mostly peroxidases, but could also identify the lectin-like xylem protein XSP30, a glycine-rich protein, serine proteases, an aspartyl protease family protein, chitinases, and a lipid transfer protein-like polypeptide. Sequence analysis predicted apoplastic secretion signals for all database entries similar to the partial xylem protein sequences. This and the lack of cross-reactivity with phloem protein-specific antibodies suggest that the proteins really originate from the xylem and do not result from phloem contamination. Most of the highly similar proteins probably function in repair and defence reactions. Some of the most abundant proteins (peroxidases, chitinases, serine proteases) were present in xylem exudate of all species analysed, often in more than one band. This indicates an important basic role of these proteins in maintaining xylem function.