Basal and cold-induced fatty acid uptake of human brown adipose tissue is impaired in obesity.

Fatty acids (FA) are important substrates for brown adipose tissue (BAT) metabolism, however, it remains unclear whether there exists a difference in FA metabolism of BAT between lean and obese healthy humans. In this study we evaluated supraclavicular BAT fatty acid uptake (FAU) along with blood perfusion in lean and obese subjects during cold exposure and at room temperature using positron emission tomography (PET)/computed tomography (CT). Additionally, tissue samples were taken from supraclavicular region (typical BAT region) from a subset of subjects to evaluate histological presence of BAT. Non-shivering cold stress elevated FAU and perfusion of BAT in lean, but not in obese subjects. Lean subjects had greater FAU in BAT compared to obese subjects during cold exposure and interestingly also at room temperature. The higher BAT FAU was related to younger age and several indicators of superior systemic metabolic health. The subjects who manifested BAT histologically had several folds higher BAT FAU compared to subjects with no such histological manifestation. Together, obese subjects have less active tissue in supraclavicular region both in basal and cold-activated state and the FA metabolism of BAT is blunted in obesity.

MRI evaluation of the endolymphatic space in otosclerosis and correlation with clinical findings.

PURPOSE: The purpose of this study was to investigate the clinical features of ears with otosclerosis and their correlation with endolymphatic hydrops and blood-labyrinth barrier (BLB) impairment on 3T magnetic resonance imaging (MRI). MATERIALS AND METHODS: This was a single-center retrospective imaging study. Thirty-nine ears from 29 patients (17 men, 12 women; mean age 52±12 [SD] years; range 27-74 years) with non-operated otosclerosis were included. All patients underwent three-dimensional fluid attenuated inversion recovery (FLAIR) MRI sequences performed 4hours after the intravenous administration of a single dose of gadolinium-based contrast material. MRI examinations were analyzed by two radiologists for the presence of saccular hydrops (SH) and BLB impairment. Results of MRI examinations were compared with clinical findings, hearing levels and extent of otosclerotic lesions based on high-resolution computed tomography findings. BLB impairment was evaluated using the signal intensity ratio, ratio of intensities between the basal turn of the cochlea and the medulla. RESULTS: SH was observed in 1/39 (3%) otosclerotic ears and BLB impairment in 8/39 (21%) while 8/29 patients with otosclerosis (28%) had vertigo. No significant associations were found between SH or BLB impairment on MRI, and the presence of vertigo or the degree of sensorineural hearing loss. CONCLUSION: Clinical manifestations of otosclerosis (sensorineural hearing loss and rotatory vertigo) were not significantly associated with MRI findings such as BLB impairment and endolymphatic hydrops. SH was only observed in one patient with obstruction of the vestibular aqueduct by an otosclerotic focus.

Prosthetic Rehabilitation with Implant-Supported Mandibular Overdenture after Partial Glossectomy and Radiation Therapy: A Case Report.

Implant-supported overdenture is a well-established treatment option for many patients who have functional problems with conventional dentures. It may be primary choice for patients with altered jaw anatomy, neuromuscular disorders, pronounced gag reflex, severe residual ridge resorption and oral tissue defects. In this article we describe a case report, where tongue cancer patients occlusion was rehabilitated with an implantretained overdenture. In 2001 patient was operated for squamous cell carcinoma on the left side of the tongue. Before preoperative radiation therapy, small residual mandibular dentition was removed because of its poor prognosis. Radiation dose on mandible was 57-66 Gy. After tumor surgery patient received conventional complete dentures. Ten years later, the patient was referred again to the Turku University Central Hospital due to constant ulceration under the mandibular denture. The residual ridge of the mandible was severely resorbed. Patient's existing lower complete denture was replaced with a milled bar-retained overdenture on four implants. Treatment turned out to be challenging due to severely restricted tongue movement and tissue defects.

Rehabilitation referrals and outcomes in the early period after hematopoietic cell transplantation.

In a cohort of inpatient hematopoietic cell transplantation (HCT) recipients, we assessed patterns of referral to rehabilitation treatment, functional performance and short-term outcomes in patients who received post-transplant rehabilitation in comparison with those who did not. Among 201 first-time HCT recipients, 53 (26%) were referred to an inpatient rehabilitation provider, had an assessment of functional performance using the Functional Independence Measure scale and underwent rehabilitation treatments to address functional needs. Patients who received rehabilitation therapy were more likely to be females (P=0.02), older than 60 years of age (P=0.0146), employed (P=0.01), have hypertension (P=0.02), peripheral vascular disease (P=0.01) and pre-transplant Karnofsky Performance Score (KPS) <90 (P=0.02). Mean functional performance scores for transfers and ambulation increased significantly in the group with rehabilitation interventions (P=0.0022 and P<0.0001, respectively). There was no difference between the groups that did and did not receive rehabilitation treatments in 30-day re-admission rates. Patients who are 60 years of age or older, with pre-transplant KPS<90, and pre-transplant hypertension were more likely to be referred for rehabilitation treatments in the early period after HCT. Future studies should be designed to determine the optimal timing and cost effectiveness of functional assessment and rehabilitation treatments in this high-risk population.

Maternal diabetes induces changes in the umbilical cord gene expression.

INTRODUCTION: Since maternal diabetes may affect fetal development and the umbilical cord provides an extension of the fetal vasculature, we decided to investigate cords' biological responses to maternal diabetic milieu. METHODS: Using microarray analysis, we determined the gene expression profiles in the umbilical cords of six neonates born to type 1 diabetic mothers and in six control cords. Umbilical cord tissue was collected immediately after elective cesarean section. Expression data were confirmed by real-time polymerase chain reaction (11 genes). Additionally, the same umbilical cords were analyzed histologically. RESULTS: Two hundred eighty six genes were differentially expressed in the umbilical cords from diabetic pregnancies compared to the controls (fold change ±1.5 and P < 0.01). Maternal diabetes had a major effect on the expression of genes involved in vascular development (Bone morphogenetic protein 4, Delta-like 1, and Notch homolog 4), vessel wall integrity (Collagen type VIII alpha 1, Myocyte enhancer factor 2C, and Matrix metalloproteinase 2), and vascular function (Natriuretic peptide precursor B, Endothelin 1, Endothelin receptor B, Cyclooxygenase 1, and Phosphodiesterase 5A). Maternal diabetes was associated with thicker umbilical vein intima-media layers and larger umbilical vein and artery intima-media areas compared to the controls. DISCUSSION: Maternal diabetic environment seems to alter umbilical cord expression of genes involved in the regulation of vascular development and function with simultaneous umbilical vessel muscle layer thickening. These alterations suggest vascular phenotypic modifications, which in turn may lead to long-term vascular consequences in various tissues in infants of diabetic mothers.

Brown adipose tissue triglyceride content is associated with decreased insulin sensitivity, independently of age and obesity.

The aim of the present study was to determine whether single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) can non-invasively assess triglyceride content in both supraclavicular fat depots and subcutaneous white adipose tissue (WAT) to determine whether these measurements correlate to metabolic variables. A total of 25 healthy volunteers were studied using (18)F-fluorodeoxyglucose positron emission tomography (PET) and (15)O-H2O PET perfusion during cold exposure, and (1)H-MRS at ambient temperature. Image-guided biopsies were collected from nine volunteers. The supraclavicular triglyceride content determined by (1)H-MRS varied between 60 and 91% [mean ± standard deviation (s.d.) 77 ± 10%]. It correlated positively with body mass index, waist circumference, subcutaneous and visceral fat masses and 8-year diabetes risk based on the Framingham risk score and inversely with HDL cholesterol and insulin sensitivity (M-value; euglycaemic-hyperinsulinaemic clamp). Subcutaneous WAT had a significantly higher triglyceride content, 76-95% (mean ± s.d. 87 ± 5%; p = 0.0002). In conclusion, the triglyceride content in supraclavicular fat deposits measured by (1)H-MRS may be an independent marker of whole-body insulin sensitivity, independent of brown adipose tissue metabolic activation.

Meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia in Tampere University Hospital: a case-control study, Finland October 2002 to January 2010.

Meticillin-resistant Staphylococcus aureus (MRSA) has emerged as a frequent pathogen in blood cultures in Pirkanmaa Hospital District (HD), Finland. To study risk factors for MRSA bacteraemia and the adequacy of empirical antimicrobial treatment, we retrospectively reviewed the hospital records of 102 patients, 51 with MRSA, and 51 with meticillin-sensitive Staphylococcus aureus (MSSA) bacteraemias respectively, who had been admitted to Tampere University Hospital in Pirkanmaa HD, from October 2002 to January 2010. For each patient with MRSA bacteraemia, one consecutively detected unmatched patient with MSSA bacteraemia was chosen as control. Patients with MRSA bacteraemias were significantly older (median age: 73 years vs 59 years, p=0.001), were more likely to have been transferred directly from another healthcare facility or were already in the hospital at the onset of bacteraemia (39/51 vs 26/51, p=0.007) and had a higher McCabe class than patients with MSSA bacteraemia (p=0.005). Patients with MRSA bacteraemia more seldom received adequate empirical antimicrobial therapy when compared to those with MSSA bacteraemia (13/51 vs 43/51, p<0.001). Of previously known MRSA carriers 10 of 29 received adequate empirical antimicrobial therapy for their condition. The percentage of MRSA bacteraemias among all S. aureus bacteraemias in Pirkanmaa HD is high compared to corresponding figures for the whole of Finland.

Reactive arthritis in a population exposed to an extensive waterborne gastroenteritis outbreak after sewage contamination in Pirkanmaa, Finland.

OBJECTIVES: To assess the occurrence, clinical picture, and triggering infections of reactive arthritis (ReA) associated with a large waterborne gastroenteritis outbreak. METHODS: After an extensive sewage contamination of the water supply system, an estimated 8453 of the 30 016 inhabitants of the town of Nokia fell ill. General practitioners and occupational physicians were advised to refer any patients with suspicion of new ReA to rheumatological examination including faecal culture, human leucocyte antigen (HLA)-B27 and antibody tests for Campylobacter, Salmonella, and Yersinia. RESULTS: Forty-five patients (33 females, 12 males) aged 16-77 years (median 53) were referred. ReA was diagnosed in 21, postinfectious arthralgia in 13, and other musculoskeletal conditions in 11 patients. HLA-B27 was positive in five out of 44 patients (11%). Of the 21 patients with ReA, possible triggering infections were observed in seven (33%), Campylobacter in four, Yersinia in three, and Salmonella in one, who also had Campylobacter infection. ReA was mild in all but one patient who presented with persistent Salmonella enterica serotype enteritidis infection. CONCLUSIONS: Taking into account the large population contaminated with potentially arthritogenic agents, the occurrence of ReA was rare and mild in character.

Plasma level of soluble urokinase-type plasminogen activator receptor as a predictor of disease severity and case fatality in patients with bacteraemia: a prospective cohort study.

OBJECTIVES: Urokinase-type plasminogen activator receptor (uPAR) is expressed on a variety of different immune cells and vascular endothelial cells during inflammation. Previous studies indicate that a high plasma concentration of the soluble form of the receptor (suPAR) predicts poor outcome in infectious diseases. DESIGN: A prospective cohort study. SUBJECTS AND METHODS: Plasma suPAR levels were measured in 132 patients with bacteraemia caused by Staphylococcus aureus, Streptococcus pneumoniae, ß-haemolytic streptococcae or Escherichia coli using a commercial enzyme-linked immunosorbent assay (ELISA). Values were measured on days 1-4 after a positive blood culture, on days 13-18 and on recovery. RESULTS: The maximum suPAR values on days 1-4 were markedly higher in nonsurvivors compared to survivors (15.8 vs. 7.3 ng mL(-1) , P < 0.001) and the area under the receiver operating characteristic curve (AUC(ROC) ) in the prediction of case fatality was 0.84 (95% confidence interval (CI) 0.76-0.93, P < 0.001). At a cut-off level of 11.0 ng mL(-1) , the sensitivity and specificity of suPAR for fatal disease was 83% and 76%, respectively. A high level of suPAR (≥ 11 ng mL(-1) ) was associated with hypotension (mean arterial pressure < 70 mmHg) (odds ratio (OR) 6.5; 95% CI 2.9-14.6) and high sequential organ failure assessment score (≥ 4) (OR 9.3; 95% CI 4.0-21.9). A high suPAR level remained an independent risk factor for case fatality in a logistic regression model adjusted for potential confounders. CONCLUSION: Plasma suPAR level is a sensitive and specific independent prognostic biomarker in patients with bacteraemia.

An extensive gastroenteritis outbreak after drinking-water contamination by sewage effluent, Finland.

An inappropriate cross-connection between sewage- and drinking-water pipelines contaminated tap water in a Finnish town, resulting in an extensive waterborne gastroenteritis outbreak in this developed country. According to a database and a line-list, altogether 1222 subjects sought medical care as a result of this exposure. Seven pathogens were found in patient samples of those who sought treatment. To establish the true disease burden from this exposure, we undertook a population-based questionnaire investigation with a control population, infrequently used to study waterborne outbreaks. The study covered three areas, contaminated and uncontaminated parts of the town and a control town. An estimated 8453 residents fell ill during the outbreak, the excess number of illnesses being 6501. Attack rates were 53% [95% confidence interval (CI) 49.5-56.4] in the contaminated area, 15.6% (95% CI 13.1-18.5) in the uncontaminated area and 6.5% (95% CI 4.8-8.8) in the control population. Using a control population allowed us to differentiate baseline morbidity from the observed morbidity caused by the water contamination, thus enabling a more accurate estimate of the disease burden of this outbreak.

PLA2 (group IIA phospholipase A2) as a prognostic determinant in stage II colorectal carcinoma.

BACKGROUND: Approximately 30% of all colorectal cancer (CRC) patients are diagnosed with stage II disease. Adjuvant therapy is not widely recommended. However, it is well established that a subgroup of patients with stage II are at high risk for recurrence within their lifetime and should be considered for adjuvant chemotherapy. The present work was designed to assess the value of group IIA phospholipase A2 (PLA2) as a predictor of disease outcome in stage II CRC patients with long-term follow-up. PATIENTS AND METHODS: The present study comprises a series of 116 patients who underwent bowel resection for stage II CRC during 1981-1990 at Turku University Hospital. Archival paraffin-embedded CRC tissue samples were used to prepare tissue microarray blocks for immunohistochemical staining with PLA2. RESULTS: Fifty-five percent of all tumors were positive for PLA2. There was no significant correlation between PLA2 expression and age, sex, depth of invasion and lymph node status. In Kaplan-Meier survival analysis, there was a significant (P = 0.010) difference in disease-free survival (DFS) between patients with negative tumors (longer DFS) and those with positive tumors. The same was true with disease-specific survival (DSS), patients with PLA2-negative tumors living significantly longer (P = 0.025). In multivariate (Cox) survival analysis, however, PLA2 was not an independent predictor of DFS or DSS. In subgroup analysis, the right-sided tumors with negative PLA2 staining had remarkably better prognosis (P = 0.010) than PLA2-positive left-sided tumors. CONCLUSIONS: Quantification of PLA2 expression seems to provide valuable prognostic information in stage II CRC, particularly in selecting the patients at high risk for recurrent disease who might benefit from adjuvant therapy.

Acetaminophen bioactivation by human cytochrome P450 enzymes and animal microsomes.

Acetaminophen is a widely used analgesic antipyretic agent. When used at low doses, it is a safe drug, but at higher doses it can cause acute hepatic necrosis in humans and experimental animals. The key mechanism in the hepatotoxicity is cytochrome P450 (CYP)-catalysed formation of the reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI) that is capable of binding to cellular macromolecules and in that way an LC/MS liquid chromatography/mass spectrometry (LC/MS) method was developed to measure NAPQI formation by trapping it to reduced glutathione. This method was used to determine the bioactivation of acetaminophen at two concentrations: 50 microM therapeutic and 1 mM toxic by using nine human recombinant CYP enzymes: CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4; and with different microsomes from experimental animals. At the toxic concentration the formation of NAPQI-glutathione was highest with CYP3A4 followed by CYP2E1, CYP1A2, and CYP2D6. At the therapeutic concentration, CYP3A4 had also the highest bioactivation capacity. In a comparison of the enzyme kinetics, CYP3A4 was the most efficient CYP with the lowest K(m) value 130 microM (95% confidence interval = 63-210 microM). Dexamethasone-induced rat liver microsomes had the most effective bioactivation capacity at therapeutic and toxic acetaminophen concentrations. This study suggests that CYP3A4 is the major CYP enzyme form catalysing acetaminophen oxidation to NAPQI in human liver.

Enzymatic hydrolysis of native cellulose nanofibrils and other cellulose model films: effect of surface structure.

Model films of native cellulose nanofibrils, which contain both crystalline cellulose I and amorphous domains, were used to investigate the dynamics and activities of cellulase enzymes. The enzyme binding and degradation of nanofibril films were compared with those for other films of cellulose, namely, Langmuir-Schaefer and spin-coated regenerated cellulose, as well as cellulose nanocrystal cast films. Quartz crystal microbalance with dissipation (QCM-D) was used to monitor the changes in frequency and energy dissipation during incubation at varying enzyme concentrations and experimental temperatures. Structural and morphological changes of the cellulose films upon incubation with enzymes were evaluated by using atomic force microscopy. The QCM-D results revealed that the rate of enzymatic degradation of the nanofibril films was much faster compared to the other types of cellulosic films. Higher enzyme loads did not dramatically increase the already fast degradation rate. Real-time measurements of the coupled contributions of enzyme binding and hydrolytic reactions were fitted to an empirical model that closely described the cellulase activities. The hydrolytic potential of the cellulase mixture was found to be considerably affected by the nature of the substrates, especially their crystallinity and morphology. The implications of these observations are discussed in this report.

Gene-environment interaction between MBL2 genotype and smoking, and the risk of gram-positive bacteraemia.

Mannose-binding lectin (MBL) insufficiency caused by point mutations in the MBL2 gene has been associated with increased susceptibility to bacteraemic infections. We here investigated the effect of MBL2 polymorphisms on the susceptibility and clinical course of bacteraemia. The study cohort comprised 145 patients with bacteraemia and 400 controls. In the case of patients with bacteraemia, laboratory findings and clinical data were registered on admission and during six consecutive days. MBL2 structural polymorphisms at codons 52 (CGT-->TGT; designated D or O), 54 (GGC-->GAC; B or O) and 57 (GGA-->GAA; C or O) in exon 1 of the MBL2 gene and promoter region polymorphisms at position -221 (G-->C, designated Y or X alleles) were determined. No difference in MBL2 genotype frequencies between the bacteraemic patients and controls was detected, and MBL2 genotype had no independent effect on mortality, nor disease severity. However, smoking proved a significant risk factor for Gram-positive (Staphylococcus aureus, Streptococcus pneumoniae or beta-haemolytic streptococci) bacteraemia in patients carrying the variant O allele (53% current smokers in Gram-positive bacteraemia patients compared with only 21% in controls, odds ratios 4.2, 95% confidence intervals 2.0-9.0; P < 0.001), while it did not have an effect in those homozygous for the A allele. The same effect was not detected in Escherichia coli bacteraemia. In conclusion, MBL2 genotypes representing MBL insufficiency were not associated with the overall risk of bacteraemia or disease severity, but smoking in carriers of the structural variant O allele may have a deleterious effect increasing the risk of Gram-positive bacteraemia.

Transmembrane protein 50b (C21orf4), a candidate for Down syndrome neurophenotypes, encodes an intracellular membrane protein expressed in the rodent brain.

Transmembrane protein 50b, Tmem50b, previously referred to as C21orf4, encodes a predicted transmembrane protein and is one of few genes significantly over-expressed during cerebellar development in a Down syndrome mouse model, Ts1Cje. In order to assess potential mechanisms by which Tmem50b could contribute to Down syndrome-related phenotypes, we determined the expression patterns of Tmem50b mRNA, as well as Tmem50b protein distribution, expression and subcellular localization. In situ hybridization in mice at embryonic day 14.5 showed cortical plate and spinal cord mRNA expression. By postnatal day 7, strong mRNA expression was seen in the cerebellum, hippocampus and olfactory bulb, with diffuse cortical expression. Quantitative PCR of adult mouse tissue showed Tmem50b mRNA expression in the brain, heart and testis. A rabbit polyclonal antibody was generated against Tmem50b and rat and mouse tissue screening by Western blot, and immunohistochemistry showed that protein expression concurred with mRNA expression. Double immunofluorescence revealed that Tmem50b is highly expressed in rat and mouse glial fibrillary acidic protein-positive cells in vivo and in vitro, but less so in neuronal MAP2- or beta-tubulin II-positive cells in vitro. Tmem50b is invariably expressed in cultured mouse neural precursor cells. In adult mouse cerebellum sections, Tmem50b immunoreactivity was found in Purkinje and Golgi cell somata and in Bergmann glial processes. Electron microscopy confirmed that Tmem50b was present on endoplasmic reticulum (ER) and Golgi apparatus membranes. Results indicate that Tmem50b is a developmentally-regulated intracellular ER and Golgi apparatus membrane protein that may prove important for correct brain development through functions associated with precursor cells and glia.

Model films from native cellulose nanofibrils. Preparation, swelling, and surface interactions.

Native cellulose model films containing both amorphous and crystalline cellulose I regions were prepared by spin-coating aqueous cellulose nanofibril dispersions onto silica substrates. Nanofibrils from wood pulp with low and high charge density were used to prepare the model films. Because the low charged nanofibrils did not fully cover the silica substrates, an anchoring substance was selected to improve the coverage. The model surfaces were characterized using atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS). The effect of nanofibril charge density, electrolyte concentration, and pH on swelling and surface interactions of the model film was studied by quartz crystal microbalance with dissipation (QCM-D) and AFM force measurements. The results showed that the best coverage for the low charged fibrils was achieved by using 3-aminopropyltrimethoxysilane (APTS) as an anchoring substance and hence it was chosen as the anchor. The AFM and XPS measurements showed that the fibrils are covering the substrates. Charge density of the fibrils affected the morphology of the model surfaces. The low charged fibrils formed a network structure while the highly charged fibrils formed denser film structure. The average thickness of the films corresponded to a monolayer of fibrils, and the average rms roughness of the films was 4 and 2 nm for the low and high charged nanofibril films, respectively. The model surfaces were stable in QCM-D swelling experiments, and the behavior of the nanofibril surfaces at different electrolyte concentrations and pHs correlated with other studies and the theories of Donnan. The AFM force measurements with the model surfaces showed well reproducible results, and the swelling results correlated with the swelling observed by QCM-D. Both steric and electrostatic forces were observed and the influence of steric forces increased as the films were swelling due to changes in pH and electrolyte concentration. These films differ from previous model cellulose films due to their chemical composition (crystalline cellulose I and amorphous regions) and fibrillar structure and hence serve as excellent models for the pulp fiber surface.

Heme oxygenase 1 gene polymorphisms and outcome of renal transplantation.

Heme oxygenase isoenzyme HO-1 has been linked to several cytoprotective functions with a potentially beneficial role in transplantation. In the present study, the effect of genetic variation in HO-1 on renal allograft outcome was investigated. Six hundred and eighty patients subject to renal transplantation in a single transplant unit and their cadaveric kidney donors were included in this study. Four single-nucleotide polymorphisms and one microsatellite marker in the HO-1 gene region were analysed. Some statistically nominally significant associations were observed in preliminary analyses between polymorphisms studied and clinical outcomes, but after correction for multiple comparisons none remained significant. Our data suggest that the HO-1 gene polymorphisms studied have no significant role on outcome of kidney transplantation in the Finnish population.