Strong interference of hemoglobin concentration on CSF total protein measurement using the trichloroacetic acid precipitation method.

BACKGROUND: Among other methods, trichloroacetic acid precipitation is used to quantify total protein in cerebrospinal fluid (CSF). METHODS: We analyzed the influence of hemoglobin on total protein concentration assayed by the trichloroacetic acid method and compared the results to the benzethonium chloride method. RESULTS: Four CSF samples were spiked with different amounts of hemoglobin, leading to overestimation of protein concentration when assayed by the trichloroacetic acid method. Using the benzethonium chloride method, measurement of protein concentration was minimally disturbed. In addition, albumin and total protein concentrations were measured in 135 clinical samples. The total protein/albumin ratio remained constant when protein was measured with the benzethonium chloride method, while ratios increased when protein was assayed by the trichloroacetic acid method. CONCLUSIONS: Strong interference by hemoglobin leads to overestimation of the total protein concentration in CSF when assayed by the trichloroacetic acid method and may lead to false conclusions when evaluating the blood-brain barrier.     

Systematic review of organisation‐wide,trauma‐informed care models in out‐of‐home care (OoHC) settings

Trauma in early childhood has been shown to adversely affect children's social, emotional, and physical development. Children living in out‐of‐home care (OoHC) have better outcomes when care providers are present for children, physically, psychologically, and emotionally. Unfortunately, the high turnover of out‐of‐home carers, due to vicarious trauma (frequently resulting in burnout and exhaustion) can result in a child's trauma being re‐enacted during their placement in OoHC. Organisation‐wide therapeutic care models (encompassing the whole organisation, from the CEO to all workers including administration staff) that are trauma‐informed have been developed to respond to the complex issues of abuse and neglect experienced by children who have been placed in OoHC. These models incorporate a range of therapeutic techniques, and provide an overarching approach and common language that is employed across all levels of the organisation. The aim of this study was to investigate the current empirical evidence for organisation‐wide, trauma‐informed therapeutic care models in OoHC. A systematic review searching leading databases was conducted for evidence of organisation‐wide, trauma‐informed, out‐of‐home care studies, between 2002 and 2017. Seven articles were identified covering three organisational models. Three of the articles assessed the Attachment Regulation and Competency framework (ARC), one study assessed the Children and Residential Experiences programme (CARE), and three studies assessed The Sanctuary Model. Risk of bias was high in six of the seven studies. Only limited information was provided on the effectiveness of the models identified through this systematic review, although the evidence did suggest that trauma‐informed care models may have significantly positive outcomes for children in OoHC. Future research should focus on evaluating components of trauma‐informed care models and assessing the efficacy of the various organisational care models currently available.     

Active video gaming improves body coordination in survivors of childhood brain tumours

Purpose: We investigated whether active video gaming (AVG) could bring about regular, enjoyable, physical exercise in children treated for brain tumours, what level of physical activity could be reached and if the children’s physical functioning improved.

Methods: Thirteen children, aged 7–17 years, were randomised to either AVG or waiting-list. After 10–12 weeks they crossed-over. Weekly Internet coaching sessions were used to sustain motivation and evaluate enjoyment. Energy expenditure (EE) levels were measured as Metabolic Equivalent of Task (MET), using a multisensory activity monitor. Single-blinded assessments of physical functioning were done, using the Bruininks–Osteretsky Test of Motor Performance, second edition, evaluating participants before and after the intervention period, as well as comparing the randomisation groups after the first period.

Results: All patients completed the study. AVG sessions (mean duration 47?minutes) were performed on 72% of all days. Mean EE level during AVG sessions was 3.0 MET, corresponding to moderate physical activity. The Body Coordination score improved by 15% (p?=?0.021) over the intervention period.

Conclusions: In this group of childhood brain tumour survivors, home-based AVG, supported by a coach, was a feasible, enjoyable and moderately intense form of exercise that improved Body Coordination.

• Implications for Rehabilitation

• Childhood brain tumour survivors frequently have cognitive problems, inferior physical functioning and are less physically active compared to their healthy peers.

• Active video gaming (AVG), supported by Internet coaching, is a feasible home-based intervention in children treated for brain tumours, promoting enjoyable, regular physical exercise of moderate intensity.

• In this pilot study, AVG with Nintendo Wii improved Body Coordination.

     

The growth hormone secretagogue hexarelin increases cell proliferation in neurogenic regions of the mouse hippocampus

ObjectiveRadiation therapy (RT) to the brain is often used in the treatment of children with different types of malignant diseases affecting the brain. However, RT in childhood may also have severe side effects including impaired brain maturation and intellectual development. For childhood cancer survivors these adverse effects of RT can cause lifelong disability and suffering. Therefore, there is an unmet need to limit late effects after RT. Precursor cells in the subgranular zone of the dentate gyrus (DG) in the hippocampus are particularly sensitive to irradiation (IR). This may be of significance as newly generated neurons in the DG are important for memory and learning. GH secretagogues (GHS) have previously been shown to promote neurogenesis and to have neuroprotective effects. In addition, several parts of the brain, including the hippocampus, have been shown to express the GHS receptor 1a (GHS-R1a). The aim of this study was to evaluate the potential effect of the GHS hexarelin on proliferation and survival of progenitor cells in the hippocampus after brain IR in a mouse model.DesignIn the present study, 10-day-old male mice received 6 Gy cranial IR. Non-irradiated sham animals were used as controls. We treated one group of irradiated and one sham group with hexarelin (100 μg/kg/day) for 28 days and used immunohistochemical labeling of bromo-deoxy uridine (BrdU) and phospho-histone H3 of the granular cell layer of the DG to evaluate proliferation and cell survival after IR at postnatal day ten.ResultsOur results show that hexarelin significantly increased the number of BrdU-positive cells in the granule cell layer by approximately 50% compared to controls.ConclusionThe increased number of BrdU-positive cells in the granule cell layer suggests a partial restoration in the pool of proliferating cells by hexarelin after IR.     

Quantitative effects of diet on fecal corticosterone metabolites in two strains of laboratory mice

The analysis of glucocorticoids excreted in feces is becoming a widespread technique for determining animal wellbeing in a wide variety of settings. In the present study an extraction protocol and an ELISA assay for quantifying fecal corticosterone metabolites (FCM) in BALB/c and C57bl/6 mice were validated. Lower ratios of solvent (ethanol) to mass of fecal sample were found to be sufficient in extracting FCM compared to what has been reported previously. Feeding mice a high energy diet, high in fat content (60% of calories from fat), significantly lowered the FCM excretion, approximately halving the FCM output. This diet also reduced the fecal mass voided to approximately a third of that of the regular diet. The two reductions were not correlated. A difference in defecation pattern was seen between the two strains, with the BALB/c mice having a more pronounced diurnal rhythm compared to the C57bl/6 mice. Furthermore, throughout the experiment, the C57bl/6 mice excreted significantly higher levels of FCM compared to the BALB/c mice. The mice were also challenged with synthetic adrenocorticotropic hormone (ACTH) and dexamethasone (DEX). The effect of the challenges could readily be detected, but had a considerably lesser impact on data than did the difference in diet. The study demonstrates some problematic consequences of expressing FCM excretion as a measure of fecal dry mass. The study also serves to emphasize the caution that must be exercised when interpreting FCM excretion in conjunction with an uncontrolled or varied diet, or perturbations of gastro-intestinal functioning.     

NK cell function and antibodies mediating ADCC in HIV-1-infected viremic and controller patients

Natural killer (NK) cells have been suggested to play a protective role in HIV disease progression. One potent effector mechanism of NK cells is antibody-dependent cellular cytotoxicity (ADCC) mediated by antiviral antibodies binding to the FcγRIIIa receptor (CD16) on NK cells. We investigated NK cell-mediated ADCC function and the presence of ADCC antibodies in plasma from 20 HIV-1-infected patients and 10 healthy donors. The HIV-positive patients were divided into two groups: six who controlled viremia for at least 8 y without treatment (controllers), and 14 who were persistently viremic and not currently on treatment. Plasma from both patient groups induced NK cell IFN-γ expression and degranulation in response to HIV-1 envelope (Env) gp140-protein-coated cells. Patient antibodies mediating ADCC were largely directed towards the Env V3 loop, as identified by a gp140 protein lacking the V3 loop. Interestingly, in two controllers ADCC-mediating antibodies were more broadly directed to other parts of Env. A high viral load in patients correlated with decreased ADCC-mediated cytolysis of gp140-protein-coated target cells. NK cells from both infected patients and healthy donors degranulated efficiently in the presence of antibody-coated HIV-1-infected Jurkat cells. In conclusion, the character of ADCC-mediating antibodies differed in some controllers compared to viremic patients. NK cell ADCC activity is not compromised in HIV-infected patients.     

High-frequency electrocardiogram analysis in the ability to predict reversible perfusion defects during adenosine myocardial perfusion imaging

Background

A previous study has shown that analysis of high-frequency QRS components (HF-QRS) is highly sensitive and reasonably specific for detecting reversible perfusion defects on adenosine myocardial perfusion imaging (MPI) scans. The purpose of the present study was to try to reproduce those findings.

Methods

Twelve-lead high-resolution electrocardiogram recordings were obtained from 100 patients before (baseline) and during adenosine ^99mTc-tetrofosmin MPI tests. The HF-QRS were analyzed regarding morphology and changes in root mean square voltages from before the adenosine infusion to peak infusion.

Results

The best area under the curve (AUC) was found in supine patients (AUC = 0.736) in a combination of morphology and root mean square changes. None of the measurements, however, were statistically better than tossing a coin (AUC = 0.5).

Conclusion

Analysis of HF-QRS was not significantly better than tossing a coin for determining reversible perfusion defects on MPI scans.     

Increased proportion of CD56bright natural killer cells in active and inactive systemic lupus erythematosus

Natural killer (NK) cells belong to the innate immune system but can also affect adaptive immune reactions. This immune regulatory function is often ascribed to the CD56(bright) subpopulation of NK cells that is prevalent in secondary lymphoid tissues and has potent cytokine-producing ability. The NK cells have been described as affecting autoimmune disease and stimulating B-cell production of antibodies, but their role in systemic lupus erythematosus (SLE) pathology has not been extensively studied. We have studied NK cells in SLE, a B-cell-driven systemic autoimmune disease, and phenotypically characterized peripheral blood NK cells in comparison to NK cells from patients with immunoglobulin A nephritis, rheumatoid arthritis and healthy individuals. We have found an increased proportion of CD56(bright) NK cells in SLE, regardless of disease activity. We detected a somewhat increased expression of the activating receptor NKp46/CD335 on NK cells from SLE patients, although neither the percentage of NK cells of all lymphocytes nor the expression of other NK receptors analysed (LIR-1/CD85j, CD94, NKG2C/CD159c, NKG2D/CD314, NKp30/CD337, NKp44/CD336, CD69) differed between patient groups. We show that type I interferon, a proinflammatory cytokine known to be abundant in SLE, can cause increases of CD56(bright) NK cells in vitro. We confirmed that serum levels of interferon-alpha were increased in active, but not in inactive, disease in the SLE patient group. In conclusion, we found an increased proportion of CD56(bright) NK cells in the blood of SLE patients, although it remains to be examined whether and how this relates to the disease process.     

Human CMV infection induces 5-lipoxygenase expression and leukotriene B4 production in vascular smooth muscle cells

Leukotrienes (LTs) are powerful proinflammatory lipid mediators that may play a central role in cardiovascular diseases, including arteriosclerosis, myocardial infarction, and stroke. Owing to restricted expression of 5-lipoxygenase (5-LO), the enzyme required for their synthesis, LTs are almost exclusively produced by myeloid cells. Here, we report that human cytomegalovirus (HCMV) infection of human vascular smooth muscle cells (SMCs) increases 5-LO mRNA levels by up to 170-fold in a dose- and time-dependent manner. Infected cells expressed 5-LO protein, as shown by immunohistochemistry, enabling them to synthesize bioactive LTB(4). HCMV-infected vascular SMCs expressing 5-LO protein were readily detected in tissue samples from CMV-infected patients with inflammatory bowel disease or AIDS. Thus, pathogen-induced LT production in HCMV-infected tissues may contribute to local inflammation, consistent with the ability of HCMV to control cellular and immunological functions. HCMV-induced LT biosynthesis in SMCs offers a molecular mechanism to explain HCMV-induced pathogenesis in inflammatory diseases.