25 research outputs found

    Impact of Monetary Uncertainty and Economic Uncertainty on Money Demand in Africa

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    This dissertation investigates the role that economic uncertainties and monetary uncertainties play in the money demand function for 21 African countries. The Auto-regressive Distributive Lag (ARDL) and F-test approach are employed using quarterly time series data covering the period from 1971I-2012IV. In particular, this paper aims to demonstrate both short and long-run relationships between the dependent variables, Real Money Aggregate (M2), and the independent variables that include real income (Y), inflation rate nominal effective exchange rate (NEX), output uncertainty (VY), and monetary uncertainty (VM). We apply GARCH methodology to approximate the uncertainty measures. The empirical results show that except for Egypt, monetary VM and VY have significant short-run as well as long-run effects on money demand in all the countries, with some variables carrying negative or positive coefficient. We find that the coefficients of Y in all the countries is positive while that of and NEX are negative, implying depreciation of domestic currency decreases demand for money. The results also indicate that CUSUM and CUSUMSQ test are stable, thus M2 is stable in all the countries except Egyp

    Recommendations for the Use of Antibiotics in Primary and Secondary Esthetic Breast Surgery

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    The use of systemic prophylactic antibiotics to reduce surgical-site infection in esthetic breast surgery remains controversial, although the majority of surgeons prefer to utilize antibiotics to prevent infection. Nonetheless, postoperative acute and subclinical infection and capsular fibrosis are among the most common complications following implant-based breast reconstruction. After esthetic breast augmentation, up to 2.9% of women develop infection, with an incidence rate of 1.7% for acute infections and 0.8% for late infections. After postmastectomy reconstruction (secondary reconstruction), the rates are even higher. The microorganisms seen in acute infections are Gram-positive, whereas subclinical late infections involving microorganisms are typically Gram-negative and from normal skin flora with low virulence. In primary implantation, a weight-based dosing of cefazolin is adequate, an extra duration of antibiotic cover does not provide further reduction in superficial or periprosthetic infections. Clindamycin and vancomycin are recommended alternative for patients with β-lactam allergies. The spectrum of microorganism found in late infections varies (Gram-positive and Gram-negative), and the antibiotic prophylaxis (fluoroquinolones) should be extended by vancomycin and according to the antibiogram when replacing implants and in secondary breast reconstruction, to target microorganisms associated with capsular contracture. All preoperative antibiotics should be administered <60 minutes before incision to guarantee high serum levels during surgical procedure

    Orexins/Hypocretins Acting at Gi Protein-Coupled OX2 Receptors Inhibit Cyclic AMP Synthesis in the Primary Neuronal Cultures

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    Orexins A and B are newly discovered neuropeptides with pleiotropic activity. They signal through two G protein-coupled receptors: OX1 and OX2. In this study, we examined the expression of orexin receptors and effects of the receptors’ activation on cyclic AMP formation in the primary neuronal cell cultures from rat cerebral cortex. Both types of orexin receptors were expressed in rat cortical neurons; the level of OX2R was markedly higher compared to OX1R. Orexin A (an agonist of OX1R and OX2R) and [Ala11-D-Leu15]orexin B (a selective agonist of OX2R) did not affect basal cyclic AMP formation in the primary neuronal cell cultures. Both peptides (0.001–1 μM) inhibited, in a concentration-dependent manner and IC50 values in low nanomolar range, the increase in the nucleotide production evoked by forskolin (1 μM; a direct activator of adenylyl cyclase), pituitary adenylate cyclase-activating polypeptide (PACAP27; 0.1 μM), and vasoactive intestinal peptide (VIP; 3 μM). Effects of orexin A on forskolin-, PACAP27-, and VIP-stimulated cyclic AMP synthesis were blocked by TCS OX2 29 (a selective antagonist of OX2R), and unaffected by SB 408124 (a selective antagonist of OX1R). Pretreatment of neuronal cell cultures with pertussis toxin (PTX) abolished the inhibitory action of orexin A on forskolin- and PACAP-stimulated cyclic AMP accumulation. It is suggested that in cultured rat cortical neurons orexins, acting at OX2 receptors coupled to PTX-sensitive Gi protein, inhibit cyclic AMP synthesis

    Towards a unified protocol for handling of CSF before β-amyloid measurements

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    Background: Widespread implementation of Alzheimer's disease biomarkers in routine clinical practice requires the establishment of standard operating procedures for pre-analytical handling of cerebrospinal fluid (CSF). Methods: Here, CSF collection and storage protocols were optimized for measurements of β-amyloid (Aβ). We investigated the effects of (1) storage temperature, (2) storage time, (3) centrifugation, (4) sample mixing, (5) blood contamination, and (6) collection gradient on CSF levels of Aβ. For each study participant, we used fresh CSF directly collected into a protein low binding (LoB) tube that was analyzed within hours after lumbar puncture (LP) as standard of truth. Aβ42 and Aβ40 were measured in de-identified CSF samples using EUROIMMUN and Mesoscale discovery assays. Results: CSF Aβ42 and Aβ40 were stable for at least 72 h at room temperature (RT), 1 week at 4 °C, and 2 weeks at - 20 °C and - 80 °C. Centrifugation of non-blood-contaminated CSF or mixing of samples before the analysis did not affect Aβ levels. Addition of 0.1-10% blood to CSF that was stored at RT without centrifugation led to a dose- and time-dependent decrease in Aβ42 and Aβ40, while Aβ42/Aβ40 did not change. The effects of blood contamination were mitigated by centrifugation and/or storage at 4 °C or - 20 °C. Aβ levels did not differ between the first to fourth 5-ml portions of CSF. Conclusions: CSF can be stored for up to 72 h at RT, 1 week at 4 °C, or at least 2 weeks at either - 20 °C or - 80 °C before Aβ measurements. Centrifugation of fresh non-blood-contaminated CSF after LP, or mixing before analysis, is not required. In case of visible blood contamination, centrifugation and storage at 4 °C or - 20 °C is recommended. After discarding the first 2 ml, any portion of up to 20 ml of CSF is suitable for Aβ analysis. These findings will be important for the development of a clinical routine protocol for pre-analytical handling of CSF

    How to handle adsorption of cerebrospinal fluid amyloid β (1–42) in laboratory practice? Identifying problematic handlings and resolving the issue by use of the Aβ42/Aβ40 ratio

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    Introduction We aimed to investigate factors defining amyloid β (1–42) (Aβ1–42) adsorption during preanalytical workup of cerebrospinal fluid (CSF). Methods CSF was transferred to new tubes ≤4 times. Variables tested were different polypropylene tube brands, volumes, CSF Aβ1–42 concentrations, incubation times, pipettes, vortex intensities, and other CSF proteins, including hyperphosphorylated tau and Interleukin 1 Receptor Accessory Protein (IL-1RAcP). An enquiry assessed the number of transfers in current practice. Results In diagnostic practice, the number of transfers varied between 1 and 3. Every tube transfer resulted in 5% loss of Aβ1–42 concentration, even 10% in small volumes. Adsorption was observed after 30 seconds and after contact with the pipette tip. Tube brand, vortexing, or continuous tube movement did not influence adsorption. Adsorption for Aβ1–40 was similar, resulting in stable Aβ1–42/Aβ1–40 ratios over multiple tube transfers. Discussion We confirmed that adsorption of CSF Aβ1–42 during preanalytical processing is an important confounder. However, use of the Aβ1–42/Aβ1–40 ratio overcomes this effect and can therefore contribute to increased diagnostic accuracy

    Cerebrospinal fluid levels of neurogranin in Parkinsonian disorders

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    Background: CSF concentration of neurogranin has been suggested as a biomarker for synapse dysfunction. Objectives: To investigate CSF neurogranin in parkinsonian disorders compared to controls and Alzheimer's disease and the possible correlations between neurogranin and cognitive and motor impairment. Methods: We included 157 patients with PD, 29 with PD with dementia, 11 with dementia with Lewy bodies, 26 with MSA, 21 with PSP, 6 with corticobasal syndrome, 47 controls, and 124 with Alzheimer's disease. CSF neurogranin was measured using two enzyme-linked immunosorbent assays; from EUROIMMUN and the University of Gothenburg. Results: We found a strong correlation between CSF neurogranin-EI and CSF neurogranin–University of Gothenburg (Rs = 0.890; P < 0.001). Neurogranin was decreased in PD, PD with dementia, MSA, and PSP compared to controls and Alzheimer's disease. Neurogranin did not correlate with motor or cognitive impairment, longitudinal decline, or progression to dementia in PD. Conclusions: CSF neurogranin is decreased in parkinsonian disorders compared to controls, emphasizing the importance of synaptic dysfunction in these disorders

    Optimized Standard Operating Procedures for the Analysis of Cerebrospinal Fluid Aβ42 and the Ratios of Aβ Isoforms Using Low Protein Binding Tubes

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    Background: Reduced cerebrospinal fluid (CSF) concentration of amyloid-β1-42 (Aβ1-42) reflects the presence of amyloidopathy in brains of subjects with Alzheimer's disease (AD). Objective: To qualify the use of Aβ1-42/Aβ1-40 for improvement of standard operating procedures (SOP) for measurement of CSF Aβ with a focus on CSF collection, storage, and analysis. Methods: Euroimmun ELISAs for CSF Aβ isoforms were used to set up a SOP with respect to recipient properties (low binding, polypropylene), volume of tubes, freeze/thaw cycles, addition of detergents (Triton X-100, Tween-20) in collection or storage tubes or during CSF analysis. Data were analyzed with linear repeated measures and mixed effects models. Results: Optimization of CSF analysis included a pre-wash of recipients (e.g., tubes, 96-well plates) before sample analysis. Using the Aβ1-42/Aβ1-40 ratio, in contrast to Aβ1-42, eliminated effects of tube type, additional freeze/thaw cycles, or effect of CSF volumes for polypropylene storage tubes. 'Low binding' tubes reduced the loss of Aβ when aliquoting CSF or in function of additional freeze/thaw cycles. Addition of detergent in CSF collection tubes resulted in an almost complete absence of variation in function of collection procedures, but affected the concentration of Aβ isoforms in the immunoassay. Conclusion: The ratio of Aβ1-42/Aβ1-40 is a more robust biomarker than Aβ1-42 toward (pre-) analytical interfering factors. Further, 'low binding' recipients and addition of detergent in collection tubes are able to remove effects of SOP-related confounding factors. Integration of the Aβ1-42/Aβ1-40 ratio and 'low-binding tubes' into guidance criteria may speed up worldwide standardization of CSF biomarker analysis
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