Subacute transverse myelitis with Lyme profile dissociation

Introduction: Transverse myelitis is a very rare neurologic syndrome with an incidence per year of 1-5 per million population. We are presenting an interesting case of subacute transverse myelitis with its MRI (magnetic resonance imaging) and CSF (cerebrospinal fluid) findings

IDENTIFICATION OF NONLINEAR DYNAMIC SYSTEMS USING THE FORCE-STATE MAPPING TECHNIQUE

PhDThe identification of the dynamic characteristics of nonlinear systems is of increasing interest in the field of modal testing. In this work an investigation has been carried out into the force-state mapping approach to identification of nonlinear systems proposed by Masri and Caughey. They originally suggested a nonparametric identification technique based on curve fitting the restoring force in terms of the velocity and displacement using two dimensional Chebyshev polynomials. It has been shown that the use of Chebyshev polynomials is unnecessarily restrictive and that a simpler approach based on ordinary polynomials and special functions provides a simpler, faster and more accurate identification for polynomial and nonpolynomial types of nonlinearity. This simpler approach has allowed the iterative identification technique for multi-degree of freedom systems to be simplified and a direct identification approach, which is not subject to bias errors, has been suggested. A new procedure for identifying both the type and location of nonlinear elements in lumped parameter systems has been developed and has yielded encouraging results. The practical implementation of the force-state mapping technique required the force, acceleration, velocity and displacement signals to be available at the same instants of time for each measurement station. In order to minimise the instrumentation required, only the force and acceleration are measured and the remaining signals are estimated by integrating the acceleration. The integration problem has been investigated using several approaches both in the frequency and time domains. An analysis of the sensitivity of the estimated parameters with respect to any amplitude and phase measurement errors has been carried out for single-d.o.f. linear systems. Estimates are shown to be extremely sensitive to phase errors for lightly damped structures. The estimation of the mass or generalised mass and modal matrices required for the identification of single or multi-d.o.f. nonlinear systems respectively, has also been investigated. Initial estimates were obtained using a linear multi-point force appropriation method, normally used for the excitation of normal modes. These estimates were then refined using a new technique based on studying the sensitivity of the mass with respect to the estimated system parameters obtained using a nonlinear model. This sensitivity approach seemed promising since accurate results were obtained. It was also shown that accurate estimates for the modal matrix were not essential for carrying out a force-state mapping identification. Finally, the technique has been applied experimentally to the identification of a cantilevered T-beam structure with stiffness and damping nonlinearity. The cases of two well separated and then two fairly close modes were considered. Reasonable agreement between the behaviour of the nonlinear mathematical model and the structure was achieved considering inaccuracies in the measurement set-up. Conclusions have been drawn and some ideas for future work presented.Scientific Studies and Research Centre of Syri

An additional bolus of rapid-acting insulin to normalise postprandial cardiovascular risk factors following high-carbohydrate high-fat meal in patients with type 1 diabetes: A randomised controlled trial

Aim: To evaluate an additional rapid-acting insulin bolus on postprandial lipaemia, inflammation, and pro-coagulation following high-carbohydrate high-fat feeding in people with type 1 diabetes. Methods: Ten males with type 1 diabetes (HbA1c 52.55.9 mmol/mol [7.00.5%]) underwent three conditions: 1) a low-fat meal with normal bolus insulin (LF), 2), a high-fat meal with normal bolus insulin (HF), 3) a high-fat meal with normal bolus insulin with an additional 30% insulin bolus administered 3-hrs post-meal (HFA). Meals had identical carbohydrate and protein content and bolus insulin dose determined by carbohydrate-counting. Blood was sampled periodically for 6-hr post-meal and analysed for TG, NEFA, APOB48, glucagon, TNF-α, fibrinogen, HTF activity, and PAI-1. Continuous glucose monitoring captured interstitial glucose responses.Results: TG concentrations following LF remained similar to baseline, whereas TG levels following HF were significantly greater throughout the 6-hour observation period. The additional insulin bolus (HFA) normalised TG similarly to LF 3-6-hrs following the meal.  HF was associated with late postprandial elevations in TNF-α, whereas LF and HFA was not. Fibrinogen, PAI-1, and TFP levels were similar between conditions. Conclusions: Additional bolus insulin 3-hrs following a high-carbohydrate high-fat meal prevents late rises in postprandial TGs and TNF-α, thus improving cardiovascular risk profile.Clinical trial registration: clinicaltrials.gov; Reg. no. NCT0259565

Vascular Structure and Functional Responses to Consecutive High-Fat Feeding between Insulin Treatment Regimens in Adults with Type 1 Diabetes and Matched Controls.

Background Impaired vascular health is prevalent in type 1 diabetes (T1D); however, it remains unknown whether di!erent insulin treatment regimens mediate indices of vascular structure or function. Methods Sixteen individuals with T1D receiving either multiple daily injection therapy (MDI; n=8; age: 32±13years; BMI:26.0±5.9kg.m2; HbA1c:53.7±11.2mmol/mol [7.1±3.2%]) or continuous subcutaneous insulin infusion (CSII; n=8; age:35±18years; BMI:26.3±4.6kg.m2; HbA1c: 58.6±9.7mmol/mol [7.5±3.0%]) and ten matched controls (CON; age:31±13years; BMI: 24.3±2.9kg.m2) consumed two high fat (HF) meals at 4-hour intervals. Carotid artery intima-media thickness (CIMT) and flow mediated dilation (FMD) was assessed at baseline, with further FMD assessment at 3-hrs following the ingestion of each meal using high resolution B-mode ultrasound. Bolus insulin dose was standardised using the carbohydrate-counting method. Results CIMT was significantly higher in individuals with T1D compared to controls (p=0.039); treatment stratification within T1D revealed MDI mediated this e!ect (MDI vs. CON: p=0.049; CSII vs. CON: p=0.112). FMD remained unchanged following the first meal (p=0.204) but was significantly impaired following the second meal (p=<0.001); post- hoc analysis revealed MDI mediated this e!ect of impaired FMD after the second meal (MDI vs. CON: p=0.048; CSII vs. CON: p=0.416). Conclusions Our findings indicate that patients treated with MDI therapy have higher CIMT (a structural marker of subclinical atherosclerosis) compared to controls but not CSII therapy. FMD was impaired following a second HF meal irrespective of a diabetes status. Considering the pre-existing heightened cardiovascular disease risk in T1D therapeutic strategies to reduce postprandial risk warrants further research

Coronary artery disease-associated genetic variants and biomarkers of inflammation

Introduction: Genetic constitution and inflammation both contribute to development of coronary artery disease (CAD). Several CAD-associated single-nucleotide polymorphisms (SNPs) have recently been identified, but their functions are largely unknown. We investigated the associations between CAD-associated SNPs and five CAD-related inflammatory biomarkers. Methods: We genotyped 45 CAD-associated SNPs in 701 stable CAD patients in whom levels of high-sensitivity C-reactive protein (hsRCP), interleukin-6, calprotectin, fibrinogen and complement component 3 levels had previously been measured. A genetic risk score was calculated to assess the combined risk associated with all the genetic variants. A multiple linear regression model was used to assess associations between the genetic risk score, single SNPs, and the five inflammatory biomarkers. Results: The minor allele (G) (CAD risk allele) of rs2075650 (TOMM40/APOE) was associated with lower levels of high-sensitivity C-reactive protein (effect per risk allele: -0.37 mg/l [95%CI -0.56 to -0.18 mg/l]). The inflammatory markers tested showed no association with the remaining 44 SNPs or with the genetic risk score. Conclusions: In stable CAD patients, the risk allele of a common CAD-associated marker at the TOMM40/APOE locus was associated with lower hsCRP levels. No other genetic variants or the combined effect of all variants were associated with the five inflammatory biomarkers

Aspirin, clopidogrel and prasugrel monotherapy in patients with type 2 diabetes mellitus: a double-blind randomised controlled trial of the effects on thrombotic markers and microRNA levels

Background: Despite increased atherothrombotic risk in type 2 diabetes mellitus, (T2DM) the best preventative antithrombotic strategy remains undetermined. We defined the effects of three antiplatelet agents on functional readout and biomarker kinetics in platelet activation and coagulation in patients with T2DM. Materials and methods: 56 patients with T2DM were randomised to antiplatelet monotherapy with aspirin 75 mg once daily (OD), clopidogrel 75 mg OD or prasugrel 10 mg OD during three periods of a crossover study. Platelet aggregation (PA) was determined by light-transmittance aggregometry and P-selectin expression by flow cytometry. Markers of fibrin clot dynamics, inflammation and coagulation were measured. Plasma levels of 14 miRNA were assessed by quantitative polymerase chain reactions. Results: Of the 56 patients, 24 (43%) were receiving aspirin for primary prevention of ischaemic events and 32 (57%) for secondary prevention. Prasugrel was the strongest inhibitor of ADP-induced PA (mean ± SD maximum response to 20μmol/L ADP 77.6 ± 8.4% [aspirin] vs. 57.7 ± 17.6% [clopidogrel] vs. 34.1 ± 14.1% [prasugrel], p < 0.001), P-selectin expression (30 μmol/L ADP; 45.1 ± 21.4% vs. 27.1 ± 19.0% vs. 14.1 ± 14.9%, p < 0.001) and collagen-induced PA (2 μg/mL; 62.1 ± 19.4% vs. 72.3 ± 18.2% vs. 60.2 ± 18.5%, p < 0.001). Fibrin clot dynamics and levels of coagulation and inflammatory proteins were similar. Lower levels of miR-24 (p = 0.004), miR-191 (p = 0.019), miR-197 (p = 0.009) and miR-223 (p = 0.014) were demonstrated during prasugrel-therapy vs. aspirin. Circulating miR-197 was lower in those cardiovascular disease during therapy with aspirin (p = 0.039) or prasugrel (p = 0.0083). Conclusions: Prasugrel monotherapy in T2DM provided potent platelet inhibition and reduced levels of a number of platelet-associated miRNAs. miR-197 is a potential marker of cardiovascular disease in this population. Clinical outcome studies investigating prasugrel monotherapy are warranted in individuals with T2DM. Trial registration: EudraCT, 2009-011907-22. Registered 15 March 2010, https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-011907-22/GB

Estimated glucose disposal rate demographics and clinical characteristics of young adults with type 1 diabetes mellitus: A cross-sectional pilot study

Background: Estimated glucose disposal rate (eGDR) is a practical measure of Insulin Resistance (IR) which can be easily incorporated into clinical practice. We profiled eGDR in younger adults with type 1 diabetes mellitus (T1DM) by their demographic and clinical characteristics. Methods: In this single centre study, medical records of TIDM were assessed and eGDR tertiles correlated with demographic and clinical variables. Results: Of 175 T1DM individuals, 108 (61.7%) were males. Mean age (±SD) was 22.0 ± 1.6 years and median time from diagnosis 11.0 years (range 1–23). Individuals were predominantly Caucasian (81.7%), with 27.4% being overweight (BMI: 25–30 kg/m2) and 13.7% obese (BMI > 30 kg/m2). Mean total cholesterol (TC) levels were significantly lower in high and middle eGDR tertiles (4.4 ± 1 and 4.3 ± 0.8 mmol/l, respectively) compared with low eGDR tertile (4.8 ± 1, p < 0.05 for both). Triglyceride (TG) levels showed a similar trend at 1.1 ± 0.5 and 1.1 ± 0.5 mmol/l for high and middle eGDR tertile compared to low eGDR tertile (1.5 ± 1 mmol/l, p < 0.05 for both). Renal function was similar across eGDR tertiles and no difference in retinopathy was detected. Conclusion: TC and TG are altered in individuals with T1DM and low eGDR, suggesting that this subgroup requires optimal lipid management to ameliorate their vascular risk

Circulating MicroRNA Levels Indicate Platelet and Leukocyte Activation in Endotoxemia Despite Platelet P2Y12 Inhibition

There is evidence for the effects of platelet inhibition on innate immune activation. Circulating microRNAs (miRNAs) have been implicated as markers of platelet and leukocyte activation. In the present study, we assessed the effects of P2Y12 inhibitors on platelet and leukocyte miRNAs during endotoxemia. Healthy volunteers were randomly assigned to receive oral ticagrelor (n = 10), clopidogrel (n = 8) or no drug (n = 8) for one week, followed by an intravenous bolus of 2 ng/kg endotoxin. Serum was collected at baseline, after one week of antiplatelet treatment and 6 and 24 h after endotoxin administration. MiRNAs were screened using LNA-based qPCR, followed by TaqMan-qPCR validation of candidates. Clinical validation was performed in 41 sepsis patients. Platelet-enriched miR-197, miR-223 and miR-223* were decreased in volunteers following antiplatelet therapy. Endotoxin increased platelet miRNAs, whilst the opposite effect was seen for leukocyte-enriched miR-150. Neither of these endotoxin-mediated effects were altered by P2Y12 inhibitors. Sepsis patients with fatal outcomes (n = 12) had reduced miR-150 levels compared with survivors (n = 29). In conclusion, we show that miR-150 is downregulated in experimental endotoxemia and can predict survival in sepsis but is unaffected by P2Y12 inhibition. While P2Y12 inhibition reduces platelet-associated miRNAs in healthy volunteers, it fails to attenuate the response of platelet miRNAs to endotoxemia

Can vitamin D deficiency cause diabetes and cardiovascular diseases? Present evidence and future perspectives

Several studies have shown that vitamin D may play a role in many biochemical mechanisms in addition to bone and calcium metabolism. Recently, vitamin D has sparked widespread interest because of its involvement in the homeostasis of the cardiovascular system. Hypovitaminosis D has been associated with obesity, related to trapping in adipose tissue due to its lipophilic structure. In addition, vitamin D deficiency is associated with increased risk of cardiovascular disease (CVD) and this may be due to the relationship between low vitamin D levels and obesity, diabetes mellitus, dyslipidaemia, endothelial dysfunction and hypertension. However, although vitamin D has been identified as a potentially important marker of CVD, the mechanisms through which it might modulate cardiovascular risk are not fully understood. Given this background, in this work we summarise clinical retrospective and prospective observational studies linking vitamin D levels with cardio-metabolic risk factors and vascular outcome. Moreover, we review various randomised controlled trials (RCTs) investigating the effects of vitamin D supplementation on surrogate markers of cardiovascular risk. Considering the high prevalence of hypovitaminosis D among patients with high cardiovascular risk, vitamin D replacement therapy in this population may be warranted; however, further RCTs are urgently needed to establish when to begin vitamin D therapy, as well as to determine the dose and route and duration of administration. © 2011 Elsevier B.V

Body mass index, estimated glucose disposal rate and vascular complications in type 1 diabetes: Beyond glycated haemoglobin

Aims To understand the relationship between insulin resistance (IR), assessed as estimated glucose disposal rate (eGDR), and microvascular/macrovascular complications in people with type 1 diabetes. Materials and methods Individuals with a confirmed diagnosis of type 1 diabetes were included in this cross-sectional study. BMI was categorised into normal weight (18.0–24.9 kg m−2), overweight (25.0–29.9 kg m−2) and obese groups (≥30.0 kg m−2). We categorised eGDR into four groups: eGDR >8, 6–7.9, 4–5.9 and <4 mg kg−1 min−1. Multiple logistic regression was used to identify associations with vascular complications, after adjusting for relevant confounders. Results A total of 2151 individuals with type 1 diabetes were studied. Median [interquartile range (IQR)] age was 41.0 [29.0, 55.0] with diabetes duration of 20.0 [11, 31] years. Odds ratio (OR) for retinopathy and nephropathy in obese compared with normal weight individuals was 1.64 (95% CI: 1.24–2.19; p = 0.001) and 1.62 (95% CI: 1.10–2.39; p = 0.015), while the association with cardiovascular disease just failed to reach statistical significance (OR 1.66 [95% CI: 0.97–2.86; p = 0.066]). Comparing individuals with eGDR ≥8 mg kg−1 min−1 and <4 mg kg−1 min−1 showed OR for retinopathy, nephropathy and macrovascular disease of 4.84 (95% CI: 3.36–6.97; p < 0.001), 8.35 (95% CI: 4.86–14.34; p < 0.001) and 13.22 (95% CI: 3.10–56.38; p < 0.001), respectively. Individuals with the highest eGDR category (≥8 mg kg−1 min−1) had the lowest complication rates irrespective of HbA1c levels. Conclusions Obesity is prevalent in type 1 diabetes and diabetes complications are not only related to glucose control. IR, assessed as eGDR, is strongly associated with both microvascular and macrovascular complications, regardless of HbA1c levels