Using Computed Tomography Perfusion to Evaluate the Blood-Brain-Barrier and Blood-Tumor-Barrier Response following Focused Ultrasound Sonication with Microbubble Administration

The blood-brain-barrier (BBB) is the single most limiting factor in the delivery of neurotherapeutics into the brain. Focused ultrasound sonication combined with intravenous microbubble administration (FUSwMB) is a novel technique that can transiently disrupt the BBB, with minimal vascular or tissue damage, allowing for localized drug delivery over the targeted region. The goals of this thesis are to: 1) use computed tomography (CT) perfusion to measure the permeability surface area product (PS) following USwMB in normal rabbits with an intact BBB, and 2) to evaluate the blood-tumor-barrier (BTB) PS response following FUSwMB in a C6 rat glioma model

The Impact of Perceived Procedural Justice on Dimensions of Customer Citizenship Behaviours: The Mediating Effect of Customer Perceived Support

The present study examines the influence of perceived procedural justice (PPJ) on four fundamental dimensions of customer citizenship behaviours (helping other customers, advocacy, customer tolerance, and feedback) and the mediating role of customer perceived support (CPS). Our research setting is the smartphone after-sales service sector in China. Structural equation modeling (SEM) using AMOS is employed to empirically test our hypotheses on the basis of survey data from 368 smartphonecustomers. We find that PPJ significantly contributes to the customer citizenship behaviours of helping other customers, advocacy, and feedback. Surprisingly, we do not find a significant relationship between PPJ and customer tolerance. Our evidence indicates that CPS partially mediates the relationships between PPJ and helping other customers, advocacy, and feedback, but fully mediates the effect of PPJ on customer tolerance. This research contributes to managers’ understanding of how voluntary behaviours can be effectively managed by enhancing PPJ and CPS. Further, it enriches our theoretical understanding of key antecedents of customer citizenship behaviours

Cytopenias With Traditional Therapy of Hepatitis C in Pakistani Population

Objective: To find out the frequency of blood cytopenias among the relapsers, non-responders and responders to traditional therapy of Hepatitis C in a tertiary care hospital of Rawalpindi, Pakistan.Study Design:Cross sectional descriptive study.Place and Duration of Study: Hematology and Gastroenterology departments of Military Hospital, Rawalpindi, for a period of one year, from August 2014 to July 2015.Methodology:After six months of treatment with conventional interferons and ribavirin 5mL blood was obtained in EDTA bottles from responders, relapsers and non-responders in laboratory, and was analyzed using Hematology Analyzer sysmex KX-21. The hemoglobin levels, total leukocyte counts and platelet counts were measured. The results were entered into SPSS 16 and the analysis for descriptive statistics was applied for finding out the frequencies.Results: A total of 380 patients were studied, out of which 204 were non-responders, 52 were responders and 121 were relapsers. Ninety eight patients [25.9%] had anemia, 12 [3.2%] had leukopenia and 48 [12.7%] had thrombocytopenia. Among non-responders, 56 [27.5%] had anemia, 7 [3.4%] had leukopoenia and 31 [15.2%] had thrombocytopenia. Among responders, 16 [30.8%] had anemia, 2 [3.8%] had leukopoenia and 4 [7.7%] had thrombocytopenia. Among relapsers, 26 [21.5%] had anemia, 3[2.5%] had leukopoenia and 13 [10.7%] had thrombocytopenia.Conclusions:Anemia is most common among relapsers, non-responders and responders, while leukopenia is least commonly seen.  Thrombocytopoenia occurs more commonly among non-responders and least commonly among responders

Estimation of Serum Potassium and Calcium Concentrations from Electrocardiographic Depolarization and Repolarization Waveforms

Chronic kidney disease (CKD), a condition defined by a gradual decline in kidney function over time, has become a global health concern affecting between 11 and 13% of the world population [1]. As renal function declines, CKD patients gradually lose their ability to maintain normal values of potassium concentration ([K+]) in their blood. Elevated serum [K+], known as hyperkalemia, increases the risk for life-threatening arrhythmias and sudden cardiac death [2].An increase in serum [K+] outside the physiological range is commonly silent and is only detected when hyperkalemia is already very severe or when a blood test is performed. Maintenance and monitoring of [K+] in the blood is an important component in the treatment of CKD patients because therapies for hyperkalemia management in CKD patients are designed to prevent arrhythmias and to immediately lower serum [K+] to safe ranges. However, this is currently only possible by taking a blood sample and is associated with a long analysis time. Therefore it is useful to have a simple, noninvasive method to estimate serum [K+], particularly using the electrocardiogram (ECG). Indeed, variations in serum electrolyte levels have been shown to alter the electrical behavior of the heart and to induce changes in the ECG [3¿6]. However, large inter-individual variability existsin the relationship between ion concentrations and ECG features. Previous attempts to estimate serum [K+] from the ECG have therefore shown limitations [7¿9], such as not being applicable to some common types of ECG waveforms or relying on specific ECG characteristics that may present large variations not necessarily associated with hyperkalemia.The aim of this thesis is to develop novel estimates of serum [K+] that are robust enough to detect hypokalemia (reduced [K+]) or hyperkalemia in a timely manner to provide life-saving treatment. Additionally, the effect of changes in other electrolyte levels, like calcium concentration ([Ca2+]), and in heart rate are investigated. These aims are achieved by combining novel ECG signal processing techniques with in silico modeling and simulation of cardiac electrophysiology.The specific objectives are:1. Characterization of hypokalemia or hyperkalemia and hypocalcemia (reduced [Ca2+]) or hypercalcemia (elevated [Ca2+])-induced changes in ventricular repolarization from ECGs (T wave) of CKD patients. This is addressed in chapter 3 and chapter 4. In these chapters, we describe how T waves are extracted from ECGs and how we characterize changes in T waves at varying potassium, calcium and heart rate using analyses based on time warping and Lyapunov exponents. Next, univariable and multivariable regression models including markers of T wave nonlinear dynamics in combination with warping-based markers of T wave morphology are built and their performance for [K+] estimation is assessed.2. Characterization of hypo- or hyperkalemia and hypo- or hypercalcemia-induced changes in ventricular depolarization from the QRS complex of CKD patients. This is reported in chapter 5. In this chapter, we present how QRS complexes from ECGs of CKD patients are processed and how we measure changes at varying [K+], [Ca2+] and heart rate. Univariate and multivariate regression analyses including novel QRS morphological markers in combination with T wave morphological markers are performed to assess the contribution of depolarization and repolarization features for electrolyte monitoring in CKD patients.3. Identification of potential sources underlying inter-individual variability in ECG markers in response to changes in [K+] and [Ca2+]. In silico investigations of cardiac electrophysiology are conducted and ECG features are computed. Simulation results are compared with patient data. This is explained in chapter 3 using one-dimensional (1D) fibers and in chapter 6 using three-dimensional (3D) human heart-torso models. Chapter 6 includes the development of a population of realistic computational models of human ventricular electrophysiology, based on human anatomy and electrophysiology, to better understand how changes in individual characteristics influence the ECG (QRS and T wave) markers that we introduced in previous chapters. ECG waveforms are characterized by their amplitude, duration and morphology. Simulations are performed with the most realistic available techniques to model the electrophysiology of the heart and the resulting ECG. We establish mechanisms that contribute to inter-individual differences in the characterized ECG features.In conclusion, we identify several markers of ECG morphology, including depolarization and repolarization features, that are highly correlated with serum electrolyte (potassium and calcium) concentrations. ECG morphological variability markers vary significantly with [K+] and [Ca2+] in both simulated and measured ECGs, with a wide range of patterns observed for such relationships. The proportions of endocardial, midmyocardial and epicardial cells have a large impact on ECG markers, particularly for serum electrolyte concentrations out of their physiological levels. This suggests that transmural heterogeneities can modulate ECG responses to changes in electrolyte concentrations in CKD patients. Agreement between actual potassium and calcium levels and their estimates derived from the ECG is promising, with lower average errors than previously proposed markers in the literature. These findings can have major relevance for noninvasive monitoring of serum electrolyte levels and prediction of arrhythmic events in these patients.<br /

The association between right ventricular function and exercise capacity for hypertensive patients

Background: Transthoracic echocardiography (TTE) would be used to evaluate right ventricular (RV) function in patients with arterial hypertension, and the link between RV dysfunction and exercise capacity was studied in the study population.Objective: To establish a correlation with exercise capability in the study group by using transthoracic echocardiography (TTE) to evaluate RV function in patients with arterial hypertension.Patients and Methods: Patients with hypertension were surveyed in a cross-sectional research; those known and treated; whether controlled or not and patients who were recently discovered to be hypertensive. Ninety patients were included; gender and age were taken into account. A thorough examination was performed on each patient (TTE) as well as six minute walking distance (6MWD). For all we had a written informed consent prior to enrollment. Results: Patients with untreated and uncontrolled hypertension showed significantly reduced right ventricular systolic and diastolic functions compared to those with well-controlled hypertension. Patients with untreated or uncontrolled hypertension had significant (P &lt;0.001) deterioration on S', wave and diastolic dysfunction parameters (E/A, DTt, E/e t and IVRT). Untreated and uncontrolled hypertension patients showed a significant decrease in 6MWD compared to the well-controlled individuals (P &lt;0.001). Conclusion: Untreated or ineffectively treated hypertension individuals had considerably reduced right ventricular function and exercise capacity, according to our findings. In the entire research population, right ventricular functions are strongly linked to exercise ability

Emerging relationship between vitamin D and LL-37 in the immune system’s response to infection and their possible role in combating sepsis

Background: In patients who are critically unwell, sepsis could be one of major causes of mortality as well as many complications. Sepsis is the medical term describing dysfunctional body reaction to infection that results in dysfunctions in various body systems and hence severe organ failure could occur. A rise of 2 or more points in the sequential organ failure evaluation is an early indicator of organ dysfunction (SOFA score). Severe organ failure can occur if sepsis is left untreated. An infection-controlling effect of vitamin D has been demonstrated. With an increase in cathelicidin antimicrobial peptide (AMP) LL-37, human skin, blood plasma, monocytes, and macrophages are all affected. LL-37 and other AMPs, which operate directly against bacteria, regulate numerous innate and adaptive immunological functions. Objective: To make an overview of role of lack of vitamin D (25(OH) D) as well as AMP, LL-37, as risk factors for sepsis. Conclusion: Severe infections, as well as sepsis, have been linked to a deficiency of vitamin D. However, it is not yet clear what the underlying linkage and its clinical consequence is between sepsis and respiratory tract infections as well as critical illness

Fasting headache, a cross-sectional study

Headache is a predominant disorder in general population and is classified into primary and secondary forms by the International Headache Society. Fasting headache is currently classified in Group 10 of ICHD-III as “Headache attributed to disorders of homeostasis”. In spite of continuing research, there is still indistinctness regarding the exact cause of fasting headache. Hypoglycaemia, previous history of headache, stress, caffeine withdrawal, lack of sleep and female gender have been speculated as causative factors. Our rationale for this study is to find out what percentage of the population experiences fasting headache and to find out any link between the occurrence of this phenomenon and any associated factors

Monitoring of serum potassium and calcium levels in end-stage renal disease patients by ecg depolarization morphology analysis

Objective: Non-invasive estimation of serum potassium, [K+], and calcium, [Ca2+], can help to prevent life-threatening ventricular arrhythmias in patients with advanced renal disease, but current methods for estimation of electrolyte levels have limitations. We aimed to develop new markers based on the morphology of the QRS complex of the electrocardiogram (ECG). Methods: ECG recordings from 29 patients undergoing hemodialysis (HD) were processed. Mean warped QRS complexes were computed in two-minute windows at the start of an HD session, at the end of each HD hour and 48 h after it. We quantified QRS width, amplitude and the proposed QRS morphology-based markers that were computed by warping techniques. Reference [K+] and [Ca2+] were determined from blood samples acquired at the time points where the markers were estimated. Linear regression models were used to estimate electrolyte levels from the QRS markers individually and in combination with T wave morphology markers. Leave-one-out cross-validation was used to assess the performance of the estimators. Results: All markers, except for QRS width, strongly correlated with [K+] (median Pearson correlation coefficients, r, ranging from 0.81 to 0.87) and with [Ca2+] (r ranging from 0.61 to 0.76). QRS morphology markers showed very low sensitivity to heart rate (HR). Actual and estimated serum electrolyte levels differed, on average, by less than 0.035 mM (relative error of 0.018) for [K+] and 0.010 mM (relative error of 0.004) for [Ca2+] when patient-specific multivariable estimators combining QRS and T wave markers were used. Conclusion: QRS morphological markers allow non-invasive estimation of [K+] and [Ca2+] with low sensitivity to HR. The estimation performance is improved when multivariable models, including T wave markers, are considered. Significance: Markers based on the QRS complex of the ECG could contribute to non-invasive monitoring of serum electrolyte levels and arrhythmia risk prediction in patients with renal diseas