Electronic data storage system

Práce pojednává o návrhu a praktickém funkčním řešení informačního systému, jenž bude sloužit jako elektronický disk s možností administrace a přístupu z prostředí webového prohlížeče. Řešení problematiky v skriptovacím jazyce PHP za pomoci využití relační databáze MySQL. Rozebíraná je problematika PHP a databáze SQL, základní poznatky a vzájemné propojení jednotlivých modulu do jednoho komplexního celku. Práce rozebírá také základní principy elektronické platby přes internet. Systém obsahuje kompletní souboroví manažment pro správu a práci se soubory. Nastavení pracovních pravomocí jednotlivých uživatelů. Aplikace na požádaní zobrazí některá zaujímává statistiky. Výsledky práce jsou demonstrované na web stránce.The work presents the design and real world implementation of an information system serving as an electronic disk with web based access and administration. The task is being solved using the PHP scripting language and MySQL relational database management system. The study examines PHP and SQL databases, states basic facts and explains how they are connected to create one single complex system. Issues of an internet based payment system are being considered too. The proposed system features complete file management capabilities. Separate access rights can be set for individual users. The administrator of the application can display several interesting statistics. Results of the work are being demonstrated on the final web application.

Multinuclear Magnetic Resonance Spectroscopy of Human Skeletal Muscle Metabolism in Training and Disease

In this chapter, techniques and application of multinuclear (1H, 13C, and 31P) in vivo magnetic resonance spectroscopy (MRS) for the assessment of skeletal muscle metabolism in health and disease are described. Studies focusing on glucose transport and utilization, lipid storage and consumption, handling of energy rich phosphates, and measurements of newly emerging noninvasive biomarkers, i.e., acetylcarnitine and carnosine are summarized. Muscle metabolism connections to exercise physiology and the development as well as possible treatment of metabolic diseases, such as obesity and diabetes are also discussed. Taken together, multinuclear in vivo MRS on humans helped to uncover defects in skeletal muscle metabolic pathways in insulin-resistant conditions; and to discover links between defects in mitochondrial activity/capacity and lipid metabolism, as well as defects in whole-body and/or muscle glucose metabolism. There is also to mention that several of the MR-derived readouts are affected by both training status and metabolic disease in a specific way, and thus could serve as potential markers of training status and metabolic flexibility

Aircondition of sport club

Cieľom bakalárskej práce je navrhnutie vzduchotechniky pre hotel s futbalovým ihriskom. Riešené sú izby pre hostí a administratíva časť budovy. Navrhnuté sú vetracie jednotky vráta-ne spätného získavania tepla, ktoré sú doplnené jednotkami SPLIT pre pokrytie tepelnej záťaže v letnom období.The objective of bachelor thesis is to propose air conditioning for hotel with football pitch. Design is focused on guest rooms and business part of the building. The project includes de-sign of ventilation units with heat recovery, which are supplemented with SPLIT units to smother heat load in summer time.

Residential rooms and air quality

Diplomová práca rieši kvalitu vnútorného vzduchu v hotelových izbách na základe koncentrácie oxidu uhličitého CO2. V prvej časti práce sa zaoberá vnútorným prostredím budov, kde popisuje jednotlivé druhy mikroklím. Experimentálna časť sa zaoberá meraním koncentrácie CO2 v pobytovej miestnosti, infiltráciou vzduchu oknom a následne ich analýzou. V poslednej časti sú použité výsledky z experimentu na vhodný návrh a optimalizáciu hygienického vetrania s čo najmenšími nákladmi na obstaranie a prevádzku systému.The master thesis solves indoor air quality in hotel rooms based on CO2 levels. The first part deals with indoor climate of buildings, where each form of indoor climate is described separately. The experimental part deals with CO2 level measurement in residual room, air infiltration through window and their analysis. The last part of thesis deals with results of the experiment, which are used to design and optimize hygienic ventilation, based on acquisition costs and operating expenses.

Compartment-based reconstruction of acquisition-weighted 31P cardiac MRSI reduces sensitivity to cardiac motion and scan planning

Motivation: 31P magnetic resonance spectroscopic imaging (31P MRSI) is a powerful technique for investigating the metabolic effects of treatments for heart failure in vivo, allowing a better understanding of their mechanism of action in patient cohorts. Unfortunately, cardiac 31P MRSI is fundamentally limited by low SNR, which leads to compromises in acquisition, such as no cardiac or respiratory gating or low spatial resolution, in order to achieve reasonable scan times. Spectroscopy with linear algebra modeling (SLAM) reconstruction may be able to address these challenges and therefore improve repeatability by incorporating a segmented localizer into the reconstruction. Methods: Six healthy volunteers were scanned twice in a test–retest procedure to allow quantification of repeatability. Each scan consisted of anatomical localizers and two acquisition-weighted (AW) 31P MRSI acquisitions, which were acquired with and without cardiac gating. Five patients with heart failure with a preserved ejection fraction were then scanned with the same 31P MRSI sequence without cardiac gating. All 31P MRSI datasets were reconstructed with both conventional Fourier transform (FT)-based reconstruction and SLAM reconstruction, which were compared statistically. The effect of shifting the 31P MRSI acquisition field of view was also investigated. Results: In the healthy volunteer cohort, the spectral fit of the SLAM reconstructions had significantly improved Cramer–Rao lower bounds (CRLBs) compared to the FT-based reconstruction of non-cardiac gated data, as well as improved coefficients of variability and repeatability. The SLAM reconstruction found a significant difference in the PCr/ATP ratio between the healthy volunteer and patient cohorts, which the FT-based reconstruction did not find. Furthermore, the SLAM reconstruction was less influenced by the placement of the field of view (FOV) of the 31P MRSI acquisition in post hoc analysis. Discussion: The experimental benefits of the SLAM reconstruction for AW data were demonstrated by the improvements in fit confidence and repeatability seen in the healthy volunteer cohort and post hoc FOV analysis. The benefit of SLAM reconstruction of AW data for clinical studies was then illustrated by the patient cohort, which suggested improved sensitivity to clinically significant changes in the PCr/ATP ratio

Role of cardiac energetics in aortic stenosis disease progression: identifying the high-risk metabolic phenotype

Background: Severe aortic stenosis (AS) is associated with left ventricular (LV) hypertrophy and cardiac metabolic alterations with evidence of steatosis and impaired myocardial energetics. Despite this common phenotype, there is an unexplained and wide individual heterogeneity in the degree of hypertrophy and progression to myocardial fibrosis and heart failure. We sought to determine whether the cardiac metabolic state may underpin this variability. Methods: We recruited 74 asymptomatic participants with AS and 13 healthy volunteers. Cardiac energetics were measured using phosphorus spectroscopy to define the myocardial phosphocreatine to adenosine triphosphate ratio. Myocardial lipid content was determined using proton spectroscopy. Cardiac function was assessed by cardiovascular magnetic resonance cine imaging. Results: Phosphocreatine/adenosine triphosphate was reduced early and significantly across the LV wall thickness quartiles (Q2, 1.50 [1.21–1.71] versus Q1, 1.64 [1.53–1.94]) with a progressive decline with increasing disease severity (Q4, 1.48 [1.18–1.70]; P=0.02). Myocardial triglyceride content levels were overall higher in all the quartiles with a significant increase seen across the AV pressure gradient quartiles (Q2, 1.36 [0.86–1.98] versus Q1, 1.03 [0.81–1.56]; P=0.034). While all AS groups had evidence of subclinical LV dysfunction with impaired strain parameters, impaired systolic longitudinal strain was related to the degree of energetic impairment (r=0.219; P=0.03). Phosphocreatine/adenosine triphosphate was not only an independent predictor of LV wall thickness (r=−0.20; P=0.04) but also strongly associated with myocardial fibrosis (r=−0.24; P=0.03), suggesting that metabolic changes play a role in disease progression. The metabolic and functional parameters showed comparable results when graded by clinical severity of AS. Conclusions: A gradient of myocardial energetic deficit and steatosis exists across the spectrum of hypertrophied AS hearts, and these metabolic changes precede irreversible LV remodeling and subclinical dysfunction. As such, cardiac metabolism may play an important and potentially causal role in disease progression

Efficacy and tolerability of an endogenous metabolic modulator (AXA1125) in fatigue-predominant long COVID: a single-centre, double-blind, randomised controlled phase 2a pilot study

Background: ‘Long COVID’ describes persistent symptoms, commonly fatigue, lasting beyond 12 weeks following SARS-CoV-2 infection. Potential causes include reduced mitochondrial function and cellular bioenergetics. AXA1125 has previously increased β-oxidation and improved bioenergetics in preclinical models along with certain clinical conditions, and therefore may reduce fatigue associated with Long COVID. We aimed to assess the efficacy, safety and tolerability of AXA1125 in Long COVID. / Methods: Patients with fatigue dominant Long COVID were recruited in this single-centre, double-blind, randomised controlled phase 2a pilot study completed in the UK. Patients were randomly assigned (1:1) using an Interactive Response Technology to receive either AXA1125 or matching placebo in a clinical based setting. Each dose (33.9 g) of AXA1125 or placebo was administered orally in a liquid suspension twice daily for four weeks with a two week follow-up period. The primary endpoint was the mean change from baseline to day 28 in the phosphocreatine (PCr) recovery rate following moderate exercise, assessed by 31P-magnetic resonance spectroscopy (MRS). All patients were included in the intention to treat analysis. This trial was registered at ClinicalTrials.gov, NCT05152849. / Findings: Between December 15th 2021, and May 23th 2022, 60 participants were screened and 41 participants were randomised and included in the final analysis. Changes in skeletal muscle phosphocreatine recovery time constant (τPCr) and 6-min walk test (6MWT) did not significantly differ between treatment (n = 21) and placebo group (n = 20). However, treatment with AXA1125 was associated with significantly reduced day 28 Chalder Fatigue Questionnaire [CFQ-11] fatigue score when compared with placebo (least squares mean difference [LSMD] −4.30, 95% confidence interval (95% CI) −7.14, −1.47; P = 0.0039). Eleven (52.4%, AXA1125) and four (20.0%, placebo) patients reported treatment-emergent adverse events; none were serious, or led to treatment discontinuation. / Interpretation: Although treatment with AXA1125 did not improve the primary endpoint (τPCr-measure of mitochondrial respiration), when compared to placebo, there was a significant improvement in fatigue-based symptoms among patients living with Long COVID following a four week treatment period. Further multicentre studies are needed to validate our findings in a larger cohort of patients with fatigue-dominant Long COVID. / Funding: Axcella Therapeutics

Measuring inorganic phosphate and intracellular pH in the healthy and hypertrophic cardiomyopathy hearts by in vivo 7T 31P-cardiovascular magnetic resonance spectroscopy.

BACKGROUND: Cardiovascular phosphorus MR spectroscopy (31P-CMRS) is a powerful tool for probing energetics in the human heart, through quantification of phosphocreatine (PCr) to adenosine triphosphate (ATP) ratio. In principle, 31P-CMRS can also measure cardiac intracellular pH (pHi) and the free energy of ATP hydrolysis (ΔGATP). However, these require determination of the inorganic phosphate (Pi) signal frequency and amplitude that are currently not robustly accessible because blood signals often obscure the Pi resonance. Typical cardiac 31P-CMRS protocols use low (e.g. 30°) flip-angles and short repetition time (TR) to maximise signal-to-noise ratio (SNR) within hardware limits. Unfortunately, this causes saturation of Pi with negligible saturation of the flowing blood pool. We aimed to show that an adiabatic 90° excitation, long-TR, 7T 31P-CMRS protocol will reverse this balance, allowing robust cardiac pHi measurements in healthy subjects and patients with hypertrophic cardiomyopathy (HCM). METHODS: The cardiac Pi T1 was first measured by the dual TR technique in seven healthy subjects. Next, ten healthy subjects and three HCM patients were scanned with 7T 31P-MRS using long (6 s) TR protocol and adiabatic excitation. Spectra were fitted for cardiac metabolites including Pi. RESULTS: The measured Pi T1 was 5.0 ± 0.3 s in myocardium and 6.4 ± 0.6 s in skeletal muscle. Myocardial pH was 7.12 ± 0.04 and Pi/PCr ratio was 0.11 ± 0.02. The coefficients of repeatability were 0.052 for pH and 0.027 for Pi/PCr quantification. The pH in HCM patients did not differ (p = 0.508) from volunteers. However, Pi/PCr was higher (0.24 ± 0.09 vs. 0.11 ± 0.02; p = 0.001); Pi/ATP was higher (0.44 ± 0.14 vs. 0.24 ± 0.05; p = 0.002); and PCr/ATP was lower (1.78 ± 0.07 vs. 2.10 ± 0.20; p = 0.020), in HCM patients, which is in agreement with previous reports. CONCLUSION: A 7T 31P-CMRS protocol with adiabatic 90° excitation and long (6 s) TR gives sufficient SNR for Pi and low enough blood signal to permit robust quantification of cardiac Pi and hence pHi. Pi was detectable in every subject scanned for this study, both in healthy subjects and HCM patients. Cardiac pHi was unchanged in HCM patients, but both Pi/PCr and Pi/ATP increased that indicate an energetic impairment in HCM. This work provides a robust technique to quantify cardiac Pi and pHi.This work was funded by a Sir Henry Dale Fellowship from the Wellcome Trust and the Royal Society (grant #098436/Z/12/B to C.T.R.) and by an Erwin Schrödinger Fellowship from the Austrian Science Fund (grant #J4043). Authors also acknowledge the support of the NIHR Oxford Biomedical Research Centre and the Oxford British Heart Foundation Centre of Research Excellence. The support of the Slovak Grant Agency VEGA (grant #2/0001/17) and APVV (grant #15-0029) is also acknowledged

Efficacy and tolerability of an endogenous metabolic modulator (AXA1125) in fatigue-predominant long COVID: a single-centre, double-blind, randomised controlled phase 2a pilot study

Background ‘Long COVID’ describes persistent symptoms, commonly fatigue, lasting beyond 12 weeks following SARS-CoV-2 infection. Potential causes include reduced mitochondrial function and cellular bioenergetics. AXA1125 has previously increased β-oxidation and improved bioenergetics in preclinical models along with certain clinical conditions, and therefore may reduce fatigue associated with Long COVID. We aimed to assess the efficacy, safety and tolerability of AXA1125 in Long COVID. Methods Patients with fatigue-dominant Long COVID were recruited in this single-centre, double-blind, randomised controlled phase 2a pilot study completed in the UK. Patients were randomly assigned (1:1) using an Interactive Response Technology to receive either AXA1125 or matching placebo in a clinical-based setting. Each dose (33.9 g) of AXA1125 or placebo was administered orally in a liquid suspension twice daily for four weeks with a two-week follow-up period. The primary endpoint was the mean change from baseline to day 28 in the phosphocreatine (PCr) recovery rate following moderate exercise, assessed by 31P-magnetic resonance spectroscopy (MRS). All patients were included in the intention to treat analysis. This trial was registered at ClinicalTrials.gov, NCT05152849. Findings Between December 15th 2021, and May 23th 2022, 60 participants were screened, and 41 participants were randomised and included in the final analysis. Changes in skeletal muscle phosphocreatine recovery time constant (τPCr) and 6-min walk test (6MWT) did not significantly differ between treatment (n = 21) and placebo group (n = 20). However, treatment with AXA1125 was associated with significantly reduced day 28 Chalder Fatigue Questionnaire [CFQ-11] fatigue score when compared with placebo (least squares mean difference [LSMD] −4.30, 95% confidence interval (95% CI) −7.14, −1.47; P = 0.0039). Eleven (52.4%, AXA1125) and four (20.0%, placebo) patients reported treatment-emergent adverse events; none were serious or led to treatment discontinuation. Interpretation Although treatment with AXA1125 did not improve the primary endpoint (τPCr-measure of mitochondrial respiration), when compared to placebo, there were significant improvements in fatigue-based symptoms among patients living with Long COVID following a four-week treatment period. Further multicentre studies are needed to validate our findings in a larger cohort of patients with fatigue-dominant Long COVID. Funding Axcella Therapeutics

Brain volume loss in multiple sclerosis is independent of disease activity and might be prevented by early disease-modifying therapy

Introduction. Neurodegeneration is likely to be present from the earliest stages of multiple sclerosis (MS). MS responds poorly to disease-modifying treatments (DMTs) and leads to irreversible brain volume loss (BVL), which is a reliable predictor of future physical and cognitive disability. Our study aimed to discover the relationship between BVL, disease activity, and DMTs in a cohort of patients with MS. Material and methods. A total of 147 patients fulfilled our inclusion criteria. Relevant demographic and clinical data (age, gender, time of MS onset, time of treatment initiation, DMT characteristics, Expanded Disability Status Scale (EDSS), number of relapses in the last two years prior to MRI examination) were correlated with MRI findings. Results. Patients with progressive MS had significantly lower total brain and grey matter volumes (p = 0.003; p < 0.001), and higher EDSS scores (p < 0.001), compared to relapsing-remitting patients matched by disease duration and age. There was no association between MRI atrophy and MRI activity (c2 = 0.013, p = 0.910). Total EDSS negatively correlated with the whole brain (rs = −0.368, p < 0.001) and grey matter volumes (rs = −0.308, p < 0.001), but was not associated with the number of relapses in the last two years (p = 0.278). Delay in DMT negatively correlated with whole brain (rs = −0.387, p < 0.001) and grey matter volumes (rs = −0.377, p < 0.001). Treatment delay was connected with a higher risk for lower brain volume (b = −3.973, p < 0.001), and also predicted a higher EDSS score (b = 0.067, p < 0.001). Conclusions. Brain volume loss is a major contributor to disability progression, independent of disease activity. Delay in DMT leads to higher BVL and increased disability. Brain atrophy assessment should be translated into daily clinical practice to monitor disease course and response to DMTs. The assessment of BVL itself should be considered a suitable marker for treatment escalation