Breath acetone concentration: too heterogeneous to constitute a diagnosis or prognosis biomarker in heart failure? A systematic review and meta-analysis

Introduction: Exhaled breath acetone (ExA) has been investigated as a biomarker for heart failure (HF). Yet, barriers to its use in the clinical field have not been identified. The aim of this systematic review and meta-analysis was to assess the ExA heterogeneity and factors of variability in healthy controls (HC), to identify its relations with HF diagnosis and prognostic factors and to assess its diagnosis and prognosis accuracy in HF patients. Methods: A systematic search was conducted in PUBMED and Web of Science database. All studies with HC and HF patients with a measured ExA were included and studies providing ExA’s diagnosis and prognosis accuracy were identified. Results: Out of 971 identified studies, 18 studies involving 833 HC and 1009 HF patients were included in the meta-analysis. In HC, ExA showed an important heterogeneity (I²=99%). Variability factors were fasting state, sampling type and analytical method. The mean ExA was 1.89 times higher in HF patients vs. HC (782 [531-1032] vs. 413 [347-478] ppbv; p<0.001). One study showed excellent diagnosis accuracy, and one showed a good prognosis value. ExA correlated with New York Heart Association (NYHA) dyspnea (p<0.001) and plasma brain natriuretic peptide (p<0.001). Studies showed a poor definition and reporting of included subjects. Discussion: Despite the between-study heterogeneity in HC, the evidence of an excellent diagnosis and prognosis value of ExA in HF from single studies can be extended to clinical populations worldwide. Factors of variability (ExA procedure and breath sampling) could further improve the diagnosis and prognosis values of this biomarker in HF patients.

Determination of optimal feed profile in semi-batch reactor: DFT and experimental studies on a Case Study of parallel and serial reactions take place

Semi-batch reactor systems can be used at different areas due to its advantages of the feed manipulation. Common practices are temperature control of the exothermic reactions or selectivity adjustment of the production process include serial and parallel reactions. Bisphenol A (BPA) is theoretically synthesized with 2 moles of phenol and 1 mol of acetone. During the reaction, a stoichiometric ratio or high acetone concentration causes the formation of by-products. This situation has been confirmed by density functional theory (DFT) calculations. In these calcula-tions, the B3LYP method and the 6-311++G(d, p) basis set were used. DFT calculations show that by-products can be formed in the synthesis of bisphenol a. The common method used to solve the by-product problem is to work with high molar phenol/acetone ratios. But this brings additional operating and investment costs. In this study, semi-batch reaction experiments were performed which stoichiometric acetone was fed in reactor with various pulsed modes in the presence of homogenous and heterogonous catalysts. Time versus conversion and selectivity data were collected at various catalyst concentrations. All runs were compared with the results of batch and semi-batch runs performed in over molar ratio of phenol/acetone. As a result, it has been shown that high conversion and selectivity can be achieved by providing energy efficiency with pulsed mode semi batch reactor.

Quantification of Volatile Acetone Oligomers Using Ion-Mobility Spectrometry

Background. Volatile acetone is a potential biomarker that is elevated in various disease states. Measuring acetone in exhaled breath is complicated by the fact that the molecule might be present as both monomers and dimers, but in inconsistent ratios. Ignoring the molecular form leads to incorrect measured concentrations. Our first goal was to evaluate the monomer-dimer ratio in ambient air, critically ill patients, and rats. Our second goal was to confirm the accuracy of the combined (monomer and dimer) analysis by comparison to a reference calibration system. Methods. Volatile acetone intensities from exhaled air of ten intubated, critically ill patients, and ten ventilated Sprague-Dawley rats were recorded using ion-mobility spectrometry. Acetone concentrations in ambient air in an intensive care unit and in a laboratory were determined over 24 hours. The calibration reference was pure acetone vaporized by a gas generator at concentrations from 5 to 45 ppbv (parts per billion by volume). Results. Acetone concentrations in ambient laboratory air were only slightly greater (5.6 ppbv; 95% CI 5.1–6.2) than in ambient air in an intensive care unit (5.1 ppbv; 95% CI 4.4–5.5; p < 0.001 ). Exhaled acetone concentrations were only slightly greater in rats (10.3 ppbv; 95% CI 9.7–10.9) than in critically ill patients (9.5 ppbv; 95% CI 7.9–11.1; p < 0.001 ). Vaporization yielded acetone monomers (1.3–5.3 mV) and dimers (1.4–621 mV). Acetone concentrations (ppbv) and corresponding acetone monomer and dimer intensities (mV) revealed a high coefficient of determination (R2 = 0.96). The calibration curve for acetone concentration (ppbv) and total acetone (monomers added to twice the dimers; mV) was described by the exponential growth 3-parameter model, with an R2 = 0.98. Conclusion. The ratio of acetone monomer and dimer is inconsistent and varies in ambient air from place-to-place and across individual humans and rats. Monomers and dimers must therefore be considered when quantifying acetone. Combining the two accurately assesses total volatile acetone.

Determination of chemical and microbiological characteristics of meat products treated by radiation

Radiation treatment of food products carried out to increase their shelf life can result in chemical transformations initiated by free radicals. Volatile compounds (alcohols, aldehydes, ketones, etc.) formed, in particular, as a result of lipid oxidation, impair the organoleptic properties of products. Method of gas chromatography-mass spectrometry (GC-MS) makes it possible to identify the fact of food processing by detection of volatile marker compounds: in the case of meat products, the existing standard brings under regulation detection of 2-alkylcyclobutanones, however, the products with a reduced fat content, such as turkey and chicken, require an alternative marker. The results of GKh-MS study revealed the dependence of microbiological parameters and the content of various volatile organic substances in chilled turkey meat on the dose of electron radiation. It is shown that the total amount of alcohols, ketones and aldehydes (11 compounds) decreases exponentially with an increase in the absorbed dose. An increase in the radiation dose leads to a higher content of carbonyl compounds (aldehydes and acetone), which results in a specific taste and smell of the irradiated products. At the same time, the acetone concentration increases linearly with the absorbed dose, which makes it possible to use acetone as a potential marker of the degree of irradiation of low-fat meat products. Irradiation in the «working» doses (0.5 – 1 kGy) significantly suppresses the pathogenic microflora and keeps the organoleptic properties of the product.

DFT and experimental studies on synthesis of bisphenol a: Determination of optimal feed profile in semi-batch reactor

Bisphenol A (BPA) is theoretically synthesized with 2 moles of phenol and 1 mol of acetone. During the reaction, a stoichiometric ratio or high acetone concentration causes the formation of by-products. This situation has been confirmed by density functional theory (DFT) calculations in addition to the literature information. In these calculations, the B3LYP method and the 6-311++G(d, p) basis set were used. DFT calculations show that by-products can be formed in the synthesis of bisphenol a. The common method used to solve this problem is to work with high molar phenol/acetone ratios. But this brings additional operating and investment costs. In this study, semi-batch reaction experiments were performed which stoichiometric acetone was fed in reactor with various pulsed modes in the presence of homogenous and heterogonous catalysts. As a result, it has been shown that high conversion and selectivity can be achieved by providing energy efficiency

Recovery of Bioactive Compounds from Industrial Exhausted Olive Pomace through Ultrasound-Assisted Extraction

Exhausted olive pomace (EOP) is the main agro-industrial waste of the olive pomace extracting industries. It contains phenolic compounds and mannitol, so the extraction of these bioactive compounds should be considered as a first valorization step, especially if EOP is used as biofuel. Therefore, EOP was subjected to bath-type ultrasound-assisted extraction (UAE), and the effects of the acetone concentration (20–80%, v/v), solid load (2–15%, w/v), and extraction time (10–60 min) on the extraction of antioxidant compounds were evaluated according to a Box–Behnken experimental design. By means of the response surface methodology, the optimum conditions were obtained: 40% acetone, 8.6% solids, and 43 min. For all the extracts, the total phenolic content (TPC), flavonoid content (TFC), and antioxidant activity (DPPH, ABTS, and FRAP) were determined. With the aim of shortening the extraction time, a two-level factorial experiment design was also carried out using a probe-type UAE, keeping the solid load at 8.6% (w/v) and the acetone concentration at 40% (v/v), while the amplitude (30–70%) and the extraction time (2–12 min) were varied to maximize the aforementioned parameters. Finally, a maximum of phenolic compounds was reached (45.41 mg GAE/g EOP) at 12 min and 70% amplitude. It was comparable to that value obtained in the ultrasonic bath (42.05 mg GAE/g EOP), but, remarkably, the extraction time was shortened, which translates into lower costs at industrial scale. Moreover, the bioactive compound hydroxytyrosol was found to be the major phenolic compound in the extract, i.e., 5.16 mg/g EOP (bath-type UAE) and 4.96 mg/g EOP (probe-type UAE). Other minor phenolic compounds could be detected by capillary zone electrophoresis and liquid-chromatography–mass spectrometry. The sugar alcohol mannitol, another bioactive compound, was also found in the extract, and its content was determined. Thus, the use of this technology can support the valorization of this waste to obtain bioactive compounds, including mannitol, hydroxytyrosol, and other derivatives, before being applied for other uses.

ZnS Quantum Dot Based Acetone Sensor for Monitoring Health-Hazardous Gases in Indoor/Outdoor Environment

This study reports the ZnS quantum dots (QDs) synthesis by a hot-injection method for acetone gas sensing applications. The prepared ZnS QDs were characterized by X-ray diffraction (XRD) and transmission electron microscopy analysis. The XRD result confirms the successful formation of the wurtzite phase of ZnS, with a size of ~5 nm. Transmission electron microscopy (TEM), high-resolution TEM (HRTEM), and fast Fourier transform (FFT) images reveal the synthesis of agglomerated ZnS QDs with different sizes, with lattice spacing (0.31 nm) corresponding to (111) lattice plane. The ZnS QDs sensor reveals a high sensitivity (92.4%) and fast response and recovery time (5.5 s and 6.7 s, respectively) for 100 ppm acetone at 175 °C. In addition, the ZnS QDs sensor elucidates high acetone selectivity of 91.1% as compared with other intrusive gases such as ammonia (16.0%), toluene (21.1%), ethanol (26.3%), butanol (11.2%), formaldehyde (9.6%), isopropanol (22.3%), and benzene (18.7%) for 100 ppm acetone concentration at 175 °C. Furthermore, it depicts outstanding stability (89.1%) during thirty days, with five day intervals, for 100 ppm at an operating temperature of 175 °C. In addition, the ZnS QDs acetone sensor elucidates a theoretical detection limit of ~1.2 ppm at 175 °C. Therefore, ZnS QDs can be a promising and quick traceable sensor nanomaterial for acetone sensing applications.

Acetone Bio-Sniffer (Gas-Phase Biosensor) for Monitoring of Human Volatile Using Enzymatic Reaction of Secondary Alcohol Dehydrogenase

We developed a highly sensitive acetone bio-sniffer (gas-phase biosensor) based on an enzyme reductive reaction to monitor breath acetone concentration. The acetone bio-sniffer device was constructed by attaching a flow-cell with nicotinamide adenine dinucleotide (NADH)-dependent secondary alcohol dehydrogenase (S-ADH) immobilized membrane onto a fiber-optic NADH measurement system. This system utilizes an ultraviolet light emitting diode as an excitation light source. Acetone vapor was measured as the fluorescence of NADH consumption by the enzymatic reaction of S-ADH. A phosphate buffer that contained oxidized NADH was circulated into the flow-cell to rinse the products and the excessive substrates from the optode; thus, the bio-sniffer enables the real-time monitoring of acetone vapor concentration. A photomultiplier tube detects the change in the fluorescence emitted from NADH. The relationship between the fluorescence intensity and acetone concentration was identified to be from 20 ppb to 5300 ppb. This encompasses the range of concentration of acetone vapor found in the breath of healthy people and of those suffering from disorders of carbohydrate metabolism. Then, the acetone bio-sniffer was used to monitor the exhaled breath acetone concentration change before and after a meal. When the sensing region was exposed to exhaled breath, the fluorescence intensity decreased and reached saturation immediately. Then, it returned to the initial state upon cessation of the exhaled breath flow. We anticipate its future use as a non-invasive analytical tool for the assessment of lipid metabolism in exercise, fasting and diabetes mellitus.

The Effect of Processing Parameters on the Properties of Fish Gelatin Hydrolysate Nanoparticle

Fish gelatin hydrolysate is a well- known fish by-product that is high in protein content. It is produced from by-product waste from the fish processing industry, which includes fish skin, head, and bones. Gelatin hydrolysates have recently received much attention due to its high protein content and bioactivity, which includes antioxidant, antimicrobial and antihypertensive activities. The transformation of gelatin hydrolysate into nanoparticles is believed to increase its economic value. Furthermore, reduction into nano-size increases the absorption characteristic of this material. Here, fish gelatin hydrolysate nanoparticles are prepared for the first time using desolvation method. The effects of concentration of gelatin hydrolysate, pH of solution, and acetone concentration on nanoparticle size are determined. The prepared gelatin hydrolysate nanoparticles were found to have spherical shape with sizes varying from 300-400 nm with a mean size of 408 ± 11.4 nm, zeta potential of -16.4 ± 1.2 mV and PDI 0.203 ± 0.07. This study showed that concentration of gelatin hydrolysate, pH and concentration of solvent have significant effects on nanoparticle size. The gelatin hydrolysate nanoparticles can be applied in the pharmaceutical industry for the encapsulation of drugs to facilitate delivery to target sites.

In-Line Analysis of Diffusion Processes in Micro Channels by Long Distance Raman Photometric Measurement Technology—A Proof of Concept Study

This work presents a novel method for the non-invasive, in-line monitoring of mixing processes in microchannels using the Raman photometric technique. The measuring set-up distinguishes itself from other works in this field by utilizing recent state-of-the-art customized photon multiplier (CPM) detectors, bypassing the use of a spectrometer. This addresses the limiting factor of integration times by achieving measuring rates of 10 ms. The method was validated using the ternary system of toluene–water–acetone. The optical measuring system consists of two functional units: the coaxial Raman probe optimized for excitation at a laser wavelength of 532 nm and the photometric detector centered around the CPMs. The spot size of the focused laser is a defining factor of the spatial resolution of the set-up. The depth of focus is measured at approx. 85 µm with a spot size of approx. 45 µm, while still maintaining a relatively high numerical aperture of 0.42, the latter of which is also critical for coaxial detection of inelastically scattered photons. The working distance in this set-up is 20 mm. The microchannel is a T-junction mixer with a square cross section of 500 by 500 µm, a hydraulic diameter of 500 µm and 70 mm channel length. The extraction of acetone from toluene into water is tracked at an initial concentration of 25% as a function of flow rate and accordingly residence time. The investigated flow rates ranged from 0.1 mL/min to 0.006 mL/min. The residence times from the T-junction to the measuring point varies from 1.5 to 25 s. At 0.006 mL/min a constant acetone concentration of approx. 12.6% was measured, indicating that the mixing process reached the equilibrium of the system at approx. 12.5%. For prototype benchmarking, comparative measurements were carried out with a commercially available Raman spectrometer (RXN1, Kaiser Optical Systems, Ann Arbor, MI, USA). Count rates of the spectrophotometer surpassed those of the spectrometer by at least one order of magnitude at identical target concentrations and optical power output. The experimental data demonstrate the suitability and potential of the new measuring system to detect locally and time-resolved concentration profiles in moving fluids while avoiding external influence.