Properties such as carbonation, water absorption rate, pull-off adhesion strength were evaluated for all coatings, and tensile strength, Young’s modulus, and elongation percentage were calculated for mineral coatings. According to the results, the EP coating showed the best performance with the highest pull-off adhesion strength (2.55 MPa) and lowest absorption rate, about 0.02 ± 0.002 g/m2 day in saltwater and 0.03 ± 0.002 g/m2 day in regular water. In addition, EP coatings also presented the lowest carbonation rate and the highest suppress ratio. The excellent performance of epoxy coatings is mainly due to their low porosity and the ability to decrease chloride diffusion, making them better than other types of coatings investigated in this study.This paper assesses the behavior of mineral, epoxy (EP), solvent, and water-soluble coatings when exposed to salt and regular water for 28 days. Also, it evaluates the  Different researchers have studied carbonation and have proposed prediction models to analyze and understand carbonation phenomena in different environments4. For example, Park5 presented a carbonation model considering the diffusion of carbon dioxide on concrete samples protected with coating materials. As a result, polyvinyl chloride coating has a smaller diffusion coefficient than epoxy and acrylic coating, meaning that polyvinyl chloride coating decreases the carbonation depth over time. In another case, Cunha Reis et al.6 assessed the efficiency of traditional cementitious-based coatings for concrete protection against carbonation by using an accelerated method, achieving a 56% reduction in carbonation depth compared to concrete samples uncoated. Results suggest that coating materials protect concrete and reduce carbonation depth regardless of their composition.Different atmospheric conditions can highly affect concrete durability. Among the most common durability problems, carbon dioxide increases the carbonation depth causing fatal concrete deterioration and corrosion of steel reinforcement7. During the last decades, different compounds have been used to manufacture coating materials, starting from basic synthetic resins to developing high-performance resins8. The construction industry uses several of these materials to protect concrete structures against corrosion. Figure Since prehistory, coating materials have been used to protect and decorate elements and surfacesCoating materials used to protect construction elements embedded into the ground are more popular than geotextiles because of the ease of application and the lower cost of material and labor. However, nowadays, one of the major limitations of coating materials is their application on surfaces saturated with water or oil during the construction process or when the structures are previously exposed to different contaminants.13 assessed the effectiveness of coatings based on alkali-activated and epoxy materials to protect concrete samples when exposed to chlorides. The outcomes showed that epoxy and inorganic coatings presented the lowest capillary absorption coefficient. Epoxy material is characterized by its physical barrier, which makes the material limit the diffusion of chlorides by obtaining the lower current values among all coatings, showing a significant increase in the material resistivity. Suleiman et al.14 assessed the performance of bitumen-modified polyurethane coating when concrete samples are exposed to sulfate attacks. This coating shows similar properties than epoxy coating regarding the low sulfate penetration due to the thick membrane that forms on the surface of the concrete. However, it is important to highlight that this material requires proper curing of the concrete before the application since separations of the coating with the concrete sample may occur. Diamanti et al.15 evaluate cement-based coatings’ water absorption, permeability, chloride penetration, and coating adhesion properties. It is evidenced that cement-based coatings slow down the chloride penetration and reduce the water content compared with samples without coating protection. Additionally, pull-off strength is affected by the W/C ratio; with lower W/C ratios, there is a decrease in the concrete porosity, which benefits the pull-off adhesion strength results. Finally, Krzywinski et al.16 intended to improve the pull-off adhesion strength of epoxy coatings by texturizing the concrete surface with different imprinting, grabbing, and brushing methods. The results indicate that the pull-off strength could increase by about 9% when plastic cross shapes are used compared to the manufacturer’s recommendations.Different studies used coating materials to improve the concrete surface and minimize the effect of corrosion. For example, Aguirre-Guerrero et al.17. To ensure that the material is suitable for protecting concrete elements is necessary to assess some of its mechanical and physical properties. Among the essential properties of coating materials are; adhesion to the substrate, absorption rate, tensile strength, and carbonation resistance19. The test methods used in the present research include: (1) Pull-off adhesion strength according to PN-EN 14,891:201720 (2) Absorption test by immersing the samples in regular and saltwater (2% NaCl solution in water) for 28 days (3) Tensile strength according to ISO-527-201222. (iv) Carbonation depth according to23. These measures were suitable for the four coating materials used during the experimental part.Bitumen, epoxy, and mineral coatings have been used more frequently in the construction sector to protect floors, pipelines, and different concrete elementsThis research aims to evaluate the influence on the mechanical and physical properties of the mentioned coating materials when the concrete surface is exposed to external factors such as oil and water. In addition, it assesses the influence of chlorides in coating materials samples and the carbonation resistance of concrete specimens protected by MI, EP, BR, and BW coatings. Experimental tests were carried out according to our own research procedures.The methodology process involved different stages. First, the coating materials were selected based on their main compounds, i.e., epoxy, asphalt, mineral, and water. Afterward, coating samples were used to test their mechanical and physical properties. Tensile strength was measured just for the mineral coating by preparing samples of (50 × 250) mm. For absorption tests, 20 samples of each coating were exposed to salt and regular water for 28 days.To assess the pull-off adhesion strength, mineral (MI), epoxy (EP), solvent-base (BR), and water-soluble (BW) coating materials were placed in concrete slabs and divided into two groups: In the first group, the coating materials were air-dried for 28 days; in the second group, the coating materials were air-dried for 14 days, plus, 14 days in a drier at 70 °C. Both groups used water and oil to impregnate the concrete surface to assess the coating material’s pull-off adhesion on contaminated surfaces. Figure In this research, four types of coating materials commonly used in the construction sector for protecting underground concrete structures exposed to moisture were used: Epoxy coating (EP), mineral coating (MI), water-soluble coating (BW), and solvent-based coating (BR). Tables 23.Additionally, concrete slabs of (350 × 350) mm, (200 × 200) mm, and (140 × 200) mm type B30 were used to perform adhesion tests. To determine the carbonation depth, a solution with 1% of phenolphthalein in 70% ethyl alcohol was usedThe pull-off adhesion strength was assessed under different conditions: dry, wet, and oily substrate. Before the coating application, the wet and oily substrate was simulated by painting the concrete slabs with two layers of water and industrial oil.BW, MI, EP, and BR coating materials were applied according to the manufacturer’s specifications. A total of 36 concrete specimens were used during the research. Figure Concrete surface preparation A regular brush was used to clean the surface from dust particles.Impregnation of the concrete surface with oil and water Potable water and synthetic oil for car engines (type 5 W-40) was used to saturate the concrete surface’s superficial pores immediately before applying the coating materials.Preparation of coating materials There was no need for any preparation in the water-soluble coating and solvent-base case. These materials come ready to be applied. However, the epoxy resin had to be mixed with polyamide hardener for 8 min before application, and mineral coating needed to be prepared with 20% of water relative to the weight of the used material.Application of coatings to the surface of the concrete slabs The application varied according to the type of coating material.Epoxy coatings After mixing the coating compounds, one layer of the mix was applied with a regular brush on the surface of each concrete sample.Water-soluble and solvent-based coatings According to the manufacturer’s recommendations, three layers of the material were applied using a regular brush. The second and third layers were applied after the previous layer dried to touch, about 30 min for solvent-based coating and about 1 h for water-soluble coating.ineral coating After mixing the material with water, two layers were applied with a spatula, distributing the material uniformly on the concrete slab’s surface. The second layer was applied after the first layer had dried to touch after about 1.5 h.MThe application process of the coating materials is described below.After the application of the coating materials, the concrete samples were divided into two drying groups: in the first group, the concrete samples remained at room temperature of 20 °C ± 1 °C for 28 days, and in the second group, concrete samples remained at room temperature of 20 °C ± 1 °C for 14 days, followed by 14 days of drying in an electric drier.20 and ASTM D 4541 standard24.A traction dynamometer with a maximum tensile strength of 5 kN was used to perform the pull-off adhesion test. Before placing the metallic discs (dollies) on the concrete surface, it was necessary to drill a circular notch to define the measured surface accurately. Afterward, 50 mm-diameter/20 mm-height dollies were glued to the surface using a standard epoxy-based adhesive. Figure 23. This solution is characterized by being a colorless liquid commonly used as an acid-base indicator that changes to purple when the pH is higher than 9. As a result, the non-carbonated concrete surface, where the specimen is still alkaline, turns into a purple color, and the carbonated concrete surface remains colorless due to the reduction in the alkalinity of concrete.After applying the coating material, concrete samples were stored in an indoor controlled environment at 20 ± 2 °C and 75% ± 5% relative humidity for 90 days. Next, phenolphthalein solution was sprayed onto the fresh broken concrete surface according to the CPC-18 RILEM25, the performance of coating materials against corrosion can be measured by the carbonation suppression ratio , and some individual coating samples were made for epoxy and solvent-based types. Figure Tensile strength in mineral coatings was assessed by using samples of size (250 mm × 50 mm) and conditioned at 20 ± 2 °C and 75% ± 5% relative humidity. Tensile tests were performed at 14 and 28 days of air-drying using a testing machine with a maximum test load of 5 kN. The free distance between the holders was about 205 ± 1 mm, and the transverse speed was set to 10 mm/min. A total of eight specimens were tested. Elastic modulus, tensile strength, and strain at fracture in tension were calculated at the maximum load.2.The samples were prepared by bonding end-tabs of epoxy tape, resulting in an available cross-area of approximately 60 mmThis paper was limited to English articles found in the following journals: Elsevier “Construction and building materials,” Springer “Journal of Materials Science,” MDPI “buildings,” MDPI “Coatings,” which excludes literature published in other languages and is also limited to academic publications. Moreover, it does not consider the results from industrial practice.Figure Only the EP coating products presented physical changes after applying the different coating materials on the concrete slabs. In the oily substrate, it was evidenced that epoxy coating could not interact with the oil molecules, making the coating repelling and leaving certain areas without coating material. In the case of wet and dry substrates, no physical changes were evidenced. Figure The results indicate that epoxy materials presented the highest adhesion strength values in all scenarios by exceeding the maximum possible measure of the dynamometer (5 kN). These values follow the values given by the manufacturer. It is noteworthy that all EP samples presented substrate failure under the load, evidencing a concrete substrate strength weakness. Figure 27, a glue failure was evidenced in all samples; this can be attributed to the drying process in the oven. The coating reduced its mechanical properties and did not chemically interact with the epoxy resin, leaving a weak joint. For samples exposed to air drying for 28 days, a reduction in the strength adhesion was evidenced; these specimens showed a decrease of 42% in samples saturated with oil and 19% in samples saturated with water. Even though there is a reduction in the strength values, the specimens presented a cohesive failure within the coating layer, which is considered the ideal type of failure in the pull-off test. Figure For concrete slabs with BR Coating, the maximum pull-off adhesion strength values were observed in the samples dried for 14 days in the air plus 14 days in the oven by achieving the maximum pull force value (5 kN). However, according to the types of failures presented in the ASTM D 4541 standard and ISO 4264The mineral coating was the only material where the presence of oil influenced the failure type. Samples exposed to air-drying presented 50% adhesive and 50% Fig. b cohesivpull-off adhesion strength for the specimens subjected to oven drying.The BW coatings presented 100% cohesive failures in all samples. The results show a slight increase in 27 was used to assess the fracture type. Figure ISO 4264According to Fig. 24 range established between 1.37 and 3.45 MPa. BW coating also showed a reduction in the pull-off adhesion strength of 44% and 59% for the wet and dry surfaces. Again, similar to MI, these results were invalid due to non-compliance with the standard.Among the results, the decrease in the pull-off adhesion strength was mainly evidenced in concrete samples saturated with oil. The presence of oil reduced the strength values for MI coating by 84% and 81% compared to wet and dry surfaces; this made the results invalid since they did not comply with the ASTM D 4541 standardBased on the previous results, the air-dry method and the samples saturated with regular water were selected as optimal samples because their physical and mechanical properties were not widely affected. The average carbonation depth and the suppression ratio were calculated to assess the reduction in the carbonation caused by the application of MI, EP, BW, and BR materials. Table 28.A notorious carbonation depth reduction in samples protected with EP coating was evidenced, going from 4.63 mm to 1.98 mm (57% reduction) compared to MI coating, which only presented a drop of about 3%. EP coatings have shown adequate concrete protection against carbonation compared with other materials such as polyurethane, acrylic, and chlorinated rubber when exposed to accelerated aging methodsOn the other hand, water-soluble coating presented a higher suppression ratio compared to solvent-based coating, approximately 20% higher; this is mainly due to the evaporation of solvent components during the oven’s drying process, causing a decrease in the protection of concrete against carbonation.Figure 29, the low water absorption is caused by hydrocarbon constituents, showing a slight tendency to absorb water over the years. Additionally, physical changes were noticeable after seven days of contact. In the case of regular water, changes in the sample color were evident due to the chemical changes produced by the presence of oxygen that interacts with the basic components of the material, changing from black to brown color. For saltwater, some samples showed cracks in their surface, accelerating the corrosion of specimens. Figure According to the results, MI, EP, and BR coatings presented similar absorption coefficients between each of them during the three stages when exposed to regular and saltwater. However, BW coating was widely affected by regular water, showing a total increment in the absorption coefficient after 28 days of exposition of around 21% in regular water, 10% more than in saltwater. According to Anderson et al.It is noteworthy that EP coating presented the lowest water absorption values during the exposition time attributable to its low shrinkage performance by controlling expansive chemicals and minimizing cracks due to internal stresses. As a result, the samples showed a smaller gain in weight and a maximum absorption value of 1% after the 28th day, which was aligned with the manufacturer’s specifications. There is no evidence of physical change in the presence of regular or saltwater for the EP samples. In contrast, since the initial stage, the MI coating showed the highest absorption results among all samples during the exposition time, increasing from 9.47% after 24 h of exposition to 21.30% on the 28th day for saltwater. And from 10.71 to 22.76% for regular water.Furthermore, after seven days of exposition, the MI coating presented small filaments perpendicular to the surface of the specimen; this appears to be an accumulation of salts. In the case of regular water, any physical change was evidenced.29, this material has a significant amount of hydrocarbons in its chemical composition, which decreases the tendency to absorb water. However, asphalt materials may contain inorganic salt in small proportions that could promote water absorption when moving through the membrane.It is important to mention that BR samples did not change in weight after 24 h of exposure. Therefore, water absorption occurred only during the first 24 h; however, the specimens exposed to regular water showed the appearance of apparent bubbles on the surface. According toData presented in Fig. 2 day) and 0.60–0.90 g/m2 day, followed by the BW coat with a range of (0.1–0.28 g/m2 day) and (0.15–0.67 g/m2 day) in regular water and in saltwater, respectively. The lowest absorption results were obtained in the case of EP and BR. EP coating presented values between (0.02–0.03 g/m2 day) in salty and regular water. BR coat showed values of (0–0.18 g/m2 day) and (0–0.11 g/m2 day) in salty and regular water. As expected, the materials that presented the best performance were the epoxy and the solvent-based coatings because of their low permeability properties, which minimize water penetration. On the other hand, mineral coating samples presented the highest absorption values caused by the presence of clinker Portland cement, which is characterized by increased concrete water absorption30 due to different salt combinations of sodium, potassium, and calcium31.MI coating samples obtained the highest absorption rate, which was between (0.54–0.76 g/mFigure After the test, samples were carefully photographed, and the failure type was determined according to the ASTM D 3039 standard. Figure Table The elastic modulus values of the MI coatings were evaluated after 14 and 28 days of air drying. The results for the samples dried during 14 days ranged from 30 to 35 MPa at room temperature and tripled their values after 28 days of drying, with a range of 90–97 MPa. These results demonstrate that the material increases its stiffness over time. In addition, the results were aligned with the manufacturer’s values. In the case of strain at breaking, the elongation results remained steady, showing a minimum variation among the results of 1% at 14 and 28 days at room temperature.The influence of salt and regular water and different types of drying methods has been studied and analyzed using four types of coating materials; mineral coating, epoxy coating, solvent-based coating, and water-soluble coating.The study results have shown that the pull-off adhesion strength when the samples are air-dried for 28 days is reduced when the coating material is applied on an oily saturated surface. Mineral coating presented a dramatic fall of about 85% in its adhesion strength compared to 63% for water-soluble coatings and 35% for solvent-based coating. The presence of oil also affected the mineral coating, reducing about 83% of its strength when air or oven-dried. On the other hand, the pull-off adhesion strength increased by 20% for water-soluble coatings and 74% for solvent-based coatings when dried in the oven compared to the air-dried process. Based on this, it is possible to conclude that incorporating an oven-drying process increases the adhesion of the coating material to concrete by evaporating water and solvent residues.During the exposition to salty and regular water, all samples showed changes in their physical appearance, presenting differences in color, manageability, and physical form. The presence of salts reduced water absorption mainly in the water-soluble specimens due to the non-hydrocarbon constituents presented in the material.The epoxy coating was the only material not affected either by the drying method or by the presence of salts. EP showed the highest pull-off adhesion strength in both types of the drying processes, where the presence of oil or water did not impact the eventual results. In addition, this coating material presented the lowest absorption values among all samples, increasing its weight only by around 1% after 28 days of exposition.It was evidenced that all coating materials improved the concrete resistance against carbonation by reducing carbonation depth at 90 days of standard curing. Based on the carbonation suppression ratio, the ranking order of the four types of coating material is EP > BW > BR > MI.Finally, the tensile strength of MI coating demonstrates that the material’s stiffness increases over time; this is mainly because its the low water/cement ratio [W/C 0.20].


VITUS Smart XXL using the software AnthroScan Professional. Anthropometric measurements were standardized and associated with CRF by sex-stratified linear regression models adjusted for age and height. Anthropometric markers were ranked according to the  − log- p values derived from these regression models. In men a greater left and right thigh-knee-ratio, a longer forearm-fingertip length, a greater left thigh circumference and greater left upper arm circumference were most strongly associated with a higher VO2peak. In women a greater left and right thigh circumference, left calf circumference, thigh thickness and right calf circumference were most strongly associated with a higher VO2peak. The detected VO2peak-related anthropometric markers could be helpful in assessing CRF in clinical routine. Commonly used anthropometric markers, e.g. waist and hip circumference, were not among the markers associated with VO2peak.The assessment of cardiorespiratory fitness (CRF) is an important tool for prognosis evaluation of cardiovascular events. The gold standard to measure CRF is cardiopulmonary exercise testing (CPET) to determine peak oxygen uptake (VO2peak). However, CPET is not only time consuming but also expensive and is therefore not widely applicable in daily practice. The aim of our study was to analyze, whether and which anthropometric markers derived from a 3D body scanner were related to VO2peak in a general population-based study. We analyzed data (SHIP-START-3) from 3D body scanner and CPET of 1035 subjects . A total of 164 anthropometric markers were detected with the 3D body scanner  The burden of CVD might be reduced by early risk detection and preventive strategies2. The assessment of cardiorespiratory fitness (CRF) is an important tool for prognosis of cardiovascular events3. Low CRF is an independent risk factor for CVD as well as cardiovascular and all-cause mortality in the general population6. CRF decreases with age and that decrease is further accelerated by unhealthy and sedentary lifestyles that are highly prevalent in Western societies7. The gold standard to measure CRF is cardiopulmonary exercise testing (CPET) to determine the peak oxygen uptake (VO2peak) as a central parameter. However, CPET is not only time consuming but also expensive and is, therefore, not widely applicable in daily practice. For clinical assessment it would be helpful to identify predictors of CRF that are easier to obtain such as anthropometric parameters. Waist circumference (WC) is a widely used example of an anthropometric marker8. Previous studies found a low CRF in individuals with high WC11.Cardiovascular diseases (CVD) are responsible for one-third of all deaths in the adult population14. In line with these findings is a study in 1077 Japanese women which suggested that the waist-to-height ratio may be a better predictor of multiple Coronary Heart Disease (CHD) than BMI or the waist-to-hip ratio (WHR)15.Additively a sport specific study found strong correlations between calf girth, hip girth, height, sitting height, limb length and shoulder breadth with VO2peak for rowers, which may be based on better leverages. Moreover various studies did point out waist-to-height ratio as a better screening tool than WC and body mass index (BMI) for adult cardiometabolic risk factorsBeyond WC and WHR there may be other body surface related anthropometric parameters, which may be even more tightly related to CRF. The advantage of anthropometric parameters is that the assessment of them is cheaper and takes less time compared to CPET. In clinical practice symptom related anthropometric markers could help to estimate CRF and optimize therapy.The aim of our study was to analyze associations of 164 anthropometric markers derived from a 3D body scanner with CRF as determined by VO2peak from a CPET in a population-based study. With this systematic approach we aimed to identify anthropometric markers, which are highly predictive for VO2peak and, thus, may add value for the clinical setting. This study may be used as a first step in identifying new anthropometric indicators that may be measured in clinical settings using cheaper tools such as measuring tape.17. A sample of the 212,157 inhabitants was selected from population registrar’s office. A representative sample, comprising 7008 adults aged 20–79 years with 292 persons of each sex in each of the twelve 5 year age strata, was drawn. The net sample (without migrated or deceased people) consisted of 6267 eligible subjects, of whom 4308 individuals participated in the baseline study of SHIP-START-0 from 1997 to 2001.The Study of Health in Pomerania (SHIP) is a population-based study assessing a multitude of risk factors, resources and determinants of health and disease in the adult population of West Pomerania, a region in the northeast of GermanyWe used data from the 3rd follow-up, SHIP-START-3, which was conducted between February 2014 and March 2016. Data from 3D body scanner and CPET was available in 1,035 participants . A PRISM diagram shows the selection of participants , work related PA (WPA) and leisure time related PA (LTPA)20. Domain specific physical activity was assessed using the well-established Baecke questionnaire20. Briefly, the questionnaire consists of 16 questions in three distinct sections: physical activity during leisure time excluding sport , SPA (i.e. identification of the sports played followed by questions regarding duration per week and months per year) and WPA . Most questions are scored on a five-point Likert scale, ranging from never to always or very often. For the reported sport activities, additional questions query the number of months per year and hours per week of participation. The three derived indices, LTPA, SPA and WPA, are scored in arbitrary units ranging from 1 to 5.Information on age, sex, physical activity (PA), smoking status , medication use and medical history was gathered by trained and certificated staff during a standardized computer-assisted interview. Individuals who did not participate in leisure time physical activity (LTPA), for at least one hour per week, during summer or winter were classified as sedentary21. Standardized measurement of weight was performed with calibrated scales. Body mass index (BMI) was calculated as weight (kg)/height2 (m2). After a resting period of at least five minutes systolic and diastolic blood pressure were measured three times on the right arm of seated subjects using an oscillometric digital blood pressure monitor  with an interval of three minutes between readings. For the present analyses the mean of the second and third measurements was used. Hypertension was defined as a systolic blood pressure ≥ 140 and/or a diastolic blood pressure ≥ 90 mmHg or use of antihypertensive medication .Information on medication intake was categorized according to the anatomical therapeutic chemical classification (ATC) code21. Serum aliquots were stored at − 80 °C. Glycosylated hemoglobin was determined by high-performance liquid chromatography . Glucose concentration was measured photometrically . Diabetes mellitus was defined as self-reported and/or use of antidiabetic medication (ATC code A10) and/or glycated hemoglobin ≥ 6.5% and/or fasting glucose ≥ 7.0 mmol/l and/or non-fasting glucose ≥ 11.1 mmol/l. History of myocardial infarction was self-reported.Non-fasting venous blood samples were obtained from all study participants between 07:00 a.m. and 04:00 p.m. while sitting23. Anthropometric markers were measured with a 3D body scanner  using the software AnthroScan Professional  which provides a 3D image of the body surface. Based on four eye-safe lasers, eight cameras, and optical triangulation, the body surface scan generates a 3D point cloud depicting the body surface within 12 s8. Following international norms24, 164 anthropometric measures were determined from the 3D picture , e.g. WC, arm circumference, etc. The body surface scan was calibrated daily using a cylinder tube of defined measurements according to the manufacturer’s instructions. All tests were performed at room temperature, because the measurement was performed in ideally tight-fitting underwear wearing a bathing cap to cover hair. Each participant was instructed to stand upright with head positioned according to the Frankfort Horizontal plane26, legs hip wide positioned, arms slightly angled without body contact, and hands making a fist with thumbs outside showing forward, if possible. Breathing should be normal.  to measure the anthropometric markersErgoselect 100, Ergoline, Germany) was performed according to a modified Jones protocol  as previously described32. All tests were performed according to current guidelines for exercise testing33, with continuous monitoring of ECG, blood pressure and oxygen saturation. Gas exchange and ventilatory variables were analyzed breath by breath averaged over 10 s intervals using a computer-based system. Exercise duration was measured from the start of exercise (without resting period) up to its termination. In the absence of chest pain and ECG abnormalities, all tests were continued as symptom-limited . VO2peak was defined as the highest 10 s average of absolute oxygen uptake in the last minute of exercise32. A sex-specific analysis was performed a priori due to sex-specific differences of anthropometric markers for VO2peak34. The median time interval between body scan examination and CPET was 21 days .A symptom-limited exercise test using a calibrated electromagnetically braked cycle ergometer  ≥ 3.542) was considered as statistically significant. All statistical analyses were performed using Stata 16.0 .From the 164 markers derived from body scanning we excluded parameters which were highly correlated with variables already selected, e.g. shoulder height measured in sitting position was not used because sitting height was already selected or shoulder breadth and acromial breadth. Moreover, we deleted parameters which one cannot measure in clinical practice e.g. distance back to the wall Fig. . The res2. Women, on the other hand, had a BMI of 27.1 kg/m2. HbA1c was 5.8% in men and 5.7% in women. The absolute VO2peak was 2281.2 ml/min for men and 1610.6 ml/min in women.The main characteristics of the study population are provided in Table p 11.3; CI (− 208.4 to − 84.6), respectively) and a greater right thigh-knee-ratio ), a longer forearm-fingertip length ), a greater left thigh circumference ) and a greater left upper arm circumference ). ) and a greater right thigh circumference ), a greater left calf circumference ), a greater thigh thickness ) and a greater right calf circumference ) (Table p) ≥ 3.542; Fig. In women, the five strongest higher VO2peak-related anthropometric markers were a greater left thigh circumference  and WHR, were not significantly associated with VO2peak. Our findings potentially support the use of anthropometric markers as predictors for CRF if there is no access or no time for CPET. Their precision in estimating CRF could improve clinical assessment of patients.20. Historically, anthropometric markers have been used to characterize physical health. For example, mid-upper arm muscle circumference has been used as a marker of protein-energy malnutrition36. Hence, this measurement may provide a direct assessment of underlying muscle which is representative of skeletal muscle mass. Skeletal muscle mass may be increased by strength training. In men the strongest association for VO2peak were thigh circumference values. Greater thigh-knee-ratios were strongly associated with a higher VO2peak in men. A large thigh-knee-ratio is defined by thin knees and thick thighs. In order to influence this ratio one could increase thigh thickness through appropriate training or decrease knee thickness by lowering fat tissue around the knee. Moreover, an average healthy, untrained person, should get more muscular thighs through adequate training37.We previously reported that an inverse association between CRF and mortality39. High CRF was associated with a lower BMI, independent of gender40. Here we report that other anthropometric markers besides the WC show stronger associations with CRF. This could be related to the fact that previous studies simply did not have a 3D body scanner available to test other anthropometric markers. Therefore, “new” leg circumference based markers may be taken into account. Despite the fact that HC and WC were not significantly associated with VO2peak in our study population, we acknowledge that these measures are still clinically meaningful due to their association with morbidity and mortality10.Previous studies showed inverse associations between CRF and WC41. The forearm-fingertip length, which showed a strong association with VO2peak in men, is mainly based on the sum of bone length of the forearm and hand, which are mostly genetically determined and/or childhood influenced. While one may argue that this could be a finding by chance, a previous study reported that the right-left digit ratio (2D:4D) was also related to maximal oxygen uptake. The authors could show that a low 2D:4D ratio is associated with sensitivity to testosterone measured by the number of cytosine-adenine-guanine triplet repeats in exon 1 of the androgen receptor gene42. Another parameter of a strong association with the VO2peak is sitting height in men but not in women.In contrast to modifiable anthropometric markers, fixed anthropometric markers such as upper arm length or leg length are genetically determined. The values of fixed anthropometric variables change very little or not at all upon full physical body development43, volleyball, rowing44 and swimming45. A study among a group of fifteen male elite and fifteen university rowers found strong relationships between manually measured anthropometric markers  to fitness level variables in an ex-post-facto design. Therefore, one may assume that anthropometrics and fitness level have a strong relationship toward rowers’ performance44.Moreover, the length of extremities in certain competitive sports can be seen as performance-determining part. Athletes with short height and extremities, e.g. arm and leg length, are usually not found in world class competitions in high jump, sprint, basketball, handball46. Conclusively, fixed anthropometric markers could be used to indicate someone’s baseline level of CRF.This could point to a new estimation approach of VO2peak indicating fixed anthropometric parameters. Furthermore, it must be taken into account that a certain part of CRF is also genetically determined20. Second, in order to confirm which anthropometric marker is the most appropriate, the ability of each of these anthropometric markers to predict certain events needs to be analyzed in further studies. These strong associations of anthropometric markers with a higher VO2peak should be used as indicators in clinical practice. To predict certain events the physician needs to take various clinical markers into account and weighing them up wisely for his general view of the patient. Our findings may help the physician in making diagnosis.Even though, SHIP comprises a population-based and methodologically rigorous regionally representative survey of Germany, the findings of our analyses need to be interpreted in the context of several limitations. First, our analysis consisted of white Europeans living in rural areas and it is not known whether our results are also applicable to other ethnicitiesIrrespective of these limitations, strengths of our study are the population-based setting, the use of standardized data collection methods, the capacity to perform adjustment for a variety of clinical risk factors and the availability of CPET results from 1035 participants.The detected VO2peak-related anthropometric markers in this study could be helpful in estimating CRF in clinical routine. Commonly used anthropometric markers, e.g. WC and HC, did not show the strongest association with VO2peak. Potential interventions to increase VO2peak may measure modifiable anthropometric markers like thigh-knee-ratios in men or thigh circumferences in women. Fixed anthropometric markers should be investigated in the future to assess whether these are findings by chance or if they are indeed biologically related to CRF. In conclusion, future research should assess whether the sex-specific anthropometric markers identified in this study can be used to improve CVD risk assessment in the general population.Supplementary Information.


This paper proposes a combined inspection method for thermally damaged concrete under a hygrothermal environment. Experiments were conducted to verify the feasibility of the proposed method. Concrete samples with different water–cement ratios  and moisture contents  were exposed to elevated temperatures of 200 °C, 400 °C, 600 °C, and 800 °C for 4 h. After cooling to room temperature, infrared thermal imaging (IRT), ultrasonic pulse velocity (UPV) measurements, and mechanical tests were carried out for the damaged concrete samples. The mechanical behavior of thermally damaged concrete with different degrees of water saturation was examined based on mechanical testing. The results show that water can affect the compressive strength and UPV of concrete under certain circumstances, and the residual strength and the heating temperature of the thermally damaged concrete can be evaluated by IRT and UPV measurements. When 50% saturated concrete specimens with a W/C ratio of 0.3, 0.5, and 0.7 are exposed to 200 °C, 12.6%, 27.4%, and 34.6% increases in normalized compressive strength were observed before dropping to approximately 40% at 800 °C. With various moisture contents, the normalized compressive strength variation can be up to 40% at 400 °C in cases with W/C = 0.5 and 0.7. As for UPV, it generally decreases with the increase in moisture content when the peak temperature is 800 °C. On the contrary, whether concrete is saturated or not, there is little difference in temperature change in IRT detection. To obtain a more precise evaluation of concrete structures, IRT can be used to scan a large area to determine the damaged concrete area and areas suspected to be damaged, while UPV could be used to detect concrete members in suspected areas after the completion of IRT scanning. Fire disasters are one of the most serious problems for reinforced concrete (RC) structures because of the decomposition of cementitious materials and cracking of concrete. When concrete is exposed to elevated temperatures, the mechanical performance of concrete structures can be degraded due to damage ,2. To enFor fire-damaged RC structures, there are several conventional detection methods. Before the nondestructive inspection is carried out, spot observation and destructive testing methods are used to detect the fire-damaged RC structures. First, the inspectors enter the spot to observe the environment as well as the damaged RC structures and take some samples from the damaged RC structures. According to the residues left in the environment, the scope of the peak temperatures can be assessed. After that, samples are used for strength testing by the testing organization, and the evaluation of fire-damaged structures is presented . HoweverHowever, when the damaged area is quite large, the UPV inspection method has difficulty detecting all the damaged concrete members in a short period of time. Therefore, to improve inspection efficiency, an additional inspection method should be combined with UPV inspection. It is worth mentioning that infrared thermography (IRT) also has great potential and has been widely used to scan concrete damage based on changes in thermal conductivity ,33. At pIn practice, a variety of testing methods have been chosen to evaluate damaged concrete structures ,4. The UFrom the above discussions, this paper presents a combined inspection method based on UPV and IRT for thermally damaged concrete. To determine the effect of the hygrothermal environment, concrete samples composed of ordinary concrete with varying water-to-cement ratios and moisture contents were used. After experimental procedures of elevated heating, nondestructive inspection, and compression tests, the results of UPV, IRT, and strength evaluation of damaged concrete suffering from elevated temperatures were analyzed and compared with those obtained for undamaged concrete samples. Finally, the limitations of the combined inspection method with IRT and UPV are discussed.The overall experimental program is illustrated in 3. The fine and coarse aggregates were composed of siliceous river sand and natural granite crushed stone, respectively. The maximum size and fineness modulus for the fine aggregate were 5 mm and 2.34, respectively. The water absorption and moisture content were 1.10% and 0.01%, respectively. For the coarse aggregate, the maximum size was 20 mm, and the water absorption and moisture content were 0.07% and 0.008%, respectively. The densities of the fine and coarse aggregates were 2.62 g/cm3 and 2.66 g/cm3, respectively. Specimens with three W/C ratios were prepared. The detailed mixture designs for the concrete, mortar, and cement-paste specimen are summarized in 3 [In this study, a total of one hundred thirty-five cubic concrete specimens were prepared. For comparison, another nine normal concrete specimens, nine mortar, and nine cement paste specimens were cured in the ambient environment. All the specimens have the same dimensions of 100× 100 × 100 mm. When casting the specimens, ordinary Portland cement that was provided by the Guangzhou Shijing Cement Plant  was used. The density of the cement was 3.07 g/cmzed in 3 .After casting, the specimens were left in the mold for 24 h at ambient temperature. The top of the specimens was covered with a plastic film to reduce the early cracking caused by water vaporization . Once deIn this study, 5 heating conditions, i.e., 200 °C, 400 °C, 600 °C, and 800 °C, were considered . The driAs shown in To evaluate the mechanical properties of the concrete after heat exposure, an axial compression test was conducted for the concrete specimens. A MATEST 4000 kN testing machine produced by MATEST company  was employed to complete all the axial compression tests. The compression for the test was controlled at 0.3 MPa per second. After the axial compressive force dropped to 80% of the peak value, the test was terminated.The compressive strength of concrete specimens conditioned in a different environment is presented in When the temperature is higher than 400 °C, the compressive strength is generally decreased with temperature regardless of the water-to-cement ratio and moisture content . To bettWith the above test results, it can be seen that the fire performance of concrete is related to the moisture content within the concrete. As far as the cases investigated in this study, a 50% saturation can benefit the concrete compressive strength when the temperature is below 200 °C. In such a scenario, the postcuring of concrete plays an important role. However, as the heating temperature increases, the concrete compressive strength decreases due to the decomposition of the hydration product ,49. TherRepresentative IRT images before and after heat exposure for concrete specimens with W/C = 0.3 are presented in To quantitatively analyze the thermal damage based on the IRT inspection results, the average temperature change ( follows :(1)ΔT=TaThe temperature change history for all the tested concrete specimens is presented in Combined with the aforementioned results of the IRT inspection and strength testing, the correlation of average temperature change and strength for thermally damaged concrete is presented in When concrete structures suffer fire damage, microcracks are formed at the bonding interface between the aggregate and mortar as well as the concrete surface due to thermal expansion and the decomposition of cementitious materials. As such, the velocity of the ultrasonic pulse is reduced . The UPVTo further investigate the influence of the W/C ratio on the UPV in concrete subject to elevated temperatures, the UPVs of specimens with all the saturation conditions are summarized in When the concrete specimens are exposed to temperatures above 200 °C, the concrete specimens with W/C = 0.3 show an almost linear decrease in UPV, and the decreasing rate is much greater than that of the other two types of concrete. This can be attributed to the fact that denser concrete is prone to cracking due to high internal pressure. Therefore, more microcracks within concrete will occur under elevated temperatures, and the UPV will decrease faster. In addition, the reduction rate for the UPV in concrete specimens with W/C = 0.3 slows down when the exposed temperature reaches 600 °C, indicating that the microcracks within the concrete become stable. Such a change in the UPV reduction rate is absent in the other two types of concrete specimens. Moreover, for the dried specimens, the difference in the UPV of concrete with different W/C ratios is much less significant than that for the saturated specimens.With the above discussion, it can be briefly concluded that the UPV of concrete drops as temperature increases, regardless of the W/C ratio and moisture content. As UPV mainly reflects the elastic property of the material that is exploited to transmit the ultrasonic pulse, a decrease in the UPV indicates a degradation of the modulus of the concrete suffering from exposure to high temperatures caused by fire. It should be noted that although the concrete modulus deteriorates when exposed to elevated temperatures, the concrete strength can increase in certain cases, as discussed in the previous section. This is justified by the fact that the concrete modulus is related to the microcracks formed within the concrete, while the concrete strength is more related to the macrocracks. A decrease in the concrete modulus does not necessarily entail a drop in the concrete strength.According to the UPV and compressive strength results, the relationship between the strength and UPV can be discussed, which is illustrated in According to the results of IRT–normalized compressive strength see , when thHowever, when the UPV ranges between 3.0 km/s and 3.5 km/s, the concrete quality is doubtful and becomes difficult to evaluate. Consequently, it is of great importance to evaluate the normalized UPV when concrete quality is doubtful. The normalized UPV was calculated using Equation (2) :(2)ωC=vDn et al.  proposed(5)–(6)) .(5)mCEρ (7)–(8) .(7)wC=wThe results obtained from the application of these equations are presented in Based on the results shown in a.Before the temperature reaches 400 °C, the moisture inside concrete can absorb a certain quantity of heat during heating, which can reduce the change in the average surface temperature determined by IRT. For an elevated temperature of over 600 °C, chemical decomposition becomes the key factor affecting the average temperature change determined from IRT inspection. The UPV is found to generally increase with moisture content for exposure to temperatures above 600 °C but decreases with exposure to temperatures below 600 °C. In contrast, at 800 °C, the UPVs for the fully saturated specimens are lower than those obtained for the dried and 50% saturated specimens.b.Suffering from thermal damage, the compressive strength of concrete is gradually decreased with elevated temperatures but not in a monotonic manner. Instead, for fully saturated concrete, the compressive strength remains almost unchanged until 400 °C. In particular, at 200 °C, the concrete strength in 50% saturated cases under W/C ratios of 0.3, 0.5, and 0.7 is 12.6%, 27.4%, and 34.6% higher than that of the control group due to the postcuring effect, which verifies the results obtained from characterization by IRT and UPV.c.IRT can be used to distinguish damaged concrete areas and suspected areas, while UPV can be further used to evaluate the performance of concrete in suspected areas, which can lead to more efficient inspection of fire-damaged concrete. However, the quantitative relationship between UPV, IRT, and compressive strength still requires further investigation.This paper proposes an effective combined inspection method for the evaluation of fire-damaged concrete based on UPV and IRT techniques. Experiments were carried out to study thermally damaged concrete in a hygrothermal environment and to verify the effectiveness of the proposed nondestructive detection method. From the results and discussions, the following conclusions are reached:


Quality indicators are used to quantify the quality of care. A large number of quality indicators makes assessment of overall quality difficult, time consuming and impractical. There is consequently an increasing interest for composite measures based on a combination of multiple indicators.To examine the use of different approaches to construct composite measures of quality of care and to assess the use of methodological considerations and justifications.We conducted a literature search on PubMed and EMBASE databases (latest update 1 December 2020). For each publication, we extracted information on the weighting and aggregation methodology that had been used to construct composite indicator(s).A total of 2711 publications were identified of which 145 were included after a screening process. Opportunity scoring with equal weights was the most used approach  followed by all-or-none scoring . Other approaches regarding aggregation or weighting of individual indicators were used in 32 publications (22%). The rationale for selecting a specific type of composite measure was reported in 36 publications (25%), whereas 22 papers (15%) addressed limitations regarding the composite measure.Opportunity scoring and all-or-none scoring are the most frequently used approaches when constructing composite measures of quality of care. The attention towards the rationale and limitations of the composite measures appears low.Considering the widespread use and the potential implications for decision-making of composite measures, a high level of transparency regarding the construction process of the composite and the functionality of the measures is crucial. Quality of health care is essential for all healthcare stakeholders, including, patients, healthcare providers, institutes, insurers, policy makers, and government. Hence, valid assessment of the quality is crucial in order to monitor, evaluate and improve the quality of healthcare services. Quality indicators are measurement tools that are used to quantify the quality of care. They serve various purposes such as documenting the quality, benchmarking, setting priorities, facilitating quality improvement and supporting patient choice of providers. The indicators can be classified in various ways with Donabedian’s structure, process and outcome indicator classification being the most frequently adopted approach . The useA composite measure can be defined as a combination of multiple individual indicators . IndividHowever, composite indicators also come with limitations. Differences and relationships between individual indicators may be masked and information regarding specific aspect(s) of performance can be lost . Using dDetailed recommendations on the construction of reliable composite indicators have been published previously , 7. The The aim of this study was to investigate the use of composite measures of quality of care based on process indicators in the peer-reviewed literature. In addition, we examined whether methodological considerations were provided in the publications.This review was done in accordance with the recommendations in the PRISMA statement .Different approaches for construction of composite indicators exist, which mostly differ in terms of weighting and aggregation of individual indicators. Some of the methods to construct composite indicators are introduced .In patient average, all-or-none scoring and 70% standard approaches, composite scores are calculated at patient-level and requires patient-level information. The scores obtained for each patient can subsequently be averaged to get provider-level, region-level or other levels of interest scores.There are several approaches for assigning weights to individual indicators before aggregating them into composites. Some of the methods to assign weights to individual indicators are provided .denominator-based weights approach and is a weighted average for which the weights are the rate of eligibility for each indicator. In our review, we preferred to distinguish between this kind of weights which occurs naturally due to aggregation method and the weights which are additionally assigned to indicators by investigators according to each indicator’s association with the outcome, reliability, feasibility, importance or an expert judgement. Therefore, if opportunity scoring is used in a study without further assignment of weights to individual indicators and no differentiation is made between indicators, we referred this method as “opportunity scoring with equal weights”. Furthermore, the scores obtained by using patient average, overall percentage and indicator average methods will be the same if all of the patients are eligible for all indicators, even though the interpretation of the results will differ. Finally, it should be emphasised that weighting individual indicators before aggregation is not relevant in all-or-none scoring.Note that in the literature opportunity scoring is sometimes also referred to as We conducted a literature search to identify publications that used composite measures to assess quality of care. We queried the PubMed and EMBASE databases (latest update 1 December 2020), using the following terms: composite measures, quality of health care and other variations . We did In this review, we included studies using composite measures based exclusively on process of care indicators. Process indicators  have some advantages over outcome indicators. First, these indicators reflect actual care delivered to the patients, hence, they can be more actionable. Second, outcome indicators like 30-day mortality or readmission rate may be influenced by confounding factors, e.g., age, sex, severity of underlying disease or level of comorbidity, which may not be completely eliminated by risk adjustment . Third, Whereas clinical process indicators reflect actual delivered care, indicators reflecting utilization or access to care were not included as they reflect a complex result of organizational factors, patient preferences and patient compliance . These iEven though patient-reported indicators may carry useful information, they typically lack details on the timeliness and appropriateness of individual clinical processes, which are crucial when evaluating the quality of care. Therefore, the studies that used these types of indicators in the composite measure were also excluded in the current review.The exclusion criteria were as follows: (1) the composite measure included other types of indicators besides process indicators, (2) the composite measure included indicators related to access or utilization, (3) the composite measure included patient-reported indicators, (4) the scientific contribution was a protocol, trial design, purely methodological, letter, comment, editorial or a review, (5) the publication was not in English and (6) full text was not available.Study selection was performed using Rayyan . RecordsFor each publication, we extracted information on the weighting and aggregation methodology that had been used to construct the composite indicator(s).In addition, we registered justifications made for the selected methodology. We defined “justification” as the presence of any stated methodological argument for the methodology that had been used in the individual publications. We preferred not to use a very strict and detailed criterion to prevent subjective use and understanding of the term. We also obtained information on limitations and advantages of using composite indicators stated in the included publications. Finally, we examined whether publications using a single approach for construction of composite measures mentioned any alternative approaches.We preferred to accept publications that only provided reference to these information  as “provided information”. We recognize that especially when the main aim is not to assess the use of composite indicators directly, but rather to use composite indicators to support operational use , providing detailed information about composite indicators may seem out of the scope of the publications. However, it is still important to provide the reader with some information about presence of potential limitations in relation to these indicators and the approaches used to construct them.The search resulted in a total of 2711 publications, 1835 publications from PubMed database and 876 publications from EMBASE database. After removing 549 duplicates, 2162 unique publications were screened. First, title and abstracts were assessed for eligibility and 1889 publications were excluded since at least one of the exclusion reasons mentioned above was present. A total of 273 publications were included for the full-text screening and 145 of those met the full inclusion criteria. The list of included publications are provided . DetaileWe categorized the publications according to (1) methodology that was used, (2) whether the publication used a single approach or multiple approaches to construct composite indicator(s), and (3) context. For context, we classified the primary objective of the publications under two main categories: operational use  and research purposes  . We provOf the publications classified as operational use , 51 publications –66 invesOf the studies classified as research , 25 publications –101 repoOut of 145 publications, three included composite measures for mental health care, including depression , and oveOpportunity scoring was the most used scoring method and represented in 89 (61%) publications. Of these, 62 (43%) publications had applied the overall percentage approach and 28 (19%) publications applied patient average. The second most used method was all-or-none scoring . Out of 145 publications, 8 (6%) publications used 70% standard and other thresholds approach. Indicator average approach was present in 19 (13%) publications. Other approaches included two publications using latent variable models, one publication with principal component analysis and one publication with 70% standard approach on indicator level rather than patient-level . ReferenWeighting of individual indicators before aggregation were not relevant in the 27 publications using only all or none score approach. Of the remaining 118 publications, 107 used equal weights. Differential weights were present in 16 publications: 7 publications used weights obtained by expert opinion/subjective assessment, one publication used regression weights, three publications used weights obtained by item response theory, one publication used weights obtained by Bayesian approach, one publication used the benefit of doubt approach  and three publications applied principal component analysis based weights . ReferenOne publication  used patAll of the studies that were conducted in order to support operational use preferred either equal weights or expert weights whereas more diverse approaches were used in publications with research purposes.It was not possible to determine the methodology in four publications , 95, 97.Justification for the selected methodology used in the construction of the composite measure was found in 36 (25%) publications. The justifications included both limited justifications and justifications that were referenced . ExampleOf 145 publications, methodological limitations of composite measures were addressed in 22 (15%) publications, including limitations that were referenced . The repOf 145 publications, 42 (29%) publications mentioned specific advantages of composite indicators . ReporteOf the 119 publications, which used a single composite score methodology, a total of 10 (8%) publications mentioned the presence of alternative methods for the construction of composite indicators .Some examples regarding methodological statements found in the literature is provided .Despite the importance and widespread use of composite indicators to summarize the quality of health care, we found that methodological considerations were not addressed in the majority of the publications and that there was only modest variation regarding the chosen methodology for construction of the composite measure(s). Opportunity-based scoring, indicator average and all-or-none scoring were the most frequently preferred approaches to obtain composite measures, whereas use of other methods was sparse.To our knowledge, this is the first review that investigates the use of composite measures of quality of health care based on process indicators. Some strengths of this review were: (1) It complied with the PRISMA guideline for systematic reviews whenever possible, (2) A large number of studies were included as we did not restrict our search to a specific clinical condition but considered all clinical conditions and disease areas relevant, (3) all publications were carefully screened by two independent reviewers to reduce possible bias.This review has several limitations. First, it was restricted to peer-reviewed publications included in the PubMed and EMBASE databases. However, these two databases cover a substantial amount of publications within the field. Second, relevant publications might have been excluded if they were not in English. And third, although guidelines for validating composite measures of quality of health care have been developed , we did Composite measures have the advantage of summarizing the quality of care with a single number and have been increasingly used to evaluate the quality of healthcare services. One of the concerns regarding use of composite measures is the lack of a standard approach to construct them and possible effects and consequences of using different approaches. Several studies in the literature examined the effects of using different approaches regarding weighting and aggregation. However, the findings have been contradictory with some studies indicating that the use of different methods provided substantially different results, whereas others have found highly correlated results, e.g., in healthcare provider rankings, using different methods.Jacobs et al.  investigIn contrast, Eapen et al.  comparedKolfschoten et al.  investigThe requirements for specific clinical conditions should be taken into account when selecting the most suitable methodology. As an example, the two most commonly used approaches, opportunity-based scoring and all-or-none scoring, emphasize different aspects of quality. Opportunity-based scoring awards partial performance and improvements, whereas all-or-none scoring promotes excellence and defect-free care. While using all-or-none scoring can be more suitable for conditions that require 100% adherence and anything other than ideal care is not enough to achieve success, opportunity-based scoring can be more useful to investigate and award improvements over time. For statistical approaches for construction, using principal component analysis can be beneficial when individual indicators are highly correlated with each other and can be grouped together , whereas regression weights can be considered when there is a gold standard end point .Selection of individual indictors to be included in the composite requires careful evaluation. Investigating overall structure of the dataset including correlations and interrelationships between indicators may be useful and important to have meaningful composite measures and to prevent possible problems, such as double counting and can be a primer for the decision regarding assigning weights to individual indicators. Including clinical experts  for indicator selection and weighting of indicators can be also considered in order to achieve potentially more clinically meaningful composite indicators.Validation of the final composite indicator is an important step of construction in order to assure the composite indicator is fit for purpose, reliable, accurate and robust. National Quality Forum states that even if studies use already validated individual indicators, the final composite measure may not be the true reflection of quality after weighting and aggregation steps . Hence, This review provides an overview of the methodologies for composite measures used in the peer-reviewed literature to evaluate the quality of care based on process indicators, including the justifications and methodological considerations made regarding these measures. An increased awareness among researchers and healthcare professionals is warranted regarding the presence of alternative methodologies and the importance of a transparent and robust methodology when constructing and reporting composite measures of process quality of health care.S1 Appendix(DOCX)Click here for additional data file.S1 Checklist(DOC)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.S4 Table(DOCX)Click here for additional data file.S5 Table(DOCX)Click here for additional data file.S6 Table(DOCX)Click here for additional data file.S7 Table(DOCX)Click here for additional data file.


Combined training intervention—as part of an antibiotic stewardship program—can be effective in avoiding unnecessary urinalysis and reducing antibiotic consumption.Inappropriate diagnosis of urinary tract infections (UTI) contributes to antimicrobial overuse. A combined training intervention for medical and nursing staff mainly addressing the analytic process reduced UTI events (9.20 vs. 7.36 per 1000 PD, −20.0%,  E. coli, they are a major target of ASPs [Urinary tract infections (UTIs) are the third most common type of healthcare-associated infections in Germany and the fifth most common in the United states accounting for a considerable amount of in-hospital antibiotic consumption , 2. UTIs of ASPs . Especia of ASPs , 6. ASPsThe analytic process consists of preanalytics , analytics (species identification and antibiotic susceptibility testing), and postanalytics . Analytics and early stages of postanalytics  are subjects to the laboratory process and may therefore be controlled straightforwardly . HoweverEducation can change behavior of medical personnel. It is a core element of ASPs and has the power to influence all persons responsible in the pre and postanalytical processes . NursingThis educational intervention was carried out between January and June 2019 at Wuerzburg University Hospital (UKW), a 1430 beds tertiary care hospital in Bavaria, Germany. We identified both medical and nursing staff as target groups and conducted training on pre and postanalytics of urinary tract infections.For physicians, particular emphasis was placed on indication for UTI diagnostics, diagnostic criteria of UTI and management of ASB, and antibiotic therapy of UTI. Training was held in 14 departments . Nursing staff was addressed in monthly held educational sessions. Nursing staff at UKW is advised to participate in these sessions once per year. Attendance of training was documented for 48% of nurses in 2019. Focus was set on indications for UTI diagnostics , sampling , and transport .To quantify the impact of the training intervention, we assessed the following indicators before (July–October 2018) and after intervention (July–October 2019): access frequency to the local guideline for UTI, number of urinalysis, number of urine culture, UTI events, and antibiotic use rate (AUR) of ciprofloxacin, fosfomycin and nitrofurantoin, which were appraised on a monthly basis.In Germany, hospital revenues are standardized by diagnosis related groups (DRG). UTI events were requested from the hospitals controlling based on ICD-10 diagnosis N39.0 (urinary tract infection).The recommendation of the local guidelines is based on local antibiotic resistance. Results of susceptibility testing of urinary samples at UKW in 2019 are provided in Supplementary t-test was used on UTI diagnosis (significantly different variances in Levene's test) and Student's t-test on all other indicators (no significantly different variances). Two-tailed significance level α was set to 0.05.IBM SPSS® Statistics version 24  and Microsoft® Excel® 2016  were used for statistical analysis. No variable showed a significant aberrance from normal distribution using the Shapiro–Wilk test. Welch's p = 0.09, Access frequency to the hospital guideline for UTI almost doubled after intervention. While from July to October 2018, it was accessed 44 times, between July and October 2019, and staff consulted the document 86 times . The number urine cultures from indwelling catheters increased from 4.29 to 5.11 per 1000 PD (+19.0% p = 0.038). This increase in appropriate UTI diagnostic leads to a significant decrease in diagnosed UTIs, classified on the basis of ICD-10, after intervention .The number of urinalysis decreased slightly after intervention, but did not reach statistical significance  and use of parenteral ciprofloxacin declined from 11.6 to 3.5 RDD per 1000 PD  after intervention. Total ciprofloxacin AUR was reduced from 11.6 to 3.5 RDD per 1000 PD . At the same time, AUR of nitrofurantoin doubled, but as a result of the low initial level, this did not reach statistical significance .In parallel with the reduction of ciprofloxacin, the AUR of fosfomycin decreased slightly  are in routine use. In a study by Lim et al. on nurses` knowledge, perception, and practice around urinalysis, performing urinalysis on all new admissions was identified as routine practice by 89% and 35% of patients with indwelling catheters . HoweverAccording to national and international guidelines, the triad of clinical symptoms, pyuria, and cultural pathogen detection has to be fulfilled to diagnose UTI , 16. ComRegarding antibiotic choice of treatment of UTI, the key message of our training intervention was the recommendation against the use of fluoroquinolones. AUR rates of intravenous and oral ciprofloxacin dropped significantly (−69.6% and −63.8%). The choice of agent was addressed in the training events, and alternatives to fluoroquinolones were advocated for complicated and uncomplicated UTI. For uncomplicated UTI, clinicians preferably chose nitrofurantoin (+93.7%) over fosfomycin (−17.8%). One reason for the preference of nitrofurantoin over fosfomycin might be that the latter is considered as a last-resort antibiotic even when it comes to uncomplicated urinary tract infections. The advantage of nitrofurantoin in the treatment of uncomplicated UTI has recently been demonstrated, although the known adverse effects, e.g., liver injuries or interstitial pneumonitis, should be not lost out of focus .Our study has important limitations. At UKW, electronic patient record is not available for all wards. Therefore, diagnosis-related assessment of AUR was not possible, and AUR of ciprofloxacin includes prescription for other indications than UTI. The intensified warning of the German Federal Institute of Drugs and Medical Devices  in April 2019 on risks of adverse events caused by fluoroquinolones may have influenced physicians in their prescribing behavior. Furthermore, we did not evaluate the knowledge pre and postintervention, neither did we measure the satisfaction scale of the target group. Reduction of AUR of fluoroquinolones is a main target of our ASP and rates dropped from 10.5% to 40.7% per year since 2016 (data not shown). Our intervention reinforced the efforts of reducing AUR of ciprofloxacin and so did other ongoing measures as ward rounds, local guidelines, and selective antibiotic reporting. Last, owing to its retrospective design, the study was not controlled for other factors that might have influenced the outcome.The implementation of a combined training intervention involving medical and nursing staff can be effective in curtailing unnecessary urinalysis, subsequent UTI events, and antibiotic consumption.


MET gene, known as MET proto-oncogene receptor tyrosine kinase, was first identified to induce tumor cell migration, invasion, and proliferation/survival through canonical RAS-CDC42-PAK-Rho kinase, RAS-MAPK, PI3K-AKT-mTOR, and β-catenin signaling pathways, and its driver mutations, such as MET gene amplification (METamp) and the exon 14 skipping alterations (METex14), activate cell transformation, cancer progression, and worse patient prognosis, principally in lung cancer through the overactivation of their own oncogenic and MET parallel signaling pathways. Because of this, MET driver alterations have become of interest in lung adenocarcinomas since the FDA approval of target therapies for METamp and METex14 in 2020. However, after using MET target therapies, tumor cells develop adaptative changes, favoring tumor resistance to drugs, the main current challenge to precision medicine. Here, we review a link between the resistance mechanism and MET signaling pathways, which is not only limited to MET. The resistance impacts MET parallel tyrosine kinase receptors and signals shared hubs. Therefore, this information could be relevant in the patient’s mutational profile evaluation before the first target therapy prescription and follow-up to reduce the risk of drug resistance. However, to develop a resistance mechanism to a MET inhibitor, patients must have access to the drugs. For instance, none of the FDA approved MET inhibitors are registered as such in Chile and other developing countries. Constant cross-feeding between basic and clinical research will thus be required to meet future challenges imposed by the acquired resistance to targeted therapies.The  EGFR, ALK, ROS1, HER2, and MET (among others) had demonstrated advantages favoring cell transformation, leading to the expansion of the altered clone, which could be followed by tumor formation and its evolution.The principal hallmark of tumorigenesis is cell transformation, involving the transition of normal cells into the tumorigenic state, followed by an enhanced cell proliferation, and anchorage-independent growth, which result in cell migration, invasion, and finally metastasis. However, depending on the signaling pathways altered by the driver mutations, the tumor mass would be highly proliferative, invasive, angiogenic, and or metastatic . AssuminMET gene encodes a member of the receptor tyrosine kinase (RTK) family of proteins, and, since the early 1980s, different authors have studied the effect of MET on cancer development, starting by Cooper et al., who were the pioneers in recognizing MET gene as a “driver gene” when this concept did not exist yet, describing it as a transforming gene detected in chemically transformed cells [METamp would be able to induce cell transformation and hepatocellular carcinoma (HCC) in mice overexpressing a wild-type allele of human MET, although the carcinoma only arose in cooperation with the constitutively active β-catenin expression [MET transgenes induced the regression of HCC [PTEN deletion leads to prostate neoplasia and prostatic adenocarcinomas, inducing an epithelial-mesenchymal transition and an increase of metastasis events [METex14, which is by far the most common MET mutation. In this review, we will discuss the current therapeutic opportunities for MET driver alterations and the current understanding of MET resistance mechanisms.The ed cells . Afterwapression . Perhapsn of HCC . In the s events . As a reMET mutation or with the gene copy number gain (GCN) [MET as an oncogenic driver. As METamp has been recognized as a bad prognosis biomarker in NSCLC, HCC, gastric cancer, and triple-negative breast cancer [In 1996, Ichimura et al. revealed that MET protein and its specific ligand, hepatocyte growth factor (HGF), were highly expressed in lung cancer cell lines, as well as in non-small cell lung cancer (NSCLC) biopsies . Howeverin (GCN) , which ct cancer ,11,12, it cancer .METamp frequency in different solid cancers could be estimated thanks to the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE), which is an international pan-cancer registry [METamp represents a 2% in non-small cell lung cancer , a 1.2% in renal (1556 patients), and hepatobiliary (1854 patients) cancers, followed by a 0.4% in colorectal (7370 patients), 0.2% in ovarian (4481 patients), breast cancer (8365 patients), and prostate cancers (3530 patients). NSCLC has the highest METamp and driver mutations frequency , which is key for MET protein degradation. The METex14 causes the loss of JMD when mutations at the splice donor or acceptor sites result in exon 14 loss, such as base substitutions, insertions, deletions, and intronic noncoding regions immediately adjacent to the splice acceptor site and the whole-exon deletion. When some of these alternatives derived in a truncated MET receptor, it shows a constitutive expression because the loss of the Tyr1003 residue located in the JMD prevents the binding of the E3 ubiquitin ligase Cbl and proteasomal degradation, which have shown overactive MET signaling pathways, triggering an exacerbate cell proliferation and invasion, contributing to the evolution of cancer and bad prognosis [Normally, in rognosis ,20.METex14 occurs in 3 to 4% of NSCLC patients , which were searched in the GENIE public database, and, as a result, only D1010N was found, representing 9.6% of 439 MET driver mutations , followed by the X963_splice (20.9%) and D1010H (9.7%)  .MET mutations had not been functionally or clinically validated yet , followed by the polypyrimidine tract (15%), the splice acceptor site (~5%), and both the splice acceptor site and the polypyrimidine tract (13%). All these alterations resulted in the elimination of exon 14 with an mRNA containing the exon 13 fused to exon 15 [Still, the validation and approval of additional utations ,25. Inde exon 15 .METex14 revealed in mRNA, the diagnosis sensitivity could challenge the identification of them in DNA assays. In contrast, RNA approaches directly identify 13–15 exons fusion in the transcript. For this reason, the amplicon-based approaches may fail to find METex14 alterations because it does not allow the detection of large deletions. However, hybrid capture is more amenable to detecting the alterations leading to METex14. Furthermore, this method generally isolates larger fragments of DNA, including sequences that flank the regions of interest, compared with amplicon-based methods when using DNA as the input material [Thereby, given the diversity of alterations leading to material . Additiomaterial . Likewismaterial , so RNA MET mutations [METamp and METex14, have shown their actionability in NSCLC, such as prognosis, and expanding the therapeutic opportunities for patients without EGFR and ALK as usual alterations [The validation of new driver alterations and their actionability helps improve target drug availability, which contributes to the development of precision medicine . As it iutations , to dateerations .The NSCLC subtype adenocarcinoma has been the most advanced cancer subtype in the implementation of targeted therapies, and at the current date, two categories of MET tyrosine kinase inhibitors (TKI) have been validated , such asMETamp in NSCLC patients [METamp, not all GCN levels experience the same therapeutic results, as was demonstrated in the clinical trial PROFILE-1001 in 2021 (NCT00585195), where low levels (≥1.8–≤2.2 copies), medium (>2.2–<4 copies), and high (>5 copies) experienced a progression-free survival (PFS) of 1.8, 1.9, and 6.7 months, respectively [Crizotinib was validated in 2010 for patients , and in patients . Howeverectively . Drilon ectively  reportedTepotinib is a kinase inhibitor that targets MET alterations, including METex14. It was FDA approved in 2021 for patients with metastatic NSCLC (mNSCLC). Tepotinib inhibits the hepatocyte growth factor of dependent and independent MET phosphorylation and MET-dependent downstream signaling pathways . In the METamp was higher in tumors with a high GCN than in those with a lower GCN (METamp in combination with gefitinib (NCT01610336 and NCT01324479) in NSCLC with METex14 and MET GCN > 6 (high) [METex14 skipping mutations who previously had received one or two lines of therapies, with an overall response in 41% of the patients but showed limited activity in patients who had METamp with a gene copy number of less than 10 (Capmatinib is a selective MET TKIs ATP-competitive MET inhibitor (type Ib) and was screened against >400 kinases, showing high selectivity for MET. In 2020, capmatinib was FDA approved for patients with mNSCLC harboring METex14 showing a significant antitumor activity, particularly in those not previously treated, and this drug has been approved in several countries including UE, the EU, US, Switzerland, and Japan. The overall response rate observed with capmatinib in patients with METex14 skipping mutation was 41% in 69 patients who had received previous treatment and an ORR of 68% in patients naïve to treatment. In terms of time of response, 82% of patients who had been previously treated with other lines of therapy had tumor response at the first CT scan of evaluation. Capmatinib showed high response rates in patients with intracranial disease with 33% of patients achieving complete response. In addition, the response to ower GCN . Capmati6 (high) . Lower e than 10 .Savolitinib is a potent and highly selective oral MET TKI that provides clinical benefits for patients with mNSCLC papillary and clear cell renal cell carcinoma (RCC), gastric cancer, and colorectal cancer . In a phMET alterations have gained relevance since NSCLC patients with low MET GCN (METamp GCN ≤ 10) have been treated with immune checkpoint inhibitors (ICI), which showed a median survival of 19 versus 8 months with chemotherapy. Nevertheless, in patients with high amplification levels (GCN ≥10), the median survival was 36 months with ICI compared to 4 months with chemotherapy. However, the patients with METex14 did not present significant differences, and there was a trend toward improved survival with ICI therapy compared to chemotherapy (16.0 months versus 10.0 months) [In relationship with the immunotherapy,  months) .In general, the treatment for mNSCLC, which occurs in one-third of METex14-altered lung cancers at diagnosis , currentMETamp shows a vast heterogeneity in GCN; however, the best therapy prognosis has been seen in the high levels (GCN > 10) as depicted in METamp is increased without any known actionable alteration that drives the tumor, the evaluation of immunotherapy additional to MET TKIs is recommended. As such, the MET inhibitors plus immune checkpoint inhibitors (ICIs) strategy has been improving pancreatic cancer immunotherapeutic efficacy [MET alterations.The efficacy , evidencefficacy . FurtherAdditionally, an mNSCLC case report treated with chemotherapy switched to pembrolizumab (PD-L1 70%) with tepotinib that enabled stable disease following this therapeutic decision for 31 months . AccordiEven though targeted therapies have increased the life expectancy of patients with druggable driver alterations , their eAlthough the study of signaling pathways has been confined to basic science, it gives insight into relevant information for precision medicine when the driver alterations are spatially localized in their signaling pathways to predict future resistance mechanisms according to a personalized somatic mutational profile analysis, which does not only consider the diagnosis of actionable mutations with the highest mutation frequency, because intratumor low-frequency alterations should also be considered as a possible future resistance mutation. The manual curation of somatic mutations after the NGS bioinformatic analysis is rich in information to envisage possible sensitivity and resistance alterations when considering known variants at low frequency could then be stimulated by the target drugs based on the sub clonal evolution, where the treatments may serve as a selective pressure to increase the frequency of these possible resistance mutations .The scene of resistance mechanisms to MET TKIs has not been well characterized, and its frequency impact is unknown. However, acquiring resistance mutations could have on-target preference after MET-TKIs fail A. One foMETex14 NSCLC patients demonstrated known and suspected resistance mechanisms in 15 patients. The on-target acquired resistance mechanisms, including MET kinase domain mutations in codons H1094, G1163, L1195, D1228, and Y1230 in seven patients (35%), showed high MET exon 14-mutant allele amplification [METex14 using in vitro models .MET activation is an effective resistance mechanism to targeted therapies against several RTKs, including  as BRAF . An examMETamp [EGFR mutations, and the results do not show significant improvement in OS compared to standard chemotherapy; one reason for this response is that this combination may have better response rates in high MET overexpression (IHC3+) or METamp (GCN ≥ 5).The concomitant use of MET inhibitors, such as crizotinib, in combination with osimertinib, can improve the sensitivity of patients with osimertinib-resistant EGFR mutations and with amplified MET, which were detected using ctDNA . CurrentMETamp  positiveMETamp due to gefitinib resistance drives the drug bypass through ERBB3 dependent activation of PI3K [METamp cell lines treated with capmatinib have suggested that the activation of EGFR-PIK3CA signaling may mediate the resistance without any EGFR activating mutation or amplification , where Akt/mTOR is a crucial signaling component through which Met protects multiple myeloma cells from chemotherapy-induced growth inhibition and apoptosis. c-Met/Akt/mTOR pathway is a potential therapeutic target to overcome the chemoresistance of MM [This signaling pathway is activated by the HGF/SF receptor and includes the generation of D-3-phosphorylated inositol phospholipids B, which l models . MET hasce of MM . In factce of MM .A study investigated the therapeutic potential of cabozantinib using a large panel of HCC cell lines, and distinct oncogene-driven HCC in mice, where cabozantinib inhibited c-MET and its MAPK signaling activity; however, it was ineffective in inhibiting the MET/Akt/mTOR cascade, but mixing cabozantinib and pan-mTOR inhibitors, has shown synergistic properties in inhibiting HCC growth in vitro and in driving tumor regression in mice .Focal adhesion kinase (FAK) regulates the reorganization of the actin cytoskeleton, cell polarization, cell migration, and adhesion, spreading through MET in medulloblastoma . The comThe inhibition of MET alone has been demonstrated to have limited efficacy in colon cancer; although the Src inhibitor, dasatinib, reduced MET autophosphorylation and decreased MET phosphorylation by stimulating factors, the inhibition is not complete. In addition, the simultaneous inhibition of MET and Src demonstrated that the combination treatment reduced cell viability and increased the apoptosis rate in mutant and wild-type Ras colon cancer cells .In recent years, it has been reported that activation of the MET/FAK signaling axis leads to CDK4/6-independent CDK2 activation, and the blockage of the three targets reduces cell proliferation and enhances tumor growth inhibition in vivo . In addiA series of studies confirmed the importance of FAK/Src signaling in resistance to first-(erlotinib), second- (afatinib), and third-generation (osimertinib) EGFR TKIs; thus, with the current diagnosis and mono target therapies against MET, this signaling could be implicated in MET-TKI resistance with an emphasis in metastatic tumors because it activates the signaling pathways such as MET/FAK involved in polymerization and contraction of the actin cytoskeleton to cell migration, followed by intra-extravasation through invasion of basal membrane and metastasis.Crosstalk among signaling in HCC, such as the MET/β-Catenin axis, resulting in FAK is required for MET/β-Catenin-driven hepatocarcinogenesis. Additionally, in this study, the authors demonstrated that FAK deficiency in hepatocytes largely blocks HCC development induced by MET/β-catenin ,35.The crosstalk between HGF/Met and Wnt/β-catenin is strongly implicated in hepatocarcinogenesis ,87. It hA mechanism of c-Met inhibitor resistance in melanoma was suggested using melanoma in vivo and in vitro models with high levels of phospho Met. After inducing the resistance to MET-TKI (SU11274 and JNJ38877605), cell lines displayed upregulation of phosphorylated Met and overactive β-catenin, suggesting the involvement of the Wnt pathway B. When MFinally, we used all resistance mutations from MET gene are facing a significant disparity in the access to target therapies. In Chile, comprehensive tumor profiling is not part of the lung cancer standard of care, or any national health policies. Precision medicine, and target drugs’ implementation is challenging due to the high cost and lack of biomarker testing options. Patients diagnosed with NSCLC should undergo examination for EGFR, ALK, ROS1, and PDL-1 protein expression according to the drugs registered and available in Chile. Therefore, MET mutations are not considered in the evaluation, and there are no registered MET inhibitors in Chile, except for crizotinib, but it is approved only for patients with ALK and ROS1 alterations. If a lung cancer patient in Chile is diagnosed with a MET actionable alteration, off label use of crizotinib or participation in MET specific inhibitor clinical trial are possibilities. Standard of care treatment option would include surgery, chemotherapy, radiotherapy, or palliative care for these patients. As of today, there is not any public indication of any attempt to register MET inhibitors in Chile. Expectations regarding comprehensive tumor profiling and better access to high-cost drugs resurged with the implementation of recently approved legislation .A complete understanding of the driver mutations and pathways altered is essential to identify potential therapeutic options and vulnerabilities to the therapies, such as treatment resistance. The relevance of a deep analysis of tumor mutational profile in a study of METamp as a consequence of EGFR TKIs resistance therapies detected clones displaying METamp at a shallow frequency before any treatment with an EGFR TKI, suggesting that these clones were selected under therapeutic pressure . Perhaps


Saccharomyces cerevisiae has been studied for its beneficial impact on animal intestinal health. Herein, we examined how MRF affected the formation of reactive oxygen species (ROS), impacting antibiotic susceptibility in resistant Escherichia coli through the modulation of bacterial metabolism. The role of MRF in effecting proteomic change was examined using a proteomics-based approach. The results showed that MRF, when combined with bactericidal antibiotic treatment, increased ROS production in resistant E. coli by 59.29 ± 4.03% compared to the control (p ≤ 0.05). We further examined the effect of MRF alone and in combination with antibiotic treatment on E. coli growth and explored how MRF potentiates bacterial susceptibility to antibiotics via proteomic changes in key metabolic pathways. Herein we demonstrated that MRF supplementation in the growth media of ampicillin-resistant E. coli had a significant impact on the normal translational control of the central metabolic pathways, including those involved in the glycolysis–TCA cycle (p ≤ 0.05).Mannan-rich fraction (MRF) isolated from  E. coli following MRF supplementation via cellular metabolic and energetic modulation  (µM−1) = ((ΔODSAMPLE − ΔODBLANK)/Slope (µM−1)) ∗ n, where slope is the slope of the standard curve and n is the dilution factor.The NAD was supplemented into the overnight growth media of both TOP10 non-transformed E. coli and E. coli transformed with pBR322 harboring resistance to ampicillin. Untreated bacterial cultures served as the negative control. A reference control with no antibiotic was included for each analysis. Replicate analysis was conducted using a Tecan Infinite M200 Pro microplate reader, Switzerland. The viable count was measured up to 18 h with defined measurement intervals, following a 5 s medium shake. Aliquots of 200 μL per well were analyzed in triplicate at OD λ595nm in a sterile 96-well flat-bottom microtiter plate. Separately, aliquots of 5 µgmL−1 ampicillin were added per well (10 μL). To this, 20 μL aliquots of the test organism (adjusted to 0.01 OD at λ595nm (approx. 1 × 10−8 cfu/mL)) taken from the exponential growth phase  and grown for approx. 1–3 h) were added to each well. OD measurements were examined at 4, 6, 10, 14, and 18h across various test conditions to determine any modulation in growth compared to the control culture. Experiments were conducted using the same strain in identical media, and the experiment was repeated three times independently, with three replicates per sample.A kinetic growth study was performed to determine the effect of MRF on the growth of resistant +) determination, and growth analysis, one-way analysis of variance (ANOVA) and Fisher’s LSD multiple-comparisons tests were conducted to determine any significant differences among the means ). Statistical significance between the normalized peptide abundance of resistant E. coli relative to the control was determined using ANOVA, T-test between pairs assuming unequal variance (EXCEL). Significant levels were defined using p ≤ 0.05.For ROS, NAD(H/E. coli. Previously, yeast MRF was noted to result in higher oxygen consumption, and, together with these results, we propose evidence of a link between cell physiology and antibiotic effectiveness, demonstrating a potential target for improved disease prevention strategies. In this study, MRF led to a cascade of modulations in the central metabolic pathways, bacterial growth, and stress response, that together contributed to the potentiation of phenotypic resistance or physiological antibiotic susceptibility. Enhancing ROS production or interfering with protection against ROS via MRF supplementation represents a novel strategy for potentially augmenting antibiotic treatment. With the alarming increase in antibiotic resistance in bacteria, a better understanding of the potential exogenous influences that could enhance antibiotic efficacy would support future strategies to combat resistance. Increasing our knowledge of the interaction between prebiotics such as MRF and resistant microorganisms may make it possible to reduce antibiotic use whilst promoting animal health strategically and naturally.It is evident from the relevant research and the data presented here that metabolism plays a significant role in oxidative stress and the phenotypic antibiotic susceptibility of