Safe Level Research Articles

Health risk assessments and source apportionment of PM2.5-bound heavy metals in the initial eastern economic corridor (EEC): A case study of Rayong Province, Thailand

This study aimed to determine the metals in ambient PM2.5 in the expanding industrial metropolitan area of Rayong Province for health risk assessment and source apportionment from May 2022 to April 2023, covering wet and dry seasons. The mean annual PM2.5 concentration was 15.2 ± 12.0 μg m−3, whereas that of wet and dry seasons were 8.4 ± 5.4 μg m−3 and 21.8 ± 12.9 μg m−3, respectively. The annual PM2.5 level exceeded the limit set by the World Health Organization (WHO) (5 μg m−3) and the standard of Thailand (15 μg m−3). A substantial decrease in the Cd, Pb, Zn, Cu, Fe, Mn, and K concentrations was observed during the wet season compared with that of the dry season. The levels of annual Cr in PM2.5 were 40 times higher than the WHO limit. Cd, Pb, and Zn are tracers of anthropogenic activities. Using the enrichment factor (EF) and Igeo, the contamination of As, Cd, Pb, and Zn suggested that the initial Eastern Economic Corridor (EEC) in Rayong Province was highly polluted. The results of the non-carcinogenic risk indicated that human health was notably affected by toxic metals in PM2.5, and the Cr-related carcinogenic risk in PM2.5 exposure suggested a safe or reasonable risk level (10−6 to 10−4). Exposure to toxic metals in PM2.5 increases the risk of developing cancer in adults, potentially owing to the accumulation of these metals within the tissues in the body. Positive matrix factorisation (PMF) suggested that the source apportionment of PM2.5-bound heavy metals was motor vehicles (34.7%), industrial activities (26.3%), biomass burning (22.7%), and road dust (18.5%).

Inactivation of Aeromonas hydrophila in water by dielectric barrier discharge plasma: Efficiency, mechanism, and application safety

Aeromonas hydrophila (A. hydrophila) is a typical zoonotic pathogen that commonly found in water environments, capable of infecting various aquatic animals and causing different diseases in both animals and humans. In this study, the dielectric barrier discharge plasma (DBDP) is used to inactivate the A. hydrophila in water. The efficiency and mechanism of A. hydrophila inactivation by DBDP were investigated, and the application safety of DBDP also were examined. The results demonstrate that DBDP treatment for 8 min can reduce the concentration of A. hydrophila from 108 CFU/mL to 0 CFU/mL under optimal conditions. Higher discharge voltage and lower concentration is beneficial for the inactivation of A. hydrophila, and O2 as carrier gas and alkaline environment can improve the inactivation efficiency. Reactive oxygen species (ROS) produced in the DBDP system play a significant role in A. hydrophila inactivation. However, molecules like O3 and H2O2 long-lived are likely the main forces responsible for the initial destruction of cell membranes. Subsequently, ROS penetrates the cell membrane, and result in the destruction of main virulence genes of A. hydrophila and the loss of bacterial infectivity. The silver carp challenge experiment indicates that mortality rates and septicemia symptoms in silver carp are not significantly different from the control group when treated with DBDP. Moreover, the total bacterial count in the main organs can be reduced to a safe level. These findings suggest that DBDP is a safe and reliable method for inactivating A. hydrophila in water bodies.

Research on the spiral case and external concrete structural response under limit operation state

Abstract As the key component of hydroelectric generating units, the spiral case is primarily responsible to make the fluid flow out in a uniform and axisymmetric way. The structural response of the spiral case and external concrete under hydraulic pressure will have an effect on the operational security and power generation efficiency of the whole unit. In this paper, a three-dimensional fluid-structure coupling model of the spiral case and concrete under limit operation state is established. Based on the computational fluid mechanics theory, the flow domain inside the spiral case is simulated to study the stress and deformation structural response of the spiral case and external concrete under the action of maximum inner hydraulic pressure. The value and position of the maximum stress and deformation are determined. The fluid-structure coupling simulation shows that severe turbulence occurs in the middle of the flow channel. The maximum equivalent stress of the spiral case is located near its tongue and there would possibly be a risk of local structural damage. The external concrete can effectively share part of the load from the spiral case, so as to keep the strength and stiffness of the overall structure being within safe levels under the limit state. The results can provide support to the structural optimization and construction of the spiral case, which is helpful for the safety and stability of station operation.

Wirelessly Powered and Bi-Directional Data Communication System With Adaptive Conversion Chain for Multisite Biomedical Implants Over Single Inductive Link.

A wirelessly powered and data communication system is presented which is implemented as a full system, designed for multisite implanted biomedical applications. The system is capable of receiving wireless power and data communication for each implant separately, using inductive links with different resonance frequencies. To achieve this, dual-band coils are presented in the system. In addition, the system supports bi-directional half-duplex data communication, utilizing amplitude and load shift keying (ASK and LSK) modulation schemes over a single inductive link. The system employs a digitally assisted active rectifier and an automatic resonance tuning system, to improve the power transfer efficiency (PTE) through various coupling coefficients, while minimizing the reverse current and power dissipation. The power control unit enables closed-loop monitoring to prevent high or low power delivery, and it can detect inefficient or excessive wireless power transmission or prevent temperature elevation by limiting the voltage to a safe level. A new structure of self-sampling separated- Vb ASK demodulator is proposed in the paper which is utilized within the data conversion chain, serving both the external and implanted units. The whole system is fabricated using a standard 180-nm 1.8/3.3 V CMOS process with a core area of 0.82 mm[Formula: see text]. The system is tested with coupled multisite inductive links and offers the maximum overall PTE of 31.2%, from the Tx coil to the implant load.

Automatic Pedestrian Safety in Automobiles through Microcontroller and RF Technology

One of the government's top priorities for creating a safe driving environment is pedestrian safety. To guarantee safety in all respects, many safety measures have been put into place by the government and adopted by the populace. The main goal of this study is to indirectly lower the number of accidents by eliminating their core causes. Careless driving and excessive speeding are the main causes of accidents. This document ensures that a car is designed to travel at a specific pace in each area, keeping it within safe speed limit. This lessens the impact of accidents, including material and human loss. This is accomplished by using the proper microcontroller, RF transmitter, and receiver through a comparison process. The car equipped with a receiver, receives the data signal from the traffic sign board, compares it to the output, and adjusts the speed of the vehicle to a safe level. By doing this, the car is always forced to go at the designated speed, and driving behaviour is altered, reducing the likelihood of accidents. This offers a supplementary safety precaution that focuses on eliminating the primary sources of mishaps.

Assessment of the impact on atmospheric air on the example of the Passenger Carriage Depot Vladivostok enterprise of the Far Eastern branch of the Federal Passenger Company, Vladivostok city

The relevance of the topic of the work is to assess the degree of negative impact of the Passenger Carriage Depot Vladivostok enterprise of the Far Eastern branch of the Federal Passenger Company, Vladivostok on atmospheric air. 35 pollutants are released into the atmosphere from the enterprise. The work takes into account 39 sources of atmospheric pollution at the enterprise, operating at the time of the inventory, including 25 organized and 14 unorganized. In order to analyze the amount of pollutants entering the atmospheric air, calculations were performed using a unified program — UPRZA Ecologist version 4.6. Based on these calculations, an analysis of emissions of pollutants into the atmospheric air was carried out. The gross emission of 35 pollutants into the atmosphere is 18,998710 tons/year, including solid 5,055938 tons/year, liquid/gaseous 13,942773 tons/year. Of the 17 solid pollutants, the main share of emissions is 0121 diesel trioxide (iron oxide; iron sesquioxide) and 2902 Suspended solids. Of the 18 liquid/gaseous pollutants, the amount of 3 pollutants prevails. These substances include: 2732 Kerosene, 2752 White Spirit and 0616 Dimethylbenzene (xylene). The largest number of emissions from the enterprise are substances that have an approximately safe level of exposure. Of the pollutants that have an approximately safe level of exposure, the most substances emitted per year are: 2732 Kerosene (direct distilled kerosene; deodorized kerosene), 2752 White Spirit. The purpose of this article is to assess the impact of the Passenger Carriage Depot Vladivostok of the Far Eastern branch of the Federal Passenger Company on atmospheric air.

Scientific opinion on the tolerable upper intake level for iron.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the tolerable upper intake level (UL) for iron. Systematic reviews were conducted to identify evidence regarding high iron intakes and risk of chronic diseases, adverse gastrointestinal effects and adverse effects of iron supplementation in infancy, young childhood and pregnancy. It is established that systemic iron overload leads to organ toxicity, but no UL could be established. The only indicator for which a dose-response could be established was black stools, which reflect the presence of large amounts of unabsorbed iron in the gut. This is a conservative endpoint among the chain of events that may lead to systemic iron overload but is not adverse per se. Based on interventions in which black stools did not occur at supplemental iron intakes of 20-25 mg/day (added to a background intake of 15 mg/day), a safe level of intake for iron of 40 mg/day for adults (including pregnant and lactating women) was established. Using allometric scaling (body weight0.75), this value was scaled down to children and adolescents and safe levels of intakes between 10 mg/day (1-3 years) and 35 mg/day (15-17 years) were derived. For infants 7-11 months of age who have a higher iron requirement than young children, allometric scaling was applied to the supplemental iron intakes (i.e. 25 mg/day) and resulted in a safe level of supplemental iron intake of 5 mg/day. This value was extended to 4-6 month-old infants and refers to iron intakes from fortified foods and food supplements, not from infant and follow-on formulae. The application of the safe level of intake is more limited than a UL because the intake level at which the risk of adverse effects starts to increase is not defined.

Safety of soy leghemoglobin from genetically modified Komagataella phaffii as a food additive.

The EFSA Panel on Food Additive and Flavourings (FAF Panel) provides a scientific opinion on the safety of soy leghemoglobin from genetically modified Komagataella phaffii as a food additive in accordance with Regulation (EC) No 1331/2008. The proposed food additive, LegH Prep, is intended to be used as a colour in meat analogue products. The yeast Komagataella phaffii strain MXY0541 has been genetically modified to produce soy leghemoglobin; the safety of the genetic modification is under assessment by the EFSA GMO Panel (EFSA-GMO-NL-2019-162). The amount of haem iron provided by soy leghemoglobin from its proposed uses in meat analogue products is comparable to that provided by similar amounts of different types of meat. The exposure to iron from the proposed food additive, both at the mean and 95th percentile exposure, will be below the 'safe levels of intake' established by the NDA Panel for all population groups. Considering that the components of the proposed food additive will be digested to small peptide, amino acids and haem B; the recipient (non GM) strain qualifies for qualified presumption of safety status; no genotoxicity concern has been identified and no adverse effects have been identified at the highest dose tested in the available toxicological studies, the Panel concluded that there was no need to set a numerical acceptable daily intake (ADI) and that the food additive does not raise a safety concern at the proposed use in food category 12.9 and maximum use level. The Panel concluded that the use of soy leghemoglobin from genetically modified Komagataella phaffii MXY0541 as a new food additive does not raise a safety concern at the proposed use and use level. This safety evaluation of the proposed food additive remains provisional subject to the ongoing safety assessment of the genetic modification of the production strain by the GMO Panel (EFSA-GMO-NL-2019-162).

In Silico Antibacterial Activity of Polyacetilene Derivatives Against Mycobacterium tuberculosis and In-Vitro Antioxidant Properties from Ethanol Extraction of Blackjack (Bidens pilosa L.)

Blackjack (Bidens pilosa L.) has a bioactive compound, one of which is polyacetylene, which can inhibit the growth of antimicrobials in general. This study aims to conduct an in silico study to determine the antibacterial activity against Mycobacterium Tuberculosis of 20 derivatives polyacetylene; TPC was determined by Folin–Ciocalteu colorimetric method using gallic acid as standard, and various concentrations of the extract solutions were measured at 741 nm. TFC was calculated using an aluminum chloride colorimetric assay. Quercetin was used as standard, and the absorbance was measured at 426 nm. Antioxidant activity was evaluated using DPPH scavenging 517 nm and Frap Assay 596 nm. The molecular docking results showed that the compounds (5-(2-Phenylethynyl)-2-b-glucosylmethyl-thiophene, Glucopyranosyloxy-3-hydroxy-6(E)-tetradecane-8,10,12-triyne and Phenylhexa-1,3,5-triyn-1-yl acetate were most potentially anti-tuberculosis on the target protein InhA with the binding energy produced <-6.55 Kcal/mol and the lowest inhibitory cost of 1.838×10-6. The compound has amino acids similar to natural ligands and standard compounds of isoniazid. The given ADME-T predictions showed good pharmacokinetic properties and safe levels of toxicity (5-(2-Phenylethynyl)-2-b-glucosylmethyl-thiophene, Glucopyranosyloxy-3-hydroxy-6(E)-tetradecane-8,10,12-triyne in hepatotoxic and LD50. The highest antioxidant properties in blackjack are produced by FRAP assay 722.905±7.985 mMTE/gr. This proves that blackjack has antioxidant activity and is required for bioassay-guided isolation testing against Mycobacterium tuberculosis.

Coastal ecological security assessment in Laizhou Bay, China: from the perspective of demographic-social-economic-natural complex ecosystem.

Assessment of ecological security is essential for understanding the status of bay ecosystem and developing appropriate management strategy. Based on the driving force-pressure-state-impact-response (DPSIR) model, the demographic, economic, social, and ecological data of Laizhou Bay and its three neighboring counties were selected for the period from 2015 to 2021. An ecological security evaluation index system of Laizhou Bay containing 26 indicators was established, and the weights of each indicator were determined by the methods of AHP and EWM, and a comprehensive evaluation of the ecological security of Laizhou Bay was carried out by ESI. Correlations between indicators were analyzed by the Spearman's rank coefficient of correlation. The results showed that there were significant correlations between marine conditions and indicators such as population size in the surrounding area, mariculture area, industrial and domestic wastewater discharge, and treatment rate. Overall, from 2015 to 2021, the ecological security of Laizhou Bay showed a favorable trend, from a relatively unsafe level to a generally safe level, and then to a relatively safe level. Through the comprehensive evaluation of the ecological security of Laizhou Bay, we can recognize the utilization of marine resources and ecological carrying capacity, guide the rational development and utilization of marine resources, and promote the sustainable development of the marine economy.

High-efficient stabilization and solidification of municipal solid waste incineration fly ash by synergy of alkali treatment and supersulfated cement

Municipal solid waste incineration fly ash (IFA) designated as hazardous waste poses risks to environment and human health. This study introduces a novel approach for the stabilization and solidification (S/S) of IFA: a combined approach involving alkali treatment and immobilization in low-carbon supersulfated cement (SSC). The impact of varying temperatures of alkali solution on the chemical and mineralogical compositions, as well as the pozzolanic reactivity of IFA, and the removal efficiency of heavy metals and metallic aluminum (Al) were examined. The physical characteristics, hydration kinetics and effectiveness of SSC in immobilizing IFA were also analyzed. Results showed that alkali treatment at 25 °C effectively eliminated heavy metals like manganese (Mn), barium (Ba), nickel (Ni), and chromium (Cr) to safe levels and totally removed the metallic Al, while enhancing the pozzolanic reactivity of IFA. By incorporating the alkali-treated IFA and filtrate, the density, compressive strength and hydration reaction of SSC were improved, resulting in higher hydration degree, finer pore structure, and denser microstructure compared to untreated IFA. The rich presence of calcium-aluminosilicate-hydrate (C-(A)-S-H) and ettringite (AFt) in SSC facilitated the efficient stabilization and solidification of heavy metals, leading to a significant decrease in their leaching potential. The use of SSC for treating Ca(OH)2- and 25°C-treated IFA could achieve high strength and high-efficient immobilization.

Frequent Dietary Multi-Mycotoxin Exposure in UK Children and Its Association with Dietary Intake.

Mycotoxins are potent fungal toxins that frequently contaminate agricultural crops and foods. Mycotoxin exposure is frequently reported in humans, and children are known to be particularly at risk of exceeding safe levels of exposure. Urinary biomonitoring is used to assess overall dietary exposure to multiple mycotoxins. This study aims to quantify multi-mycotoxin exposure in UK children and to identify major food groups contributing to exposure. Four repeat urine samples were collected from 29 children (13 boys and 16 girls, aged 2.4-6.8 years), and food diaries were recorded to assess their exposure to eleven mycotoxins. Urine samples (n = 114) were hydrolysed with β-glucuronidase, enriched through immunoaffinity columns and analysed by LC-MS/MS for deoxynivalenol (DON), nivalenol (NIV), T-2/HT-2 toxins, zearalenone (ZEN), ochratoxin A (OTA) and aflatoxins. Food diaries were analysed using WinDiet software, and the daily intake of high-risk foods for mycotoxin contamination summarised. The most prevalent mycotoxins found in urine samples were DON (95.6% of all samples), OTA (88.6%), HT-2 toxin (53.5%), ZEN (48.2%) and NIV (26.3%). Intake of total cereal-based foods was strongly positively associated with urinary levels of DON and T-2/HT-2 and oat intake with urinary T-2/HT-2. Average daily mycotoxin excretion ranged from 12.10 µg/d (DON) to 0.03 µg/d (OTA), and co-exposure to three or more mycotoxins was found in 66% of samples. Comparing mycotoxin intake estimates to tolerable daily intakes (TDI) demonstrates frequent TDI exceedances (DON 34.2% of all samples, T-2/HT-2 14.9%, NIV 4.4% and ZEN 5.2%). OTA was frequently detected at low levels. When mean daily OTA intake was compared to the reference value for non-neoplastic lesions, the resulting Margin of Exposure (MoE) of 65 was narrow, indicating a health concern. In conclusion, this study demonstrates frequent exposure of UK children to multiple mycotoxins at levels high enough to pose a health concern if exposure is continuous.

ESIT – a digital twin of air surveillance infrastructure

Civil air traffic surveillance and management depends heavily on the use of aircraft transponders replying to radio interrogations from cooperative surveillance systems such as secondary surveillance radars, multilateration and collision avoidance systems. A high number of such surveillance systems combined with a high aircraft density can cause a large quantity of interrogations, therefore having a detrimental impact on transponder behavior and sometimes even causing a loss of replies and thus a deterioration in aircraft surveillance. In order to ensure the safe operation of European air traffic management, the European Commission obligates the member states to take measures to ensure that the transponder load in their air spaces does not exceed a safe level. EUROCONTROL, in its function as network manager responsible for supporting the monitoring, management and coordination of the scarce spectrum resource, has contracted the implementation of a European simulation tool to Austro Control in collaboration with SeRo Systems and the Institute of Microwave and Photonic Engineering as subcontractors. This paper examines the development and use of this tool as well as the functionality it provides.

Prenatal exposure to alcohol and its impact on reward processing and substance use in adulthood

Heavy maternal alcohol drinking during pregnancy has been associated with altered neurodevelopment in the child but the effects of low-dose alcohol drinking are less clear and any potential safe level of alcohol use during pregnancy is not known. We evaluated the effects of prenatal alcohol on reward-related behavior and substance use in young adulthood and the potential sex differences therein. Participants were members of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) prenatal birth cohort who participated in its neuroimaging follow-up in young adulthood. A total of 191 participants (28–30 years; 51% men) had complete data on prenatal exposure to alcohol, current substance use, and fMRI data from young adulthood. Maternal alcohol drinking was assessed during mid-pregnancy and pre-conception. Brain response to reward anticipation and reward feedback was measured using the Monetary Incentive Delay task and substance use in young adulthood was assessed using a self-report questionnaire. We showed that even a moderate exposure to alcohol in mid-pregnancy but not pre-conception was associated with robust effects on brain response to reward feedback (six frontal, one parietal, one temporal, and one occipital cluster) and with greater cannabis use in both men and women 30 years later. Moreover, mid-pregnancy but not pre-conception exposure to alcohol was associated with greater cannabis use in young adulthood and these effects were independent of maternal education and maternal depression during pregnancy. Further, the extent of cannabis use in the late 20 s was predicted by the brain response to reward feedback in three out of the nine prenatal alcohol-related clusters and these effects were independent of current alcohol use. Sex differences in the brain response to reward outcome emerged only during the no loss vs. loss contrast. Young adult men exposed to alcohol prenatally had significantly larger brain response to no loss vs. loss in the putamen and occipital region than women exposed to prenatal alcohol. Therefore, we conclude that even moderate exposure to alcohol prenatally has long-lasting effects on brain function during reward processing and risk of cannabis use in young adulthood.

Systematic testing, verification and validation of laser treatments for unglazed earthenware affected by lichens and fungi biodeterioration

In recent years, there has been a growing interest in exploring environmentally friendly and healthy alternatives to conventional solvent cleaning and biocides in the conservation of stone artworks. Here, we focus on the potential of laser-based photonic methods for treating biodeteriorated earthenware artefacts. The investigation was conducted on Roman dolia (jars) of the International Museum of Ceramics, Faenza, Italy. Three removal methods were tested and compared: (i) brushing using a soft-bristled electric brush and water, referred to as brush cleaning; (ii) a combination of brushing and laser ablation; and (iii) biocide and brushing. Four laser systems with different wavelengths and optimized pulse durations in nanosecond or microsecond regimes were used in the tests. Systematic irradiation tests were conducted to determine the damage thresholds and define safe laser irradiation levels. The characterizations of the surfaces under treatment were carried out pre- and post-laser irradiation using optical microscopy, 3D photogrammetry, and Pulse-Amplitude-Modulated Chlorophyll-Fluorometry. Furthermore, spectroscopic methods based on FTIR, Raman, and LIBS techniques were used to assess the effectiveness of the removal process and the composition of uncovered surfaces. Results have indicated that gentle brushing and water is the most effective approach for safely removing around 60% of the bio-colonization weakly anchored to the substrate over the area under treatment. This comprised viable species, whereas the remaining 40% of the area included endolithic species, mostly thalli of Verrucaria nigrescens and rock-dwelling fungi. The eradication of the latter was the real conservation concern requiring attention. Following the experimentation, the optimal method for safely uncovering the earthenware surface was a combination of water-assisted brushing and 1064 nm laser irradiation as a finishing treatment.

Ventricular arrhythmia burden during different physical activities in patients with arrhythmogenic right ventricular cardiomyopathy: preliminary analysis

Abstract Background Patients suffering from arrhythmogenic right ventricular cardiomyopathy (ARVC) should avoid intense endurance exercise to reduce the risk of adverse cardiac events and disease progression. While an active lifestyle would be preferable to a sedentary one, evidence for safe levels of physical activity in ARVC, however, is scarce. Purpose This study aimed to describe the ventricular arrhythmia burden experienced during exercise and immediate recovery - estimated as the prevalence of premature ventricular contractions (PVC) - of different exercise modalities and intensities on ARVC patients. Methods This preliminary analysis includes four (1F, 33±12 yrs, BMI 24±4 kg/m2) ARVC patients harboring a pathogenic plakophilin-2 variant and carrying an implantable cardioverter-defibrillator that performed different exercises while monitored via 12-lead ECG. The order of modalities was randomized and participants instructed to stop when surpassing perceived exertion of 15 on the Borg 6-20 scale. Resistance exercises included two-legged squats and single arm biceps curls (20 repetitions and 2 min duration). Endurance exercise included 5 min of treadmill walking and 3-min cycling bouts at heart rates (HR) of 80, 100 and 120 bpm, as well as cycling at 120 bpm with 2 additional min of active cool down. Blood lactate concentration was assessed after each cycling bout. Results No adverse cardiac event or early termination for medical reasons occurred. Figure 1 summarizes the relationship between HR, perceived exertion and PVC burden. During walking (HR 76 ± 8 bpm), PVC burden was 11 ± 6% (range 4 – 18%). Cycling at 82 ± 4 bpm induced a PVC burden of 7 ± 5% (range 3 – 14%), which increased to 13 ± 8% (range 3 – 21%) at 93 ± 2 bpm and increased further to 16 ± 16% (range 7 – 37%) at 105 ± 3 bpm. In all three intensities the PVC burden was higher in the first 3 min of recovery than during the activity itself. Adding a 2-min active cool down increased the PVC burden to 25 ± 16% (range 6 – 45%). 2-legged squats (HR 101 ± 15 bpm) had a PVC burden of 9 ± 12%, which increased to 19 ± 14% at recovery. One arm biceps curls (HR 75 ± 13 bpm) had a PVC burden of 4 ± 3% during the activity and 9 ± 5% during recovery. Perception of effort varied widely when cycling at 80 bpm (range 6 – 12) or 100 bpm (range 8 – 14), but less so at 120 bpm (range 13 – 15). Blood lactate concentration when cycling at 120 bpm ranged between 2.2 and 3.5 mmol/L, typically associated with exercise in the "heavy" intensity domain. Conclusions PVC burden was high and seemingly intensity-dependent during exercise and immediate recovery. The wide range of PVC burden for physiological or subjective markers of effort call for personalized recommendations on physical activity. Exercises with small muscle mass such as biceps curls seem to minimize the PVC burden, thus, training the different muscles separately could be an interesting avenue to maintain physical fitness in ARVC patients.

#2831 A randomised controlled study of a Combined Home-based ExERcISe and Nutritional ApproacH to improve frailty in kidney transplant recipients (CHERISH)

Abstract Background and Aims Post-transplantation frailty is common, with a prevalence of up to 52% in kidney transplant recipients (KTRs), and is associated with increased mortality, recurrent hospitalisation and inferior quality of life (QoL). Resistance exercise training (RET) was found to improve frailty in this patient group. Both high and low protein intakes were associated with potential risk of graft failure. To date, no studies have evaluated the safety and efficacy of RET combined with protein supplementation (RETPS) in KTRs. The objectives of this study were to investigate the effect of RETPS on kidney function and frailty status in KTRs, and assess its impact on QoL. Method Forty clinically stable KTRs ≥1 year post-transplantation [mean age = 54 ± 14 years; 50% male, median time post-transplantation = 7 years] were enrolled and randomised to either RET (n = 20) or RETPS (n = 20). All participants completed a 30-minute home-based progressive RET regimen 2-3 times weekly for 12 weeks, guided by an exercise worksheet and a study-specific video link. Participants received weekly telephone call to ensure safety and compliance of the interventions. The RETPS group received additional body-weight adjusted whey protein supplementation 1-hour post exercise. Total daily dietary protein intake did not exceed 1.40 g/kg/day to confine to a safe level of protein consumption in KTRs. Kidney function was measured by estimated glomerular filtration rate (eGFR), creatinine, and albumin-creatinine ratio (ACR). Frailty was evaluated using Fried Frailty Phenotype (FFP), Short Performance Physical Battery (SPPB), 60-second Sit-to-Stand test (60s-STST), handgrip- (HG) and back-leg-chest- (BLC) derived muscle strength, bioimpedance-derived lean tissue index (LTI), and ultrasound-derived thigh muscle thickness (TMT). QoL was assessed using Short Form (SF) -36 questionnaire. All measurements were performed at baseline and at week 12. Results Kidney function did not differ significantly between baseline and week 12 in both RET [eGFR: 62.1 vs 59.7 ml/min; creatinine: 107.3 vs 111.5 μmol/L; ACR: 12.8 vs 10.4 mg/mmol] and RETPS [eGFR: 61.2 vs 60.7 ml/min; creatinine: 101.1 vs 102.2 μmol/L; ACR: 17.6 vs 20.9 mg/mmol] groups. Frailty status assessed by FFP and SPPB improved in both RET [FFP: 2.5 vs 1.3, P < .001; SPPB: 7.2 vs 11.6, P < .001] and RETPS [FFP: 2.8 vs 1.1, P < .001; SPPB: 6.4 vs 10.9, P < .001] groups, but the improvements did not differ significantly between groups (P > 0.23). Improvements in 60s-STST, HG-derived muscle strength, BLC-derived muscle strength, and ultrasound-derived TMT were observed in both RET [60s-STST: 23 vs 27, P < .001; HG-derived muscle strength: 24 vs 30 kg, P < .001; BLC-derived muscle strength: 62 vs 71 kg, P < .001; ultrasound-derived TMT: 15 vs 19 mm, P < .001] and RETPS [60s-STST: 20 vs 29, P < .001; HG-derived muscle strength: 24 vs 32 kg, P < .001; BLC-derived muscle strength: 57 vs 80 kg, P < .001; ultrasound-derived TMT: 14 vs 21 mm, P < .001] groups, with greater improvements in RETPS group for 60s-STST (P < .01), HG-derived muscle strength (P < .05), BLC-derived muscle strength (P < .05), and ultrasound-derived TMT (P < .001). For bioimpedance-derived LTI, improvement was observed only in RETPS group [12.8 vs 14.8 kg/m2, P < .05]. SF-36-derived overall-, physical- and mental- related QoL improved in both groups (P < .05 for all), with RETPS group reporting a greater improvement in physical-related QoL (P < .05). Conclusion This represents the first study demonstrating RET combined with protein supplementation is safe and effective in improving frailty and QoL in KTRs. Protein supplementation augments increased muscle mass and strength beyond RET effect, further enhancing improvement in physical-related QoL.

Over-The-Counter Hearing Aids: Are They Safe and Effective?

In 2022, the Food and Drug Administration established a new regulatory category for over-the-counter (OTC) hearing aids for mild to moderate hearing loss. Herein, we aim to better compare the safety and efficacy of these devices to that of prescription hearing aids. Comparative-effectiveness model. Academic Audiology Center. The safety and efficacy of prescription and OTC hearing aids was compared using the AudioScan Verifit 2 Testbox software. Three types of hearing loss (downsloping, sharp downsloping, and reverse sloping) were analyzed. Efficacy was tested at 3 volume inputs and was measured by calculating the average difference in test points (produced by the devices) and target points (estimated by the software). Safety was assessed by calculating the average difference in test points and the maximally safe hearing level (produced by the software). Prescription hearing aids were found to have a better safety profile by being further from the safety threshold compared to OTC devices at the 8000 Hz frequency for the 2 types of downsloping hearing loss patterns studied (48vs30.5 dB, P = .04; 51vs32.5 dB, P = .03). Prescription hearing aids also carried a statistically significant advantage at 3 test points. OTC hearing aids generally had a greater difference between test and target points. OTC and prescription hearing aids are comparably safe, though OTC hearing aids are slightly less efficacious. Further evaluation of the OTC hearing aid efficacy is warranted to ensure it provides the gain of benefit needed for different types of hearing loss.

Improving approaches to hygienic rationing of antimicrobial drugs

Introduction. Currently, the production of medicines, including those with antimicrobial properties, is expanding at chemical and pharmaceutical enterprises. However, scientific approaches to hygienic regulation of the content of specific antimicrobials in the air of the work area are not yet available. The study aims to substantiate approaches to predicting approximate safe levels of exposure (ASLE) to substances with a specific antimicrobial effect. Materials and methods. The scientists have carried out the research in two stages. The first stage is an experimental study of the single inhalation effect of an antibiotic clarithromycin at concentrations of 54.2; 25.4; 15.3; 9.1; 2.8 and 0.9 mg/m3 on mongrel female rats weighing 230–250 g. The authors have evaluated the indicators of toxic (morphological and functional parameters of the nervous, cardiovascular and respiratory systems, biochemical parameters of the liver and kidneys, as well as the composition of peripheral blood) and specific effects (qualitative and quantitative composition of the microbiota of the large intestine of rats). The second stage was the analysis of the database on hygienic rationing of chemicals, which consisted in searching for hygienic standards (ASLE, MPC), threshold concentrations for the general toxic (Limint) and specific (Limbact) effects of antimicrobials. Results. During the experiment, experts have established the threshold of acute inhalation exposure (Limac int) of clarithromycin at a concentration of 25.4 mg/m3 according to the total toxic effects (peripheral blood counts, liver and kidney function). When exposed to an antibiotic at a concentration of 2.8 mg/m3, there was an imbalance of the intestinal microflora in the absence of a general toxic effect, which indicated a specific and selective antimicrobial effect of the drug. Based on the analysis of literature data, the parameters of toxicometry of 21 substances with antimicrobial effect were determined, their representative sample was justified and its regression analysis was carried out. Conclusion. Based on experimental and literary data, the authors established a significantly strong correlation (r=0.729) between the values of MPC (ASLE) and the threshold of antimicrobial action (Limbact). They also developed a mathematical equation to predict safe levels of antimicrobials based on their specific and selective activity.

Immunogenicity Risk Assessment of Process-Related Impurities in An Engineered T Cell Receptor Cellular Product

Cell therapies such as genetically modified T cells have emerged as a promising and viable treatment for hematologic cancers and are being aggressively pursued for a wide range of diseases and conditions that were previously difficult to treat or had no cure. The process development requires genetic modifications to T cells to express a receptor (engineered T cell receptor (eTCR)) of specific binding qualities to the desired target. Protein reagents utilized during the cell therapy manufacturing process, to facilitate these genetic modifications, are often present as process-related impurities at residual levels in the final drug product and can represent a potential immunogenicity risk upon infusion. This manuscript presents a framework for the qualification of an assay for assessing the immunogenicity risk of AA6 and Cas9 residuals. The same framework applies for other residuals; however, AAV6 and Cas9 were selected as they were residuals from the manufacturing of an engineered T cell receptor cellular product in development. The manuscript: 1) elucidates theoretical risks, 2) summarizes analytical data collected during process development, 3) describes the qualification of an in vitro human PBMC cytokine release assay to assess immunogenicity risk from cellular product associated process residuals; 4) identifies a multiplexed inflammatory innate and adaptive cytokine panel with pre-defined criteria using relevant positive controls; and 5) discusses qualification challenges and potential solutions for establishing meaningful thresholds. The assessment is not only relevant to establishing safe exposure levels of these residuals but also in guiding risk assessment and CMC strategy during the conduct of clinical trials.