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Background: The risk of inflammatory diseases is sex-dependent, but it rema ins unknown whether this is due to the impact of sex hormones or sex chromo somes. Transgender individuals represent a unique cohort for studying the relative influence of endocrine and chromosomal factors. Here we compared serum levels of B-cel l activating-factor (BAFF) and tumor necrosis factor (TNF) in transgender men (TM), transgender women (TW), cisgender women (CW) and cisgender men (CM). Methods: BAFF and TNF were measured in the serum of 26 CW, 30 CM, 27 TM and 16 TW individuals. To determine the responsiveness of immune cells, T NF was measured in bacterial lipopolysaccharide (LPS)-treated peripheral leukocytes. Results: BAFF was higher in CF (998 pg/mL) and TW (973 pg/mL) compared to CM (551 pg/mL) (P < 0.0001) and TM (726 pg/mL) (P < 0.0001). No difference in BAFF levels was shown between subjects grouped according to the number of X chr omosomes. TNF was higher in CM (174 pg/mL) than TW (2.3 pg/mL) ( P = 0.027) and TM (27.4 pg/mL) (P = 0.028). LPS-induced TNF was higher in CM (2524 pg/mL) and TM (2078 pg/mL) than in CW (1332 pg/mL) (both P < 0.0001) and TW (1602 pg/mL) (both P = 0.009). Discussion: Sex hormones and sex chromosomes have different impacts on cyto kines involved in the sex-dependent inflammatory response. The concent ration of BAFF and LPS-stimulated TNF secretion depended on sex hormone levels, wh ereas basal TNF was regulated by both sex hormone-dependent and -independent factors.

Abstract Dose–response association between level of impairment of semen quality and risk of morbidity or premature death has been reported. Therefore, it can be presumed that men utilizing donated spermatozoa, i.e. patients with non-obstructive azoospermia, are at highest risk for adverse health outcomes. To evaluate the risks of prescription of medications for common metabolic disturbances and testosterone replacement therapy (TRT) among men who father children with donated spermatozoa—who presumably do it due to severe impairment of fertility. We used Swedish nationwide register data on all fathers who had a live-born child between 2007 and 2014 in order to compare men who fathered children with donated spermatozoa to the ones who became fathers by using own gametes. Cox regression analysis was used in order to estimate the post-conception incidence of prescription of medicines for hypertension (HT), diabetes (type 1 and 2), dyslipidaemia (DLE) or TRT. Starting the follow up at time of conception, models were adjusted for age, educational level, and previous cancer treatment. In total 410,119 childbirths were included in the analysis. Among them, for 390 fathers donated spermatozoa were utilized. Fathers to children conceived with donated spermatozoa had higher risk for having TRT prescribed (HR: 18.14; 95%CI: 11.71–28.10; p ≪ 0.001). Same was true for DLE (HR: 2.08; 95%CI: 1.27–3.39; p = 0.003) but not diabetes. Fathers to children conceived by use of donated spermatozoa are at significantly increased risk for testosterone treatment and dyslipidaemia, necessitating stringent follow up and inclusion in prevention programs.

The versatile reactivity of propargylic epoxides and alcohols, due to the presence of a triple bond, is used in the synthesis of various organic compounds and building blocks. However, there are not many known methods for the preparation of optically pure propargylic epoxides and alcohols, and the existing ones often require specific reagents. Halohydrin dehalogenases (HHDHs) can be used to obtain enantiomerically pure compounds from racemic epoxides. These important biocatalysts facilitate epoxide ring‐opening reactions with unnatural nucleophiles such as azides. Here we report the biocatalytic transformation of propargylic epoxides using HHDHs. Six propargylic epoxides with different substituents were synthesized. Kinetic resolution reactions catalyzed by HHDHs in the presence of azide were performed. Two enzymes with opposite stereoselectivities, HheC and HheA2‐N178A were used and yielded azido alcohols (98–>99% ee, E‐value >200) and epoxides (29–88% ee). The best performing p‐tolyl propargylic epoxide derivative was used in a sequence of two enzymatic reactions to obtain both enantiomers of the β‐azido alcohol and the (R)‐enantiomer of the α‐azido alcohol, each in >99% ee, through complete conversion of the starting epoxide. The obtained azido alcohols were used in further transformations. The click reactions with terminal acetylenes gave triazolyl propargylic alcohols (>99% ee, 90–98% yield). In the case of the α‐azido alcohol, the click reaction was followed by intramolecular cyclization to form the dihydrofuranyl triazole motif that is found in biologically active compounds. [ABSTRACT FROM AUTHOR]

Abstract Childless men are reported to have a higher risk of cardiovascular disease (CVD) and mortality. Information on inherited genetic risk for CVD has improved the predictive models. Presuming that childlessness is a proxy of infertility we aimed to investigate if childless men inherit more often genetic traits for CVD and if combining genetic and parenthood information improves predictive models for CVD morbidity and mortality. Data was sourced from a large prospective population-based cohort where genetic risk score (GRS) was calculated using two sets of either 27 (GRS 27) or 50 (GRS 50) single nucleotide polymorphisms (SNPs) previously found to be associated with CVD. Part of the participants (n = 2572 men) were randomly assigned to a sub-cohort with focus on CVD which served as an exploratory cohort. The obtained statistically significant results were tested in the remaining (confirmatory) part of the cohort (n = 9548 men). GRS distribution did not differ between childless men and fathers (p-values for interaction between 0.29 and 0.76). However, when using fathers with low GRS as reference high GRS was a strong predictor for CVD mortality, the HR (95% CI) increasing from 1.92 (1.10–3.36) for GRS 50 and 1.54 (0.87–2.75) for GRS 27 in fathers to 3.12 (1.39–7.04) for GRS50 and 3.73 (1.75–7.99) for GRS27 in childless men. The confirmatory analysis showed similar trend. Algorithms including paternal information and GRS were more predictive for CVD mortality at 5 and 10 years follow-ups when compared to algorithms including GRS only (AUC 0.88 (95% CI 0.84–0.92) and 0.86 (95% CI 0.84–0.90), and, AUC 0.81 (95% CI 0.75–0.87) and 0.78 (95% CI 0.73–0.82), respectively). Combining information on parental status and GRS for CVD may improve the predictive power of risk algorithms in middle-aged men. Childless men and those with severe infertility problem may be an important target group for prevention of CVD.

Cataract is a leading cause of reversible blindness. Secondary cataract is the result of migration, proliferation, and epithelial-mesenchymal transformation (EMT) of lens epithelial cells (LECs), induced by transforming growth factor β (TGFβ). The extracellular signal-regulated kinases 1 and 2 (ERK 1/2) and casein kinase 2 (CK2) are important for fundamental cellular processes. This study aimed to evaluate the role of CK2 in the EMT of LECs. Primary LECs cultures were obtained from age-related and type 2 diabetes-induced cataracts. Diabetic LECs were capable of spontaneous in vitro differentiation. Treatment of LECs with TGFβ2-stimulated ERK1/2 activity, which correlated with the expressed α-smooth muscle actin (α-SMA). siRNA-mediated attenuation of the endogenous catalytic subunit (α) of CK2-inhibited ERK1/2 activity and decreased α-SMA expression. This study shows evidence that the function of ERK1/2 is regulated by the constitutively active heterotetrameric protein kinase CK2 in this cellular phenotype. This study enriches the knowledge on LECs physiology in normal and in pathological conditions.

Transmitted HIV drug resistance in Bulgaria was first reported in 2015 using data from 1988–2011. We determined the prevalence of surveillance drug resistance mutations (SDRMs) and HIV-1 genetic diversity in Bulgaria during 2012–2020 using polymerase sequences from 1053 of 2010 (52.4%) antiretroviral therapy (ART)-naive individuals. Sequences were analyzed for DRM using the WHO HIV SDRM list implemented in the calculated population resistance tool at Stanford University. Genetic diversity was inferred using automated subtyping tools and phylogenetics. Cluster detection and characterization was performed using MicrobeTrace. The overall rate of SDRMs was 5.7% (60/1053), with 2.2% having resistance to nucleoside reverse transcriptase inhibitors (NRTIs), 1.8% to non-nucleoside reverse transcriptase inhibitors (NNRTIs), 2.1% to protease inhibitors (PIs), and 0.4% with dual-class SDRMs. We found high HIV-1 diversity, with the majority being subtype B (60.4%), followed by F1 (6.9%), CRF02_AG (5.2%), A1 (3.7%), CRF12_BF (0.8%), and other subtypes and recombinant forms (23%). Most (34/60, 56.7%) of the SDRMs were present in transmission clusters of different subtypes composed mostly of male-to-male sexual contact (MMSC), including a 14-member cluster of subtype B sequences from 12 MMSC and two males reporting heterosexual contact; 13 had the L90M PI mutation and one had the T215S NRTI SDRM. We found a low SDRM prevalence amid high HIV-1 diversity among ART-naive patients in Bulgaria during 2012–2020. The majority of SDRMs were found in transmission clusters containing MMSC, indicative of onward spread of SDRM in drug-naive individuals. Our study provides valuable information on the transmission dynamics of HIV drug resistance in the context of high genetic diversity in Bulgaria, for the development of enhanced prevention strategies to end the epidemic.

Background. In Bulgaria the second most predominant HIV-1 strain after subtype B is CRF01_AE. Material and Methods. 270 HIV-1 polymerase (pol) CRF01_AE sequences collected between 1995–2019 were analyzed with the phylogenetic approach. To identify transmission clusters, we used two different genetic distance thresholds (d), i. e. 1.5% and 0.5%. Results. Genetic distance d=1.5% defined more distant infections in a huge cluster of 154 sequences composed mostly of people, who inject drugs (PWID), whereas when (d) was reduced to 0.5%, we determined more recent transmissions and the large cluster disintegrated into smaller ones. Different drug resistance mutations (DRM) were detected in patient’s HIV-1 pol sequences and were most common in male heterosexual (HET) single sequences. Conclusions. Our data showed repeated introduction of CRF01_AE in Bulgaria and rapid spread of the infection among PWID groups. Molecular monitoring of the epidemic among PWID communities could help reduce the spread of HIV-1 infection.

The authors analyze the implementation of the concept of flexible use of airspace in the Republic of Serbia, which deals with problems related to airspace capacity. The problem of airspace capacity and air traffic that takes place in it was not seriously considered in Europe before the Second World War, due to the simple fact that the number of flights in that period was relatively small. Achieving this goal and solving the problem is being sought in a better organization of the airspace of Europe, which directly influences the organization and strategy of the development of the airspace of all countries in Europe and the Republic of Serbia (as a signatory and a member of international organizations dealing with traffic management and airspace organization ). The concept of flexible use of airspace should provide a solution to this problem. The implementation of the concept requires some legal and organizational solutions, so a wider national concept is needed for a consistent implementation of the concept. The problems encountered by the creators of the concept in Europe and Serbia and the solutions that have been made are the subject of this paper. The content of the paper is presented through several questions to give an overview of the problem of airspace capacity and an increase expected in the upcoming period. The paper also deals with the division of airspace in the world and in our country; planning, registering and announcing flights; the concept of flexible use of airspace; and the problems of applying the concept in Serbia. / В данной статье представлен анализ концепции гибкого использования воздушного пространства, делая особый акцент на вызовы при ее внедрении в Республики Сербия, учитывая все проблемы, связанные с размером и границами воздушного пространства. Надо подчеркнуть, что проблемой размеров и границ воздушного пространства, также как и вопросами воздушных маршрутов до Второй мировой войны в Европе никто всерьез не занимался, по причине малого количества полетов в те времена. В качестве решения настоящей проблемы авторы данной статьи предлагают улучшение организации воздушного пространства Европы, что напрямую влияет на организацию и стратегию развития воздушного пространства всех европейских стран, в том числе и Республики Сербия (как члена и подписчика международных организаций, которые занимаются управлением авиамаршрутов и организацией воздушного пространства). Концепция гибкого использования воздушного пространства должна решить эти проблемы. Однако для внедрения вышеупомянутой концепции требуется пересмотреть раннее законодательские и организационные нормативы, и соответственно первоначально достичь национального консенсуса, в целях последовательного внедрения данной концепции. Проблемы, с которыми столкнулись создатели концепции в Европе и Сербии и решения, которые могут помочь решить эти проблемы представлены в настоящей работе. Структура работы была организована в виде ответов на многие ключевые вопросы по данной тематике, приведен обзор проблем, связанных с размером и границами воздушного пространства и улучшенных перспектив, которые ожидаются в ближайшее время; приведена сопоставительная классификация воздушного пространства; а также методы планировки, регистрации и объявлении о полете, описана концепция гибкого использования воздушного пространства и освещены проблемы при ее применении в Республике Сербия. / U radu je analizirana implementacija koncepta fleksibilnog korišćenja vazdušnog prostora u Republici Srbiji, koji se bavi problemima koji se odnose na kapacitet vazdušnog prostora. Pre Drugog svetskog rata kapacitet vazdušnog prostora i avio-saobraćaj koji se odvijao u njemu nije ozbiljnije razmatran u Evropi, zbog činjenice da je broj letova u tom periodu bio relativno mali. Danas se traži da se vazdušni prostor Evrope bolje organizuje, što direktno utiče i na organizaciju i strategiju razvoja vazdušnog prostora svih zemalja u Evropi, pa i Republike Srbije (kao potpisnika i člana međunarodnih organizacija koje se bave upravljanjem saobraćaja i organizacijom vazdušnog prostora). Koncept fleksibilnog korišćenja vazdušnog prostora treba da da rešenje za taj problem. Njegova implementacija zahteva neka zakonska i organizacijska rešenja, pa je neophodan širi nacionalni konsenzus. Problemi sa kojima su se susreli tvorci koncepta u Evropi i Srbiji i rešenja koja su doneta predmet su ovog rada. Sadržaj rada izložen je kroz nekoliko pitanja: dat je osvrt na problem kapaciteta vazdušnog prostora i povećanje koje se očekuje u narednom periodu; prikazana je podela vazdušnog prostora u svetu i kod nas; opisan je način na koji se vrši planiranje, prijava i najava letova, kao i sam koncept fleksibilnog korišćenja vazdušnog prostora i problemi koji se javljaju pri primeni koncepta u Srbiji.

Membrane oxygenators are devices that benefit from automatic control. This is especially true for implantable membrane oxygenators—a class of wearable rehabilitation devices that show high potential for fast recovery after lung injury. We present a performance comparison for reference tracking of carbon dioxide partial pressure between three control algorithms—a classical proportional-integral (PI) controller, a modern non-linear model predictive controller, and a novel deep reinforcement learning controller. The results are based on simulation studies of an improved compartmental model of a membrane oxygenator. The compartmental model of the oxygenator was improved by decoupling the oxygen kinetics from the system and only using the oxygen saturation as an input to the model. Both the gas flow rate and blood flow rate were used as the manipulated variable of the controllers. All three controllers were able to track references satisfactorily, based on several performance metrics. The PI controller had the fastest response, with an average rise time and settling time of 1.18 s and 2.24 s and the lowest root mean squared error of 1.06 mmHg. The NMPC controller showed the lowest steady state error of 0.17 mmHg and reached the reference signal with less than 2% error in 90% of the cases within 15 s. The PI and RL reached the reference with less than 2% error in 84% and 50% of the cases, respectively, and showed a steady state error of 0.29 mmHg and 0.5 mmHg.

Abstract Animal blood is used in mock circulations or in forensic bloodstain pattern analysis. Blood viscosity is important in these settings as it determines the driving pressure through biomedical devices and the shape of the bloodstain. However, animal blood can never exactly mimic human blood due to erythrocyte properties differing among species. This results in the species‐specific shear thinning behavior of blood suspensions, and it is therefore not enough to adjust the hematocrit of an animal blood sample to mimic the behavior of human blood over the entire range of shear rates that are present in the body. In order to optimize experiments that require animal blood, we need models to adapt the blood samples. We here offer mathematical models derived for each species using a multi linear regression approach to describe the influence of shear rate, hematocrit, and temperature on blood viscosity. Results show that pig blood cannot be recommended for experiments at low flow conditions (

Kinetic resolution of a series of fluorinated styrene oxide derivatives was studied using halohydrin dehalogenase. A mutant HheC-W249P catalysed nucleophilic ring-opening with azide and cyanide ions with excellent enantioselectivity (E-values up to >200), which gives access to various enantiopure β-substituted alcohols and epoxides. It was found that the enzyme tolerates substrates in concentrations over 50 mM. However, different side reactions were observed at elevated concentrations and with prolonged reaction time. The biocatalytic azidolysis and cyanolysis of racemic 4-trifluoromethylstyrene oxide were performed on preparative scale, affording (R)-2-azido-1-(4-trifluoromethyl-phenyl)-ethanol in 38% yield and 97% ee, and (S)-3-hydroxy-3-(4-trifluoromethyl-phenyl)-propionitrile in 30% yield and 98% ee.

Background. The purpose of this study was to analyse the underlying HIV transmission clusters of individuals from different vulnerable groups infected with the recombinant forms of HIV-1 – CRF01_AE and CRF02_AG, between 1986 and 2011 using sequencing and phylogenetic analysis. Material and methods. Blood samples from randomly selected 242 individuals diagnosed with HIV-1 CRF01_AE and CRF02_AG in Bulgaria were analysed. HIV-1 pol gene fragment was sequenced using the ViroSeq HIV-1 Genotyping Test (Abbott) and/or TruGene DNA Sequencing System. The phylogenetic tree reconstruction was performed with the IQ-TREE program. Identification of the phylogenetic clusters was performed using the ClusterPicker program with two parameters to identify recent and distant infection. Results.Two main local independent epidemics confined to different geographical regions of the country were caused by HIV-1 CRF01_AE and CRF02_AG. The various viral strains circulate predominantly in two major separate regions – CRF01_AE in Sofia and CRF02_AG in Plovdiv. Most of the individuals infected with viral strains analysed in this study were people who inject drugs (PWID) or heterosexuals and only a few were men who have sex with men. The phylogenetic analysis revealed transmission clusters in both recombinant forms, few in number when confined within a short period of time and multiple clusters over an extended timeframe. Conclusions. The introduction and rapid spread of two different strains of HIV-1 into geographically distant groups of PWID triggered local epidemic outbreaks. The phylogenetic analysis indicated the accelerated transmission of HIV, which is a characteristic of the spread through injection practices. Our study demonstrated that transmission cluster monitoring is important for better understanding of the development of epidemic and could be used as a tool for the identification of risk indicator populations.

Unprecedented tandem allylic alkylation/intermolecular Michael addition was used in the preparation of novel bicyclic azalides. NMR spectroscopy was used not only to unambiguously determine and characterize the structures of these unexpected products of chemical reaction but also to investigate the effect the rigid bicyclic modification has on the conformation of the whole molecule. Thus, some of the macrolides prepared showed antibacterial activity in the range of well-known antibiotic drug azithromycin.

Several studies have shown the association between decreased insulin sensitivity and the risk of male hypogonadism. Homeostatic model assessment of insulin resistance (HOMA-IR) is a well-established marker of decreased insulin sensitivity. The triglyceride–glucose index (TyG), calculated as ln ðfasting triglyceride ðmg=dLÞ × fasting glucose ðmg=dLÞ=2Þ, was recently suggested to be a cheaper and a reliable surrogate marker to detect insulin resistance (IR). Our aim was to compare the performance of those two indexes in the prediction of male hypogonadism. The data on 192 men from infertile couples (18–50 years; sperm concentration <20 x 106 /mL) and 199 population-based matched controls collected during the years 2009–2012 (baseline) were evaluated retrospectively. Half of these subjects (72 subfertile men and 122 controls) were reinvestigated 5–10 years later (median year (range): 7 (5–10)). The patients receiving any hormonal therapy were excluded. Hypogonadism was defined as fasting, morning serum testosterone below 12 nmol/L. In receiver operating characteristic curve analysis, the optimal diagnostic cutoff values for baseline HOMA-IR and TyG to predict MetS at re-examination were 2.68 (Area Under Curve (AUC)=0.886, p < 0.001) and 8.60 (AUC=0.816, p <0:001), respectively. Moreover, in binary logistic regression analysis performed on the whole cohort using these thresholds for high values of HOMAIR and high TyG, the odds-ratios (ORs) for hypogonadism were 6.48 (95% Confidence Interval (CI): 3.77–11.2; p <0:001) and 3.58 (95% CI: 2.17–5.94; p <0:001), respectively. Even though high HOMA-IR levels provided better risk estimates, high TyG was also highly related to the risk of hypogonadism. These markers can be utilized to identify men being at high risk of hypogonadism. [ABSTRACT FROM AUTHOR]

Clays are essential across industries due to their chemical, mineralogical, and physical properties. They also create favorable conditions for the activation of landslides and soil subsidence during construction activities. Understanding their characteristics is crucial for improving industrial efficiency and reducing environmental risks. This paper examines the mineralogical, chemical and physical properties of Neogene clays from the Rakevo wedge in the Krivodol Formation, with a focus on their suitability for industrial applications and environmental stability. The results show significant mineral diversity, including dominant phases with quartz, kaolinites, smectites, and, notably in certain samples, high aragonite content, influencing each sample's technical performance and susceptibility to environmental hazards. Physical parameters such as water content, plasticity, and grain size distribution indicate that the clays from the area of Golemanovo village, which exhibits the highest clay minerals content are most suitable for ceramics. In addition, the high aragonite content in samples from the area of Dimovo town poses potential instability risks where water infiltration may lead to structural weakening of the slopes. Findings underscore the importance of detailed mineralogical, chemical and physical characterization in determining the clays performance for industrial use and in natural risk management strategies. [ABSTRACT FROM AUTHOR]

In a recent population-based study, an elevated risk of the Metabolic syndrome (MetS) and type 2 diabetes was found in childless men compared to those who have fathered one or more children. Therefore, by using a larger cohort of more than 22 000 men from the Malmo Preventive Project (MPP) we aimed to expand our observations in order to evaluate the metabolic profile of childless men and to evaluate if childlessness is an additional and independent predictor of major adverse cardiovascular events (MACE), mortality and incident diabetes when accounting for well-known biochemical, anthropometric, socio-economic and lifestyle related known risk factors. Logistic regression was used to assess risk of MACE, diabetes and MetS at baseline. Multivariate Cox regression was used to evaluate the risks of MACE and mortality following the men from baseline screening until first episode of MACE, death from other causes, emigration, or end of follow-up (31st December 2016) adjusting for age, family history, marital status, smoking, alcohol consumption, educational status, body mass index, prevalent diabetes, high blood lipids, increased fasting glucose and hypertension. Childless men presented with a worse metabolic profile than fathers at the baseline examination, with elevated risk of high triglycerides, odds ratio (OR) 1.24 (95%CI: 1.10-1.42), high fasting glucose OR 1.23 (95%CI: 1.05-1.43) and high blood pressure, OR 1.28 (95%CI: 1.14-1.45), respectively. In the fully adjusted prospective analysis, childless men presented with elevated risk of cardiovascular mortality, HR: 1.33 (95% CI: 1.18-1.49) and all-cause mortality, HR 1.23 (95%CI: 1.14-1.33), respectively. In conclusion, these results add to previous studies showing associations between male reproductive health, morbidity and mortality. Male childlessness, independently of well-known socio-economic, behavioral and metabolic risk factors, predicts risk of cardiovascular disease and mortality. Consequently, this group of men should be considered as target population for preventive measures.

Membrane oxygenators or artificial lungs have become a reliable and live saving clinical technique. To limit side effects on blood platelet parameters the high extrinsic surface introduced by the hollow fiber membrane packing has to be decreased. This adjustment must be accompanied with an improvement of gas exchange performance to guarantee sufficient blood gas transfer. Computational fluid dynamics (CFD) provides a spatial and temporal resolution of the membrane oxygenation process and enables systematic optimization of artificial lungs. In scope of this research a new CFD approach to examine the gas exchange performance of oxygenators was developed. Blood and sweep gas flow in the fiber packing as well as blood gas exchange through the membrane between blood and sweep fluid are fully resolved and simulated. The results were compared to in vitro experiments comprising determination of blood side pressure loss and CO2 exchange performance of a prototype membrane module. While flow simulations were conducted for the complete prototype module, gas exchange simulations were limited to a representative fiber packing segment. The presented simulation approach provides a basis for the design of future artificial lungs.

CO2 removal via membrane oxygenators has become an important and reliable clinical technique. Nevertheless, oxygenators must be further optimized to increase CO2 removal performance and to reduce severe side effects. Here, in vitro tests with water can significantly reduce costs and effort during development. However, they must be able to reasonably represent the CO2 removal performance observed with blood. In this study, the deviation between the CO2 removal rate determined in vivo with porcine blood from that determined in vitro with water is quantified. The magnitude of this deviation (approx. 10%) is consistent with results reported in the literature. To better understand the remaining difference in CO2 removal rate and in order to assess the application limits of in vitro water tests, CFD simulations were conducted. They allow to quantify and investigate the influences of the differing fluid properties of blood and water on the CO2 removal rate. The CFD results indicate that the main CO2 transport resistance, the diffusional boundary layer, behaves generally differently in blood and water. Hence, studies of the CO2 boundary layer should be preferably conducted with blood. In contrast, water tests can be considered suitable for reliable determination of the total CO2 removal performance of oxygenators.

Extracorporeal membrane oxygenators are essential medical devices for the treatment of patients with respiratory failure. A promising approach to improve oxygenator performance is the use of microstructured hollow fiber membranes that increase the available gas exchange surface area. However, by altering the traditional circular fiber shape, the risk of low flow, stagnating zones that obstruct mass transfer and encourage thrombus formation, may increase. Finding an optimal fiber shape is therefore a significant task. In this study, experimentally validated computational fluid dynamics simulations were used to investigate transverse flow within fiber packings of circular and microstructured fiber geometries. A numerical model was applied to calculate the local Sherwood number on the membrane surface, allowing for qualitative comparison of gas exchange capacities in low-velocity areas caused by the microstructured geometries. These adverse flow structures lead to a tradeoff between increased surface area and mass transfer. Based on our simulations, we suggest an optimal fiber shape for further investigations that increases potential mass transfer by up to 48% in comparison to the traditional, circular hollow fiber shape.

CO2 removal via membrane oxygenators during lung protective ventilation has become a reliable clinical technique. For further optimization of oxygenators, accurate prediction of the CO2 removal rate is necessary. It can either be determined by measuring the CO2 content in the exhaust gas of the oxygenator (sweep flow-based) or using blood gas analyzer data and a CO2 solubility model (blood-based). In this study, we determined the CO2 removal rate of a prototype oxygenator utilizing both methods in in vitro trials with bovine and in vivo trials with porcine blood. While the sweep flow-based method is reliably accurate, the blood-based method depends on the accuracy of the solubility model. In this work, we quantified performances of four different solubility models by calculating the deviation of the CO2 removal rates determined by both methods. Obtained data suggest that the simplest model (Loeppky) performs better than the more complex ones (May, Siggaard-Anderson, and Zierenberg). The models of May, Siggaard-Anderson, and Zierenberg show a significantly better performance for in vitro bovine blood data than for in vivo porcine blood data. Furthermore, the suitability of the Loeppky model parameters for bovine blood (in vitro) and porcine blood (in vivo) is evaluated.