Passive Filtration Research Articles

Exothermic characteristics evaluation of the Pt coated α-Al2O3 catalyst in bed for passive airborne radioactive material reduction system under forced flow conditions

After the severe accident at the Fukushima nuclear power plant, there has been heightened interest in the development of severe accident countermeasures. As part of these efforts, a passive filtration system capable of passive operation during power loss is under development.This paper focuses on evaluating the performance of a catalyst-filled bed designed to create a temperature gradient through exothermic reactions between combustible gases generated during accidents and a catalyst. The temperature gradient facilitates the formation of natural convection within the system, enabling passive operation. The catalytic bed is designed in a bed-type configuration filled with exothermic catalysts. To ensure physical and chemical stability under severe accident conditions, heat resistance tests were conducted using inorganic materials as a base to select an optimized exothermic catalyst. A test apparatus was designed for unit evaluation testing of the catalyst-filled bed equipped with the catalytic bed. Exothermic characteristics evaluation tests were conducted by varying the hydrogen volume fraction and face velocity, measuring heat generation in the catalytic bed under each condition. The correlation between these variables and the heat generation performance of the catalytic bed was determined. These findings will be utilized to inform the design parameters of the passive airborne radioactive material reduction system.

Charge barriers in the kidney elimination of engineered nanoparticles

The renal elimination pathway is increasingly harnessed to reduce nonspecific accumulation of engineered nanoparticles within the body and expedite their clinical applications. While the size of nanoparticles is recognized as crucial for their passive filtration through the glomerulus due to its limited pore size, the influence of nanoparticle charge on their transport and interactions within the kidneys remains largely elusive. Herein, we report that the proximal tubule and peritubular capillary, rather than the glomerulus, serve as primary charge barriers to the transport of charged nanoparticles within the kidney. Employing a series of ultrasmall, renal-clearable gold nanoparticles (AuNPs) with precisely engineered surface charge characteristics as multimodal imaging agents, we have tracked their distribution and retention across various kidney components following intravenous administration. Our results reveal that retention in the proximal tubules is governed not by the nanoparticle's zeta-potential, but by direct Coulombic interactions between the positively charged surface ligands of the AuNPs and the negatively charged microvilli of proximal tubules. However, further enhancing these interactions leads to increased binding of the positively charged AuNPs to the peritubular capillaries during the initial phase of elimination, subsequently facilitating their slow passage through the glomeruli and interaction with tubular components in a charge-selective manner. By identifying these two critical charge-dependent barriers in the renal transport of nanoparticles, our findings offer a fundamental insight for the design of renal nanomedicines tailored for selective targeting within the kidney, laying down a foundation for developing targeting renal nanomedicines for future kidney disease management in the clinics.

Physiologically-Based Pharmacokinetic Modeling and Dosing Optimization of Cefotaxime in Preterm and Term Neonates

BackgroundCefotaxime is commonly used in treating bacterial infections in neonates. To characterize the pharmacokinetic process in neonates and evaluate different recommended dosing schedules of cefotaxime, a physiologically-based pharmacokinetic (PBPK) model of cefotaxime was established in adults and scaled to neonates. MethodsA whole-body PBPK model was built in PK-SIM® software. Three elimination pathways are composed of enzymatic metabolism in the liver, passive filtration through glomerulus, and active tubular secretion mediated by renal transporters. The ontogeny information was applied to account for age-related changes in cefotaxime pharmacokinetics. The established models were verified with realistic clinical data in adults and pediatric populations. Simulations in neonates were conducted and 100 % of the dosing interval where the unbound concentration in plasma was above the minimum inhibitory concentration (fT>MIC) was selected as the target index for dosing regimen evaluation. ResultsThe developed PBPK models successfully described the pharmacokinetic process of cefotaxime in adults and were scaled to the pediatric population. Good verification results were achieved in both adults’ and neonates’ PBPK models, indicating a good predictive performance. The optimal dosage regimen of cefotaxime was proposed according to the postnatal age (PNA) and gestational age (GA) of neonates. For preterm neonates (GA < 36 weeks), dosages of 25 mg/kg every 8 h in PNA 0–6 days and 25 mg/kg every 6 h in PNA 7–28 days were suggested. For term neonates (GA ≥ 36 weeks), dosages of 33 mg/kg every 8 h in PNA 0–6 days and 33 mg/kg every 6 h in PNA 7–28 days were recommended. ConclusionsOur study may provide useful experience in practicing PBPK model-informed precision dosing in the pediatric population.

Retraction for Belkacemi et al., "Passive Filtration, Rapid Scanning Electron Microscopy, and Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry for Treponema Culture and Identification from the Oral Cavity".

Retraction for Belkacemi et al., "Passive Filtration, Rapid Scanning Electron Microscopy, and Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry for Treponema Culture and Identification from the Oral Cavity".

Analysis of the possibility of using LC passive filtration methods in reducing the radiated emission of brushed universal motors

Analysis of the possibility of using LC passive filtration methods in reducing the radiated emission of brushed universal motors

Sphingosine-1-phosphate receptor 3 regulates the transendothelial transport of high-density lipoproteins and low-density lipoproteins in opposite ways.

The entry of lipoproteins from blood into the arterial wall is a rate-limiting step in atherosclerosis. It is controversial whether this happens by filtration or regulated transendothelial transport.Because sphingosine-1-phosphate (S1P) preserves the endothelial barrier, we investigated in vivo and in vitro, whether S1P and its cognate S1P-receptor 3 (S1P3) regulate the transendothelial transport of lipoproteins. Compared to apoE-haploinsufficient mice (CTRL), apoE-haploinsufficient mice with additional endothelium-specific knock-in of S1P3 (S1P3-iECKI) showed decreased transport of LDL and Evan's Blue but increased transport of HDL from blood into the peritoneal cave. After 30 weeks of high-fat diet feeding, S1P3-iECKI mice had lower levels of non-HDL-cholesterol and less atherosclerosis than CTRL mice. In vitro stimulation with an S1P3 agonist increased the transport of 125I-HDL but decreased the transport of 125I-LDL through human aortic endothelial cells (HAECs). Conversely, inhibition or knock-down of S1P3 decreased the transport of 125I-HDL but increased the transport of 125I-LDL. Silencing of SCARB1 encoding scavenger receptor B1 (SR-BI) abrogated the stimulation of 125I-HDL transport by the S1P3 agonist. The transendothelial transport of 125I-LDL was decreased by silencing of SCARB1 or ACVLR1 encoding activin-like kinase 1 but not by interference with LDLR. None of the three knock-downs prevented the stimulatory effect of S1P3 inhibition on transendothelial 125I-LDL transport. S1P3 regulates the transendothelial transport of HDL and LDL oppositely by SR-BI-dependent and SR-BI-independent mechanisms, respectively. This divergence supports a contention that lipoproteins pass the endothelial barrier by specifically regulated mechanisms rather than passive filtration.

#2989 SELECTIVE RENAL DISPOSITION OF THE CALCINEURIN INHIBITORS VOCLSOPORIN, CYCLOSPORINE, AND TACROLIMUS

Abstract Background and Aims The calcineurin inhibitors (CNI) cyclosporine (CSA) and tacrolimus (TAC) were revolutionary immunosuppressants when first introduced for solid organ transplantation in the 1980s. Voclosporin (VCS), a novel CNI, recently became the first oral therapy approved in the United States, Great Britain, and Europe for the treatment of active lupus nephritis based on positive results from Phase 2 and 3 clinical trials. Unlike CSA and TAC, VCS has demonstrated a consistent pharmacokinetic and pharmacodynamic profile, eliminating the need for therapeutic drug monitoring. Further, VCS is associated with a more favorable metabolic profile and has not been associated with electrolyte disturbances. Emerging evidence indicates small molecule therapeutics may display differential disposition within organ tissues. This suggests that CNIs may be differentially distributed and retained in the kidney, potentially explaining the difference in their efficacy and safety profiles. To evaluate renal disposition of CSA, TAC, and VCS, we assessed in mice and humans the disposition of each CNI in the kidney relative to its systemic drug exposure. Method Single 30 mg/kg doses of CSA, TAC and VCS were administered intravenously to mice. Following intravenous administration, kidneys were collected at 15 minutes, 30 minutes, 1 hour and 2 hours, flash frozen in liquid nitrogen, and stored at −20 °C until sectioning. Sections of 10 μm kidney tissue were mounted on indium tin oxide coated glass slides. Matrix of 10 mg/mL α-Cyano-4-hydroxycinnamic acid in 85% acetonitrile/13% ethanol + 2% water + 0.1% trifluoroacetic acid was sprayed on the tissue using an HTX tissue sprayer, dried for 10 minutes in the vacuum, and subjected to Matrix-assisted Laser Desorption and Ionization Mass Spectrometry Imaging (MALDI-MSI). The systemic and renal clearance in humans of CSA and TAC were obtained from the literature; pharmacokinetic data on VCS was obtained from data on file. Renal secretion of each drug was compared to its expected passive filtration based on glomerular filtration rate (GFR), fraction unbound in plasma (fu), and respective systemic drug exposure. Results MALDI-MSI demonstrated significantly higher concentrations of drug and more diffuse tissue disposition of CSA in mouse kidney compared to VCS (Figure 1). CSA was retained in all kidney tissues up to 2 hours post-administration. Higher concentrations and more diffuse disposition of TAC was also noted compared to VCS at 15 and 30 minutes; TAC was distinctively retained in the cortex and medulla. VCS had moderate distribution in the cortex and was rapidly excreted with low levels of drug present in the kidney after 1 hour. According to published data, CSA has a measured renal clearance of 1.48 mL/min in healthy human subjects, representing approximately 10% of expected passive filtration of 12.5 mL/min (Table 1). TAC has a renal clearance of 0.014 mL/min representing &amp;lt;2% of expected passive filtration of 1.25 mL/min. VCS has a renal clearance of 7.82 mL/min representing approximately 200% of its expected passive filtration rate of 3.75 mL/min. Conclusion MALDI-MSI revealed differential retention and distribution of CSA, TAC and VCS in mice, consistent with their respective renal clearances in humans. Higher drug exposure and &amp;gt;90% renal reabsorption was observed for both CSA and TAC in this study, whereas the renal handling of VCS suggested a significant component of tubular secretion. The higher rate of secretion and lower overall exposure of kidney tissue to VCS may be associated with an improved safety profile when compared to the more diffuse distribution and greater renal retention of CSA and TAC.

DNA metabarcoding of trawling bycatch reveals diversity and distribution patterns of sharks and rays in the central Tyrrhenian Sea

AbstractConservation and management of chondrichthyans are becoming increasingly important, as many species are particularly vulnerable to fishing activities, primarily as bycatch, which leads to incomplete catch reporting, potentially hiding the impact on these organisms. Here, we aimed at implementing an eDNA metabarcoding approach to reconstruct shark and ray bycatch composition from 24 hauls of a bottom trawl fishing vessel in the central Mediterranean. eDNA samples were collected through the passive filtration of seawater by simple gauze rolls encapsulated in a probe (the “metaprobe”), which already showed great efficiency in detecting marine species from trace DNA in the environment. To improve molecular taxonomic detection, we enhanced the 12S target marker reference library by generating sequences for 14 Mediterranean chondrichthyans previously unrepresented in public repositories. DNA metabarcoding data correctly identifies almost all bycaught species and detected five additional species not present in the net, highlighting the potential of this method to detect rare species. Chondrichthyan diversity showed significant association with some key environmental variables (depth and distance from the coast) and the fishing effort, which are known to influence demersal communities. As DNA metabarcoding progressively positions itself as a staple tool for biodiversity monitoring, we expect that its melding with opportunistic, fishery-dependent surveys could reveal additional distribution features of threatened and elusive megafauna.

Expression of Concern for Belkacemi et al., "Passive Filtration, Rapid Scanning Electron Microscopy, and Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry for Treponema Culture and Identification from the Oral Cavity".

Expression of Concern for Belkacemi et al., "Passive Filtration, Rapid Scanning Electron Microscopy, and Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry for Treponema Culture and Identification from the Oral Cavity".

Moving environmental DNA (eDNA) technologies from benchtop to the field using passive sampling and PDQeX extraction

AbstractEnvironmental DNA (eDNA) metabarcoding has shown great promise as an effective, non‐invasive monitoring method for marine biomes. However, long filtration times and the need for state‐of‐the‐art laboratories are restricting sample replication and in situ species detections. Methodological innovations, such as passive filtration and self‐contained DNA extraction protocols, have the potential to alleviate these issues. We explored the implementation of passive sampling and a self‐contained DNA extraction protocol by comparing fish diversity obtained from active filtration (1 L; 0.45 μm cellulose nitrate [CN] filters) to five passive substrates, including 0.45 μm CN filters, 5 μm nylon filters, 0.45 μm positively charged nylon filters, artificial sponges, and fishing net. Fish diversity was then compared between the PDQeX Nucleic Acid Extractor and the conventional Qiagen DNeasy Blood &amp; Tissue protocol. Experiments were conducted in both a controlled mesocosm and in situ at the Portobello Marine Laboratory, New Zealand. No significant differences in fish diversity were observed among active filtration and more porous passive materials (artificial sponges and fishing net) for both the mesocosm and harbor waters. For the in situ comparison, all passive filter membranes detected a significantly lower number of fish species, resulting from partial sample drop‐out. While no significant differences in fish eDNA signal diversity were observed between either DNA extraction methods in the mesocosm, the PDQeX system was less effective at detecting fish for the in situ comparison. Our results demonstrate that a passive sampling approach using porous substrates can be effectively implemented to capture eDNA from seawater, eliminating vacuum filtration processing. The large variation in efficiency observed among the five substrate types, however, warrants further optimization of the passive sampling approach for routine eDNA applications. The PDQeX system can extract high‐abundance DNA in a mesocosm with further optimization to detect low‐abundance eDNA from the marine environment.

An Inventory of Good Management Practices for Nutrient Reduction, Recycling and Recovery from Agricultural Runoff in Europe’s Northern Periphery and Arctic Region

The excess loading of nutrients generated by agricultural activities is a leading cause of water quality impairment across the globe. Various management practices have been developed and widely implemented as conservation management strategies to combat water pollution originating from agricultural activities. In the last ten years, there has also been a widespread recognition of the need for nutrient harvesting from wastewaters and resource recovery. In Europe’s Northern Periphery and Arctic (NPA) areas, the expertise in water and runoff management is sporadic and needs to be improved. Therefore, the objective of this research was to perform a comprehensive review of the state of the art of Good Agricultural Practices (GAPs) for the NPA region. A set of questionnaires was distributed to project partners combined with a comprehensive literature review of GAPs focusing on those relevant and/or implemented in the NPA region. Twenty-four GAPs were included in the inventory. This review reveals that there is a large level of uncertainty, inconsistency, and a gap in the knowledge regarding the effectiveness of GAPs in nutrient reduction (NRE), their potential for nutrient recycling and recovery (NRR), and their operation and maintenance requirements (OMR) and costs. Although the contribution of GAPs to water quality improvement could not be quantified, this inventory provides a comprehensive and first-of-its-kind guide on available measures and practices to assist regional and local authorities and communities in the NAP region. A recommendation for incorporating and retrofitting phosphorus retaining media (PRMs) in some of the GAPs, and/or the implementation of passive filtration systems and trenches filled with PRMs to intercept surface and subsurface farm flows, would result in the enhancement of both NRE and NRR.

Wild boars as reservoir for Campylobacter and Arcobacter

Campylobacteriosis is a significant public health concern with Campylobacter jejuni and Campylobacter coli as main causative agents. Moreover, there is an increasing recognition of other pathogenic Campylobacter species and Campylobacter-like organisms as Arcobacter. However, current knowledge on presence of Arcobacter species in wild boars (Sus scrofa) is lacking, and knowledge on Campylobacter species is based on methods favoring growth of thermotolerant species. In this study, fecal samples originating from 76 wild boars hunted in Campania region (Italy) were examined for the presence of Campylobacter(-like) organisms by a culture dependent approach. Three isolation protocols were performed in parallel: Arcobacter-selective agar plates, mCCDA plates and isolation by passive filtration onto non-selective blood agar plates were used as quantitative isolation methods. Enrichment broths, i.e. Arcobacter selective enrichment broth, Preston broth and CAT broth were used for qualitative detection of low levels or stressed Campylobacter(-like) organisms. The Arcobacter and Campylobacter isolates were identified at species level using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S ribosomal RNA (rRNA) sequence analysis. Overall, 41 (53.9%) of the animals excreted Arcobacter or Campylobacter while 38 (50.0%) shed Campylobacter and 8 (10.5%) Arcobacter. Campylobacter lanienae predominated and was isolated from 31 (40.8%) animals. No statistical difference between the age groups or gender with regard to the fecal excretion of Campylobacter(-like) organisms was observed. Thirty animals (39.5%) shed Campylobacter spp. exceeding levels of 10 ³ CFU g−1 feces. As samples were obtained from hunted wild boars intended for consumption, a potential contamination of meat with these bacterial pathogens must be considered.

Apolipoprotein M and Sphingosine-1-Phosphate Receptor 1 Promote the Transendothelial Transport of High-Density Lipoprotein.

Objective: ApoM enriches S1P (sphingosine-1-phosphate) within HDL (high-density lipoproteins) and facilitates the activation of the S1P1 (S1P receptor type 1) by S1P, thereby preserving endothelial barrier function. Many protective functions exerted by HDL in extravascular tissues raise the question of how S1P regulates transendothelial HDL transport. Approach and Results: HDL were isolated from plasma of wild-type mice, Apom knockout mice, human apoM transgenic mice or humans and radioiodinated to trace its binding, association, and transport by bovine or human aortic endothelial cells. We also compared the transport of fluorescently-labeled HDL or Evans Blue, which labels albumin, from the tail vein into the peritoneal cavity of apoE-haploinsufficient mice with (apoE-haploinsufficient mice with endothelium-specific knockin of S1P1) or without (control mice, ie, apoE-haploinsufficient mice without endothelium-specific knockin of S1P1) endothelium-specific knockin of S1P1. The binding, association, and transport of HDL from Apom knockout mice and human apoM-depleted HDL by bovine aortic endothelial cells was significantly lower than that of HDL from wild-type mice and human apoM-containing HDL, respectively. The binding, uptake, and transport of 125I-HDL by human aortic endothelial cells was increased by an S1P1 agonist but decreased by an S1P1 inhibitor. Silencing of SR-BI (scavenger receptor BI) abrogated the stimulation of 125I-HDL transport by the S1P1 agonist. Compared with control mice, that is, apoE-haploinsufficient mice without endothelium-specific knockin of S1P1, apoE-haploinsufficient mice with endothelium-specific knockin of S1P1 showed decreased transport of Evans Blue but increased transport of HDL from blood into the peritoneal cavity and SR-BI expression in the aortal endothelium. Conclusions: ApoM and S1P1 promote transendothelial HDL transport. Their opposite effect on transendothelial transport of albumin and HDL indicates that HDL passes endothelial barriers by specific mechanisms rather than passive filtration.

Clinical application of serological Alzheimer's disease diagnosis using a highly sensitive biosensor with hydrogel-enhanced dielectrophoretic force

Analysis of a ratio between amyloid beta 1–40 and 1–42 (Aβ1-40 and Aβ1-42) presented in plasm enables a highly accurate diagnosis of Alzheimer's disease (AD). However, the analysis of plasma Aβs is not routinely conducted because of the lack of Aβ detection techniques sensitive enough to specifically detect Aβ from thousands of biomaterials present in the plasma. We developed a hydrogel-patterned spiral microelectrode sensor combined with a hopping dielectrophoretic (DEP) force, combining the negative DEP and positive DEP forces, for Aβ detection. The hydrogel effectively increased the number of immobilized fragmented antibodies in the reaction region of the sensor and enabled size-exclusive passive filtration of non-specific plasma proteins from that region. The hopping DEP force further concentrated the Aβs and removed the non-specific plasma proteins. Consequently, our sensor achieved a limit of detection (LOD) of approximately ∼ 0.15 pg/mL for both Aβ1-40 and Aβ1-42 in the standard plasma. Finally, comparing the ratio between Aβ1-40 and Aβ1-42 signals, we distinguished AD patients from cognitively normal subjects with 95.83% accuracy and 92.31% precision (n = 24, p < 0.0001, One-way ANOVA).

Filtration performance of biaxial circular seamless knitted filter material based on electrostatic adsorption

In order to solve the problem of dust accumulation at the joints of traditional filter materials and the reduction of filtration efficiency, weft knitting was selected to make the fabric cylindrical unwinding machine. The cylindrical filter material was formed by cylindrical needling machine in the later period. This type of novel seamless filter material was compared with the traditional one on the filtration performance and numerical simulation of filtration performance. The results show that when the warp and weft lining yarns in the seamless filter material were PTFE monofilaments containing tourmaline particles, the filtration efficiency was the optimal due to the presence of the surface static voltage. The filtration efficiency could greatly be improved by 7.24%. The relationship between the surface static voltage and distance was exponential. The filter material with electrostatic field on the surface increased the active filtration of electrostatic adsorption in addition to the passive filtration. This type of seamless filter material provided research and development ideas and theoretical guidance for the development and application of filter materials.

High-Yielding Separation and Collection of Plasma from Whole Blood Using Passive Filtration.

Lateral flow tests and hand-held analyzers facilitate diagnostic testing in resource limited settings and at the point-of-care. However, many of these devices require sample preparation such as plasma separation to remove cells and isolate the liquid portion of blood. Specifically, the separation of plasma from blood is necessary for routine health assessments such as comprehensive metabolic panels and chronic HIV viral load monitoring. Away from laboratories, this type of processing has been addressed by unconventional, hand-operated centrifuge devices (high volume) or plasma separation membranes (PSM) coupled with lateral flow tests (low volume). Herein, we describe a device that separates and stores plasma from undiluted blood using only passive filtration in less than 10 min. Integrating a PSM with a prefilter and absorbent material yields a 3-fold increase in separation efficiency compared to similar devices using passive filtration. We demonstrate the reproducibility of our device across the physiological range of hematocrits (20-50%) with an average recovered plasma volume of 61.7 ± 2.6 μL. Maximum separation efficiency (53.8%, 65.6 ± 3.9 μL plasma) was achieved for a sample of whole blood (30% hematocrit) in 10 min. We evaluate the purity of our plasma sample by quantitation of hemoglobin and report hemolysis as either minimal (≤5%) or undetectable (≤1%). Specific recovery of human IgG, IFN-γ, and HIV-1 RNA indicate the diagnostic utility of plasma obtained from our device is unchanged compared to plasma obtained via centrifugation. Finally, we demonstrate the use of recovered plasma, applied via "stamping", to successfully conduct a commercial lateral flow immunochromatographic assay for tetanus antibodies. This device platform is capable of producing pure plasma samples from blood to facilitate tests in resource limited settings to improve access to healthcare.

A novel passive filtration system for splash-lubricated gearboxes: Part 1

Splash-lubricated gearboxes are widely used in many industries. Contaminant removal systems are rarely employed in splash-lubricated gearboxes, such as some gearboxes are used in helicopters and mining machines. The maintenance of lubrication systems in those machines relies on periodic onsite inspection and lubricant change. However, wear debris generated during operation will suspend in lubricant and cause damage to contacting surfaces of gearbox’s components. In this first part of a two-part paper, a novel light-weight passive filtration system that utilises gravitational sedimentation and shape memory alloys is presented for unfiltered splash-lubricated gearboxes. A predictive model is developed for the estimation of flake-like wear particles’ settling behavior in the lubricant. Experiments based on a simplified test rig are also conducted to validate the theoretical results. This mathematical model can also be used to elucidate the impact of sedimentation time of wear particles on the cleanliness of the lubricant after the installation of passive filtration system.

Impact of the organic cation transporter 2 inhibitor cimetidine on the single-dose pharmacokinetics of the glucosylceramide synthase inhibitor lucerastat in healthy subjects.

Lucerastat is an orally available glucosylceramide synthase inhibitor with a potential to provide substrate reduction therapy for Fabry patients independent of their α-galactosidase A genotype. In humans, lucerastat is mainly eliminated as unchanged parent compound through renal excretion both by active secretion and passive filtration. In vitro studies indicated that lucerastat is a substrate of human organic cation transporter 2 (OCT2) mainly expressed in the kidney. Therefore, this clinical study, conducted in 14 healthy male subjects, investigated the effect of 800 mg twice-daily oral administration of the OCT2 inhibitor cimetidine at steady state on the single-dose pharmacokinetics (PK) of 500 mg lucerastat. The safety and tolerability of lucerastat administered alone and concomitantly with cimetidine were also evaluated. Exposure to lucerastat was slightly higher upon co-administration of cimetidine indicated by geometric mean area under the plasma concentration-time curve from zero to infinity (AUC0-∞) ratio of 1.22 (90% confidence interval [CI] 1.16-1.28). Cimetidine delayed the time to reach maximum lucerastat concentrations (tmax) by 1 h but did not affect its elimination half-life (t½) or maximum plasma concentration (Cmax) as geometric mean ratios were 1.00 (0.91-1.10) and 1.04 (0.92-1.17), respectively, at cimetidine steady state. Lucerastat was safe and well tolerated when given alone and in combination with cimetidine. These results indicate that the single-dose PK of lucerastat are not changed to a clinically relevant extent by cimetidine-mediated OCT2 inhibition, allowing the concomitant use of OCT2 inhibitors with lucerastat without any need for dose adjustment. EudraCT: 2017-003725-14; ClinicalTrials.gov: NCT03380455.

Determination of creatinine level in patient blood samples by Fourier NIR spectroscopy and multivariate analysis in comparison with biochemical assay

In this paper, in vivo spectra from 23 patients’ blood samples with various Creatinine (Cr) concentration levels ranging from 0.96 to 12.5 mg/dL were measured using Fourier transform near-infrared spectrometer (FT-NIRS) and spectrum quantitative analysis method. Since Cr undergoes passive filtration, it serves as a key biomarker of kidneys function via the estimation of glomerular filtration rate. Thus, increased blood Cr concentration reflects impaired renal function. After spectra pre-processing and outlier exclusion, a spectral model was developed based on partial least squares regression (PLSR) method, wherein Cr concentrations correlated with filtered NIR spectra across several peaks, where Cr is known to absorb NIR light. Several statistical metrics were applied to estimate the model efficiency during data analysis. Comparison of spectra-derived concentrations to reference Cr measurements by the current gold-standard Jaffe’s method held in hospital lab revealed a Cr prediction accuracy of 1.64[Formula: see text]mg/dL with good correlation of [Formula: see text]. Bland-Altman plots were used to compare between our calculations and reference lab values and reveal minimal bias between the two. The finding presented the potential of FT-NIRS coupled with PLSR technique for Cr determination.

Passive Filtration, Rapid Scanning Electron Microscopy, and Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry for Treponema Culture and Identification from the Oral Cavity.

We present here a new passive-filtration-based culture device combined with rapid identification with a new electron microscope (Hitachi TM4000) for the detection and culture of Treponema species from the human oral cavity. Of the 44 oral samples cultivated, 15 (34%) were found to be positive for Treponema using electron microscopy and were also culture positive. All were subcultured on agar plates; based on genome sequencing and analyses, 10 were strains of Treponema pectinovorum and 5 were strains of Treponema denticola The 29 samples that were negative for Treponema remained culture negative. In addition, 14 Treponema species ordered from the DSMZ collection were cultured in the T-Raoult culture medium optimized here. Finally, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) was used and 30 novel spectra were added to the MALDI-TOF MS database. We have successfully developed a new and effective method for treponemal detection, culture, and identification.