Risk factors for hospital-acquired infection during the SARS-CoV-2 pandemic.

OBJECTIVE: To evaluate risk factors for hospital-acquired infection (HAI) in patients during the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, including historical and concurrent cohorts. DESIGN: Retrospective cohort. SETTING: Three Missouri hospitals, data from 1st January 2017 to 30th September 2020. PARTICIPANTS: Patients aged ≥18 years and admitted for ≥48 h. METHODS: Univariate and multi-variate Cox proportional hazards models incorporating the competing risk of death were used to determine risk factors for HAI. A-priori sensitivity analyses were performed to assess the robustness of the urine-, blood- and respiratory-culture-based HAI definition. RESULTS: The cohort included 254,792 admissions, with 7147 (2.8%) HAIs (1661 blood, 3407 urine, 2626 respiratory). Patients with SARS-CoV-2 had increased risk of HAI (adjusted hazards ratio 1.65, 95% confidence interval 1.38-1.96), and SARS-CoV-2 infection was one of the strongest risk factors for development of HAI. Other risk factors for HAI included certain admitting services, chronic comorbidities, intensive care unit stay during index admission, extremes of body mass index, hospital, and selected medications. Factors associated with lower risk of HAI included year of admission (declined over the course of the study), admitting service and medications. Risk factors for HAI were similar in sensitivity analyses restricted to patients with diagnostic codes for pneumonia/upper respiratory infection and urinary tract infection. CONCLUSIONS: SARS-CoV-2 was associated with significantly increased risk of HAI.

Progressive multifocal leukoencephalopathy in a patient post allo-HCT successfully treated with JC virus specific donor lymphocytes.

BACKGROUND: Progressive multifocal leukoencephalopathy is a demyelinating CNS disorder. Reactivation of John Cunningham virus leads to oligodendrocyte infection with lysis and consequent axonal loss due to demyelination. Patients usually present with confusion and seizures. Late diagnosis and lack of adequate therapy options persistently result in permanent impairment of brain functions. Due to profound T cell depletion, impairment of T-cell function and potent immunosuppressive factors, allogeneic hematopoietic cell transplantation recipients are at high risk for JCV reactivation. To date, PML is almost universally fatal when occurring after allo-HCT. METHODS: To optimize therapy specificity, we enriched JCV specific T-cells out of the donor T-cell repertoire from the HLA-identical, anti-JCV-antibody positive family stem cell donor by unstimulated peripheral apheresis [1]. For this, we selected T cells responsive to five JCV peptide libraries via the Cytokine Capture System technology. It enables the enrichment of JCV specific T cells via identification of stimulus-induced interferon gamma secretion. RESULTS: Despite low frequencies of responsive T cells, we succeeded in generating a product containing 20 000 JCV reactive T cells ready for patient infusion. The adoptive cell transfer was performed without complication. Consequently, the clinical course stabilized and the patient slowly went into remission of PML with JCV negative CSF and containment of PML lesion expansion. CONCLUSION: We report for the first time feasibility of generating T cells with possible anti-JCV activity from a seropositive family donor, a variation of virus specific T-cell therapies suitable for the post allo transplant setting. We also present the unusual case for successful treatment of PML after allo-HCT via virus specific T-cell therapy.

Altered white matter integrity in adults with autism spectrum disorder and an IQ >100: a diffusion tensor imaging study.

OBJECTIVE: White matter (WM) alterations have been reported in children and adults with autism spectrum disorder (ASD). In particular, impaired connectivity of limbic structures may be related to social deficits. Heterogeneous findings could be explained in terms of differences in sample characteristics and methodology. In this context, non-syndromic forms might differ substantially in WM structure from secondary ASD forms. METHOD: In an attempt to recruit a homogeneous study sample, we included adults with high-functioning ASD and an IQ > 100 to decrease the influence of syndromic forms being often associated with cognitive deficits. Diffusion tensor imaging (DTI) was performed in 30 participants with ASD and 30 pairwise-matched controls. Fractional anisotropy (FA) and mean diffusivity (MD) as surrogate imaging markers for WM integrity were calculated. RESULTS: We found a significant FA decrease in the ASD group in the genu and body of the corpus callosum (CC). Increased MD was detected in the subgenual anterior cingulate cortex (sACC). CONCLUSION: The finding of decreased WM integrity in the genu of the CC is in line with earlier studies reporting a decreased number of interhemispheric fibers in the frontal lobe of ASD. Alterations in the sACC might be associated with 'Theory of mind' deficits.

Factor XII: a novel target for safe prevention of thrombosis and inflammation.

Plasma protein factor XII (FXII) activates the procoagulant and proinflammatory contact system that drives both the kallikrein-kinin system and the intrinsic pathway of coagulation. When zymogen FXII comes into contact with negatively charged surfaces, it auto-activates to the serine proteaseactivated FXII (FXIIa). Recently, various in vivo activators of FXII have been identified including heparin, misfolded protein aggregates, polyphosphate and nucleic acids. Murine models have established a central role of FXII in arterial and venous thrombosis. Despite its central function in thrombosis, deficiency in FXII does not impair haemostasis in animals and humans. In a preclinical cardiopulmonary bypass system in large animals, the FXIIa-blocking antibody 3F7 prevented thrombosis; however, in contrast to traditional anticoagulants, bleeding was not increased. In addition to its function in thrombosis, FXIIa initiates formation of the inflammatory mediator bradykinin. This mediator increases vascular leak, causes vasodilation, and induces chemotaxis with implications for septic, anaphylactic and allergic disease states. Therefore, targeting FXIIa appears to be a promising strategy for thromboprotection without associated bleeding risks but with anti-inflammatory properties.

Disturbed cingulate glutamate metabolism in adults with high-functioning autism spectrum disorder: evidence in support of the excitatory/inhibitory imbalance hypothesis.

Over the last few years, awareness of autism spectrum disorder (ASD) in adults has increased. The precise etiology of ASD is still unresolved. Animal research, genetic and postmortem studies suggest that the glutamate (Glu) system has an important role, possibly related to a cybernetic imbalance between neuronal excitation and inhibition. To clarify the possible disruption of Glu metabolism in adults with high-functioning autism, we performed a magnetic resonance spectroscopy (MRS) study investigating the anterior cingulate cortex (ACC) and the cerebellum in adults with high-functioning ASD. Twenty-nine adult patients with high-functioning ASD and 29 carefully matched healthy volunteers underwent MRS scanning of the pregenual ACC and the left cerebellar hemisphere. Metabolic data were compared between groups and were correlated with psychometric measures of autistic features. We found a significant decrease in the cingulate N-acetyl-aspartate (NAA) and the combined Glu and glutamine (Glx) signals in adults with ASD, whereas we did not find other metabolic abnormalities in the ACC or the cerebellum. The Glx signal correlated significantly with psychometric measures of autism, particularly with communication deficits. Our data support the hypothesis that there is a link between disturbances of the cingulate NAA and Glx metabolism, and autism. The findings are discussed in the context of the hypothesis of excitatory/inhibitory imbalance in autism. Further research should clarify the specificity and dynamics of these findings regarding other neuropsychiatric disorders and other brain areas.

Direct evidence for continuous linear kinetics in the low-temperature degradation of Y-TZP.

The kinetics of the tetragonal to monoclinic (t-m) transformation of zirconia in a hydrous environment at 134°C and 3 bar pressure was studied. As surface X-ray diffraction, which is conventionally used to explore the progress, has a very limited depth of information, it distorts the quantitative results in a layer-on-layer situation and by itself is ill suited for this reason. Analyzing cross sections is more suitable; therefore, focused ion beam techniques were used to prepare artifact-free cuts. The material was subsequently investigated by scanning electron microscopy, electron backscatter diffraction and Raman spectroscopy. Only the combination of methods makes it possible to resolve the quantifiable details of the process. The transformation starts in the near-surface areas, forms a layer, and the growth of this layer proceeds into the bulk material following a simple linear time law (0.0624 µm h(-1) for material in the chosen condition), without apparent retardation or limit. The progress yields a gradientless layer with a fixed amount of residual tetragonal zirconia (~27% for 3Y-TZP in the present conditions) separated from unaffected material by a boundary, which has a roughness only in the grain size range. The kinetics indicates a reaction rate control, where the hydration reaction is the key factor, but is modified by the stepwise access of water to the reaction front opened by the autocatalytic transformation of zirconia with a critical hydration level.

Experimental determination of the Raman sampling depth in zirconia ceramics.

This study provides experimentally determined values for the actual micro-Raman spectroscopy sampling depth in zirconia ceramics (ZrO2) via line scans on a wedge-shaped sample. Common instrumental settings with metallurgical objective lenses in dry air, argon-ion, and helium-neon laser radiation of approximately 10 mW were chosen. Under those conditions effective sampling depths, defined as the depth at which 99% of the information is recorded, range from 20 to more than 50 microm, depending on the numerical aperture of the lens and the laser wavelength. These results elucidate the pitfalls of the investigation of surface phenomena in zirconia ceramics such as low-temperature degradation or mechanically induced phase transformations by Raman spectroscopy.

Phase analysis of superconducting polycrystalline MgB(2).

Superconducting MgB(2) ceramics were prepared and yield superconducting transition temperatures of about 39 K. For covering the various length scales on which inhomogeneities appear in MgB(2), electron-probe micro-analysis (EPMA) and analytical transmission electron microscopy (TEM) were applied for a phase analysis. Particularly useful were the preliminary electron spectroscopic imaging (ESI) results in the TEM. It could be shown by EPMA that the microstructure consists of a Mg-B-O matrix and boron-rich secondary phases of composition close to MgB(12). It was unclear in which form oxygen was present in the superconducting matrix. By combining the acquisition of B-K and O-K edge jump ratio images and energy-dispersive X-ray spectroscopy in the TEM, we could prove that the matrix consists of superconducting MgB(2) and MgO. Most of the MgO precipitates and grains appear with diameters between 20 and 300 nm. The size distribution of MgO was inhomogeneous and oxygen-rich areas of dimensions >1 microm were also observed. Edge jump ratio images obtained by ESI were analysed for determining the signal values and effects of multiple inelastic scattering.

Prostatitis-like symptoms: one year later.

OBJECTIVES: To re-survey (after 1 year) men identified in 1999 as having perineal and/or ejaculatory pain/discomfort severe enough to suggest a clinical diagnosis of chronic prostatitis (using the National Institutes of Health-Chronic Prostatitis Symptom Index, NIH-CPSI), and to compare them with an age-matched population of men who had no prostatitis-like symptoms in the initial survey, to determine the effect of time on specific symptoms associated with the diagnosis of chronic prostatitis. SUBJECTS AND METHODS: A comprehensive questionnaire incorporating the pain and voiding domains of the NIH-CPSI, and data on demographics, medical history, socio-economic status, health-seeking behaviour and a quality of life assessment, was sent to 67 men who had reported prostatitis-like symptoms in the 1999 survey, and to 202 age-matched controls (1 : 3) who reported no prostatitis-like symptoms in the same survey. RESULTS: Forty men (60%) with previous prostatitis-like symptoms, i.e. a mean (sd) 1999 NIH-CPSI pain score of 8.8 (0.4), and 119 (59%) of the control population completed and returned the survey. There was no difference in the 1999 demographics (P = 0.82) or NIH-CPSI pain score (P = 0.49) between patients who returned the recent questionnaire and those who could not be located or declined to complete the survey. Fifteen men (38%) identified with prostatitis in 1999 did not report similar symptoms in 2000. The initial mean NIH-CPSI pain score (0-21) for the men who had resolution of their prostatitis-like symptoms was 7.5 (0.6); 1 year later it was 0.73 (0.3). Their mean age was 51.1 (3.9) years and mean duration of symptoms 1.1 (0.3) years. Those with persistent symptoms had an initial NIH-CPSI pain score of 9.6 (0.5); 1 year later it was 8.68 (0.4), at mean age of 51.4 (2.5) years and duration of symptoms 2.2 (0.3) years. Four men (3%) in the control group who had no symptoms in 1999 reported prostatitis-like symptoms in 2000; these men had a mean age of 52.5 (5.9) and NIH-CPSI pain score of 7.0 (0.9). CONCLUSION: About a third of men reporting prostatitis-like symptoms in the general population had resolution of their symptoms (usually those with a shorter duration and less severe symptoms) 1 year later. The severity of symptoms of men with persistent chronic prostatitis remained relatively unchanged over the year.

Ultrasonic waste activated sludge disintegration for improving anaerobic stabilization.

The pretreatment of waste activated sludge by ultrasonic disintegration was studied in order to improve the anaerobic sludge stabilization. The ultrasound frequency was varied within a range from 41 to 3217 kHz. The impact of different ultrasound intensities and treatment times was examined. Sludge disintegration was most significant at low frequencies. Low-frequency ultrasound creates large cavitation bubbles which upon collapse initiate powerful jet streams exerting strong shear forces in the liquid. The decreasing sludge disintegration efficiency observed at higher frequencies was attributed to smaller cavitation bubbles which do not allow the initiation of such strong shear forces. Short sonication times resulted in sludge floc deagglomeration without the destruction of bacteria cells. Longer sonication brought about the break-up of cell walls, the sludge solids were distintegrated and dissolved organic compounds were released. The anaerobic digestion of waste activated sludge following ultrasonic pretreatment causing microbial cell lysis was significantly improved. There was an increase in the volatile solids degradation as well as an increase in the biogas production. The increase in digestion efficiency was proportional to the degree of sludge disintegration. To a lesser degree the deagglomeration of sludge flocs also augmented the anaerobic volatile solids degradation.

Activators of peroxisome proliferator-activated receptor-alpha partially inhibit mouse skin tumor promotion.

Several recent reports have suggested that peroxisome proliferator-activated receptors (PPARs) may be involved in the development of neoplasias in different tissue types. The present study was undertaken to determine whether PPARs play a role in skin physiology and tumorigenesis. In an initiation-promotion study, SENCAR mice treated topically with the PPARalpha ligands conjugated linoleic acid and 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid (Wy-14643) exhibited an approximately 30% lower skin tumor yield compared with mice treated with vehicle. The PPARgamma and PPARdelta activators troglitazone and bezafibrate, respectively, exerted little, if any, inhibitory activity. PPARalpha was detected in normal and hyperplastic skin and in papillomas and carcinomas by immunohistochemistry. In addition, PPARalpha, PPARdelta/PPARbeta, and PPARgamma protein levels were analyzed by immunoblotting in normal epidermis and papillomas. Surprisingly, the levels of all three isoforms were increased significantly in tumors as opposed to normal epidermis. In primary keratinocyte cultures, protein levels of PPARalpha and, to a lesser extent, PPARgamma were markedly increased when the cells were induced to differentiate with high-calcium (0.12 mM) conditions. In addition, we observed that Wy-14643 enhanced transcriptional activity of a peroxisome proliferator-response element-driven promoter in a mouse keratinocyte cell line. These results demonstrate that keratinocytes express functional PPARalpha, that PPARalpha may play a role in differentiation, and that ligands for PPARalpha are moderately protective against skin tumor promotion. We conclude that selective PPARalpha ligands may exert their protective role against skin tumor promotion by ligand activation of PPARalpha.

Characterization of 25-hydroxyvitamin D binding protein from intestinal cells.

We have previously purified a cytosolic vitamin D metabolite binding protein (cDBP) from rat enterocytes, which has characteristics distinct from other vitamin D binding proteins. In these studies, we demonstrate that cDBP in a semi-purified fraction from human intestinal cells (Caco-2 cells) binds 25-hydroxyvitamin D (25OHD) with at least a 1000-fold greater affinity than 1, 25-dihydroxyvitamin D (1,25(OH)(2)D) or 24,25-dihydroxyvitamin D. Treatment of cells with 1,25(OH)(2)D reduced 25OHD binding to approximately one third that of the untreated cells (0.42 CPM/mg total protein vs 1.34 CPM/mg total protein, respectively). Finally, the cDBP is not immunoreactive to antibodies prepared against the C-terminus of the nuclear vitamin D receptor (VDR). In summary, cDBP bound 25OHD with greater affinity than either 1,25(OH)(2)D or 24,25 dihydroxyvitamin D, the cytosolic binding activity was down-regulated by 1,25(OH)(2)D and cBDP is distinct from the nuclear VDR.

Inositol hexaphosphate reduces 12-O-tetradecanoylphorbol-13-acetate-induced ornithine decarboxylase independent of protein kinase C isoform expression in keratinocytes.

High-fiber diets have been shown to have beneficial effects on preventing tumorigenesis. Inositol hexaphosphate (InsP6 or phytic acid) which is a fiber-associated component of cereals and legumes has been demonstrated to inhibit cell proliferation and enhance cell differentiation, indicating its potential for chemopreventive roles. In this study, we investigated the effect of InsP6 on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ornithine decarboxylase (ODC) activity, an essential event in tumor promotion in HEL-30 cells, a murine keratinocyte cell line and SENCAR mouse skin. ODC activity was significantly reduced by 0.5 mM InsP6 in keratinocytes (P < 0.01). Furthermore, when mouse skin was treated with 10 mM InsP6, ODC induction was significantly inhibited (P < 0.05). In addition, the expression of TPA-induced c-myc mRNA was significantly inhibited by the same InsP6 treatments in HEL-30 cells and CD-1 mouse skin (P < 0.01). No changes in protein kinase C (PKC) isoform expression and phorbol dibutyrate binding due to InsP6 treatment were found in HEL-30 cells. These results indicate that InsP6 reduces TPA-induced ODC activity independent of PKC isoform expression.

Genetic definition and sequence analysis of Arabidopsis centromeres.

High-precision genetic mapping was used to define the regions that contain centromere functions on each natural chromosome in Arabidopsis thaliana. These regions exhibited dramatic recombinational repression and contained complex DNA surrounding large arrays of 180-base pair repeats. Unexpectedly, the DNA within the centromeres was not merely structural but also encoded several expressed genes. The regions flanking the centromeres were densely populated by repetitive elements yet experienced normal levels of recombination. The genetically defined centromeres were well conserved among Arabidopsis ecotypes but displayed limited sequence homology between different chromosomes, excluding repetitive DNA. This investigation provides a platform for dissecting the role of individual sequences in centromeres in higher eukaryotes.

Dietary conjugated linoleic acid normalizes impaired glucose tolerance in the Zucker diabetic fatty fa/fa rat.

Conjugated linoleic acid (CLA) is a naturally occurring fatty acid which has anti-carcinogenic and anti-atherogenic properties. CLA activates PPAR alpha in liver, and shares functional similarities to ligands of PPAR gamma, the thiazolidinediones, which are potent insulin sensitizers. We provide the first evidence that CLA is able to normalize impaired glucose tolerance and improve hyperinsulinemia in the pre-diabetic ZDF rat. Additionally, dietary CLA increased steady state levels of aP2 mRNA in adipose tissue of fatty ZDF rats compared to controls, consistent with activation of PPAR gamma. The insulin sensitizing effects of CLA are due, at least in part, to activation of PPAR gamma since increasing levels of CLA induced a dose-dependent transactivation of PPAR gamma in CV-1 cells cotransfected with PPAR gamma and PPRE X 3-luciferase reporter construct. CLA effects on glucose tolerance and glucose homeostasis indicate that dietary CLA may prove to be an important therapy for the prevention and treatment of NIDDM.

Are physicians' office laboratory results of comparable quality to those produced in other laboratory settings?

CONTEXT: In 1995, California adopted a bill that brought laboratory laws in line with the 1988 Clinical Laboratory Improvement Amendments' standards for clinical laboratories and mandated a study comparing results in physicians' office laboratories (POLs) with other settings. OBJECTIVE: To determine whether persons conducting tests in POLs produce accurate and reliable test results comparable to those produced by non-POLs. DESIGN: Survey of clinical laboratories using proficiency testing data. SETTING: All California clinical laboratories participating in the American Association of Bioanalysts proficiency testing program in 1996 (n=1110). MAIN OUTCOME MEASURES: "Unsatisfactory" (single testing event failure) and "unsuccessful" (repeated testing event failure) on proficiency testing samples. RESULTS: The unsatisfactory failure rate for POLs was nearly 3 times (21.5% vs 8.1%) the rate for the non-POLs and about 1.5 times (21.5% vs 14.0%) for POLs that used laboratory professionals as testing or supervisory personnel (P<.001). The POL unsuccessful rate was more than 4 times (4.4% vs 0.9%) the rate for non-POLs and more than twice (4.4% vs 1.8%) the rate for the POLs using laboratory professionals (P<.001). CONCLUSIONS: Significant differences exist among POLs, POLs using licensed clinical laboratory scientists (medical technologists), and non-POLs. Testing personnel in many POLs might lack the necessary education, training, and oversight common to larger facilities. We must better understand the contributing factors that result in the poorer results of POLs relative to non-POLs. In the meantime, patients should be aware that preliminary findings suggest that differences in quality of laboratory tests based on testing site may exist. Laboratory directors at all testing sites must ensure that they understand laboratory practice sufficiently to minimize errors and maximize accuracy and reliability. Directors must understand their obligation when they elect to oversee those assigned testing responsibility. Legislators may wish to reconsider the wisdom of further easing restrictions on those to whom we entrust our laboratory specimens.

Involvement of two alpha-ketoglutarate-dependent dioxygenases in enantioselective degradation of (R)- and (S)-mecoprop by Sphingomonas herbicidovorans MH.

Cell extracts of Sphingomonas herbicidovorans MH grown on (R)-mecoprop contained an enzyme activity that selectively converted (R)-mecoprop to 4-chloro-2-methylphenol, whereas extracts of cells grown on (S)-mecoprop contained an enzyme activity selective for the S enantiomer. Both reactions were dependent on alpha-ketoglutarate and ferrous ions. Besides 4-chloro-2-methylphenol, pyruvate and succinate were detected as products of the reactions. Labeling experiments with (18)O2 revealed that both enzyme activities catalyzed a dioxygenation reaction. One of the oxygen atoms of pyruvate and one of the oxygen atoms of succinate were derived from molecular oxygen. Analysis of cell extracts obtained from cells grown on different substrates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that growth on (R)-mecoprop and (S)-mecoprop caused the appearance of prominent protein bands at 34 and 32 kDa, respectively. Both protein bands were present when cells grew on the racemic mixture. The results demonstrate that S. herbicidovorans initiated the degradation of each enantiomer of mecoprop by a specific alpha-ketoglutarate-dependent dioxygenase. By comparing conversion rates of various phenoxy herbicides, we confirmed that the two enzyme activities were distinct from that of TfdA, which catalyzes the first step in the degradation of 2,4-dichlorophenoxyacetic acid in Ralstonia eutropha JMP134.

Calcium bioavailability of vegetarian diets in rats: potential application in a bioregenerative life-support system.

Calcium bioavailability of vegetarian diets containing various proportions of candidate crops for a controlled ecological life-support system (CELSS) was determined by femur 45Ca uptake. Three vegetarian diets and a control diet were labeled extrinsically with 45Ca and fed to 5-wk old male rats. A fifth group of rats fed an unlabeled control diet received an intraperitoneal (IP) injection of 45Ca. There was no significant difference in mean calcium absorption of vegetarian diets (90.80 +/- 5.23%) and control diet (87.85 +/- 5.25%) when calculated as the percent of an IP dose. The amounts of phytate, oxalate, and dietary fiber in the diets did not affect calcium absorption.

Complete microbial degradation of both enantiomers of the chiral herbicide mecoprop [(RS)-2-(4-chloro-2-methylphenoxy)propionic acid] in an enantioselective manner by Sphingomonas herbicidovorans sp. nov.

Sphingomonas herbicidovorans MH (previously designated Flavobacterium sp. strain MH) was able to utilize the chiral herbicide (RS)-2-(4-chloro-2-methylphenoxy)propionic acid (mecoprop) as the sole carbon and energy source. When strain MH was offered racemic mecoprop as the growth substrate, it could degrade both the (R) and the (S) enantiomer to completion, as shown by biomass formation, substrate consumption, and stoichiometric chloride release. However, the (S) enantiomer disappeared much faster from the culture medium than the (R) enantiomer. These results suggest the involvement of specific enzymes for the degradation of each enantiomer. This view was substantiated by the fact that resting cells of strain MH grown on (S)-mecoprop were able to degrade the (S) but not the (R) enantiomer of mecoprop. Accordingly, resting cells of strain MH grown on (R)-mecoprop preferentially metabolized the (R) enantiomer. Nevertheless, such cells could transform (S)-mecoprop at low rates. Oxygen uptake rates with resting cells confirmed the above view, as oxygen consumption was strongly dependent on the growth substrate. Cells grown on (R)-mecoprop showed oxygen uptake rates more than two times higher upon incubation with the (R) than upon incubation with the (S) enantiomer and vice versa.