Synergistic Renoprotective Effects of Green Tea Extract and Gemigliptin against Tacrolimus-Induced Nephrotoxicity in Mice / Efectos Renoprotectores Sinérgicos del Extracto de Té Verde y Gemigliptina contra la Nefrotoxicidad Inducida por Tacrolimus en Ratones

SUMMARY: Although tacrolimus (TAC) significantly reduces allograft rejection incidence in solid-organ transplantation, its long-term use is associated with an increased risk of TAC-induced nephrotoxicity. In this study, we investigated the renoprotective effects of green tea extract (GTE) with or without the dipeptidyl peptidase 4 inhibitor, gemigliptin, by assessing serum creatinine levels, the amount of proteinuria, and histopathology in TAC-induced nephrotoxicity. TAC-induced nephrotoxicity was induced by intraperitoneal TAC injection, GTE was administered via subcutaneous injection, and gemigliptin was administered orally. Mice with TAC-induced nephrotoxicity exhibited a significant increase in both serum creatinine levels and 24-hour urine protein. However, when treated with GTE via subcutaneous injection, mice showed a decrease in serum creatinine levels and the amount of proteinuria. When GTE was combined with gemigliptin, further renoprotective effects were observed in biochemical assessments, consistent with the attenuation of TAC-induced nephrotoxicity in histopathology. The expression of p53 protein was lower in the mice treated with the combination of GTE and gemigliptin compared to mice with TAC-induced nephrotoxicity. Our results demonstrate that the combination of GTE and gemigliptin treatment reveals synergistic renoprotective effects by decreasing the expression of p53 protein. These findings suggest that the combination of GTE and gemigliptin could potentially be used as a prophylactic or therapeutic strategy for TAC-induced nephrotoxicity.

Aunque tacrolimus (TAC) reduce significativamente la incidencia de rechazo de aloinjertos en trasplantes de órganos sólidos, su uso a largo plazo se asocia con un mayor riesgo de nefrotoxicidad inducida por TAC. En este estudio, investigamos los efectos renoprotectores del extracto de té verde (GTE) con o sin el inhibidor de la dipeptidil peptidasa 4, gemigliptina, mediante la evaluación de los niveles de creatinina sérica, la cantidad de proteinuria y la histopatología en la nefrotoxicidad inducida por TAC. La nefrotoxicidad inducida por TAC se indujo mediante inyección intraperitoneal de TAC, el GTE se administró mediante inyección subcutánea y la gemigliptina se administró por vía oral. Los ratones con nefrotoxicidad inducida por TAC mostraron un aumento significativo tanto en los niveles de creatinina sérica como en la proteína en orina de 24 horas. Sin embargo, cuando se trataron con GTE mediante inyección subcutánea, los ratones mostraron una disminución en los niveles de creatinina sérica y en la cantidad de proteinuria. Cuando se combinó GTE con gemigliptina, se observaron efectos renoprotectores adicionales en las evaluaciones bioquímicas, lo que concuerda con la atenuación de la nefrotoxicidad inducida por TAC en histopatología. La expresión de la proteína p53 fue menor en los ratones tratados con la combinación de GTE y gemigliptina en comparación con los ratones con nefrotoxicidad inducida por TAC. Nuestros resultados demuestran que la combinación de tratamiento con GTE y gemigliptina revela efectos renoprotectores sinérgicos al disminuir la expresión de la proteína p53. Estos hallazgos sugieren que la combinación de GTE y gemigliptina podría usarse potencialmente como estrategia profiláctica o terapéutica para la nefrotoxicidad inducida por TAC.

Viscum album Induces Apoptosis by Regulating STAT3 Signaling Pathway in Breast Cancer Cells.

In this study, we investigated the potential anticancer effects of Viscum album, a parasitic plant that grows on Malus domestica (VaM) on breast cancer cells, and explored the underlying mechanisms. VaM significantly inhibited cell viability and proliferation and induced apoptosis in a dose-dependent manner. VaM also regulated cell cycle progression and effectively inhibited activation of the STAT3 signaling pathway through SHP-1. Combining VaM with low-dose doxorubicin produced a synergistic effect, highlighting its potential as a promising therapeutic. In vivo, VaM administration inhibited tumor growth and modulated key molecular markers associated with breast cancer progression. Overall, our findings provide strong evidence for the therapeutic potential of VaM in breast cancer treatment and support further studies exploring clinical applications.

Zinc is an essential element for the maintenance of redox homeostasis and cell cycle in murine auditory hair cells.

A nutrition deficiency is one of the various causes of hearing loss. Zinc is an essential element for cell proliferation, antioxidant reactions, and the maintenance of hearing ability. Our previous studies have reported that the auditory brainstem response (ABR) threshold is increased in mice fed with zinc-deficient diets. However, the molecular mechanism of zinc involved in auditory system remains to be elucidated. In the present study, we examined the detrimental effects of zinc deficiency on cell cycle progression in murine auditory cells (HEI-OC1). The treatment of HEI-OC1 cells with 0.5 µM TPEN (N,N,N',N'-Tetrakis (2-pyridylmethyl) ethylenediamine) for 24 h inhibited cell proliferation, accumulation of reactive oxygen species (ROS), and induction of apoptosis. The cell proliferation block was caused by a G1/S phase arrest. Supplementation of the cell growth medium with 5 µM ZnCl2 after exposure to TPEN attenuated ROS accumulation and the arrest caused by the zinc deficiency. The ABR threshold was elevated in mice fed with a zinc-deficient diet. Additionally, we observed an increased expression of p21 and decreased expression of cyclin E and pRb in the spiral ganglion (SG), the organ of Corti (OC), Limbus (L), and stria vascularis (SV) in the zinc-deficient mouse cochlea. These results indicated that zinc is an essential nutrient for proliferation via the cell cycle and that a dysregulation of the cell cycle may cause hearing loss.

Evaluation of electroporated area using 2,3,5-triphenyltetrazolium chloride in a potato model.

Irreversible electroporation (IRE) is a tissue ablation method, uses short high electric pulses and results in cell death in target tissue by irreversibly permeabilizing the cell membrane. Potato is commonly used as a tissue model for electroporation experiments. The blackened area that forms 12 h after electric pulsing is regarded as an IRE-ablated area caused by melanin accumulation. Here, the 2,3,5-triphenyltetrazolium chloride (TTC) was used as a dye to assess the IRE-ablated area 3 h after potato model ablation. Comparison between the blackened area and TTC-unstained white area in various voltage conditions showed that TTC staining well delineated the IRE-ablated area. Moreover, whether the ablated area was consistent over time and at different staining times was investigated. In addition, the presumed reversible electroporation (RE) area was formed surrounding the IRE-ablated area. Overall, TTC staining can provide a more rapid and accurate electroporated area evaluation.

Photobiomodulation as an antioxidant substitute in post-thawing trauma of human stem cells from the apical papilla.

Cryopreservation, the most common method of preserving stem cells, requires post-processing because it produces trauma to the cells. Post-thawing trauma typically induces cell death, elevates reactive oxygen species (ROS) concentration, and lowers mitochondrial membrane potential (MMP). Although this trauma has been solved using antioxidants, we attempted to use photobiomodulation (PBM) instead of chemical treatment. We used a 950-nm near-infrared LED to create a PBM device and chose a pulsed-wave mode of 30 Hz and a 30% duty cycle. Near-infrared radiation (NIR) at 950 nm was effective in reducing cell death caused by hydrogen peroxide induced-oxidative stress. Cryodamage also leads to apoptosis of cells, which can be avoided by irradiation at 950 nm NIR. Irradiation as post-processing for cryopreservation had an antioxidant effect that reduced both cellular and mitochondrial ROS. It also increased mitochondrial mass and activated mitochondrial activity, resulting in increased MMP, ATP generation, and increased cytochrome c oxidase activity. In addition, NIR increased alkaline phosphatase (ALP) activity, a biomarker of differentiation. As a result, we identified that 950 nm NIR PBM solves cryodamage in human stem cells from the apical papilla, indicating its potential as an alternative to antioxidants for treatment of post-thawing trauma, and further estimated its mechanism.

Zinc deficiency and its association with treatment-related toxicity in children with cancer.

BACKGROUND: Nutritional deficiencies in children with cancer at time of diagnosis and during treatment may negatively affect disease outcome and increase treatment-related toxicity. Yet zinc, an essential nutrient important for supporting immune function and known for reducing diarrheal episodes, is rarely assessed in these children. PROCEDURES: Fifty children (1 month to 18 years) with recently diagnosed cancer were enrolled in this study. An age and gender matched control group (n = 50) was also recruited. Plasma and urinary zinc, plasma copper, and C-reactive protein (CRP) levels were measured at baseline, 3, and 6 months following diagnosis. A retrospective review of the toxicity profile was performed in the cohort of children with cancer for the first 4 years after initial diagnosis. RESULTS: CRP and plasma copper (both acute-phase reactants) were elevated in patients with cancer compared to controls at baseline, both p < .03. Plasma zinc levels were not significantly different from controls at baseline, but decreased by 11% in the cancer group over 6 months of treatment, 83.2 ± 15.6 to 74.3 ± 14.8 µg/dl, p = .01. Plasma zinc dropped to deficient levels in 35% of cases over the initial 6 months. Zinc deficiency at 6 months was related to an increased incidence of severe diarrhea during 4 years of follow-up, p < .001. CONCLUSIONS: Zinc deficiency is an underrecognized problem among patients undergoing treatment for cancer and is associated with severe diarrhea. Further studies are needed to evaluate causes for zinc deficiency, related effects, and a possible role for zinc supplementation.

UPLC-ESI-Q-TOF-MS-Based Metabolite Profiling, Antioxidant and Anti-Inflammatory Properties of Different Organ Extracts of Abeliophyllum distichum.

Plant extracts have gained more attention as natural therapeutic agents against inflammation characterized by an overproduction of several inflammatory mediators such as reactive oxygen species and pro-inflammatory cytokines. Although Abeliophyllum distichum Nakai is generally known for its ornamental value, recent pharmacological research has demonstrated its potential therapeutic properties. Thus, to further evaluate the applicability of A. distichum in the food, cosmetic, and medical industries, we identified the phytochemicals in three organ extracts (fruits: AF, branches: AB, leaves: AL) of A. distichum and determined their antioxidant and anti-inflammatory activities. Using UPLC-ESI-Q-TOF-MS, a total of 19 compounds, including dendromoniliside D, forsythoside B, isoacteoside, isomucronulatol 7-O-Glucoside, plantamajoside, and wighteone were identified in the A. distichum organ extracts. AB exhibited a strong reducing power, an oxygen radical antioxidant capacity, and radical scavenging values compared with other samples, whereas AL exhibited the best anti-inflammatory properties. Gene expression, western blot, and molecular docking analyses suggested that the anti-inflammatory effect of AL was mediated by its ability to suppress lipopolysaccharide (LPS)-induced production of reactive oxygen species and/or inhibit LPS-stimulated activation of extracellular signal-regulated protein kinases (ERK1/2) in RAW264.7 cells. Collectively, these results indicate that AL is a potential source of phytochemicals that could be used to treat inflammation-associated diseases.

Interpreting auditory brainstem evoked responses and distortion product otoacoustic emissions in diabetic patients with normal hearing.

OBJECTIVE: Hearing impairment is a reported late complication of diabetes mellitus (DM). Previous studies have suggested that microangiopathic complications may cause cochlear nerve function deterioration. We evaluated the auditory brainstem evoked responses (ABRs) and distortion product otoacoustic emission (DPOAE) results according to the presence of DM in subjects with normal hearing. METHODS: A cross-sectional comparative study was conducted from January 2016 to January 2018. Auditory function tests including ABR and DPOAE were performed for outpatients complaining of unilateral tinnitus. All of analyses were conducted in ears without tinnitus on contralateral side of tinnitus ears. We included subjects showing hearing thresholds within 25 dB at 0.5, 1k, 2k, and 4k on pure tone audiometry. 45 ears in patients with type 2 diabetes mellitus and 85 ears in non-diabetic patients were finally enrolled in our study. RESULTS: Diabetic subjects showed significantly more prolonged absolute peak latencies (I, III, V) and inter-peak latencies (I-V, III-V) than non-diabetic subjects. However, there was no significant difference in the inter-peak latency (I-III) between these two groups. Diabetic subjects also showed significantly lower amplitudes at f2 frequencies of 1001, 1200, 1587, 4004, 5042, and 6348 Hz than non-diabetic subjects. Additionally, the prevalence of a DPOAE response, defined as 3 dB above the noise floor, was significantly lower in diabetic subjects than that in non-diabetic subjects. CONCLUSION: Diabetic patients with normal hearing can still have abnormal ABR and DPOAE results due to diabetic neuroangiopathy. ABR and DPOAE assessments can help in detecting subclinical auditory dysfunction, which precedes the manifestation of hearing impairment in diabetic patients.

Cortical reorganization following auditory deprivation predicts cochlear implant performance in postlingually deaf adults.

Long-term hearing loss in postlingually deaf (PD) adults may lead to brain structural changes that affect the outcomes of cochlear implantation. We studied 94 PD patients who underwent cochlear implantation and 37 patients who were MRI-scanned within 2 weeks after the onset of sudden hearing loss and expected with minimal brain structural changes in relation to deafness. Compared with those with sudden hearing loss, we found lower gray matter (GM) probabilities in bilateral thalami, superior, middle, inferior temporal cortices as well as the central cortical regions corresponding to the movement and sensation of the lips, tongue, and larynx in the PD group. Among these brain areas, the GM in the middle temporal cortex showed negative correlation with disease duration, whereas the other areas displayed positive correlations. Left superior, middle temporal cortical, and bilateral thalamic GMs were the most accurate predictors of post-cochlear implantation word recognition scores (mean absolute error [MAE] = 10.1, r = .82), which was superior to clinical variables used (MAE: 12.1, p < .05). Using the combined brain morphological and clinical features, we achieved the best prediction of the outcome (MAE: 8.51, r = .90). Our findings suggest that the cross-modal plasticity allowing the superior temporal cortex and thalamus to process other modal sensory inputs reverses the initially lower volume when deafness becomes persistent. The middle temporal cortex processing higher-level language comprehension shows persistent negative correlations with disease duration, suggesting this area's association with degraded speech comprehensions due to long-term deafness. Morphological features combined with clinical variables might play a key role in predicting outcomes of cochlear implantation.

Establishment of a UPLC-PDA/ESI-Q-TOF/MS-Based Approach for the Simultaneous Analysis of Multiple Phenolic Compounds in Amaranth (A. cruentus and A. tricolor).

We used ultraperformance liquid chromatography coupled with a photodiode-array detector and electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-PDA/ESI-Q-TOF/MS) to rapidly and accurately quantify 17 phenolic compounds. Then, we applied this method to the seed and leaf extracts of two Amaranthus species to identify and quantify phenolic compounds other than the 17 compounds mentioned above. Compounds were eluted within 30 min on a C18 column using a mobile phase (water and acetonitrile) containing 0.1% formic acid, and the specific wavelength and ion information of the compounds obtained by PDA and ESI-Q-TOF/MS were confirmed. The proposed method showed good linearity (r2 > 0.990). Limits of detection and quantification were less than 0.1 and 0.1 µg/mL, respectively. Intra- and interday precision were less than 2.4% and 1.8%, respectively. Analysis of amaranth seed and leaf extracts using the established method showed that the seeds contained high amounts of 2,4-dihydroxybenzoic acid and kaempferol, and leaves contained diverse phenolic compounds. In addition, six tentatively new phenolic compounds were identified. Moreover, seeds potentially contained 2,3-dihydroxybenzaldehyde, a beneficial bioactive compound. Thus, our method was an efficient approach for the qualitative and quantitative analysis of phenolic compounds, and could be used to investigate phenolic compounds in plants.

Phytochemicals and Antioxidant Activity of Korean Black Soybean (Glycine max L.) Landraces.

Black soybean (Glycine max L.) has been used as a traditional medicine because its seed coat contains various natural phenolic compounds such as anthocyanins. The objective of this study was to reveal the genetic variation in the agricultural traits, phytochemicals, and antioxidant activity of 172 Korean black soybean landraces (KBSLs) and establish a relationship among them. The evaluation of three agricultural traits (days to 50% flowering, maturity, and 100-seed weight), six phytochemicals (delphinidin-3-glucoside, cyaniding-3-glucoside, petunidin-3-glucoside, daidzin, glycitin, and genestin), and four antioxidant activities (2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS), ferric-reducing antioxidant power (FRAP), and the total polyphenol content (TPC) of 172 KBSLs were analyzed in 2012 and 2015. The agricultural traits, phytochemicals, and antioxidant activities of the 172 KBSLs showed wide variation among the accessions and years. In correlation analysis, the agricultural traits and phytochemicals showed positive and negative correlations with phytochemicals and antioxidant activity, respectively. The principal component analyses result indicated that phytochemicals accounted for most of the variability in the KBSLs. In clustering analysis, the 172 KBSLs were classified into four clusters. These results could lead to expanding the knowledge of the agricultural traits, phytochemicals, and antioxidant activity of the KBSLs, which are valuable materials for the development of new soybean varieties.

Hyperbaric oxygen (HBO) therapy as an effective approach to the treatment of patients with severe idiopathic sudden sensorineural hearing loss.

Background: The potential etiology of idiopathic sudden sensorineural hearing loss (ISSNHL) is cochlear ischemia, therefore, hyperbaric oxygen (HBO) therapy is a promising treatment, particularly in patients with severe hearing loss (≥70 dB).Aims/objectives: To evaluate the efficacy of HBO therapy.Material and methods: The medical records of patients diagnosed with ISSNHL were retrospectively reviewed (≥70 dB). Patients received HBO therapy 14 times in addition to systemic and intratympanic steroid therapy (HBO group), or systemic and intratympanic steroid therapy only (control group).Results: Data from a total of 82 patients (83 ears) were included in the analysis; 37 (38 ears) in the HBO group and 45 (45 ears) in the control group. After 2 weeks' treatment, hearing was significantly improved in the HBO group versus controls (weighted four-frequency average 28.1 ± 26.9 dB versus 14.8 ± 13.5 dB, respectively; p < .05), particularly in the low frequency groups (0.5 kHz, 1 kHz, 2 kHz; p < .05).Conclusion and significance: These data demonstrate that HBO therapy is an effective initial treatment option for patients with ISSNHL suffering from severe hearing loss.

Development of genomic simple sequence repeat markers for Glycyrrhiza lepidota and cross-amplification of other Glycyrrhiza species.

BACKGROUND: Licorice (Glycyrrhiza spp. L.) is used as a natural sweetener and medicinal herb in European and Asian countries. Molecular studies have been conducted to find differences between wild and cultivated species because most wild species are highly resistant to abiotic and biotic stresses compared with their cultivated species. However, few molecular markers have been developed for studying the genetic diversity and population structure of licorice species and to identify differences between cultivars. Thus, the present study aimed to develop a set of genomic simple sequence repeat (SSR) markers for molecular studies of these species. METHODS: In the present study, we developed polymorphic SSR markers based on whole-genomesequence data of Glycyrrhiza lepidota. Then, based on the sequence information, the polymorphic SSR markers were developed. The SSR markers were applied to 23 Glycyrrhiza individual plants. We also evaluated the phylogenetic relationships and interspecies transferability among samples. RESULTS: The genetic diversity analysis using these markers identified 2-23 alleles, and the major allele frequency, observed heterozygosity, genetic diversity, and polymorphism information content were 0.11-0.91, 0-0.90, 0.17-0.94, and 0.15-0.93, respectively. Interspecies transferability values were 93.5%, 91.6%, and 91.1% for G. echinata, G. glabra, and G. uralensis, respectively. Phylogenetic analysis clustered cultivated (group 1) and wild (group 2) species into three and two subgroups, respectively. The reported markers represent a valuable resource for the genetic characteri z ation of Glycyrrhiza spp. for theanalysis of its genetic variability, and as a tool for licorice transferability. This is the first intraspecific study in a collection of Glycyrrhiza spp. germplasm using SSR markers.

Associations of Dietary Riboflavin, Niacin, and Retinol with Age-related Hearing Loss: An Analysis of Korean National Health and Nutrition Examination Survey Data.

Because age-related hearing loss (ARHL) is irreversible, prevention is very important. Thus, investigating modifying factors that help prevent ARHL is critical for the elderly. Nutritional status or nutritional factors for the elderly are known to be associated with many problems related to aging. Emerging studies suggest that there was the interaction between nutrition and ARHL. We aimed to investigate the possible impact of dietary nutrients on ARHL using data from the fifth Korean National Health and Nutrition Examination Survey (KNHANES) which included 4742 subjects aged ≥ 65 years from 2010 to 2012. All participants underwent an otologic examination, audiologic evaluation, and nutritional survey. The associations between ARHL and nutrient intake were analyzed using simple and multiple regression models with complex sampling adjusted for confounding factors, such as BMI, smoking status, alcohol consumption, and history of hypertension and diabetes. Higher intake groups of riboflavin, niacin and retinol was inversely associated with ARHL prevalence (riboflavin aOR, 0.71; 95% CI, 0.54-0.94; p = 0.016, niacin aOR, 0.72; 95% CI, 0.54-0.96; p = 0.025, retinol aOR 0.66; 95% CI, 0.51-0.86; p = 0.002, respectively). Our findings suggest the recommended intake levels of riboflavin, niacin, and retinol may help reduce ARHL in the elderly.

Effects of pulsing of light on the dentinogenesis of dental pulp stem cells in vitro.

Low power light (LPL) treatment has been widely used in various clinical trials, which has been known to reduce pain and inflammation and to promote wound healing. LPL was also shown to enhance differentiation of stem cells into specific lineages. However, most studies have used high power light in mW order, and there was lack of studies about the effects of very low power light in µW. In this study, we applied 810 nm LPL of 128 µW/cm2 energy density in vitro. Upon this value, continuous wave (CW) irradiation did not induce any significant changes for differentiation of human dental pulp stem cells (hDPSCs). However, the membrane hyperpolarization, alkaline phosphatase activity, and intracellular oxidative stress were largely enhanced in the pulsed wave (PW) with 30% of duty cycle and 300-3000 Hz frequencies-LPL in which LED driver work in the form of square wave. After 21 days of daily LPL treatment, Western blot revealed the dentinogenesis in this condition in vitro. This study demonstrates that the very low power light at 810 nm enhanced significant differentiation of hDPSCs in the PW mode and there were duty cycle dependency as well as pulsing frequency dependency in the efficiency.

Pulse frequency dependency of photobiomodulation on the bioenergetic functions of human dental pulp stem cells.

Photobiomodulation (PBM) therapy contributes to pain relief, wound healing, and tissue regeneration. The pulsed wave (PW) mode has been reported to be more effective than the continuous wave (CW) mode when applying PBM to many biological systems. However, the reason for the higher effectiveness of PW-PBM is poorly understood. Herein, we suggest using delayed luminescence (DL) as a reporter of mitochondrial activity after PBM treatment. DL originates mainly from mitochondrial electron transport chain systems, which produce reactive oxygen species (ROS) and adenosine triphosphate (ATP). The decay time of DL depends on the pulse frequencies of applied light, which correlate with the biological responses of human dental pulp stem cells (hDPSCs). Using a low-power light whose wavelength is 810 nm and energy density is 38 mJ/cm2, we find that a 300-Hz pulse frequency prolonged the DL pattern and enhanced alkaline phosphatase activity. In addition, we analyze mitochondrial morphological changes and their volume density and find evidence supporting mitochondrial physiological changes from PBM treatment. Our data suggest a new methodology for determining the effectiveness of PBM and the specific pulse frequency dependency of PBM in the differentiation of hDPSCs.

Development of Genome-Wide SSR Markers from Angelica gigas Nakai Using Next Generation Sequencing.

Angelica gigas Nakai is an important medicinal herb, widely utilized in Asian countries especially in Korea, Japan, and China. Although it is a vital medicinal herb, the lack of sequencing data and efficient molecular markers has limited the application of a genetic approach for horticultural improvements. Simple sequence repeats (SSRs) are universally accepted molecular markers for population structure study. In this study, we found over 130,000 SSRs, ranging from di- to deca-nucleotide motifs, using the genome sequence of Manchu variety (MV) of A. gigas, derived from next generation sequencing (NGS). From the putative SSR regions identified, a total of 16,496 primer sets were successfully designed. Among them, we selected 848 SSR markers that showed polymorphism from in silico analysis and contained tri- to hexa-nucleotide motifs. We tested 36 SSR primer sets for polymorphism in 16 A. gigas accessions. The average polymorphism information content (PIC) was 0.69; the average observed heterozygosity (HO) values, and the expected heterozygosity (HE) values were 0.53 and 0.73, respectively. These newly developed SSR markers would be useful tools for molecular genetics, genotype identification, genetic mapping, molecular breeding, and studying species relationships of the Angelica genus.

Impact of Vancomycin MIC on Treatment Outcomes in Invasive Staphylococcus aureus Infections.

There are conflicting data on the association of vancomycin MIC (VAN-MIC) with treatment outcomes in Staphylococcus aureus infections. We investigated the relationship between high VAN-MIC and 30-day mortality and identified the risk factors for mortality in a large cohort of patients with invasive S. aureus (ISA) infections, defined as the isolation of S. aureus from a normally sterile site. Over a 2-year period, 1,027 adult patients with ISA infections were enrolled in 10 hospitals, including 673 (66%) patients with methicillin-resistant S. aureus (MRSA) infections. There were 200 (19.5%) isolates with high VAN-MIC (≥1.5 mg/liter) by Etest and 87 (8.5%) by broth microdilution (BMD). The all-cause 30-day mortality rate was 27.4%. High VAN-MIC by either method was not associated with all-cause 30-day mortality, and this finding was consistent across MIC methodologies and methicillin susceptibilities. We conclude that high VAN-MIC is not associated with increased risk of all-cause 30-day mortality in ISA infections. Our data support the view that VAN-MIC alone is not sufficient evidence to change current clinical practice.

Electronic Alerts with Automated Consultations Promote Appropriate Antimicrobial Prescriptions.

BACKGROUND: To promote appropriate antimicrobial use in bloodstream infections (BSIs), we initiated an intervention program consisting of electronic alerts and automated infectious diseases consultations in which the identification and antimicrobial susceptibility test (ID/AST) results were reported. METHODS: We compared the appropriateness of antimicrobial prescriptions and clinical outcomes in BSIs before and after initiation of the program. Appropriateness was assessed in terms of effective therapy, optimal therapy, de-escalation therapy, and intravenous to oral switch therapy. RESULTS: There were 648 BSI episodes in the pre-program period and 678 in the program period. The proportion of effective, optimal, and de-escalation therapies assessed 24 hours after the reporting of the ID/AST results increased from 87.8% (95% confidence interval [CI] 85.5-90.5), 64.4% (95% CI 60.8-68.1), and 10.0% (95% CI 7.5-12.6) in the pre-program period, respectively, to 94.4% (95% CI 92.7-96.1), 81.4% (95% CI 78.4-84.3), and 18.6% (95% CI 15.3-21.9) in the program period, respectively. Kaplan-Meier analyses and log-rank tests revealed that the time to effective (p<0.001), optimal (p<0.001), and de-escalation (p = 0.017) therapies were significantly different in the two periods. Segmented linear regression analysis showed the increase in the proportion of effective (p = 0.015), optimal (p<0.001), and de-escalation (p = 0.010) therapies at 24 hours after reporting, immediately after program initiation. No significant baseline trends or changes in trends were identified. There were no significant differences in time to intravenous to oral switch therapy, length of stay, and 30-day mortality rate. CONCLUSION: This novel form of stewardship program based on intervention by infectious disease specialists and information technology improved antimicrobial prescriptions in BSIs.