Systemic inflammatory regulators and preeclampsia: a two-sample bidirectional Mendelian randomization study.

Background: Systemic inflammatory regulators have been associated with preeclampsia (PE) during pregnancy; however, there is inconsistent evidence from animal models and observational results. Methods: Using summary data from genome-wide association studies (GWASs), we performed a bidirectional Mendelian randomization (MR) analysis of two samples of systemic inflammatory regulators (n = 8,186) and PE (n = 267,242) individuals of European ancestry. As our primary analysis, we used the random-effects inverse-variance weighted (IVW) approach. Sensitivity and pleiotropy analyses were conducted using the MR-Egger method, weighted median, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and Cochran's Q test. Results: The results indicate that there is a correlation between a higher circulating level of tumor necrosis factor alpha (TNF-α) and interleukin-9 (IL-9) and an increased risk of PE (odds ratio [OR] = 1.32, 95% confidence interval [CI] = 1.09-1.60, p = 0.004 and OR = 1.28, 95% CI: 1.02-1.62, p = 0.033, respectively). Conversely, lower levels of stem cell growth factor beta (SCGF-ß) (OR = 0.89, 95% CI: 0.80-0.99, p = 0.027) and interleukin-5 (IL-5) (OR = 0.80, 95% CI: 0.65-0.98, p = 0.030) are linked to an increased risk of PE. The macrophage migration inhibitory factor (MIF) is the downstream inflammatory regulator of PE, according to reverse magnetic resonance imaging studies. Conclusion: Our study suggests that SCGF-ß, IL-5, IL-9, and TNF-α causally affect the PE risk, while PE is causally associated with MIF. Further studies are needed to validate these biomarkers in managing PE.

The relationship between cadmium exposure and preeclampsia: a systematic review and meta-analysis.

Background: Cadmium (Cd) is a heavy metal associated with several human disorders. Preeclampsia is a major cause of maternal mortality worldwide. The association between maternal Cd exposure and preeclampsia remains elusive. Methods: To better understand this relationship, we conducted a systematic review and meta-analysis of eligible studies from five databases (PubMed, Embase, Web of Science, Scopus, and CNKI) from their inception to September 10, 2022. The quality of these studies was evaluated using the Newcastle-Ottawa quality assessment scale (NOS). We use random-effects models to calculate overall standardized mean differences (SMDs) and 95% confidence intervals (CIs). Sensitivity analyses were performed to assess the robustness of our results. We also evaluated publication bias using Egger's and Begg's tests. Additionally, we conducted meta-regression and sub-group analyses to identify potential sources of heterogeneity between studies. Results: Our analysis included a total of 17 studies with 10,373 participants. We found a significant association between maternal cadmium exposure and the risk of preeclampsia (SMD 0.27, 95% CI 0.09-0.44, p < 0.01). No significant publication bias was detected in Begg's or Egger's tests. Meta-regression suggested that geographical location, year of publication, cadmium samples, sample size, and measurement methods did not contribute to heterogeneity between studies. Conclusion: Our findings suggest that maternal blood cadmium levels are associated with an increased risk of preeclampsia. In contrast, the pregnant women's urine or placental levels of cadmium may not suggest preeclamptic risk during pregnancy. Further high-quality clinical studies and animal experiments are needed to understand this association better. Systematic review registration: PROSPERO, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=361291, identifier: CRD42022361291.

A comparison of two different remote OSCEs during the COVID-19 pandemic: A candidate's perspective.

The Membership of the Royal College of Obstetricians and Gynaecologists (MRCOG) and the European Fellowship in Obstetrics and Gynaecology (EBCOG) exams are both well-renowned specialty qualifications that assess the competency of obstetricians and gynaecologists. In this article, an exam candidate shares his perspective on the changes made during the COVID-19 pandemic. Despite changing to an online format to allow candidates to take the exam remotely, the MRCOG Part 3 exam maintained its main exam structures: (1) simulated patient task to evaluate the candidates' interactions with well-trained patients in a tele-interview: (2) structure discussion with the clinical examiners based on some certain topics. In contrast, the EBCOG has created a brand new structure to suit the online model to assess the candidates' core clinical skills in broader aspects. Although it is unclear whether online exam will exist in future, this has been a unique experience for candidates during pandemic.

CpxA/R-Controlled Nitroreductase Expression as Target for Combinatorial Therapy against Uropathogens by Promoting Reactive Oxygen Species Generation.

The antibiotic resistances emerged in uropathogens lead to accumulative treatment failure and recurrent episodes of urinary tract infection (UTI), necessitating more innovative therapeutics to curb UTI before systematic infection. In the current study, the combination of amikacin and nitrofurantoin is found to synergistically eradicate Gram-negative uropathogens in vitro and in vivo. The mechanistic analysis demonstrates that the amikacin, as an aminoglycoside, induced bacterial envelope stress by introducing mistranslated proteins, thereby constitutively activating the cpxA/R two-component system (Cpx signaling). The activation of Cpx signaling stimulates the expression of bacterial major nitroreductases (nfsA/nfsB) through soxS/marA regulons. As a result, the CpxA/R-dependent nitroreductases overexpression generates considerable quantity of lethal reactive intermediates via nitroreduction and promotes the prodrug activation of nitrofurantoin. As such, these actions together disrupt the bacterial cellular redox balance with excessively-produced reactive oxygen species (ROS) as "Domino effect", accelerating the clearance of uropathogens. Although aminoglycosides are used as proof-of-principle to elucidate the mechanism, the synergy between nitrofurantoin is generally applicable to other Cpx stimuli. To summarize, this study highlights the potential of aminoglycoside-nitrofurantoin combination to replenish the arsenal against recurrent Gram-negative uropathogens and shed light on the Cpx signaling-controlled nitroreductase as a potential target to manipulate the antibiotic susceptibility.

Natural flavonoids disrupt bacterial iron homeostasis to potentiate colistin efficacy.

In the face of the alarming rise in global antimicrobial resistance, only a handful of novel antibiotics have been developed in recent decades, necessitating innovations in therapeutic strategies to fill the void of antibiotic discovery. Here, we established a screening platform mimicking the host milieu to select antibiotic adjuvants and found three catechol-type flavonoids-7,8-dihydroxyflavone, myricetin, and luteolin-prominently potentiating the efficacy of colistin. Further mechanistic analysis demonstrated that these flavonoids are able to disrupt bacterial iron homeostasis through converting ferric iron to ferrous form. The excessive intracellular ferrous iron modulated the membrane charge of bacteria via interfering the two-component system pmrA/pmrB, thereby promoting the colistin binding and subsequent membrane damage. The potentiation of these flavonoids was further confirmed in an in vivo infection model. Collectively, the current study provided three flavonoids as colistin adjuvant to replenish our arsenals for combating bacterial infections and shed the light on the bacterial iron signaling as a promising target for antibacterial therapies.

Exploring the Mechanism of Wenshen Huatan Quyu Decotion for PCOS Based on Network Pharmacology and Molecular Docking Verification.

Objective: To identify the active chemical in Wenshen Huatan Quyu Decotion (WHQD) and to explore its possible network interactions with the polycystic ovary syndrome (PCOS). Methods: The Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform (TCMSP) and the Bioinformatics Analysis Tool for Molecular Mechanisms in Chinese Medicine (BATMAN-TCM) were used to decompose compound formulations, detect active chemicals and their corresponding target genes, and then convert them into UniProt gene symbols. Meanwhile, PCOS-related target genes were collected from GeneCards to construct a protein-protein interaction (PPI) network, which was further analyzed by STRING online database. Gene Ontology (GO) functional analysis was also performed afterwards to construct the component-target gene-disease network to visualize the correlation between WHQD and PCOS. We then performed an in silico molecular docking study to validate the predicted relationships. Results: WHQD consists of 14 single drugs containing a total of 67 chemical components. 216 genes were predicted as possible targets. 123 of the 216 target genes overlapped with PCOS. GO annotation analysis revealed that 1968 genes were associated with biological processes, 145 with molecular functions, and 71 with cellular components. KEGG analysis revealed 146 pathways involved PPI, and chemical-target gene-disease networks suggest that PGR, AR, ADRB2, IL-6, MAPK1/8, ESR1/2, CHRM3, RXRA, PPARG, BCL2/BAX, GABRA1, and NR3C2 may be key genes for the pharmacological effects of WHQD on PCOS. Molecular docking analysis confirmed that hydrogen bonding was the main interaction between WHQD and its targets. Conclusion: WHQD exerts its pharmacological effects by improving insulin sensitivity, subfertility, and hormonal imbalance, increasing ovulation rates, which in turn may increase pregnancy rates in patients with significant efficacy.

A Global Perspective of Correlation Between Maternal Copper Levels and Preeclampsia in the 21st Century: A Systematic Review and Meta-Analysis.

Background: Preeclampsia (PE) is a common multi-system disorder in pregnancy and a major cause of maternal and perinatal morbidity and mortality globally. Copper is a crucial micronutrient for human health. Methods: A systematic review was performed according to Preferred Reporting Item for Systematic Reviews and Meta-analysis (PRISMA) guidelines to synthesize the best available evidence regarding the correlation between maternal copper levels and PE from women with different geographical and economic backgrounds. Results: A total of 34 studies containing 2,471 women with PE and 2,888 healthy pregnant controls across 16 countries were included for research. All studies were systematically reviewed and assessed with the Newcastle-Ottawa Scale (NOS), The Agency of Healthcare for Research and Quality (AHRQ) assessment tools according to the study types. Globally, there was no significant difference in maternal serum copper levels between women with PE and control (Mean difference 5.46, 95% CI -9.63, 20.54). Sub-group analysis from geographical and economic perspectives revealed contrasting results. In conclusion, copper is associated with PE, but the levels of copper leading to increased risk of PE varied across regions and economic development. Conclusions: The deranged maternal copper levels are correlated with risks of PE, but it presents variously across different geographical and economic contexts. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=306536. Identifier: CRD42022306536.

Case Report: TNF-Alpha Inhibitors to Rescue Pregnancy in Women With Potential Pregnancy Loss: A Report of Ten Cases.

Miscarriage poses a significant threat to pregnant women globally. Recurrent miscarriages or potential poor embryonic development indicated by early drops in serum human chorionic gonadotrophin (hCG) are even more catastrophic for pregnant women. However, these patients receive either individualized medical intervention supported by limited evidence or no treatment at all. In this study, we report ten patients who shared at least one episode of an early decline of hCG in the first trimester and were treated with compassionate use of tumor necrosis factor-alpha inhibitor (TNFi). They were then followed up regularly with caution. Their hCG trajectory all resumed a normal pattern within one week and the obstetric outcomes were promising. No adverse fetal, neonatal, or maternal health issues have been observed. This case series supports current safety evidence of TNFi and provides new insight into its use in pregnancy when the embryo is in danger. Further well-designed clinical trials should be carried out to consolidate the evidence.

A global perspective of correlation between maternal blood lead levels and risks of preeclampsia: An updated systematic review and meta-analysis.

Background: Preeclampsia (PE) is a specific hypertensive disorder in pregnancy. Lead (Pb) is a heavy metal that affects women's reproductive health. However, it is unclear whether lead exposure during can predispose maternal risk of developing preeclampsia. This systematic review and meta-analysis study aimed to explore the association. Methods: We searched studies from three databases (PubMed, Web of Science, Embase). Only case-control, cross-sectional, and cohort studies reporting maternal blood lead levels (BLL) and PE were included from database inception to 31st July 2022. Pregnant women with blood lead levels measured were eligible. Those healthy pregnant women who did not develop preeclampsia were assessed as comparators. Letters, comments, case reports, and reviews were excluded. Newcastle-Ottawa Scale (NOS) and its adaptive form were applied for assessment. The random-effects method (REM) was applied to calculate the standardized mean difference (SMD) with a 95% confidence interval (CI). Stata 16.0 and RevMan 5.3 were the software used for data extraction and analysis. Results: 25 studies out of 1,808 articles made the finalist for systematic reviews, of which 21 underwent further quantity analysis. A total of 1,533 preeclamptic women and 10,998 healthy pregnant controls were included in the meta-analysis. The overall result revealed that maternal lead exposure was significantly higher in women with preeclampsia (SMD: 1.06, 95% CI 0.69, 1.43); (I 2 = 96.40%; P = 0.000). Conclusion: This study demonstrates that maternal lead exposure is associated with preeclampsia during pregnancy. The association is present even in low blood lead levels. The conclusion should be taken seriously and women should avoid unexpected exposure to a lead-containing environment as much as possible. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=347220, identifier: CRD42022347220.

MALDI-TOF MS for rapid detection and differentiation between Tet(X)-producers and non-Tet(X)-producing tetracycline-resistant Gram-negative bacteria.

The extensive use of tetracycline antibiotics has led to the widespread presence of tetracycline-resistance genes in Gram-negative bacteria and this poses serious threats to human and animal health. In our previous study, we reported a method for rapid detection of Tet(X)-producers using MALDI-TOF MS. However, there have been multiple machineries involved in tetracycline resistance including efflux pump, and ribosomal protection protein. Our previous demonstrated the limitation in probing the non-Tet(X)-producing tetracycline-resistant strains. In this regard, we further developed a MALDI-TOF MS method to detect and differentiate Tet(X)-producers and non-Tet(X)-producing tetracycline-resistant strains. Test strains were incubated with tigecycline and oxytetracycline in separate tubes for 3 h and then analyzed spectral peaks of tigecycline, oxytetracycline, and their metabolite. Strains were distinguished using MS ratio for [metabolite/(metabolite+ tigecycline or oxytetracycline)]. Four control strains and 319 test strains were analyzed and the sensitivity was 98.90% and specificity was 98.34%. This was consistent with the results obtained from LC-MS/MS analysis. Interestingly, we also found that the reactive oxygen species (ROS) produced by tetracycline-susceptible strains were able to promote the degradation of oxytetracycline. Overall, the MALDITet(X)-plus test represents a rapid and reliable method to detect Tet(X)-producers, non-Tet(X)-producing tetracycline-resistant strains, and tetracycline-susceptible strains.

Lilium spp., as unnoticed environmental vector, spreading OptrA-carrying Enterococcus spp.

Flower is an essential element in the human lifestyle but its role in disseminating antimicrobial resistance (AMR) between the environment and humans is unclear. In this study, we screened fresh flowers (Lilium spp.) collected from planting bases, market and florists in Guangzhou China aiming to investigate the prevalence of AMR genes, particularly cfr, optrA and poxtA mediating resistance to linezolid, a first-line drug for the treatment of different Gram-positive bacterial infections. We found 223 Enterococcus isolates consisting of Enterococcus faecalis, Enterococcus faecium and Enterococcus mundtii, and >50% of these isolates exhibited multiple-drug resistance. Additionally, 31 optrA-positive Enterococcus including 22 E. faecalis and 9 E. mundtii strains were recovered, however cfr and poxtA were not detected. The 22 E. faecalis strains were belonged to 7 Multilocus sequence types in which ST202 and ST376 were predominant and 9 E. mundtii strains from the same plantation bases were divided into three PFGE groups. Genetically, the majority of optrA were located on the chromosome and shared similar insertion sites and transpositions mediated by Tn554 family members. Plasmid-bearing optrA were identified in 6 E. faecalis strains where IS1216 family played key roles in horizontal transfer of optrA. These findings emphasize that the prevalence of drug resistant Enterococcus in fresh flowers is a latent danger and increases the risk of AMR dissemination to humans from the environment.

Network Pharmacology-Based and Molecular Docking Analysis of Resveratrol's Pharmacological Effects on Type I Endometrial Cancer.

BACKGROUND: Resveratrol is a natural polyphenol commonly seen in foods. It has demonstrated an inhibitive effect on endometrial cancer, but the molecular action is still not known. OBJECTIVE: We aimed to use network pharmacology to systematically study the possible mechanisms of resveratrol's pharmacological effects on type I endometrial cancer. METHODS: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) were used to predict resveratrol's possible target genes. They were then converted to UniProt gene symbols. Simultaneously, type I endometrial cancer-related target genes were collected from GeneCards. All data were pooled to identify common target genes. The protein-protein interaction (PPI) network was constructed and further analyzed via STRING Online Database. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were also performed afterward. To visualise resveratrol's overall pharmacological effects on type I endometrial cancer, a network of drug components-target gene-disease (CTD) was constructed. Then, we performed in silico molecular docking study to validate the possible binding conformation between resveratrol and candidate targets. RESULTS: There are 150 target genes of resveratrol retrieved after UniProt conversion; 122 of them shared interaction with type I endometrial cancer. Some important oncogenes and signaling pathways are involved in the process of resveratrol's pharmacological effects on endometrioid cancer. Molecular docking analysis confirmed that hydrogen bonding and hydrophobic interaction are the main interaction between resveratrol and its targets. CONCLUSION: We have explored the possible underlying mechanism of resveratrol in antagonising type I endometrial cancer through a network pharmacology-based approach and in-silico verification. However, further experiments are necessary to add to the evidence identifying resveratrol as a promising anti-type I endometrial cancer agent.

A Nomogram-Based Risk Classification System Predicting the Overall Survival of Patients With Newly Diagnosed Stage IVB Cervix Uteri Carcinoma.

Background: This study constructed and demonstrated a model to predict the overall survival (OS) of newly diagnosed distant metastatic cervical cancer (mCC) patients. Methods: The SEER (Surveillance, Epidemiology, and End Results) database was used to collect the eligible data, which from 2010 to 2016. Then these data were separated into training and validation cohorts (7:3) randomly. Cox regression analyses was used to identify parameters significantly correlated with OS. Harrell's Concordance index (C-index), calibration curves, and decision curve analysis (DCA) were further applied to verify the performance of this model. Results: A total of 2,091 eligible patients were enrolled and randomly split into training (n = 1,467) and validation (n = 624) cohorts. Multivariate analyses revealed that age, histology, T stage, tumor size, metastatic sites, local surgery, chemotherapy, and radiotherapy were independent prognostic parameters and were then used to build a nomogram for predicting 1 and 2-year OS. The C-index of training group and validation group was 0.714 and 0.707, respectively. The calibration curve demonstrated that the actual observation was in good agreement with the predicted results concluded by the nomogram model. Its clinical usefulness was further revealed by the DCAs. Based on the scores from the nomogram, a corresponding risk classification system was constructed. In the overall population, the median OS time was 23.0 months (95% confidence interval [CI], 20.5-25.5), 12.0 months (95% CI, 11.1-12.9), and 5.0 months (95% CI, 4.4-5.6), in the low-risk group, intermediate-risk group, and high-risk group, respectively. Conclusion: A novel nomogram and a risk classification system were established in this study, which purposed to predict the OS time with mCC patients. These tools could be applied to prognostic analysis and should be validated in future studies.

Emergence of fosA3 and bla CTX-M- 14 in Multidrug-Resistant Citrobacter freundii Isolates From Flowers and the Retail Environment in China.

We examined the prevalence and transmission of the fosA3 gene among Citrobacter freundii isolates from flowers and the retail environments. We identified 11 fosfomycin-resistant C. freundii strains (>256 µg/mL) from 270 samples that included petals (n = 7), leaves (n = 2), dust (n = 1) and water (n = 1). These 11 isolates were multidrug-resistant and most were simultaneously resistant to fosfomycin, cefotaxime, ciprofloxacin and amikacin. Consistently, all 11 isolates also possessed bla CTX-M- 14, bla CMY- 65 / 122, aac(6')-Ib-cr, qnrS1, qnrB13/6/38 and rmtB. These fosA3-positive isolates were assigned to two distinct PFGE patterns and one (n = 9) predominated indicating clonal expansion of fosA3-positive isolates across flower markets and shops. Correspondingly, fosA3 was co-transferred with bla CTX-M- 14 via two plasmid types by conjugation possessing sizes of 110 kb (n = 9) and 260 kb (n = 2). Two representatives were fully sequenced and p12-1 and pS39-1 possessed one and two unclassified replicons, respectively. These plasmids shared a distinctive and conserved backbone in common with fosA3-carrying C. freundii and other Enterobacteriaceae from human and food animals. However, the fosA3-bla CTX-M- 14-containing multidrug resistance regions on these untypable plasmids were highly heterogeneous. To the best of our knowledge, this is the first report of fosA3 and bla CTX-M- 14 that were present in bacterial contaminants from flower shops and markets. These findings underscore a public health threat posed by untypable and transferable p12-1-like and pS39-1-like plasmids bearing fosA3-bla CTX-M- 14 that could circulate among Enterobacteriaceae species and in particular C. freundi in environmental isolates.

Rapid Detection of High-Level Tigecycline Resistance in Tet(X)-Producing Escherichia coli and Acinetobacter spp. Based on MALDI-TOF MS.

The emergence and spread of the novel mobile Tet(X) tetracycline destructases confer high-level tigecycline and eravacycline resistance in Escherichia coli and Acinetobacter spp. and pose serious threats to human and animal health. Therefore, a rapid and robust Tet(X) detection assay was urgently needed to monitor the dissemination of tigecycline resistance. We developed a rapid and simple assay to detect Tet(X) producers in Gram-negative bacteria based on matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). This MALDITet(X) test was based on the inactivation of tigecycline by a Tet(X)-producing strain after a 3-h incubation of bacterial cultures with tigecycline. Culture supernatants were analyzed using MALDI-TOF MS to identify peaks corresponding to tigecycline (586 ± 0.2 m/z) and a tigecycline metabolite (602 ± 0.2 m/z). The results were calculated using the MS ratio [metabolite/(metabolite + tigecycline)]. The sensitivity of the MALDITet(X) test with all 216 test strains was 99.19%, and specificity was 100%. The test can be completed within 3 h. Overall, the MALDITet(X) test is an accurate, rapid, cost-effective method for the detection of Tet(X)-producing E. coli and Acinetobacter spp. by determining the unique peak of an oxygen-modified derivative of tigecycline.

A Four-Hour Carbapenem Inactivation Method (CIM B.S ) Using Bacillus stearothermophilus as Indicator Strain.

Objectives: There is an urgent need for accurate and fast diagnostic tests to identify carbapenemase-producing bacteria. Here we used Bacillus stearothermophilus as an indicator strain in the format of the carbapenem inactivation method (CIM) procedure to develop a rapid carbapenemase phenotype detection method: CIMB.S. Methods: The CIMB.S test was derived from the mCIM, where B. stearothermophilus replaced Escherichia coli as the indicator strain. The test bacteria were incubated in the presence of imipenem for 30 min, and then, aliquots were placed on colorimetric plates, and incubation was continued for 3.5 h at 60°C. We examined 134 clinical strains to evaluate the CIMB.S performance. Results: The CIMB.S can be completed in 4 h, and we successfully identified 38/39 (97.4%) carbapenemase-producing Enterobacteriaceae, including 17/18 (94.4%) carbapenemase-producing Pseudomonas aeruginosa and 18/19 (94.7%) carbapenemase-producing Acinetobacter baumannii. All non-carbapenemase producers we tested were negative and included Enterobacteriaceae (n = 36), P. aeruginosa (n = 17), and A. baumannii (n = 5). Conclusions: The CIMB.S test is a rapid carbapenemase phenotype detection method requiring only 4 h of total work time and displays high sensitivity and specificity.

Rapid detection of plasmid-mediated high-level tigecycline resistance in Escherichia coli and Acinetobacter spp.

OBJECTIVES: The emergence and spread of plasmid-encoded tet(X3/X4) genes that confer high-level tigecycline and eravacycline resistance in Escherichia coli and Acinetobacter spp. pose serious threats to human and animal health. We developed a rapid and robust assay to detect Tet(X3/X4) in Gram-negative bacteria based on eravacycline degradation by the presence of the Tet(X) enzyme in the test strain. METHODS: This tetracycline inactivation method (TIM) is based on the degradation of eravacycline by the Tet(X3/X4)-producing strain, which results in reduced eravacycline activity against an acid-producing thermophile Bacillus stearothermophilus indicator strain. For Tet(X)-negative strains, eravacycline retains its antimicrobial activity. Coupled with a pH-sensitive dye (bromocresol purple), the reduced colorimetric inhibition zone can be measured to determine the production of Tet(X3/X4). One hundred and eighteen isolates, including 30 tet(X4)-positive E. coli, 30 tet(X3)-positive Acinetobacter spp. and 58 tet(X)-negative E. coli and Acinetobacter spp., were examined to evaluate the performance of this TIM. RESULTS: The sensitivity and specificity for E. coli carrying tet(X4) was 96.7% and 100%, respectively, and for Acinetobacter spp. carrying tet(X3) both were 100%. The TIM assay can be completed within 6.5 h. CONCLUSIONS: The TIM is a simple, rapid and cost-effective method for the detection of plasmid-mediated high-level tigecycline resistance in E. coli and Acinetobacter spp.

Nitrofurantoin Combined With Amikacin: A Promising Alternative Strategy for Combating MDR Uropathogenic Escherichia coli.

Urinary tract infections (UTI) are common infections that can be mild to life threatening. However, increased bacterial resistance and poor patient compliance rates have limited the effectiveness of conventional antibiotic therapies. Here, we investigated the relationship between nitrofurantoin and amikacin against 12 clinical MDR uropathogenic Escherichia coli (UPEC) strains both in vitro and in an experimental Galleria mellonella model. In vitro synergistic effects were observed in all 12 test strains by standard checkerboard and time-kill assays. Importantly, amikacin or nitrofurantoin at half of the clinical doses were not effective in the treatment of UPEC infections in the G. mellonella model but the combination therapy significantly increased G. mellonella survival from infections caused by all 12 study UPEC strains. Taken together, these results demonstrated synergy effects between nitrofurantoin and amikacin against MDR UPEC.

High maternal serum estradiol environment in the first trimester is associated with the increased risk of small-for-gestational-age birth.

CONTEXT: There are increasing concerns that a disrupted endocrine environment may disturb the growth of the fetus. Assisted reproductive technology (ART) situates gamete/embryo in a supraphysiological estradiol (E2) environment and, thus, provides an ideal model to investigate this problem. OBJECTIVE: Our objective was to investigate whether the maternal high-E2 environment in the first trimester increases the risks of low birth weight (LBW) and small-for-gestational-age (SGA) birth. METHODS: In total, 8869 singletons born after fresh embryo transfer (ET) (n = 2610), frozen ET (n = 1039), and natural conception (NC) (n = 5220) and their mothers were included. Birth weight, LBW, SGA, and maternal serum E2 levels were investigated. RESULTS: The mean serum E2 levels of women undergoing fresh ET at 4 and 8 weeks of gestation were significantly higher than those of the women undergoing frozen ET and the women with NC (P < .01). Serum E2 levels of women undergoing fresh ET at 4 and 8 weeks of gestation were positively correlated to those on the day of human chorionic gonadotropin (hCG) administration (r = 0.5 and r = 0.4, respectively; P < 0.01). The birth weight after fresh ET was significantly lower than that after frozen ET and NC (P < 0.01), with increased incidence of LBW and SGA (P < .05). Furthermore, in the fresh ET group, singletons of mothers with high E2 levels (≥10460 pmol/L on the day of hCG administration) had higher risks of LBW (P < .01) and SGA (P < .01) than those with low E2 levels, and maternal serum E2 level on the day of hCG administration negatively correlated with the birth weight (P < .01). CONCLUSIONS: The maternal high-E2 environment in the first trimester is correlated with increased risks of LBW and SGA. Evaluation of serum E2 before ET should be adopted to reduce the possibility of high E2 exposure to gamete/embryo.