The therapeutic potential of indole hybrids, dimers, and trimers against drug-resistant ESKAPE pathogens.

Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter (ESKAPE) species as causative agents are characterized by increased levels of resistance toward multiple classes of first-line as well as last-resort antibiotics and represent serious global health concerns, creating a critical need for the development of novel antibacterials with therapeutic potential against drug-resistant ESKAPE species. Indole derivatives with structural and mechanistic diversity demonstrated broad-spectrum antibacterial activity against various clinically important pathogens including drug-resistant ESKAPE. Moreover, several indole-based agents that are exemplified by creatmycin have already been used in clinics or under clinical trials for the treatment of bacterial infections, demonstrating that indole derivatives hold great promise for the development of novel antibacterials. This review is an endeavor to highlight the current scenario of indole hybrids, dimers, and trimers with therapeutic potential against drug-resistant ESKAPE pathogens, covering articles published from 2020 to the present, to open new avenues for the exploration of novel antidrug-resistant ESKAPE candidates.

Effectiveness of heparin eye drops in paraquat-induced ocular injury.

PURPOSE: To evaluate the efficacy of heparin eye drops in the treatment of paraquat-induced ocular surface injury. DESIGN AND METHODS: In this retrospective study, we included 25 patients (31 eyes) with paraquat-induced ocular surface injury, who attended the Affiliated Hospital of Weifang Medical University between October 2008 and October 2013. The patients were split into two groups according to whether or not received heparin eye drops. The clinical data were compared between the two groups, i.e. clinical histories, results of examinations, treatments and outcomes. RESULTS: Eleven patients (group A, 15 eyes) received prompt irrigation with 0.9% saline every two hours, 0.1% pranoprofen eye drops four times a day, 20% autologous serum every two hours, recombinant bovine basic fibroblast growth factor eye-gel two times a day, oral vitamin C 2.0 g and prednisone 30 mg daily. Fourteen patients (group B, 16 eyes) received additional treatment with heparin eye drops. Ten eyes in group A and seven eyes in group B developed a pseudomembrane on the ocular surface at significantly different rate (mean ± SD) of 1.20 ± 1.01 and 0.43 ± 0.51, respectively (t = 2.66, p = 0.01). Seven eyes among 10 had a pseudomembrane reoccurred in group A while none had a pseudomembrane reoccurred in group B (Fisher's exact test, p = 0.01). No significant differences were seen in the duration of epithelial recovery between the two groups: 15.13 ± 5.13 days in group A and 16.81 ± 5.56 days in group B (t = 0.87, p = 0.39). After the treatment, mild corneal opacity and pannus were observed in five patients of group A and four patients of group B, without any significant difference between the two groups (p = 0.70). CONCLUSIONS: The paraquat-induced ocular surface injury observed in this case series was characterized by the formation of conjunctival pseudomembrane with good prognosis and mild complications. Heparin eye drops reduce the occurrence, especially the reoccurrence of pseudomembrane. Further studies are warranted.

The clinical characteristics of alcohol-related ocular rupture.

PURPOSE: To evaluate the characteristics and outcomes of drunken patients treated for ocular rupture, and to compare these results to patients injured without alcohol consumption. DESIGN AND METHODS: The medical records of 182 patients with or without alcohol consumption before injury who were treated and followed up because of ocular rupture at the Affiliated Hospital of Weifang Medical University from October 2007 to October 2011 were evaluated retrospectively. The characteristics and outcomes of 45 alcohol-related injury patients were compared with the rest in the cohort. The clinical data included in this study were: anatomic sites and length of the wound, involvement of ocular adnexa injuries, evisceration rate, and final mean visual acuity. RESULTS: Wound locations were significantly different between the alcohol-related group and the non-alcohol-related one. Compared with the non-alcohol-related ocular rupture population, the anatomic sites of the drunken patients were more likely to be located at zone I and zone II (60.0 vs 40.1 %; χ2 = 5.39,P < 0.05). The difference of wound length between the alcohol-related group and the non-alcohol-related one was significant. The alcohol-related patients had a longer wound length (Z = -8.590,P < 0.05). Compared with the non-alcohol population, the alcohol-consuming patients were more likely to suffer adnexa injuries (84.4 vs 59.8 %; χ2 = 5.86,P < 0.05), and had worse final visual acuities (Z = -7.195,P < 0.05). The evisceration rate of the alcohol-related patients was significantly higher than the non-alcohol patients (24.4 vs 9.4 %; χ2 = 6.62,P < 0.05). CONCLUSIONS: Drinking more easily leads to injury of the front part of eyes. Moreover, the drunken patients had a worse visual acuity outcome, longer wound length, higher evisceration rate, and were more prone to endure adnexa injuries. The importance of prevention and education to recognize the hazards of drinking cannot be overemphasized.

Development and validation of a noninvasive prediction model for identifying eosinophilic asthma.

BACKGROUND: Identification of eosinophilic asthma (EA) using sputum analysis is important for disease monitoring and individualized treatment. But it is laborious and technically demanding. We aimed to develop and validate an effective model to predict EA with multidimensional assessment (MDA). METHODS: The asthma patients who underwent a successful sputum induction cytological analysis were consecutively recruited from March 2014 to January 2021. The variables assessed by MDA were screened by least absolute shrinkage and selection operator (LASSO) and logistic regression to develop a nomogram and an online web calculator. Validation was performed internally by a bootstrap sampling method and externally in the validation cohort. Diagnostic accuracy of the model in different asthma subgroups were also investigated. RESULTS: In total of 304 patients in the training cohort and 95 patients in the validation cohort were enrolled. Five variables were identified in the EA prediction model: gender, nasal polyp, blood eosinophils, blood basophils and FeNO. The C-index of the model was 0.86 (95% CI: 0.81-0.90) in the training cohort and 0.84 (95% CI: 0.72-0.89) in the validation cohort. The calibration curve showed good agreement between the prediction and actual observation. The decision curve analysis (DCA) also demonstrated that the EA prediction model was clinically beneficial. An online publicly available web calculator was constructed (https://asthmaresearcherlimin.shinyapps.io/DynNomapp/). CONCLUSION: We developed and validated a multivariable model based on MDA to help the diagnosis of EA, which has good diagnostic performance and clinical practicability. This practical tool may be a useful alternative for predicting EA in the clinic.

QSEN Transcends Cultures: Leadership Lessons Learned From a Global Experience.

Quality and Safety Education for Nurses (QSEN) has global appeal, acknowledging the important role of nursing in care delivery. This article complements the Teaching Tips column, shifting from content covered to the leadership lessons that presenters must consider when preparing for and presenting to a global audience. Four critical lessons are addressed: humility and acceptance, time for translation, job role assumptions, and conceptual clarification. [J Contin Educ Nurs. 2010;51(1):9-11.].

QSEN Transcends Cultures: Teaching Quality and Safety Education in China.

There has been increasing focus on improving the quality and safety of health care globally. Understanding that the health of one nation impacts others worldwide drives initiatives for collaboration to improve the health of all. In this, the Year of the Nurse and Midwife as designated by the World Health Organization, The Quality and Safety Education for Nurses (QSEN) Competencies provide structure that transcends culture for framing the nursing role to contribute to improving patient safety and the quality of care delivery internationally. This article describes initiatives to share resources and strategies to support quality and safety education and practice with nurses across countries. [J Contin Educ Nurs. 2020;51(3):106-108.].

MicroRNA-138 targets SOX4 to regulate the proliferation and metastasis of human lung cancer cells.

PURPOSE: The current study was set with a purpose to assess the regulatory role of micro RNA (miR)-138 in human lung cancer cells with emphasis on the underlying mechanism of action. METHODS: RT-PCR based analysis was employed for gene expression studies. MTT assay was used to determine the proliferation rates of lung cancer cells. Colony forming assay was performed for the analysis of colony forming potential. DAPI and Annexin V-FITC/propidium iodide (PI) double staining methods were performed for the analysis of apoptosis. Migration and invasion of cancer cells were assessed using wound healing and transwell assays, respectively. Dual luciferase reporter assay was performed for interactional study. Western blotting was used to determine the protein concentrations. RESULTS: Cancer cells had lower levels of miR-138 transcripts. The overexpression of miR-138 reduced the proliferation of cancer cells and cells were seen to form lower number of viable colonies. This was due to the induction of cancer cell apoptosis under miR-138 overexpression. miR-138 also inhibited the metastasis of lung cancer cells. miR-138 was found to interact with SOX4 intracellularly and SOX4 protein levels decreased under miR-138. The anticancer effects of miR-138 were shown to be modulated through SOX4. CONCLUSION: MiRs have a potential to act as molecular markers in cancer prognosis. There is a need to screen for miRs specific to particular types of cancer and to look for their potential to function as anticancer entities at molecular level.

Evaluation of the subtle effects and oxidative stress response of chloramphenicol, thiamphenicol, and florfenicol in Daphnia magna.

Phenicol antibiotics, such as chloramphenicol, thiamphenicol, and florfenicol, are commonly used in the veterinary and aquaculture fields to treat diseases and have frequently been detected in aquatic environments. Nevertheless, there is limited information regarding the effects of phenicol antibiotics on aquatic nontarget species. Thus, the present study aims to investigate the long-term (21-d) influence on the reproduction and growth of and the acute (24-h) oxidative response and tissue damage in the crustacean Daphnia magna after exposure to phenicol drugs, including their environmental concentrations. The results indicate that D. magna exposed to florfenicol are likely to cause more adverse effects than those exposed to chloramphenicol and thiamphenicol over long-term (21-d) exposures. Furthermore, changes in biochemical biomarkers such as malondialdehyde (MDA), catalase (CAT), and reduced glutathione (GSH) induced by individual and mixtures of phenicol antibiotics were also observed. Low concentrations of chloramphenicol, thiamphenicol + florfenicol, and chloramphenicol + thiamphenicol significantly increased the MDA levels of D. magna after 24-h exposures, causing cellular oxidative damage in the animals. In addition, discrepancies between CAT activities and GSH levels were observed, underscoring the need to evaluate multiple indicators of oxidative stress in toxicological studies using D. magna as a model. Environ Toxicol Chem 2019;38:575-584. © 2018 SETAC.

[Investigation on deciduous dental caries among preschool children in Chongqing city].

OBJECTIVE: To investigate the status of deciduous dental caries among preschool children in Chongqing city and to compare the oral health status of preschoolers from public and private kindergarten. METHODS: According to the criteria recommended by The Third National Oral Health Investigation, the deciduous caries of 5 030 preschool children aged 3 to 6 years old from 40 private kindergartens and 16 public kindergartens in Yuzhong district of Chongqing were examined. The prevalence of dental caries and the mean dmft and filling rate were calculated. The results were analyzed using SPSS 21.0 software package. RESULTS: Maxillary deciduous central incisors and mandibular deciduous molar were most prone to decay in 5,030 children. The prevalence of dental caries was 54.08% (2,720/5,030). The mean dmft score was 2.58 and the filling rate was 0.98% (127/12,993). The prevalence of dental caries and mean dmft increased gradually as the children were growing up (P < 0.05). The rate of filling teeth of the 6 year old group was higher than other groups (P < 0.05). No significant difference between males and females were noted (P > 0.05). The prevalence rate of deciduous dental caries among private kindergartens was 61.04% (1,656/2,713), with a mean dmft of 3.12 and filling rate of 0.35% (30/8,465). The prevalence rate of deciduous dental caries among public kindergartens was 45.92% (1,064/2,317), with a mean dmft of 1.95 and filling rate of 2.14% (97/4,528). Statistical analysis revealed significant differences in the prevalence rate, mean dmft, and filling rate between two kinds of kindergarten (P < 0.05). CONCLUSION: Deciduous dental caries of preschool children is an important problem in Chongqing city and the children from private kindergarten had very low filling rate.

Reversible transfection of human melanocytes mediated by Cre/loxP site-specific recombination system and SV40 large T antigen.

OBJECTIVE: To study the reversible transfection of human melanocytes mediated by simian virus 40 large T antigen (SV40LTAg) and Cre/loxP site-specific recombination system. METHODS: The reconstructed SV40LTAg-EGFP-neo-loxP vector was transfected into primary cultured human melanocytes with Sofast(TM) transfection reagent and the positive cells were selected using G418. After expanding culture of these positive cell clones, the expression of SV40LTAg was detected by polymerase chain reaction (PCR), reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescent method. After that, these positive cells were infected by virus supernatant of Cre-ER(T2) retrovirus vector and Cre recombinase was induced to act by tamoxifen. On the 6th and 10th day after Cre recombinase acting, the expression of SV40LTAg was detected using the same methods as above, and cell tumorigenicity was studied using soft agar assay, athymic mouse study and karyotype analysis. On 10th day after tamoxifen treatment, cell biological characters were identified with immunofluorescent staining and transmission electron microscopy. Then these cells were transplanted into vitiligo animal model to observe their melanogenesis ability in vivo. RESULTS: The genome DNA and total RNA were isolated from the positive cells transfected by SV40LTAg (designated as MCT) and specific 288 bp fragment was amplificated using PCR and RT-PCR methods. The results of immunofluorescence confirmed the expression of SV40LTAg in cell nucleus. On the 6th day after tamoxifen treatment in infected cells by Cre-ER(T2) retrovirus vector (designated as MCT-Cre), there could be detected SV40LTAg expression, but on 10th day, there could not be detected SV40LTAg expression in cells. These results showed that the excised efficiency of Cre recombinase increased along with time prolongation, and would obtain complete recombination efficiency. The identification of MCT-Cre cell biological characters showed that these cells had normal parent-cell-like cell phenotype and no tumorigenicity in vitro. The pigmentation started in 4 weeks and formed black macula in 3 months after grafting. The pathological results showed that there had been significant melanocytes and melanin accumulation in epidermis and some hair follicle in transplanted area, which confirmed that MCT-Cre had melanogenesis function in vivo. CONCLUSION: Human melanocytes could be mediated by reversible transfection by SV40LTAg and Cre/loxP site-specific recombination system, which had stable parent-cell-like phenotypic characters and no tumorigenicity in vitro; moreover, these cells still had melanogenesis function in vivo.