Identifying prognostic markers in spatially heterogeneous breast cancer microenvironment.

To gain deeper insights into the microenvironment of breast cancer, we utilized GeoMx Digital Spatial Profiling (DSP) technology to analyze transcripts from 107 regions of interest in 65 untreated breast cancer tissue samples. Our study revealed spatial heterogeneity in the expression of marker genes in tumor cell enriched, immune cell enriched, and normal epithelial areas. We evaluated a total of 55 prognostic markers in tumor cell enriched regions and 15 in immune cell enriched regions, identifying that tumor cell enriched regions had higher levels of follicular helper T cells, resting dendritic cells, and plasma cells than immune cell enriched regions, while the levels of resting CD4 memory in T cells and regulatory (Treg) T cells were lower. Additionally, we analyzed the heterogeneity of HLA gene families, immunological checkpoints, and metabolic genes in these areas. Through univariate Cox analysis, we identified 5 prognosis-related metabolic genes. Furthermore, we conducted immunostaining experiments, including EMILIN2, SURF4, and LYPLA1, to verify our findings. Our investigation into the spatial heterogeneity of the breast cancer tumor environment has led to the discovery of specific diagnostic and prognostic markers in breast cancer.

[Genetic analysis of a Chinese pedigree with Lesch-Nyhan syndrome].

OBJECTIVE: To explore the genetic etiology for a Chinese pedigree affected with Lesch-Nyhan syndrome. METHODS: Members of the pedigree who had visited the Genetic Counseling Clinic of Linyi People's Hospital on February 10, 2022 were selected as the study subjects. Clinical data and family history of the proband were collected, and trio-whole exome sequencing (trio-WES) was carried out for the proband and his parents. Candidate variants were verified by Sanger sequencing. RESULTS: Trio-WES revealed that both the proband and his cousin brother had harbored a hemizygous c.385-1G>C variant in intron 4 of the HPRT1 gene, which was unreported previously. A heterozygous c.385-1G>C variant of the HPRT1 gene was also found in the proband's mother, grandmother, two aunts, and a female cousin, whilst all phenotypically normal males in his pedigree were found to have a wild type for the locus, which has conformed to an X-linked recessive inheritance. CONCLUSION: The heterozygous c.385-1G>C variant of the HPRT1 gene probably underlay the Lesch-Nyhan syndrome in this pedigree.

A two-layer nested heterogeneous ensemble learning predictive method for COVID-19 mortality.

The COVID-19 epidemic has had a great adverse impact on the world, having taken a heavy toll, killing hundreds of thousands of people. In order to help the world better combat COVID-19 and reduce its death toll, this study focuses on the COVID-19 mortality. First, using the multiple stepwise regression analysis method, the factors from eight aspects (economy, society, climate etc.) that may affect the mortality rates of COVID-19 in various countries is examined. In addition, a two-layer nested heterogeneous ensemble learning-based prediction method that combines linear regression (LR), support vector machine (SVM), and extreme learning machine (ELM) is developed to predict the development trends of COVID-19 mortality in various countries. Based on data from 79 countries, the experiment proves that age structure (proportion of the population over 70 years old) and medical resources (number of beds) are the main factors affecting the mortality of COVID-19 in each country. In addition, it is found that the number of nucleic acid tests and climatic factors are correlated with COVID-19 mortality. At the same time, when predicting COVID-19 mortality, the proposed heterogeneous ensemble learning-based prediction method shows better prediction ability than state-of-the-art machine learning methods such as LR, SVM, ELM, random forest (RF), long short-term memory (LSTM) etc.

Isoflavones from Camphorosma lessingii Inhibit the Organic Anion Transporters OAT1 and OAT3.

Phytochemical investigation of Camphorosma lessingii has resulted in the isolation of four previously unreported isoflavones (1: -4: ) and eight known compounds (5: -12: ). Nine of these compounds (1: -6, 8: -10: ) are reported for the first time from members of the family Amaranthaceae. The structures of all isolated compounds were determined by spectroscopic methods, primarily one-dimensional and two-dimensional nuclear magnetic resonance and mass spectrometry. The absolute configuration of 6: was confirmed by circular dichroism. Inhibition of the organic anion transporters, OAT1 and OAT3, by the isolated compounds was evaluated. Among them, 7, 2'-dihydroxy- 6,8-dimethoxyisoflavone (1: ), 2'-hydroxy-6,7,8-trimethoxyisoflavone (2: ), 6,2'-dihydroxy-7,8-dimethoxyisoflavone (3: ), and 7-methoxyflavone (5: ) showed a significant inhibitory effect on 6-carboxyfluorescein uptake mediated by OAT1 and OAT3.

HMME combined with green light-emitting diode irradiation results in efficient apoptosis on human tongue squamous cell carcinoma.

Hematoporphyrin monomethyl ether (HMME) is a novel and promising porphyrin-related photosensitizer for photodynamic therapy (PDT). This study aimed to investigate the efficacy and potential mechanism of HMME-PDT under irradiation of green light-emitting diode (LED) with wavelength of 530 ± 20 nm in treating human tongue squamous cell carcinoma Tca8113 cells in vitro. The HMME concentrations were 1.25, 2.5, and 5 µg/ml while the energy densities were 0.6, 1.2, 1.8, 2.4, and 3.0 J/cm(2). MTT assay demonstrated that HMME-PDT significantly inhibited the proliferation of Tca8113 cells, and the cytotoxicity was improved with increased HMME concentration and light intensity. The amount of cells decreased significantly and the morphology of cells changed drastically after HMME-PDT. Flow cytometry analysis revealed that HMME-PDT induced both apoptosis and necrosis, but apoptosis was the main form of cell death. Apoptotic morphology was confirmed by Hoechst 33342 staining. Laser scanning confocal microscopy observation showed that HMME was mainly localized in mitochondria. The production of intracellular reactive oxygen species increased remarkably after PDT treatment, and both sodium azide (the singlet oxygen quencher) and D-mannitol (the hydroxyl radical scavenger) could protect Tca8113 cells from death induced by HMME-PDT. Additionally, the activity of caspase-3 also increased markedly in treated groups, and the cell death could be rescued by a reversible inhibitor (Ac-DEVD-CHO) of caspase-3. These results demonstrated that HMME combined with green LED significantly induced apoptosis of Tca8113 cells, suggesting that HMME-PDT using green LED might be a potential therapeutic strategy for human tongue squamous cell carcinoma.

A Magnetic Separation-Assisted High-Speed Homogenization Method for Large-Scale Production of Endosome-Derived Vesicles.

Extracellular vesicles (EVs) have attracted significant attention in physiological and pathological research, disease diagnosis, and treatment; however, their clinical translation has been limited by the lack of scale-up manufacturing approaches. Therefore, this protocol provides a magnetic separation-assisted high-speed homogenization method for the large-scale production of endosome-derived nanovesicles as a new type of exosome mimics (EMs) derived from the endosomes, which have about 100-time higher yield than conventional ultracentrifugation method. In this method, magnetic nanoparticles (MNPs) were internalized by parental cells via endocytosis and were subsequently accumulated within their endosomes. Then, MNPs-loaded endosomes were collected and purified by hypotonic treatment and magnetic separation. A high-speed homogenizer was utilized to break MNP-loaded endosomes into monodisperse nanovesicles. The resulting endosome-derived vesicles feature the same biological origin and structure, characterized by nanoparticle tracking analysis, transmission electron microscope, and western blotting. Their morphology and protein composition are similar to native EVs, indicating that EMs may potentially serve as a low-cost and high-yield surrogate of native EVs for clinical translations.

Functional disruption of macrophage migration inhibitory factor (MIF) suppresses proliferation of human H460 lung cancer cells by caspase-dependent apoptosis.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is important in regulating cell proliferation and apoptosis in both normal and cancerous cells, and may be important in cancer progression and metastasis. In human non-small cell lung cancer (NSCLC), the underlying mechanisms responsible for MIF-dependent regulation of cellular proliferation, and cell death remain poorly appreciated. METHODS: The human H460 lung cancer cell-line was treated with an optimally determined dose of 50 pmol/ml MIF siRNA, following which cell proliferation, cell cycle and apoptosis were analyzed. Additionally, known pathways of apoptosis including expression of Annexin-V, enhanced production of caspases-3 and -4 and expression of the Akt signaling protein were assessed in an attempt to provide insights into the signaling pathways involved in apoptosis following disruption of MIF expression. RESULTS: Specific siRNA sequences markedly decreased MIF expression in H460 cells by 2 to 5-fold as compared with the negative control. Moreover, MIF miRNA dampened not only cellular proliferation, but increased the frequency of apoptotic cells as assessed by cell-surface Annexin-V expression. Entry of cells into apoptosis was partly dependent on enhanced production of caspases -3 and -4 while not affecting the expression of either caspase-8 or the Akt signaling pathway. CONCLUSIONS: In a model of NSCLC, knockdown of MIF mRNA expression dampened H460 proliferation by mechanisms partly dependent on entry of cells into apoptosis and enhanced production of caspase-3 and -4. MIF expression may thus be important in NSCLC progression. Targeting MIF may have clinical utility in the management of human lung cancer.

Curcumin analogue T83 exhibits potent antitumor activity and induces radiosensitivity through inactivation of Jab1 in nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus-associated malignancy that is most common in East Asia, Africa, and Alaska. Radiotherapy is the main treatment option; unfortunately, disease response to concurrent radiotherapy and chemotherapy varies among patients with NPC, and in many cases, NPC becomes resistant to radiotherapy. Our previous studies indicated that Jab1/CSN5 was overexpressed and plays a role in the pathogenesis and radiotherapy resistance in NPC. Therefore, it is important to seek for innovative therapeutics targeting Jab1/CSN5 for NPC. In this study, we explored the antitumor effect of a curcumin analogue T83 in NPC, and found T83 exhibits antitumor activity and induces radiosensitivity through inactivation of Jab1 in NPC. METHODS: NPC cell viability and proliferation were detected by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays. Cell cycle distribution was detected with use of flow cytometry. Apoptosis was examined by using the Annexin V/propidium iodide staining assay and cleavage poly(ADP-ribose polymerase (PARP) and cleavage caspase-3 expression. Jab1 expression was examined by Western blotting. RESULTS: A growth inhibitory effect was observed with T83 treatment in a dose- and time-dependent manner. T83 significantly induced G2/M arrest and apoptosis in NPC. In addition, T83 inhibited Jab1 expression and sensitized NPC cells to radiotherapy. CONCLUSION: Our data indicate that T83 exhibits potent inhibitory activity in NPC cells and induces radiotherapy sensitivity. Thus, T83 has translational potential as a chemopreventive or therapeutic agent for NPC.

Exploration of spatial heterogeneity of tumor microenvironment in nasopharyngeal carcinoma via transcriptional digital spatial profiling.

The heterogeneity of nasopharyngeal carcinoma (NPC) leads to mixed clinical outcomes. We collected 92 regions of interest from 41 biopsies of patients with untreated NPC and obtained their transcripts using GeoMx Digital Spatial Profiling (DSP) technology. Spatial heterogeneity was determined by measuring the expression of marker genes in tumor cell-enriched (PanCK-expressing), immune cell-enriched (CD45-expressing), and normal epithelial (Endo) regions. We screened 16 prognostic markers in tumor cell-enriched regions and 4 prognostic markers in immune cell-enriched regions. The levels of CD8+ T follicular helper T cells, activated NK cells, and M0 macrophage contents were higher in tumor cell-enriched regions than in immune cell-enriched regions. Conversely, plasma cell and M2 macrophage levels were lower. The follicular helper T cells in tumor cell-enriched regions were negatively correlated with resting NK cells and positively correlated with activated NK cells. In immune cell-enriched regions, this relationship was reversed. We also explored the heterogeneity of HLA gene families, immune checkpoints, and metabolism-related genes in the three regions. In tumor cell-enriched regions, we obtained 19 prognosis-related metabolism genes via univariate cox analysis. We used multiplex immunofluorescence to verify the elevated expression of SLC8A1 and MDH1 in immune cell-enriched regions and tumor cell-enriched regions, respectively, both of which were associated with prognosis of NPC. In conclusion, we explored the spatial heterogeneity of the NPC tumor environment and found specific diagnostic and prognostic markers that can be used to differentiate tumor cell-enriched regions from immune cell-enriched regions in NPC.

Interpretability-Based Multimodal Convolutional Neural Networks for Skin Lesion Diagnosis.

Skin lesion diagnosis is a key step for skin cancer screening, which requires high accuracy and interpretability. Though many computer-aided methods, especially deep learning methods, have made remarkable achievements in skin lesion diagnosis, their generalization and interpretability are still a challenge. To solve this issue, we propose an interpretability-based multimodal convolutional neural network (IM-CNN), which is a multiclass classification model with skin lesion images and metadata of patients as input for skin lesion diagnosis. The structure of IM-CNN consists of three main paths to deal with metadata, features extracted from segmented skin lesion with domain knowledge, and skin lesion images, respectively. We add interpretable visual modules to provide explanations for both images and metadata. In addition to area under the ROC curve (AUC), sensitivity, and specificity, we introduce a new indicator, an AUC curve with a sensitivity larger than 80% (AUC_SEN_80) for performance evaluation. Extensive experimental studies are conducted on the popular HAM10000 dataset, and the results indicate that the proposed model has overwhelming advantages compared with popular deep learning models, such as DenseNet, ResNet, and other state-of-the-art models for melanoma diagnosis. The proposed multimodal model also achieves on average 72% and 21% improvement in terms of sensitivity and AUC_SEN_80, respectively, compared with the single-modal model. The visual explanations can also help gain trust from dermatologists and realize man-machine collaborations, effectively reducing the limitation of black-box models in supporting medical decision making.

Novel SPTB frameshift mutation in a Chinese neonatal case of hereditary spherocytosis type 2: A case report.

Hereditary spherocytosis (HS) is an erythrocyte membrane disease with a non-specific phenotype, particularly occurring in neonatal patients, and its diagnosis is challenging. The present study reports on a patient with neonatal HS and reviewed the genetic characteristics of reported neonatal HS cases in China. The patient was admitted only a few hours after birth with jaundice. Auxiliary examination indicated anemia and hyperbilirubinemia. Spherical erythrocytes were occasionally observed in peripheral blood smears. Genetic testing suggested that the patient harbored a novel frameshift mutation (p.Asp495fsTer78) in spectrum, ß, erythrocytic (SPTB), which was carried by the father. Review of 160 cases of HS in China revealed 24 to be neonatal cases. In these neonatal cases, the frequency of ankyrin 1 (ANK1) mutations and loss-of-function mutations of pathogenic genes (including ANK1 and SPTB) was higher than that in the non-neonatal group. In conclusion, the present study further expanded the mutation spectrum of SPTB and reaffirms the diagnostic value of gene detection in neonatal HS.

Cuproptosis related genes associated with Jab1 shapes tumor microenvironment and pharmacological profile in nasopharyngeal carcinoma.

Background: Nasopharyngeal carcinoma (NPC) is the most common subcategory of head and neck squamous cell carcinoma (HNSCC). This study focused on the roles of cuproptosis related genes and Jab1 in the tumor microenvironment of NPC and HNSCC. Methods: Differential expression analysis of Jab1 and cuproptosis related genes in tumor cell enriched region (PanCK-expressing) and immune cell enriched region (CD45-expressing) of NPC microenvironment were performed by packages of R software. Survival analysis was performed using the survival and survminer packages. Corrplot package was used for correlation analysis. ConsensusClusterPlus package was used for cluster clustering among different regions of NPC, and functional enrichment analysis was performed using GSVA, GSEABase, clusterProfiler, org.Hs.eg.db and enrichplot packages. The pRRophetic package was used to predict drug sensitivity in NPC and HNSCC. Results: Relationships exist between cuproptosis related genes and Jab1 in the NPC microenvironment. The expression of cuproptosis related genes and Jab1 differed between tumor cell enriched region and immune cell enriched region. AKT inhibitor VIII, Doxorubicin, Bleomycin and Etoposide showed higher sensitivity to tumor cell than immune cell. In the high Jab1 group, higher expression of ATP7A, DBT, DLD and LIAS were associated with better prognosis of HNSCC patients. In contrast, in the low Jab1 group, higher expression of these genes is associated with worse prognosis of HNSCC patients. Conclusions: Prognostic cuproptosis related genes and Jab1 provided a basis for targeted therapy and drug development.

Analysis of lncRNA-Mediated ceRNA Crosstalk and Identification of Prognostic Signature in Head and Neck Squamous Cell Carcinoma.

Long non-coding RNA (lncRNA) can act as ceRNA to regulate the expression of target genes by sponging miRNAs, and therefore plays an essential role in tumor initiation and progression. However, functional roles and regulatory mechanisms of lncRNAs as ceRNAs in head and neck squamous cell carcinoma (HNSCC) remain to be determined. We downloaded RNA sequence profiles from The Cancer Genome Atlas (TCGA) database, and identified the differential RNAs by bioinformatics. Then we analyzed the biological processes of differential expressed RNAs (DER), and established their interaction networks and pathway analysis to find out potential biological effects of these DERs. Besides, we also explored the relationship between the DERs and prognosis of HNSCC patients. We obtained 525 tumor samples and 44 paracancerous controls, and there were 1081 DElncRNAs, 1889 DEmRNAs, and 145 DEmiRNAs. GO and KEGG pathways analysis of these DEmRNAs were mainly involved in "Protein digestion and absorption," "Calcium signaling pathway," and "ECM-receptor interaction." The analysis of the ceRNA network identified 61 DElncRNAs as functional ceRNAs whose dysregulated expression may affect the expression of oncogenes/tumor suppressor genes. Furthermore, univariate and multivariate Cox regression analysis revealed that 4 DElncRNAs, 3 EDmiRNAs, and 6 DEmRNAs can predict survival with high accuracy. Survival analysis found that 4 lncRNAs was related to prognostic, including overexpressed RP11-366H4.1, HOTTIP, RP11-865I6.2, and RP11-275N1.1 patients had a worse survival. In conclusion, through constructing the ceRNA network in HNSCC patients, we identified key lncRNA-miRNA-mRNA network in HNSCC. All the DERs might participate in varieties of pathways in the initiation, progression, and invasion of HNSCC. Furthermore, some miRNAs (hsa-mir-99a, hsa-mir-337, and hsa-mir-137) and mRNAs (NOSTRIN, TIMP4, GRB14, HOXB9, CELSR3, and ADGRD2) may be the prognostic genes of HNSCC. This study provided a new target and theoretical basis for further research on molecular mechanisms and biomarkers.

Compared to outcome pressure, observation pressure produces differences in performance of N-back tasks: an ERP study.

Previous studies have reported that observation pressure and outcome pressure impact working memory, but have not investigated whether they exert different effects on working memory. The neuronal activity in some brain areas encodes task-related information corresponding to working memory across delay periods. Therefore, changes in working memory under pressure can be further verified by exploring neuronal activity changes in brain areas under pressure. In this study, we used an N-back task and event-related potentials to explore whether the two types of pressure exert different effects on working memory. The electrophysiological results revealed that observation pressure-induced P1, P2 and late positive component amplitudes are significantly larger than corresponding outcome pressure-induced amplitudes, and the P3 amplitude induced by low-load working memory is significantly larger than that in the high-load condition. A possible explanation is that observation pressure increases attention focus, whereas outcome pressure increases attention dispersion, and a greater memory load results in more information that must be maintained and updated in working memory. These findings indicate that observation pressure and outcome pressure exert different effects on working memory.

Clinical Significance of Elevated S100A8 Expression in Breast Cancer Patients.

Breast cancer is the leading cause of female cancer-related death; however, novel biomarkers for predicting cancer recurrence still need to be explored. Aberrant expression of S100A8 has been reported to be related to tumor progression in various cancer types. This study aims to evaluate the clinical significance of S100A8 expression in breast cancer patients. In this study, data from 140 breast cancer patients were retrospectively collected to examine the association between S100A8 expression and clinical prognosis. Increased S100A8 expression was detected in breast cancer patients with relapse. The patients with increased S100A8 levels had significantly shorter disease-free survival (DFS) and overall survival (OS). In a multivariate survival analysis, a high histological grade and an elevated S100A8 level were independent factors associated with poor DFS and OS. Moreover, S100A8 expression was correlated with clinical subtype in breast cancer patients. The results showed that ER-negative and triple-negative breast cancer (TNBC) patients had significantly higher expression of S100A8 than patients with other subtypes. In conclusion, this study identified S100A8 as a potential biomarker for relapse in breast cancer patients.

An improved support vector machine-based diabetic readmission prediction.

BACKGROUND AND OBJECTIVE: In healthcare systems, the cost of unplanned readmission accounts for a large proportion of total hospital payment. Hospital-specific readmission rate becomes a critical issue around the world. Quantification and early identification of unplanned readmission risks will improve the quality of care during hospitalization and reduce the occurrence of readmission. In clinical practice, medical workers generally use LACE score method to evaluate patient readmission risks, but this method usually performs poorly. With this in mind, this study presents a novel method combining support vector machine and genetic algorithm to build the risk prediction model, which simultaneously involves feature selection and the processing of imbalanced data. This model aims to provide decision support for clinicians during the discharge management of patients with diabetes. METHOD: The experiments were conducted from a set of 8756 medical records with 50 different features about diabetic readmission. After preprocessing the data, an effective SMOTE-based method was proposed to solve the imbalance data problem. Further, in order to improve prediction performance, a hybrid feature selection mechanism was devised to select the important features. Subsequently, an improved support vector machine-based (SVM-based) method was developed and the genetic algorithm was used to tune the sensitive parameter of the algorithm. Finally, the five-fold cross-validation method was applied to compare the performance of proposed method with other methods (LACE score, logistic regression, naïve bayes, decision tree and feed forward neural networks). RESULTS: Experimental results indicate that the proposed SVM-based method achieves an accuracy of 81.02%, a sensitivity of 82.89%, a specificity of 79.23%, and outperforms other popular algorithms in identifying diabetic patients who may be readmitted. CONCLUSIONS: Our research can improve the performance of clinic decision support systems for diabetic readmission, by which the readmission possibility as well as the waste of medical resources can be reduced.

The correlation of PTPN4 expression with prognosis in breast cancer.

Precision medicine, applying knowledge of breast cancer's molecular subtypes, has improved the disease's prognosis. However, recurrence and chemoresistance are critical issues for breast cancer patients. PTPN4, a new potential therapeutic target, has not been studied sufficiently in breast cancer, and the potential role of PTPN4 in the prognosis of breast cancer patients is still unknown. In our study, data from 140 invasive breast cancer patients were retrospectively collected to identify the association between PTPN4 expression and clinical outcomes of these patients. The expressions of PTPN4 were detected by immunohistochemical analysis. Breast hyperplasia tissues showed higher expression of PTPN4. We found that PTPN4 expression was lower in breast cancer patients with relapse than in patients without relapse. Patients with an increased PTPN4 level had a significantly longer relapse-free survival and overall survival time. Decreased PTPN4 expression was an independent factor associated with relapse-free survival and overall survival, as shown by multivariate Cox regression analysis. The study found that PTPN4 is an attractive prognostic biomarker for predicting the clinical outcome and effective disease management of breast cancer patients.

Antimicrobial prophylaxis in caesarean section delivery.

Antimicrobial prophylaxis is used routinely for pre-, intra- and post-operative caesarean section. One of the most important risk factors for postpartum infection is caesarean delivery. Caesarean section shows a higher incidence of infection than vaginal delivery. It is complicated by surgical site infections, endometritis or urinary tract infection. The aim of the present study was to assess the usage of antimicrobials in women undergoing caesarean section at a Tertiary Care Hospital. A prospective study was conducted in 100 women during the period of February 2013 to August 2013 in the inpatient Department of Gynaecology and Obstetrics. Data collected included the age of the patient, gravidity, and type of caesarean section, which was analyzed for the nature and number of antimicrobials prescribed, duration of treatment, polypharmacy, fixed-dose combinations, generic/brand names used and failure of prophylaxis. Antimicrobial prophylaxis was administered to the patients. The most commonly prescribed antimicrobial was a combination of ceftriaxone and sulbactam. Of 100 patients, 87% were aged 20-35 years. The highest proportion of patients were primigravida 72%. Elective procedure was carried out in 38%, the remaining were emergency C-section in whom intra- and post-operative antimicrobial prophylaxis was given for a duration of 7 days. In total, 27% of patients were reported with infection even after the antimicrobial prophylaxis. In conclusion, pre-operative prophylaxis was given in the early rupture of membranes. Fixed-dose combinations were preferred. Incidence of infection even after antimicrobial prophylaxis was reported due to pre-existing infection, debilitating disease or prolonged rupture of membranes. Patients with recurrent infection were shifted to amoxicillin and clavulinic acid combination. Drugs were prescribed only by brand names which is of concern.

Urinary liver-type fatty acid-binding protein change in gestational diabetes mellitus.

We compared urinary liver-type fatty acid-binding protein (L-FABP) among non-pregnant and pregnant women with and without gestational diabetes mellitus (GDM). Higher urinary L-FABP was found in pregnant with and without GDM, and considerably higher urinary L-FABP was found in the GDM group compared with the non-GDM group. Hyperglycemia and anemia were related with high urinary L-FABP expression.