Growing threat of extended-spectrum ß-lactamase-producing Enterobacteriaceae colonisation in high-risk pregnancies: A cross-sectional study.

OBJECTIVE: To investigate the epidemiological changes in extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) vaginal colonisation in pregnant women deemed at high risk, and to identify independent risk factors. Further, the differences in perinatal outcomes according to maternal ESBL-E vaginal colonisation were analysed. DESIGN: Cross-sectional study. SETTING: Republic of Korea. POPULATION: A cohort of 1460 women admitted to our high-risk pregnancy unit between 14+0 and 36+6  weeks of gestation. METHODS: The trend of changes in the association of ESBL-E vaginal colonisation from January 2010 to December 2020 was analysed. The main outcomes were analysed over the study period and ESBL-E vaginal colonisation. MAIN OUTCOME MEASURES: Rate of ESBL-E vaginal colonisation, risk factors for ESBL-E vaginal colonisation and perinatal outcomes. RESULTS: The ESBL-E vaginal colonisation rate has tended to increase over the past 11 years, which was attributed to a significantly higher proportion of ESBL-producing Escherichia coli. Cerclage (RR 3.7, 95% CI 2.19-6.40) and prior antibiotic treatment (RR 4.0, 95% CI 2.44-6.54) were found as independent risk factors for ESBL-E vaginal colonisation. Earlier gestational age at delivery and higher proven early-onset neonatal sepsis (EONS) rate were observed in the ESBL-E-positive group. CONCLUSIONS: The ESBL-E vaginal colonisation rate in pregnant patients at high risk has increased over the past decade, and the independent risk factors for colonisation are cerclage and prior antibiotic treatment. Additionally, maternal ESBL-E vaginal colonisation is associated with higher rates of proven EONS.

The role of prosodic and visual information in disambiguating wh-indeterminates: The case of Korean three-year-olds.

In Korean language, questions containing ambiguous wh-words may be interpreted as either wh-questions or yes-no questions. This study investigated 43 Korean three-year-olds' ability to disambiguate eight indeterminate questions using prosodic and visual cues. The intonation of each question provided a cue as to whether it should be interpreted as a wh-question or a yes-no question. The questions were presented alongside picture stimuli, which acted as either a matched (presentation of corresponding auditory-visual stimuli) or a mismatched contextual cue (presentation conflicting auditory-visual stimuli). Like adults, the children preferred to comprehend questions involving ambiguous wh-words as wh-questions, rather than yes-no questions. In addition, children were as effective as adults in disambiguating indeterminate questions using prosodic cues regardless of the visual cue. However, when confronted with conflicting auditory-visual stimuli (mismatched), the quality of children's responses was less accurate than adults' responses.

Knockdown of PRKAR2B Results in the Failure of Oocyte Maturation.

BACKGROUND/AIMS: Cyclic adenosine monophosphate (cAMP)-dependent type 2 regulatory subunit beta (Prkar2b) is a regulatory isoform of cAMP-dependent protein kinase (PKA), which is the primary target for cAMP actions. In oocytes, PKA and the pentose phosphate pathway (PPP) have important roles during the germinal vesicle (GV) stage arrest of development. Although the roles of the PKA signal pathway have been studied in the development of oocyte, there has been no report on the function of PRKAR2B, a key regulator of PKA. METHODS: Using reverse transcription polymerase chain reaction (RT-PCR), quantitative real-time PCR (qRT-PCR), immunohistochemistry, and immunofluorescence, we determined the relative expression of Prkar2b in various tissues, including ovarian follicles, during oocyte maturation. Prkar2b-interfering RNA (RNAi) microinjection was conducted to confirm the effect of Prkar2b knockdown, and immunofluorescence, qRT-PCR, and time-lapse video microscopy were used to analyze Prkar2b-deficient oocytes. RESULTS: Prkar2b is strongly expressed in the ovarian tissues, particularly in the growing follicle. During oocyte maturation, the highest expression of Prkar2b was during metaphase I (MI), with a significant decrease at metaphase II (MII). RNAi-mediated Prkar2b suppression resulted in MI-stage arrest during oocyte development, and these oocytes exhibited abnormal spindle formation and chromosome aggregation. Expression of other members of the PKA family (except for Prkaca) were decreased, and the majority of the PPP factors were also reduced in Prkar2b-deficient oocytes. CONCLUSION: These results suggest that Prkar2b is closely involved in the maturation of oocytes by controlling spindle formation and PPP-mediated metabolism.

Cerebellar Development in Preterm Infants at Term-Equivalent Age Is Impaired after Low-Grade Intraventricular Hemorrhage.

OBJECTIVES: To investigate cerebellar development in preterm infants at term-equivalent age compared with healthy full-term infants and to examine the effect of a low-grade intraventricular hemorrhage (IVH) on cerebellar development. STUDY DESIGN: This study used 3T magnetic resonance and diffusion tensor imaging (DTI) at 36-41 weeks' postmenstrual age (PMA) in 72 preterm infants without severe brain injury and 16 full-term infants. Cerebellar volumes and DTI parameters of the cerebellar peduncles including fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity, and radial diffusivities were measured. Clinical variables that may affect brain development were collected. RESULTS: Compared with full-term infants, preterm infants showed smaller cerebellar volumes and a lower FA, greater ADC, and increased radial diffusivities in the cerebellar peduncles (all P < .05). This cerebellar impairment was associated significantly with PMA and IVH grade 2 but was independent of gestational age at birth. When we adjusted for clinical variables, an IVH grade 2 was related with 1.73 cm(3) reduction in cerebellar volumes and altered DTI parameters in the cerebellar peduncles, including decreased FA and increased radial diffusivities in the superior cerebellar peduncle and increases in ADC, axial diffusivity, and radial diffusivities of the middle cerebellar peduncle (all P < .05). Cerebellar hemispheric volumes were associated with both ipsilateral and contralateral IVH grade 2. CONCLUSION: Preterm infants without severe brain abnormalities showed impaired cerebellar development at term-equivalent age after we controlled for PMA at the time of the scan, and this is associated with IVH grade 2. These findings suggest that even a low-grade IVH has potential harmful effects on cerebellar development.

Early Single-Center Experience of DaVinci® Single-Port (SP) Robotic Surgery in Colorectal Patients.

Background: DaVinci® single-port (SP) robotic surgery offers several benefits compared to traditional multiport laparoscopic or robotic surgeries. One of the main advantages is that it allows for a minimally invasive approach, resulting in a single, smaller incision and reduced trauma to the patient's body, leading to less postoperative pain, faster recovery, and reduced risk of complications. The cosmesis of a single port with minimal visible scarring is also an attractive aspect to the patients; however, many surgeons use an additional port for energy device, stapler use, and drain insertion. Pure single-port surgery with one incision is still rare. Here, we share our experience of our first 10 cases using the SP robotic platform in colorectal surgery. Methods: From May 2023 to December 2023, colorectal patients who underwent SP robotic surgery were analyzed. Placement of the incision was the umbilicus for eight patients, and right lower quadrant for two patients, through which ileostomy maturation was performed. Data on perioperative parameters and postoperative outcomes were analyzed, with a median follow-up of 4.6 months (range 0.6-7.4 months). Results: A total of 10 colorectal patients underwent DaVinci® single-port robotic colorectal surgery at our institution during this period. The patient demographic was four males (40%) and six females (60%) with a median age of 63.5 years (range 50-75 years). Median body mass index (BMI) was 22.89 kg/m2 (range 19.92-26.84 kg/m2). Nine patients were diagnosed with colorectal cancer, and one patient was diagnosed with a rectal gastrointestinal tumor. One patient underwent anterior resection and cholecystectomy simultaneously. Mean operation time was 222 min (range 142-316 min), and mean wound size was 3.25 cm (range 2.5-4.5 cm). Nine patients underwent surgery with single incision through which a single-port trocar was inserted, and one patient had one additional port for drain insertion. Mean hospital stay was 6 days (range 4-8 days) with one postoperative complication of bleeding requiring transfusion, but there was no readmission within 30 days. Conclusions: Overall, our experience with single-port robotic colorectal surgery has been promising. With only one patient with additional port for drain insertion, all nine patients underwent SP-robotic surgery with single incision for colon as well as rectal surgeries. Compared to an average postoperative length of stay of 6.5-8 days in laparoscopic colorectal surgeries reported in literature, SP-robotic surgery 33showed faster recovery of 6 days highlighting its benefits in patient recovery and satisfaction.

Sarcopenia diagnosis in patients with colorectal cancer: a review of computed tomography-based assessments and emerging ways to enhance practicality.

Traditionally, cancer treatment has focused on the stages of the disease; however, recent studies have highlighted the importance of considering the overall health status of patients in the prognosis of cancer. Loss of skeletal muscle, known as sarcopenia, has been found to significantly affect outcomes in many different types of cancers, including colorectal cancer. In this review, we discuss the guidelines for diagnosing sarcopenia, with a specific focus on CT-based assessments. Many groups worldwide, including those in Europe and Asia, have introduced their own diagnostic guidelines for sarcopenia. Seemingly similar yet subtle discrepancies, particularly in the cutoff values used, limit the use of these guidelines in the general population, warranting a more universal guideline. Although CT-based measurements, such as skeletal muscle index and radiodensity, have shown promise in predicting outcomes, the lack of standardized values in these measurements hinders their universal adoption. To overcome these limitations, innovative approaches are being developed to assess changes in muscle mass trajectories and introduce new indices, such as skeletal and appendicular muscle gauges. Additionally, machine learning models have shown superior performance in predicting sarcopenic status, providing an alternative to CT-based diagnosis, particularly after surgery. CT has tremendous benefits and a significant role in visually as well as quantitatively retrieving information on patient body composition. In order to compensate for the limitation of standard cutoff value, 3-dimensional analysis of the CT, artificial intelligence-based body composition analysis, as well as machine learning algorithms for data interpretation and analysis have been proposed and are being utilized. In conclusion, despite the varying definitions of sarcopenia, CT-based measurements coupled with machine-learning models are promising for evaluating patients with cancer. Standardization efforts can improve diagnostic accuracy, reduce the reliance on CT examinations, and make sarcopenia assessments more accessible in clinical settings.

Is cytoreductive surgery and hyperthermic intraperitoneal chemotherapy still beneficial in patients diagnosed with colorectal peritoneal metastasis who underwent palliative chemotherapy?

BACKGROUND: With a 5-year overall survival of less than 5%, colorectal peritoneal metastasis (CPM) patients are often managed with palliative chemotherapy (CTx). In the past few decades, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been introduced as a possible curative treatment for highly selective CPM patients. We share our experience of CRS and HIPEC given the unique characteristics of the medical system and the benefit of CRS and HIPEC in palliative setting. METHODS: From April 2017 to October 2021, CPM patients who underwent CRS and HIPEC were analyzed. Patients were allocated into perioperative and palliative CTx arm based on the duration between initial diagnosis of CPM to undergoing CRS and HIPEC of 6 months. Data including perioperative parameters, postoperative outcomes, and survival were analyzed with a median follow-up of 28.5 months. RESULTS: Twenty-six CPM patients underwent CRS and HIPEC. Mean time from diagnosis of CPM to CRS and HIPEC was 5.5 months with 14 patients in the perioperative arm and 12 patients in the palliative arm. Perioperative group showed a longer RFS of 13.5 months compared to 8 months in the palliative group. Median overall survival of palliative group was 41.50 months, and 18 patients among all groups are alive at the time of this report. CONCLUSION: CRS and HIPEC could be a treatment option for a carefully selected CPM patients performed by experienced surgeons. Overall survival of 41.50 months in palliative group compared to 16.8 months from conventional systemic CTx supports CRS and HIPEC even in palliative patients.

Comparing extracorporeal, semi-extracorporeal, and intracorporeal anastomosis in laparoscopic right hemicolectomy: introducing a bridging technique for colorectal surgeons.

Purpose: Intracorporeal anastomosis (IA) in laparoscopic right hemicolectomy has been associated with faster recovery in bowel function compared to extracorporeal anastomosis (EA). However, the technical difficulty of laparoscopic suturing technique and intraabdominal fecal contamination hinder many surgeons from implementing such a procedure. We introduce and compare a bridging technique designated as "semi-extracorporeal" anastomosis (SEA), which embraces the advantages and amends the drawbacks of IA and EA. Methods: Between May 2016 and October 2022, 100 patients who underwent laparoscopic right hemicolectomy were analyzed. All patients who received laparoscopic right hemicolectomy underwent one of the 3 anastomosis methods (EA, SEA, and IA) by a single colorectal surgeon at a single tertiary care hospital. Data including perioperative parameters and postoperative outcomes were analyzed by each group. Results: A total of 100 patients were reviewed. Thirty patients underwent EA; 50 and 20 patients underwent SEA and IA, respectively. Operation time (minute) was 170 (range, 100-285), 170 (range, 110-280), and 147.5 (range, 80-235) in EA, SEA, and IA, respectively (P = 0.010). Wound size was smaller in SEA and IA compared to EA (P < 0.001). IA was associated with a shorter time (day) to first flatus compared to SEA and EA (4 [range, 2-13] vs. 4 [range, 2-7] vs. 2.5 [range, 1-4], P < 0.001). Postoperative complication showed no statistical significance between the 3 groups. Conclusion: Semi-extracorporeal was an attractive bridging option for colorectal surgeons worrisome of the technical difficulty of IA while maintaining faster bowel recovery and smaller wound incisions compared to EA.

Synergistic prognostic impact of hemoglobin and skeletal muscle index in patients with colorectal cancer.

BACKGROUND & AIMS: Recent studies have indicated that comorbidities such as sarcopenia and anemia can influence the prognosis of patients with colorectal cancer (CRC). However, the synergistic effects of sarcopenia and anemia on the survival of CRC patients are not yet comprehensively understood. This study aimed to investigate the relationship between anemia and sarcopenia and their synergistic effect on survival in patients with CRC. METHODS: A total of 1629 patients who underwent colorectal surgery were retrospectively reviewed. Patients were categorized into four hemoglobin-sarcopenia combined classifications (HS grade) according to their hemoglobin and skeletal muscle index (SMI) levels: hemoglobin low/SMI low (HS1), hemoglobin low/SMI high (HS2), hemoglobin high/SMI low (HS3), and hemoglobin high/SMI high (HS4). Association with overall survival (OS) was analyzed using both univariable and multivariable analyses. RESULTS: In total, 1024 patients with stage I-III CRC were analyzed. Patient allocation according to HS grade was 124 (12.1%) in HS1, 298 (29.1%) in HS2, 135 (13.2%) in HS3, and 467 (45.6%) in HS4. The Kaplan-Meier curves of OS showed statistically significant differences according to anemia and sarcopenia status as well as to HS grade (all P < 0.001). Univariable analysis of factors associated with OS revealed statistical significance in absence of anemia (hazard ratio [HR] 0.550, 95% confidence interval [CI] 0.400-0.756, P < 0.001], absence of sarcopenia (HR 0.560, P < 0.001), and HS grade (HS2, HR 0.515, P = 0.002; HS3, HR 0.468, P = 0.006; HS4, HR 0.325, P < 0.001). Multivariable analysis showed that compared to the HS1 group, the HS2 and HS4 groups showed significantly better OS (HS2, HR 0.527, 95% CI 0.340-0.817, P = 0.004; HS4, HR 0.574, 95% CI 0.361-0.912, P = 0.018). CONCLUSIONS: Sarcopenia, characterized by a low SMI and the presence of anemia before surgery, was associated with reduced OS among patients with non-metastatic CRC.

Varying clinical relevance of sarcopenia and myosteatosis according to age among patients with postoperative colorectal cancer.

OBJECTIVES: The present retrospective study reviewed the association among sarcopenia, myosteatosis, and overall survival (OS) in patients with postoperative colorectal cancer (CRC) with regard to age. DESIGN: A retrospective study was conducted with a five-year follow-up. SETTING: Data from all patients with CRC, who underwent surgery between February 2005 and April 2014, were reviewed. PARTICIPANTS: Data from 1053 patients (622 male [59.1%], 431 female [40.9%]; mean [± SD] age, 62.8 ± 11.8 years) were analyzed. MEASUREMENTS: Patients were divided into three groups according to age: ≤50, 51-74, and ≥75 years. Data, including perioperative parameters, and the presence of sarcopenia and myosteatosis according to skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD), respectively, were collected. Sarcopenia was evaluated using CT by calculating the SMI at the L3 level by dividing the area of the skeletal muscle by height squared (cm2/m2). SMD was also calculated using CT at the L3 level, but by evaluating fat attenuation according to Hounsfield units (HU). RESULTS: Patient allocation according to age group was as follows: ≤50 years, n = 147 (14.0%); 51-74 years, n = 742 (70.5%); and ≥75 years, n = 164 (15.5%). The presence of sarcopenia and myosteatosis were statistically significant with increasing age (P = 0.004 and P < 0.001, respectively). The 51-74 years age group exhibited a significant association in OS for myosteatosis (P < 0.001) while the ≥75 years group was significantly associated with sarcopenia (P = 0.04) with regard to OS. Multivariable analysis also revealed a statistically significant association between myosteatosis in the 51-74 years age group (P = 0.033) and sarcopenia in the ≥75 years age group (P = 0.005) even when adjusted for recurrence status. CONCLUSION: Different age groups exhibited significantly variable skeletal muscle indices. Although an abundance of irrefutable results demonstrated a correlation between CT-defined sarcopenia, myosteatosis, and clinical prognosis, data regarding age-dependent correlations are scarce. Results of this study demonstrated that sarcopenia and myosteatosis did not influence the prognosis of young patients with postoperative CRC (≤50 years of age), inferring the existence of significantly different skeletal muscle-related parameters according to age. Patients over 75 years of age showed significant association with sarcopenia while those in the 51-74 age group displayed significant link to myosteatosis. Clinicians should consider the impact of sarcopenia and myosteatosis on patient prognosis and should also be aware that the effect may differ according to patient age.

Association between cortical thickness and cognitive ability in very preterm school-age children.

Very preterm children, born before 32 weeks of gestation, are at risk for impaired cognitive function, mediated by several risk factors. Cognitive impairment can be measured by various neurodevelopmental assessments and is closely associated with structural alterations of brain morphometry, such as cortical thickness. However, the association between structural alterations and high-order cognitive function remains unclear. This study aimed to investigate the neurodevelopmental associations between brain structural changes and cognitive abilities in very preterm and full-term children. Cortical thickness was assessed in 37 very preterm and 24 full-term children aged 6 years. Cortical thickness analysis of structural T1-weighted images was performed using Advanced Normalization Tools. Associations between cortical thickness and the Wechsler Intelligence Scale for Children were evaluated by regression analysis based on ordinary least square estimation. Compared with full-term children, very preterm children showed significant differences in cortical thickness, variously associated with cognitive abilities in several brain regions. Perceptual reasoning indices were broadly correlated with cortical thickness in very preterm and full-term children. These findings provide important insights into neurodevelopment and its association with cortical thickness, which may serve as a biomarker in predictive models for neurodevelopmental diagnosis of high-order cognitive function.

Respiratory viruses in neonates hospitalized with acute lower respiratory tract infections.

BACKGROUND: The burden of respiratory syncytial virus (RSV) in neonates has not been clearly studied. The aims of this study were to determine the overall distribution of respiratory viruses in neonates hospitalized with acute lower respiratory tract infectiosns (ALRI) and to describe the clinical characteristics of RSV infections in these neonates. METHODS: From January 2009 through May 2010, neonates aged <1 month who were hospitalized with ALRI and did not have underlying disease were included in the study. Viruses were identified on multiplex reverse transcription polymerase chain reaction using nasal swab samples. Clinical variables were evaluated between the RSV and non-RSV infection groups. RESULTS: Of the 108 infants included in the study, 46 (42.6%) had RSV; human rhinovirus (18.5%), human parainfluenza virus 3 (7.5%), and human metapneumovirus (3.7%) were the next most common infections. Codetections accounted for 8.3% of the cases. Crowding increased the risk of RSV infection compared to the non-RSV group (OR, 16.5; P = 0.001). The RSV group had a greater incidence of dyspnea (P = 0.027), pneumonia (P < 0.001), requirement for oxygen (P < 0.001), and prolonged hospitalization (P = 0.011) than the non-RSV group. CONCLUSIONS: RSV was the most common viral etiology in neonates without underlying diseases who were hospitalized with ALRI. The disease severity of RSV infection was worse than that of other detected viral infections. Strict prevention strategies should be considered in overcrowded situations.

Novel quinolinylaminoisoquinoline bioisosteres of sorafenib as selective RAF1 kinase inhibitors: design, synthesis, and antiproliferative activity against melanoma cell line.

Design and synthesis of a new series of quinolinylaminoisoquinoline derivatives as conformationally restricted bioisosteres of Sorafenib are described. Their in vitro antiproliferative activity against A375P melanoma cell line was tested. Compounds 1b, 1d, 1g, and 1j showed the highest potency against A375P cell line with IC50 values in sub-micromolar scale. In addition, compound 1d exerted high selectivity towards RAF1 serine/threonine kinase with 96.47% inhibition at 10 µM, and IC50 of 0.96 µM. This compound can possess antiproliferative activity against melanoma cells through inhibition of RAF1 kinase.

Clinical efficacy of a novel method of fertility-preserving adenomyomectomy in infertile women with diffuse adenomyosis.

Beneficial and detrimental effect of surgical adenomyomectomy is still controversial in infertile women with severely diffuse adenomyosis. The primary objective of this study was to assess whether a novel method of fertility-preserving adenomyomectomy could improve pregnancy rates. The secondary objective was to evaluate whether it could improve dysmenorrhea and menorrhagia symptoms in infertile patients with severe adenomyosis. A prospective clinical trial was conducted between December 2007 and September 2016. Fifty women with infertility due to adenomyosis were enrolled in this study after clinical assessments by infertility experts. A novel method of fertility-preserving adenomyomectomy was performed on 45 of 50 patients. The procedure included T- or transverse H-incision of the uterine serosa followed by preparation of the serosal flap, excision of the adenomyotic tissue using argon laser under ultrasonographic monitoring, and a novel technique of suturing between the residual myometrium and serosal flap. After the adenomyomectomy, the changes in the amount of menstrual blood, relief of dysmenorrhea, pregnancy outcomes, clinical characteristics, and surgical features were recorded and analyzed. All patients obtained dysmenorrhea relief 6 months postoperatively (numeric rating scale [NRS]; 7.28 ±â€…2.30 vs 1.56 ±â€…1.30, P < .001). The amount of menstrual blood decreased significantly (140.44 ±â€…91.68 vs 66.33 ±â€…65.85 mL, P < .05). Of the 33 patients who attempted pregnancy postoperatively, 18 (54.5%) conceived either by natural means, in vitro fertilization and embryo transfer (IVF-ET), or thawing embryo transfer. Miscarriage occurred in 8 patients, while 10 (30.3%) had viable pregnancies. This novel method of adenomyomectomy resulted in improved pregnancy rates, as well as relief of dysmenorrhea and menorrhagia. This operation is effective in preserving fertility potential in infertile women with diffuse adenomyosis.

Genetic variants of MUC4 are associated with susceptibility to and mortality of colorectal cancer and exhibit synergistic effects with LDL-C levels.

As a disease with high mortality and prevalence rates worldwide, colorectal cancer (CRC) has been thoroughly investigated. Mucins are involved in the induction of CRC and the regulation of intestinal homeostasis but a member of the mucin gene family MUC4 has a controversial role in CRC. MUC4 has been associated with either decreased susceptibility to or a worse prognosis of CRC. In our study, the multifunctional aspects of MUC4 were elucidated by genetic polymorphism analysis in a case-control study of 420 controls and 464 CRC patients. MUC4 rs1104760 A>G polymorphism had a protective effect on CRC risk (AG, AOR = 0.537; GG, AOR = 0.297; dominant model, AOR = 0.493; recessive model, AOR = 0.382) and MUC4 rs2688513 A>G was associated with an increased mortality rate of CRC (5 years, GG, adjusted HR = 6.496; recessive model, adjusted HR = 5.848). In addition, MUC4 rs1104760 A>G showed a high probability of being a potential biomarker for CRC patients with low-density lipoprotein cholesterol (LDL-C) in the risk range while showing a significant synergistic effect with the LDL-C level. This is the first study to indicate a significant association between MUC4 genetic polymorphisms and CRC prevalence, suggesting a functional genetic variant with the LDL-C level, for CRC prevention.

Abnormal Vaginal Flora in Cervical Incompetence Patients - the Impact of Escherichia coli.

The purpose of this study was to investigate the prevalence of abnormal vaginal colonization in women with cervical incompetence and to analyze its impact on obstetric and neonatal outcomes and placental inflammation. We included 138 pregnant women diagnosed with cervical incompetence and delivered in our hospital. Patients with major fetal anomaly or multifetal pregnancy were excluded. Upper vaginal culture was performed on the day of admission. A total of 60.9% (84/138) of cervical incompetence patients had abnormal bacterial colonization, and Escherichia coli (E. coli) was the most common colonized pathogen (33.3%, 46/138). The positive vaginal E. coli group had a higher rate of prior preterm birth (p = 0.021) and an earlier gestational age at which cervical incompetence was diagnosed (p < 0.01) than the negative group. The positive vaginal E. coli group had higher rates of clinical chorioamnionitis (p = 0.008) and subchorionic microabscess of the placenta (p = 0.012). Importantly, the positive vaginal E. coli group had significantly higher rates of proven early-onset neonatal sepsis (EONS) (p = 0.046), necrotizing enterocolitis (NEC) (p = 0.001), and neonatal mortality (p = 0.023). After adjusting for confounding variables, the positive vaginal E. coli group had significantly higher risk for proven EONS (OR: 3.853, 95% CI: 1.056-14.055) and NEC (OR: 12.410, 95% CI: 1.290-119.351). In conclusion, E. coli was the most common vaginal microorganism isolated from patients with cervical incompetence. Maternal vaginal E. coli colonization was associated with adverse neonatal outcomes including proven EONS and NEC and was characterized by a higher rate of placental subchorionic microabscess.

Circular RNA circSMAD4 regulates cardiac fibrosis by targeting miR-671-5p and FGFR2 in cardiac fibroblasts.

Heart failure is a leading cause of death and is often accompanied by activation of quiescent cardiac myofibroblasts, which results in cardiac fibrosis. In this study, we aimed to identify novel circular RNAs that regulate cardiac fibrosis. We applied transverse aortic constriction (TAC) for 1, 4, and 8 weeks in mice. RNA sequencing datasets were obtained from cardiac fibroblasts isolated by use of a Langendorff apparatus and then further processed by use of selection criteria such as differential expression and conservation in species. CircSMAD4 was upregulated by TAC in mice or by transforming growth factor (TGF)-ß1 in primarily cultured human cardiac fibroblasts. Delivery of si-circSMAD4 attenuated myofibroblast activation and cardiac fibrosis in mice treated with isoproterenol (ISP). si-circSmad4 significantly reduced cardiac fibrosis and remodeling at 8 weeks. Mechanistically, circSMAD4 acted as a sponge against the microRNA miR-671-5p in a sequence-specific manner. miR-671-5p was downregulated during myofibroblast activation and its mimic form attenuated cardiac fibrosis. miR-671-5p mimic destabilized fibroblast growth factor receptor 2 (FGFR2) mRNA in a sequence-specific manner and interfered with the fibrotic action of FGFR2. The circSMAD4-miR-671-5p-FGFR2 pathway is involved in the differentiation of cardiac myofibroblasts and thereby the development of cardiac fibrosis.

New diarylureas and diarylamides possessing acet(benz)amidophenyl scaffold: design, synthesis, and antiproliferative activity against melanoma cell line.

A series of new diarylurea and diarylamide derivatives possessing acet(benz)amidophenyl scaffold was synthesized. Their in vitro antiproliferative activity was tested against A375P human melanoma cell line. Compounds 1c,d and 2c,d showed the highest potencies with IC(50) values in sub-micromolar scale. In addition, compounds 1b,e,l and 2e,l were more potent than Sorafenib but with IC(50) values in micromolar range. Moreover, compound 2c was equipotent to Vemurafenib, and 2d showed higher potency than Vemurafenib against A375P. Molar refractometry calculation and ADME profiling of the highest potent four derivatives 1c,d and 2c,d are also reported.

Altered functional connectivity in children born very preterm at school age.

Children born very preterm are at significant risk of neurodevelopmental impairment. This study sought to identify differences in cognitive function in children born very preterm compared to term-born controls and investigate alteration in white matter microstructure and functional connectivity (FC) based on tract-based spatial statistics (TBSS) and resting-state functional MRI, respectively. At 6 years of age, 36 children born very preterm (< 32 weeks' gestation) without major neurological disabilities and 26 term-born controls were tested using the Wechsler Intelligence Scale for Children, 4th edition, and Child Behavior Checklist. Whole-brain deterministic tractography and FC measurements were performed in both groups. The very preterm group had significantly lower intelligence scores than the term-born controls. The TBSS revealed no significant differences between the two groups, whereas FC was significantly increased between the frontoparietal network and the language network and was significantly decreased between the right salience network nodes in the very preterm group. The altered FC patterns between specific regions of the higher-order networks may reflect underlying deficits in the functional network architecture associated with cognitive function. Further studies are needed to demonstrate a direct connection between FC in these regions and cognitive function.

Prognostic significance of three endothelial nitric oxide synthase (eNOS) polymorphisms and metabolic syndrome (MetS) in patients with colorectal cancer.

BACKGROUND: Polymorphisms of endothelial nitric oxide synthases (eNOS) have been associated with cancer susceptibility. Also, metabolic syndrome is associated with cancer malignancy. However, the effect of eNOS polymorphisms and metabolic syndrome on colorectal cancer (CRC) prognosis remains unclear. OBJECTIVE: To investigated whether three genetic polymorphisms (- 786 T > C rs2070744, 4a4b rs869109213, and 894G > T rs1799983) in the eNOS and metabolic syndrome (MetS) were associated with CRC patient survival. METHODS: We genotyped three polymorphisms of eNOS (- 786 T > C, 4a4b, and 894G > T) in 312 CRC cases from the Korean population by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: Although the three eNOS polymorphisms were not causative of MetS, the TT genotype of the 894G > T polymorphism was associated with a worse survival rate compared with the GG genotype in the CRC group with MetS than in the CRC group without MetS (5-years survival; adjusted HR = 54.777; 95% CI 5.073-591.487 and RFS; adjusted HR = 14.909; 95% CI 1.571-141.528). CONCLUSIONS: The eNOS polymorphisms were not associated with metabolic syndrome prevalence in CRC patients. However, our findings suggest that the eNOS 894G > T polymorphism with MetS was associated with poor clinical outcomes.