Benzathine penicillin G stockouts and other barriers to documented syphilis treatment in pregnancy in Zambia.

OBJECTIVE: The prevalence of syphilis in Zambia remains high and is a critical public health concern. The Zambian Ministry of Health recommends universal screening and same-day treatment for syphilis in pregnancy, yet the syphilis screening rate is low, and treatment is poorly documented. The goal of this study was to document syphilis treatment rates and associated factors among pregnant women in care in Zambia. METHODS: This retrospective cohort study included pregnant women diagnosed with syphilis according to rapid plasma reagin (RPR) screening during routine antenatal care (ANC) in Lusaka, Zambia in 2018-2019. The main outcome of interest was lack of documented BPG treatment during pregnancy. Additional information about pregnancy and neonatal outcomes, partner referral for therapy, and facility level stockout data were included. Patient characteristics were compared by treatment status using Pearson Chi-Square Test and logistic regression models were created to estimate the association between individual level-factors, facility type, and lack of BPG treatment. A Cochran-Mantel-Haenszel test was used to evaluate facility-level data with significance set at p<0.05. RESULTS: Among 1,231 pregnant women who screened positive for syphilis at clinic, 643 (52%) lacked documented antibiotic treatment at the facility. BPG was the only antibiotic used to treat syphilis in the cohort and 8% of sex partners had evidence of referral for therapy. Preterm delivery rates were higher in women without documented BPG (43% vs 32%; p = 0.003). In adjusted models, only calendar year and hospital facility type were associated with lack of treatment. At the facility level, annual syphilis screening rates ranged from 37-65% and most (7/10) clinics reported at least one stockout of BPG. CONCLUSION: Treatment rates for syphilis in pregnancy in Zambia were low and BPG medication stockouts at the facility level were common. A consistent supply of BPG at all ANC facilities is needed to facilitate timely treatment and improve birth outcomes.

Association of Continuous Glucose Monitoring Metrics With Pregnancy Outcomes in Patients With Preexisting Diabetes.

OBJECTIVE: Continuous glucose monitoring (CGM) improves maternal glycemic control and neonatal outcomes in type 1 diabetes pregnancies compared with self-monitoring of blood glucose. However, CGM targets for pregnancy are based on expert opinion. We aimed to evaluate the association between CGM metrics and perinatal outcomes and identify evidence-based targets to reduce morbidity. RESEARCH DESIGN AND METHODS: This was a retrospective cohort study of pregnant patients with type 1 or 2 diabetes who used real-time CGM and delivered at a U.S. tertiary center (2018-2021). Multiple gestations, fetal anomalies, and early pregnancy loss were excluded. Exposures included time in range (TIR; 65-140 mg/dL), time above range (TAR), time below range (TBR), glucose variability, average glucose, and glucose management indicator. The primary outcome was a composite of fetal or neonatal mortality, large or small for gestational age at birth, neonatal intensive care unit admission, hypoglycemia, shoulder dystocia or birth trauma, and hyperbilirubinemia. Logistic regression estimated the association between CGM metrics and outcomes, and optimal TIR was calculated. RESULTS: Of 117 patients, 16 (13.7%) used CGM before pregnancy and 68 (58.1%) had type 1 diabetes. Overall, 98 patients (83.8%) developed the composite neonatal outcome. All CGM metrics, except TBR, were associated with neonatal morbidity. For each 5 percentage-point increase in TIR, there was 28% reduced odds of neonatal morbidity (odds ratio 0.72, 95% CI 0.58-0.89). The statistically optimal TIR was 66-71%. CONCLUSIONS: Nearly all CGM metrics were associated with adverse neonatal morbidity and mortality and may aid management of preexisting diabetes in pregnancy. Our findings support the American Diabetes Association recommendation of 70% TIR.

[Corrigendum] BCL­3 promotes the tumor growth of hepatocellular carcinoma by regulating cell proliferation and the cell cycle through cyclin D1.

Subsequently to the publication of the above article, the authors have alerted the Editorial Office to the fact that they identified a small number of errors concerning the assembly of Figs. 3A, 6B and 7A in their paper. Specifically, the western blotting results for the BCL­3 and GAPDH experiments in Fig. 3A, the cyclin D1 blots in Fig. 6B and the cyclin D1 blots shown in Fig. 7A were selected erroneously when choosing images from the total pool of data due to the similarity in the appearance of the data. However, the authors retained their access to the raw data, and were able to make the appropriate corrections required for these figures. The corrected versions of Figs. 3, 6 and 7, showing the correct BLC­3/GAPDH and cyclin D1 data in Fig. 3A and 6B respectively, and the correct cyclin D1 data in Fig. 7A, are shown on the next two pages. Note that these errors did not adversely affect the major conclusions reported in the study. The authors all agree to the publication of this corrigendum, and thank the Editor of Oncology Reports for allowing them the opportunity to publish this. The authors also apologize for any inconvenience caused. [Oncology Reports 35: 2382­2390, 2016; DOI: 10.3892/or.2016.4616].

Outpatient Foley Catheter for Induction of Labor in Obese Nulliparous Patients: A Secondary Analysis of OFFSITE II Randomized Controlled Trial.

OBJECTIVE: In the OFFSITE II randomized controlled trial, outpatient cervical ripening with a Foley catheter (CF) in nulliparous patients undergoing elective induction of labor (eIOL) shortened the time from admission to delivery. Given that patients with obesity have protracted labor and higher rates of failed IOL, we sought to determine if outpatient ripening with a CF may be even more beneficial for this high-risk group. STUDY DESIGN: We performed a secondary analysis of the OFFSITE II randomized controlled trial. For this analysis, all patients from the primary trial were classified by their intervention assignment (inpatient vs. outpatient) and also by their admission body mass index (BMI) class (BMI ≥ 30 and BMI < 30 kg/m2). The primary outcome was time from labor and delivery (L&D) admission to delivery. Secondary outcomes included cesarean delivery, time from admission to hospital discharge, and rates of clinically diagnosed chorioamnionitis and endometritis. RESULTS: In patients with BMI ≥ 30, the primary outcome, time from admission to delivery, (18.0 [13.5-20.9] vs. 20.4 [16.6-31.3] hours, p = 0.01), as well as total hospitalization length (3.2 [2.5-3.3] vs. 3.4 [3.1-4.3] days, p = 0.02) were shorter in the outpatient group. There were no differences in rates of chorioamnionitis or endometritis in outpatient compared with inpatient CF. Furthermore, in those with a BMI ≥ 30, the cesarean rate was significantly lower with outpatient CF (19.4% vs. 44.7%, p = 0.03); it was not statistically different in patients with BMI < 30. CONCLUSION: In this exploratory retrospective secondary analysis of the OFFSITE II randomized control trial, we found that in patients with BMI ≥ 30 undergoing eIOL, outpatient CF was associated with a lower time from L&D admission until delivery. This was also associated with a shorter time of total hospital duration and decreased the rate of cesarean, a benefit not detected in the overall analysis presented in the primary study. In nulliparas undergoing induction of labor, ripening with outpatient cervical Foley may even more significantly reduce labor duration, total hospital duration, and the rate of cesarean in patients with obesity. KEY POINTS: · Outpatient CF was associated with a lower time from L&D admission until delivery in obese nulliparas.. · Outpatient CF was associated with a shorter time of total hospital duration in obese nulliparas.. · Outpatient CF was associated with a decreased rate of cesarean birth in obese nulliparas..

Delivery timing for the opioid-exposed infant.

BACKGROUND: The prevalence of opioid use disorder and medication-assisted treatment in pregnancy is increasing. Compared with term infants, preterm infants have a lower incidence of neonatal opioid withdrawal syndrome. It is unknown whether early term delivery compared with full or late-term delivery decreases the risk of neonatal opioid withdrawal syndrome. OBJECTIVE: This study aimed to compare the neonatal outcomes among opioid-exposed infants born in the early, full, and late-term periods. STUDY DESIGN: This was a retrospective cohort study of opioid-exposed pregnancies delivering at a single center from 2010 to 2017 at ≥37 weeks gestation. Participants with multiple gestations or fetal anomalies were excluded. Maternal opioid exposure was defined as prescription (including medication-assisted treatment) or nonprescription opioid use or a positive urine drug screen in pregnancy for opiates. The primary outcome was a neonatal composite of respiratory distress syndrome, neonatal sepsis, neonatal seizures, hypoxic ischemic encephalopathy, jaundice requiring treatment, 5-minute Apgar <5, neonatal intensive care unit admission, neonatal opioid withdrawal syndrome, or neonatal death. The secondary outcomes included individual components of the primary outcome, birthweight, need for and length of neonatal opioid withdrawal syndrome treatment, length of hospital admission, and maximum Finnegan scores. Early (37-<39), full (39-<41), and late (41-<42 weeks) term groups were defined by the American College of Obstetricians and Gynecologists. RESULTS: Of 399 infants, 136 (34.1%), 229 (57.4%), and 34 (8.5%) were born in the early, full, and late-term periods, respectively. Two hundred and seventy patients (67.7%) received medication-assisted treatment for opioid use disorder, and the baseline characteristics were similar in all the groups except for history of intranasal heroin use, positive urine toxicology screen for heroin or any opiates, and delivery indication (P<.05). The primary composite outcome occurred in 313 (78.4%) neonates, and 296 (74.2%) neonates had neonatal opioid withdrawal syndrome. More than half (219 [54.9%]) of opioid-exposed neonates were admitted to the neonatal intensive care unit, and 160 (40.1%) required pharmacologic neonatal opioid withdrawal syndrome treatment for a mean duration of almost 3 weeks (19.0±16.1 days). There were no significant differences in the primary composite outcome, incidence of neonatal opioid withdrawal syndrome, or other secondary outcomes (except birthweight) between neonates born in the early, full, or late-term periods. CONCLUSION: Although neonatal morbidity was frequent among opioid-exposed neonates, the incidence and severity of neonatal opioid withdrawal syndrome or other neonatal outcomes were not different between neonates delivered in the early, full, and late-term periods, suggesting that opioid-exposed infants may not benefit from early term delivery.

The Impact of a 9-Month Booster Training Using Rapid Cycle Deliberate Practice on Pediatric Resident PALS Skills.

INTRODUCTION: The impact of booster training on pediatric resuscitation skills is not well understood. Rapid cycle deliberate practice (RCDP) to supplement pediatric advanced life support (PALS) training is beginning to be used to improve resuscitation skills. We tested the impact of booster RCDP training performed at 9 months after initial RCDP training on pediatric resuscitation skills of pediatric residents. OBJECTIVE: This study evaluated the impact of a 9-month RCDP booster training on PALS skills compared with usual practice debriefing (plus/delta) after an initial RCDP training session for PALS-certified pediatric interns. METHODS: All pediatric interns at a single institution were invited to a 45-minute RCDP training session after their initial PALS certification. The PALS performance score and times for key events were recorded for participants immediately before and after the RCDP training as well as 6, 9, and 12 months after the RCDP training. Learners were randomized to an RCDP intervention and usual practice (plus/delta) group. The intervention group received booster RCDP training after their 9-month assessment. RESULTS: Twenty eight of 30 residents participated in the initial training with 22 completing randomization at 9 months. There was no significant difference in 12-month PALS median performance scores after the booster training between the intervention and usual practice groups (83% vs. 94%, P = 0.31). There was significant improvement in PALS performance score from 51 ± 27% pre-initial RCDP assessment to 93 ± 5% post-initial RCDP training (P < 0.001). There were significant improvements in individual skills from pre- to post-initial RCDP testing, including time to verbalize pulseless, start compressions, and attach defibrillation pads (P < 0.001). CONCLUSIONS: Rapid cycle deliberate practice booster training versus plus/delta training at 9-month post-initial RCDP training did not alter 12-month performance. However, RCDP is effective at improving PALS performance skills, and this effect is maintained at 6, 9, and 12 months. Our study supports the importance of supplemental resuscitation training in addition to the traditional PALS course.

Outpatient Foley Catheter for Induction of Labor in Nulliparous Women: A Randomized Controlled Trial.

OBJECTIVE: To assess whether outpatient cervical ripening with a transcervical Foley catheter in nulliparous women undergoing elective labor induction shortens the time from admission to delivery. METHODS: We performed a randomized controlled trial of patients with singleton pregnancies undergoing elective labor induction at 39 weeks of gestation or more with a modified Bishop score less than 5. Women were randomized 1:1 to outpatient or inpatient transcervical Foley. In the outpatient group, the Foley was inserted the day before admission for scheduled induction; insertion was performed at scheduled admission in the inpatient group. The primary outcome was duration of time from admission to the labor and delivery unit to delivery. With 80% power and a two-sided α of 0.05, a sample size of 126 was estimated to detect at least a 5-hour mean difference in time from admission to delivery between groups from a baseline duration of 19±10 hours. RESULTS: From May 2018 to October 2019, 126 women were randomized, 63 in each group. Baseline characteristics were balanced between groups, except that body mass index (31±5.4 vs 34±7.5, P=.01) and group B streptococcus colonization (31% vs 54%, P=.01) were lower in the outpatient group. The time from admission to delivery was shorter in the outpatient group (17.4±7.4 vs 21.7±9.1 hours, P<.01, mean difference 4.3 hours, 95% CI 1.3-7.2). Admissions before scheduled induction were higher in the outpatient group (22% vs 5%, relative risk [RR] 4.7, 95% CI 1.4-15.4, P<.01), as was median modified Bishop score on admission (3 vs 1, P<.01). Cesarean delivery (24% vs 32%, RR 0.8, 95% CI 0.4-1.3, P=.32) and chorioamnionitis (22% vs 13%, RR 1.8, 95% CI 0.8-3.9, P=.16) were not significantly different between groups. CONCLUSION: In nulliparous patients undergoing elective labor induction at term, outpatient cervical ripening with a transcervical Foley catheter reduced the time from admission to delivery. CLINCAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03472937.

miR-615-3p promotes proliferation and migration and inhibits apoptosis through its potential target CELF2 in gastric cancer.

Gastric cancer incidence is relatively higher in China than that in developed countries; however, molecular mechanisms considering the initiation and progression of gastric cancer are still unclear. For decades, numerous microRNAs have been found to regulate a wide range of biological functions in gastric cancer. However, the oncogenic function of miR-615-3p in gastric cancer has not been reported to date. With the help of gene and microRNA chips in 10 patients, we were able to screen differential expressed genes and microRNAs compared with normal gastric tissues. After that, online bioinformatics analysis tools were used to predict microRNAs' potential targets. As a result, miR-615-3p and its potential target, CELF2, were selected for further experiments. QRT-PCR and western blot results indicated the aberrant high expression of miR-615-3p and low expression of CELF2 in gastric cancer both in vivo and in vitro. Moreover, miR-615-3p expression correlated to T and M stage. Up regulation of miR-615-3p inhibited the apoptosis, promoted proliferation and migration and led to the down-regulation of CELF2. Meanwhile, down-regulation of miR-615-3p resulted in anti-tumor effects. Immunochemistry staining of CELF2 showed its association with T, N and M stage. In addition, overexpression of CELF2 could reverse miR-615-3p's oncogenic functions stated before. These findings indicate that miR-615-3p promotes gastric cancer proliferation and migration by suppressing CELF2 expression for the first time, providing clues for future clinical practices.

P300/CBP-associated factor (PCAF) inhibits the growth of hepatocellular carcinoma by promoting cell autophagy.

Aberrant autophagic processes have been found to have fundamental roles in the pathogenesis of different kinds of tumors, including hepatocellular carcinoma (HCC). P300/CBP-associated factor (PCAF), a histone acetyltransferase (HAT), performs its function by acetylating both histone and non-histone proteins. Our previous studies showed that PCAF was downregulated in HCC tissues and its high expression was significantly associated with patient survival after surgery, serving as a prognostic marker. In this study we found that overexpression of PCAF induced autophagy of HCC cells and its knockdown depressed autophagy. As type II programmed cell death, autophagy induced by PCAF-elicited cell death in HCC cells. In vivo experiments confirmed that PCAF-induced autophagy inhibited tumor growth. Subsequent in vitro experiments showed that PCAF promoted autophagy by inhibiting Akt/mTOR signaling pathway. Our findings show that PCAF is a novel modulator of autophagy in HCC, and can serve as an attractive therapeutic strategy of HCC treatment.

[Over-expression of miR-141 inhibits the proliferation, invasion and migration of hepatocellular carcinoma MHCC-97H cells].

Objective To observe the expression level of miR-141 in tumor tissues of human hepatocellular carcinoma (HCC) and determine the effect of miR-141 level on cell proliferation, invasion and migration of MHCC-97H cells by upregulation of miR-141. Methods We checked the miR-141 expression level in HCC by real-time quantitative PCR and analyzed the relationship between the expression level of miR-141 and clinical pathological indicators as well as survival rate. MHCC-97H cells were transiently transfected with miR-141 mimics which were artificially synthesized. The proliferation of MHCC-97H cells was detected by MTT assay. Transwell(TM) assay was performed to examine the invasion and migration of MHCC-97H cells. The expression of erythropoietin-producing hepatocellular receptor A2 (EphA2), which was the potential downstream target, was determined by Western blotting and immunohistochemistry. Results The expression level of miR-141 in HCC tissues was significantly lower than that in the adjacent normal tissues, and it was obviously associated with TNM stage, portal vein infiltration and Edmondson degree. Patients in the lower miR-141 group had a worse 3-year survival than those in higher miR-141 group. Overexpression of miR-141 in MHCC-97H cells significantly suppressed cell proliferation, invasion and migration, and inhibited the protein expression of EphA2. Correlation analysis showed that miR-141 level was negatively correlated with EphA2 expression level. Conclusion miR-141 is down-regulated in HCC tissues and it is negatively correlated with EphA2 expression. Its low expression is correlated with the malignant clinical pathological features. miR-141 overexpression down-regulates EphA2 expression and subsequently inhibits the proliferation, invasion and migration of HCC cells.

MicroRNA-340 promotes the tumor growth of human gastric cancer by inhibiting cyclin G2.

Aberrant expression and function of microRNAs (miRNAs) play a critical role in the development and progression of various human cancers including gastric cancer. However, the clinical significance and underlying mechanisms of miR-340 remain largely unknown in gastric cancer. In the present study, we demonstrated that the expression of miR-340 was aberrantly elevated in both gastric cancer tissues and cells. Moreover clinical association analyses disclosed that the elevated level of miR-340 was significantly associated with unfavorable clinicopathological characteristics of the gastric cancer patients, such as poor differentiation, large tumor size and advanced tumor-node-metastasis (TNM) stage. Gastric cancer patients with high expression of miR-340 had prominently shorter overall survival and disease-free survival. Functionally, forced expression of miR-340 promoted cell viability, proliferation, colony formation and cell cycle progression in the SGC-7901 cells, while miR-340 silencing reduced cell viability, proliferation, colony formation and cell cycle progression in MGC-803 cells. Furthermore, in vivo experiments indicated that miR-340 knockdown suppressed the tumor growth of MGC-803 cells. Notably, alteration of miR-340 expression affected the luciferase activity of wild-type 3'-UTR of cyclin G2 (CCNG2) and regulated CCNG2 abundance in gastric cancer cells, indicating that CCNG2 is a direct target of miR-340. Moreover, CCNG2 knockdown eradicated the effects of miR-340 silencing on gastric cancer cells. In conclusion, our data suggest that miR-340 may potentially serve as a novel prognostic biomarker and therapeutic target for gastric cancer.

Long non-coding RNA TUSC7 acts a molecular sponge for miR-10a and suppresses EMT in hepatocellular carcinoma.

Despite advances in the roles of long non-coding RNA (lncRNA) tumor suppressor candidate 7 (TUSC7) in cancer biology, which has been identified as a tumor suppressor by regulating cell proliferation, apoptosis, migration, invasion, cell cycle, and tumor growth, the function of TUSC7 in hepatocellular carcinoma (HCC) remains unknown. In this study, we observed that the expression of TUSC7 was immensely decreased in HCC. Clinically, the lower expression of TUSC7 predicted poorer survival and may be an independent risk factor for HCC patients. Moreover, TUSC7 inhibited cell metastasis, invasion, and epithelial-to-mesenchymal transformation (EMT) through competitively binding miR-10a. Furthermore, we found that TUSC7 could decrease the expression of Eph tyrosine kinase receptor A4 (EphA4), a downstream target of miR-10a as well as an EMT suppressor, through TUSC7-miR-10a-EphA4 axis. Taken together, we demonstrate that TUSC7 suppresses EMT through the TUSC7-miR-10a-EphA4 axis, which may be a potential target for therapeutic intervention in HCC.

PCAF inhibits hepatocellular carcinoma metastasis by inhibition of epithelial-mesenchymal transition by targeting Gli-1.

UNLABELLED: The p300-CBP-associated factor (PCAF), other than its histone acetyltransferase (HAT) activity, possesses an intrinsic ubiquitination activity that is involved in various transcriptional regulators, including the transcription factor glioma-associated oncogene 1 (Gli1), a well-known regulator of epithelial-mesenchymal transition (EMT) in cancer. In present research, we detected that PCAF was down-regulated in hepatocellular carcinoma (HCC) tissues compared with the adjacent non-tumor tissues and significantly associated with malignant portal vein invasion (p < 0.05) and poor survival (p < 0.05) of HCC patients. Moreover, functional study demonstrated that downregulation of PCAF facilitated tumor cell migration, invasion via EMT. Further study found that Gli1 as a direct target of PCAF induced EMT and promoted tumor metastasis and invasion. CONCLUSION: PCAF is an anti-oncogene that plays an important role in the development of HCC by suppressing HCC cell metastasis and EMT by targeting Gli1, which indicates the potential therapeutic value of PCAF for suppression of metastasis of HCC.

BCL-3 promotes the tumor growth of hepatocellular carcinoma by regulating cell proliferation and the cell cycle through cyclin D1.

Previous studies have demonstrated the aberrant expression and oncogenic role of B-cell CLL/lymphoma-3 (BCL-3) in human malignancies. However, the clinical significance of BCL-3 and its biological function in human hepatocellular carcinoma (HCC) remain unknown. In the present study, the expression levels of BCL-3 protein and mRNA in 90 pairs of HCC and matched non-tumor tissues were analyzed using immunohistochemistry and reverse transcription­quantitative polymerase chain reaction (RT­qPCR). We found that the expression levels of BCL-3 protein and mRNA in HCC tissues were significantly higher than those in the matched tumor-adjacent tissues. In addition, positive expression of BCL-3 was associated with adverse clinicopathological characteristics of the HCC patients including hepatitis B virus (HBV) infection, tumor size, cirrhosis and advanced tumor-node-metastasis (TNM) stage. Moreover, HCC patients with positive expression of BCL-3 had significantly decreased 5-year overall survival and recurrence-free survival. Importantly, BCL-3 expression was an independent prognostic factor for indicating the survival of the HCC patients. Functionally, BCL-3 knockdown markedly inhibited cell viability, proliferation and cell cycle progression in HepG2 cells, while BCL-3 overexpression promoted these cellular processes in Huh7 cells. Accordingly, in vivo experiments indicated that BCL-3 knockdown prominently suppressed the tumor growth of HepG2 cells in nude mice. Mechanistically, we revealed that the expression of cyclin D1 was decreased after BCL-3 knockdown in the HepG2 cells and was increased after BCL-3 overexpression in the Huh7 cells. Cyclin D1 silencing was found to abrogate the functional effects of BCL-3 on cellular processes in Huh7 cells. Taken together, our data suggest that BCL-3 may serve as a promising biomarker and an effective therapeutic target of HCC.