Advances in aldo-keto reductases immobilization for biocatalytic synthesis of chiral alcohols.

Chiral alcohols are essential building blocks of numerous pharmaceuticals and fine chemicals. Aldo-keto reductases (AKRs) constitute a superfamily of oxidoreductases that catalyze the reduction of aldehydes and ketones to their corresponding alcohols using NAD(P)H as a coenzyme. Knowledge about the crucial roles of AKRs immobilization in the biocatalytic synthesis of chiral alcohols is expanding. Herein, we reviewed the characteristics of various AKRs immobilization approaches, the applications of different immobilization materials, and the prospects of continuous flow bioreactor construction by employing these immobilized biocatalysts for synthesizing chiral alcohols. Finally, the opportunities and ongoing challenges for AKR immobilization are discussed and the outlook for this emerging area is analyzed.

Continuous Glucose Monitoring for Management of Type 2 Diabetes and Perinatal Outcomes.

OBJECTIVE: To evaluate the association between continuous glucose monitoring in pregnant people with type 2 diabetes and perinatal outcomes. METHODS: This was a retrospective cohort study of pregnant people with type 2 diabetes who received prenatal care and delivered singleton, nonanomalous neonates at a single academic tertiary care center from November 1, 2019, to February 28, 2023. The primary outcome was a composite of neonatal morbidity, including hypoglycemia, hyperbilirubinemia, shoulder dystocia, large for gestational age at birth, preterm birth, neonatal intensive care unit (NICU) admission, or perinatal death. Demographics and outcomes were compared by type of monitoring (continuous glucose monitoring vs intermittent self-monitoring of blood glucose), and multivariable logistic regression estimated the association between continuous glucose monitoring use and perinatal outcomes. RESULTS: Of 360 pregnant people who met the inclusion criteria, 82 (22.7%) used continuous glucose monitoring. The mean gestational age at continuous glucose monitoring initiation was 21.3±6.4 weeks. The use of continuous glucose monitoring was associated with lower odds of the primary composite neonatal morbidity (65.9% continuous glucose monitoring vs 77.0% self-monitoring of blood glucose, adjusted odds ratio [aOR] 0.48, 95% CI, 0.24-0.94). Continuous glucose monitoring use was also associated with lower odds of preterm birth (13.4% vs 25.2%, aOR 0.48, 95% CI, 0.25-0.93) and NICU admission (33.8% vs 47.6%, aOR 0.36, 95% CI, 0.16-0.81). CONCLUSION: In pregnant people with type 2 diabetes, continuous glucose monitoring use was associated with less neonatal morbidity, fewer preterm births, and fewer NICU admissions.

Sexual risk characteristics, social vulnerability, and anal cancer screening uptake among men living with HIV in the deep south.

ABSTRACTWithout standard guidelines, there is a critical need to examine anal cancer screening uptake in the South which has the highest HIV incidence in the U.S. We identified factors associated with screening among men living with HIV (MLHIV) at a large academic HIV outpatient clinic in Alabama. Relationships between sociodemographic, clinical, sexual risk characteristics and screening were examined using T-tests, Fisher's exact, Chi-square, and logistic regression analyses. Unadjusted and adjusted odds ratios (AOR) were computed to estimate the odds of screening. Among 1,114 men, 52% had received annual anal cytology (pap) screening. Men who were screened were more likely to have multiple sexual partners compared to men who were not screened (22.8% vs. 14.8%, p = 0.002). Among men with one partner, the youngest were almost five times more likely to be screened compared to middle-aged men (AOR = 4.93, 95% CI: 2.34-10.39). Heterosexual men had lower odds and men who reported unprotected anal sex had higher odds of screening. Our findings suggest a racial disparity, with older black MLHIV being the least likely to be screened. In the South, MLHIV who are older, black, heterosexual, or live in high social vulnerability counties may be less likely to receive annual anal cancer screening.

Human Papillomavirus Types and Cervical Cancer Screening among Female Sex Workers in Cameroon.

BACKGROUND: Female sex workers (FSWs) are at high risk for sexually transmitted infections (STIs), including infection with human papillomavirus (HPV) and cervical cancer due to occupational exposure. The objective of this study was to estimate the prevalence of HPV, HPV types, and precancerous lesions of the cervix among FSWs in Cameroon. MATERIAL AND METHODS: In this cross-sectional study, FSWs in Cameroon aged 30 years and above were screened for cervical cancer using high-risk HPV testing and genotyping and visual inspection with acetic acid and Lugol's iodine (VIA/VILI) enhanced using digital cervicography (DC) simultaneously. Those who were positive for VIA/VILI-DC were provided treatment with thermal ablation (TA) immediately for cryotherapy/TA-eligible lesions while lesions meeting the criteria for large loop excision of the transformation zone (LLETZ) were scheduled at an appropriate facility for the LLETZ procedure. HPV-positive FSWs without any visible lesion on VIA/VILI-DC were administered TA. Bivariate analyses were conducted to compare demographic and clinical characteristics. Crude and adjusted logistic regression models were computed for HPV infection status and treatment uptake as outcomes in separate models and their ORs and 95% confidence intervals (95% CI) were reported. RESULTS: Among the 599 FSWs aged 30 years and older that were screened for HPV and VIA/VILI-DC, 62.1% (95% CI: (0.58-0.66)) were positive for one or more HPV types. HPV type 51 had the highest prevalence (14%), followed by types 53 (12.4%) and 52 (12.2%). Type 18 had the lowest prevalence of 2.8% followed by type 16 with 5.2%. In the multivariable model, HIV-positive FSWs were 1.65 times more likely to be infected with HPV compared to their HIV-negative counterparts (AOR: 1.65, CI: 1.11-2.45). A total of 9.9% of the 599 FSWs were positive for VIA/VILI-DC. CONCLUSION: The prevalence of HPV infection among FSWs in Cameroon is higher than the worldwide pooled FSW prevalence. HPV types 51 and 53 were the most prevalent, while types 18 and 16 were the least prevalent. HIV status was the only variable that was significantly associated with infection with HPV.

Predicting peripartum infection in laboring patients at high risk in Cameroon, Africa.

OBJECTIVE: To develop a predictive model for peripartum infection among high risk laboring patients in Cameroon, Africa. STUDY DESIGN: We conducted a secondary analysis of the Cameroon Antibiotic Prophylaxis Trial (NCT03248297), a multicenter 3-arm double-blind randomized controlled trial of oral azithromycin ± amoxicillin among term pregnancies with prolonged labor or rupture of membranes in Cameroon 1/2018-5/2020. Patients with chorioamnionitis prior to randomization, study drug contraindications, or planned cesarean were excluded. The outcome of interest was a composite of maternal peripartum infection (chorioamnionitis, endometritis, sepsis by World Health Organization criteria, wound infection/abscess) diagnosed up to 6 weeks postpartum. Potential predictors were compared between patients with and without the composite outcome, and evaluated at a 0.05 alpha level. Statistically significant exposures were analyzed using multivariable regression (to generate adjusted odds ratios and 95 % confidence intervals) with backwards selection to generate a parsimonious model. Receiver operating characteristic curves with associated area under the curve assessed the model's predictive ability. A nomogram based on the final best fit multivariable model was constructed. RESULTS: Of 756 patients in the parent trial, 652 were analyzed: 45 (7 %) had peripartum infection. Those with infection were more likely to be nulliparous, lower education level, higher gestational age, receive antibiotics per hospital protocols, and undergo cesarean. In our best-fit multivariable model, none/primary education (vs university), cesarean birth, and antibiotic receipt per physician discretion (vs for cesarean prophylaxis) were significantly associated with increased infection risk. This model was moderately predictive (AUC = 0.75, 95 % CI 0.67-0.82). When using this 3 factor model, for a patient with a cesarean birth, receipt of antibiotics per physician discretion, and university education, the probability of peripartum infection was 35 % (95 % CI 0.11-0.73). CONCLUSIONS: While several variables such as parity are associated with infectious morbidity within 6 weeks among high risk laboring patients in Cameroon, only education level, antibiotic indication, and cesarean birth were independently associated, and a model including these 3 factors was moderately predictive. Validation of our findings in a larger population is warranted.

Factors associated with adherence to post-treatment follow-up among a cohort of women with acetic acid/Lugol's iodine positive lesions of the cervix in Cameroon: A retrospective cohort study.

Background: Women treated for cervical precancerous lesions have up to a 30 % increased risk of developing cervical cancer compared to women in the general population. The aim of this study was to identify predictors for adherence to follow-up among women treated for precancerous lesions of the cervix in Cameroon. Materials and Methods: The study design was a retrospective cohort analysis of a five-year follow-up for women in Cameroon who were initially treated for cervical precancer lesions in 2013. Logistic regression models were used to determine factors associated with adherence to post-treatment follow-up. Statistical significance was set at p < 0.05. Results: Of the 344 women treated in 2013, 154 (44.77 %) never returned for a single post-treatment follow-up in five years. Marital status was the only variable statistically significantly associated with 5-year post-treatment follow-up adherence. women who had ever been married were 0.36 times (0.14 0.93)); p = 0. 0.035] less likely to adhere to post-treatment follow-up compared to women who have never been married. Although age was not statistically significant, women in the age group 30-49 years had some significance and they were 60 % [aOR, 95 %CI: 0.40 (0.18 0.89); p = 0.024] less likely to adhere to post-treatment follow-up when compared to women who were<30 years. Conclusion: Only about half of the women treated for cervical precancer in this cohort returned for post-treatment follow-up. Conducting needs assessments among these populations that are less likely to adhere to follow-up will allow us to implement and test strategies to improve adherence to follow-up.

Variations in Genes Encoding Human Papillomavirus Binding Receptors and Susceptibility to Cervical Precancer.

BACKGROUND: Cervical cancer oncogenesis starts with human papillomavirus (HPV) cell entry after binding to host cell surface receptors; however, the mechanism is not fully known. We examined polymorphisms in receptor genes hypothesized to be necessary for HPV cell entry and assessed their associations with clinical progression to precancer. METHODS: African American women (N = 1,728) from the MACS/WIHS Combined Cohort Study were included. Two case-control study designs were used-cases with histology-based precancer (CIN3+) and controls without; and cases with cytology-based precancer [high-grade squamous intraepithelial lesions (HSIL)] and controls without. SNPs in candidate genes (SDC1, SDC2, SDC3, SDC4, GPC1, GPC2, GPC3, GPC4, GPC5, GPC6, and ITGA6) were genotyped using an Illumina Omni2.5-quad beadchip. Logistic regression was used to assess the associations in all participants and by HPV genotypes, after adjusting for age, human immunodeficiency virus serostatus, CD4 T cells, and three principal components for ancestry. RESULTS: Minor alleles in SNPs rs77122854 (SDC3), rs73971695, rs79336862 (ITGA6), rs57528020, rs201337456, rs11987725 (SDC2), rs115880588, rs115738853, and rs9301825 (GPC5) were associated with increased odds of both CIN3+ and HSIL, whereas, rs35927186 (GPC5) was found to decrease the odds for both outcomes (P value ≤ 0.01). Among those infected with Alpha-9 HPV types, rs722377 (SDC3), rs16860468, rs2356798 (ITGA6), rs11987725 (SDC2), and rs3848051 (GPC5) were associated with increased odds of both precancer outcomes. CONCLUSIONS: Polymorphisms in genes that encode binding receptors for HPV cell entry may play a role in cervical precancer progression. IMPACT: Our findings are hypothesis generating and support further exploration of mechanisms of HPV entry genes that may help prevent progression to cervical precancer.

Predicting Spontaneous Labor beyond 39 Weeks among Low-Risk Expectantly Managed Pregnant Patients.

OBJECTIVES: The aim of the study was to identify the characteristics associated with spontaneous labor onset in pregnant patients undergoing expectant management at greater than 39 weeks' gestation and delineate perinatal outcomes associated with spontaneous labor compared with labor induction. STUDY DESIGN: This was a retrospective cohort study of singleton pregnancies at ≥390/7 weeks' gestation delivered at a single center in 2013. The exclusion criteria were elective induction, cesarean delivery or presence of a medical indication for delivery at 39 weeks, more than one prior cesarean delivery, and fetal anomaly or demise. We evaluated prenatally available maternal characteristics as potential predictors of the primary outcome-spontaneous labor onset. Multivariable logistic regression was used to generate two parsimonious models: one with and one without third trimester cervical dilation. We also performed sensitivity analysis by parity and timing of cervical examination, and compared the mode of delivery and other secondary outcomes between patients who went into spontaneous labor and those who did not. RESULTS: Of 707 eligible patients, 536 (75.8%) attained spontaneous labor and 171 (24.2%) did not. In the first model, maternal body mass index (BMI), parity, and substance use were identified as the most predictive factors. Overall, the model did not predict spontaneous labor (area under the curve [AUC]: 0.65; 95% confidence interval [CI]: 0.61-0.70) with high accuracy. The addition of third trimester cervical dilation in the second model did not significantly improve labor prediction (AUC: 0.66; 95% CI: 0.61-0.70; p = 0.76). These results did not differ by timing of cervical examination or parity. Patients admitted in spontaneous labor had lower odds of cesarean delivery (odds ratio [OR]: 0.33; 95% CI: 0.21-0.53) and neonatal intensive care unit (NICU) admission (OR: 0.38; 95% CI: 0.15-0.94). Other perinatal outcomes were similar between the groups. CONCLUSION: Maternal characteristics did not predict spontaneous labor onset at ≥39 weeks' gestation with high accuracy. Patients should be counseled on the challenges of labor prediction regardless of parity and cervical examination, outcomes if spontaneous labor does not occur, and benefits of labor induction. KEY POINTS: · Majority of patients will attain spontaneous labor at ≥39 weeks.. · Maternal characteristics do not predict labor at ≥39 weeks.. · Spontaneous labor has associated lower perinatal risks.. · A shared decision model should be utilized in counseling patients who may choose expectant management..

RNA-seq analysis identifies transcriptomic profiles associated with anal cancer recurrence among people living with HIV.

BACKGROUND: Chemoradiation therapy (CRT) is the standard of care for squamous cell carcinoma of the anus (SCCA), the most common type of anal cancer. However, approximately one fourth of patients still relapse after CRT. METHODS: We used RNA-sequencing technology to characterize coding and non-coding transcripts in tumor tissues from CRT-treated SCCA patients and compare them between 9 non-recurrent and 3 recurrent cases. RNA was extracted from FFPE tissues. Library preparations for RNA-sequencing were created using SMARTer Stranded Total RNA-Seq Kit. All libraries were pooled and sequenced on a NovaSeq 6000. Function and pathway enrichment analysis was performed with Metascape and enrichment of gene ontology (GO) was performed with Gene Set Enrichment Analysis (GSEA). RESULTS: There were 449 differentially expressed genes (DEGs) observed (390 mRNA, 12 miRNA, 17 lincRNA and 18 snRNA) between the two groups. We identified a core of upregulated genes (IL4, CD40LG, ICAM2, HLA-I (HLA-A, HLA-C) and HLA-II (HLA-DQA1, HLA-DRB5) in the non-recurrent SCCA tissue enriching to the gene ontology term 'allograft rejection', which suggests a CD4+ T cell driven immune response. Conversely, in the recurrent tissues, keratin (KRT1, 10, 12, 20) and hedgehog signaling pathway (PTCH2) genes involved in 'Epidermis Development,', were significantly upregulated. We identified miR-4316, that inhibit tumor proliferation and migration by repressing vascular endothelial growth factors, as being upregulated in non-recurrent SCCA. On the contrary, lncRNA-SOX21-AS1, implicated in the progression of many other cancers, was also found to be more common in our recurrent compared to non-recurrent SCCA.Our study identified key host factors which may drive the recurrence of SCCA and warrants further studies to understand the mechanism and evaluate their potential use in personalized treatment.Key MessageOur study used RNA sequencing (RNA-seq) to identify pivotal factors in coding and non-coding transcripts which differentiate between patients at risk for recurrent anal cancer after treatment. There were 449 differentially expressed genes (390 mRNA, 12 miRNA, 17 lincRNA and 18 snRNA) between 9 non-recurrent and 3 recurrent squamous cell carcinoma of anus (SCCA) tissues. The enrichment of genes related to allograft rejection was observed in the non-recurrent SCCA tissues, while the enrichment of genes related to epidermis development was positively linked with recurrent SCCA tissues.

Coevolving stability and activity of LsCR by a single point mutation and constructing neat substrate bioreaction system.

Carbonyl reductase (CR)-catalyzed bioreduction in the organic phase and the neat substrate reaction system is a lasting challenge, placing higher requirements on the performance of enzymes. Protein engineering is an effective method to enhance the properties of enzymes for industrial applications. In the present work, a single point mutation E145A on our previously constructed CR mutant LsCRM3 , coevolved thermostability, and activity. Compared with LsCRM3 , the catalytic efficiency kcat /KM of LsCRM3 -E145A (LsCRM4 ) was increased from 6.6 to 21.9 s-1 mM-1 . Moreover, E145A prolonged the half-life t1/2 at 40°C from 4.1 to 117 h, T m ${T}_{m}$ was increased by 5°C, T 50 30 ${T}_{50}^{30}$ was increased by 14.6°C, and Topt was increased by 15°C. Only 1 g/L of lyophilized Escherichia coli cells expressing LsCRM4 completely reduced up to 600 g/L 2-chloro-1-(3,4-difluorophenyl)ethanone (CFPO) within 13 h at 45°C, yielding the corresponding (1S)-2-chloro-1-(3,4-difluorophenyl)ethanol ((S)-CFPL) in 99.5% eeP , with a space-time yield of 1.0 kg/L d, the substrate to catalyst ratios (S/C) of 600 g/g. Compared with LsCRM3 , the substrate loading was increased by 50%, with the S/C increased by 14 times. Compared with LsCRWT , the substrate loading was increased by 6.5 times. In contrast, LsCRM4 completely converted 600 g/L CFPO within 12 h in the neat substrate bioreaction system.

Study on regional differences and influencing factors of energy consumption in China.

Energy is becoming more and more important in the process of development. Through cluster analysis, 30 provinces chosen from the Chinese mainland are divided into high, medium, and low energy consumption regions, and the Theil index is used to analyze the characteristics of total energy consumption and other characteristics of regional differences. Based on this, an enhanced Panel-STIRPAT model is constructed. Through data and model inspection, panel models suitable for each region are selected for comprehensive analysis. The results show that: there are regional differences in energy consumption in China, and the total regional differences mainly come from within each region. The factors affecting energy consumption in different regions are the same, but due to differences in geographical environment and stress levels, the influence of these factors on energy consumption in different regions is different. Based on this, reasonable measurements to control energy consumption in different regions are presented.

How Accurate Is Oncologist Knowledge of Fertility Preservation Options, Cost, and Time in Female Adolescents and Young Adults?

Purpose: Often cited barriers to fertility preservation (FP) among female adolescent and young adult (AYA) cancer patients include cost and time. We hypothesized that oncologists overestimate the time and costs required for female FP. Methods: We distributed an electronic survey to physicians in oncology-related departments. The survey assessed the knowledge and utilization of gonadotoxic therapies, FP options and requirements, and FP referral patterns. Student's t, Fisher's exact, ANOVA, and Wilcoxon signed-rank tests were used for continuous variables as appropriate; the chi-squared test was used for categorical variables. Results: Among respondents who reported prescribing gonadotoxic agents to AYAs (n = 38), 79% reported often/always discussing FP options, while only half referred to a reproductive specialist often/always. A smaller proportion of pediatric oncologists discussed FP often/always (p = 0.04) and most referred <25% of patients to a reproductive specialist; however, the majority of other specialists referred ≥75% of patients to a reproductive specialist (p = 0.001). While most respondents accurately estimated the time required to complete FP, the majority overestimated the cost of an FP procedure. Knowledge of FP options was inconsistent, with 63.2% reporting that suppression of the hypothalamic-pituitary-ovarian-axis is an option for FP, with 82.6% of these classifying it as standard of care. Conclusions: With variation across specialties, most oncology specialists prescribing gonadotoxic therapies for AYA females discuss FP, while a smaller proportion refer patients for FP. Despite relative accuracy in estimating the time required for FP, they overestimate costs of FP. Educational curricula related to FP are necessary across oncology specialties, especially pediatric oncology.

Timing of Adjunctive Azithromycin for Unscheduled Cesarean Delivery and Postdelivery Infection.

OBJECTIVE: To estimate the association between timing of administration of adjunctive azithromycin for prophylaxis at unscheduled cesarean delivery and maternal infection and neonatal morbidity. METHODS: We conducted a secondary analysis of a randomized trial of adjunctive azithromycin prophylaxis in patients with singleton gestations who were undergoing unscheduled cesarean delivery. The primary exposure was the timing of initiation of the study drug (after skin incision or 0-30 minutes, more than 30-60 minutes, or more than 60 minutes before skin incision). The primary outcome was a composite of endometritis, wound infection, and other maternal infections occurring up to 6 weeks after cesarean delivery. Secondary outcomes included composite neonatal morbidity, neonatal intensive care unit admission for longer than 72 hours, and neonatal sepsis. The association of azithromycin with outcomes was compared within each antibiotic timing group and presented as risk ratios (RRs) with 95% CIs. A Breslow-Day homogeneity test was applied to assess differences in association by antibiotic timing. RESULTS: Of 2,013 participants, antibiotics were initiated after skin incision (median 3 minutes, range 0-229 minutes) in 269 (13.4%), 0-30 minutes before skin incision in 1,378 (68.5%), more than 30-60 minutes before skin incision in 270 (13.4%), and more than 60 minutes before skin incision (median 85 minutes, range 61-218 minutes) in 96 (4.8%). The RRs (95% CIs) of the infectious composite outcome for azithromycin compared with placebo were significantly lower for groups that initiated azithromycin after skin incision or within 1 hour before skin incision (after skin incision: RR 0.31, 95% CI 0.13-0.76; 0-30 minutes before: RR 0.62, 95% CI 0.44-0.89; more than 30-60 minutes before: 0.31, 95% CI 0.13-0.66). Risks were not significantly different in patients who received azithromycin more than 60 minutes before skin incision (RR 0.59, 95% CI 0.10-3.36). Results were similar when endometritis and wound infections were analyzed separately. Neonatal outcomes were not significantly different for azithromycin compared with placebo across all timing groups. CONCLUSION: Adjunctive azithromycin administration up to 60 minutes before or at a median of 3 minutes after skin incision was associated with reduced risks of maternal composite postoperative infection in unscheduled cesarean deliveries. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01235546.

Factors That Influence Posthospital Infant Feeding Practices Among Women Who Deliver at a Baby Friendly Hospital in Southern United States.

Introduction: The Baby Friendly Hospital Initiative has had a positive impact on breastfeeding initiation; however, little is known about posthospital infant feeding practices among women who deliver at baby friendly hospitals. Therefore we sought to evaluate posthospital breastfeeding outcomes among women who deliver at a baby friendly hospital (BFH) by (1) estimating exclusive breastfeeding rates at the postpartum visit (PPV), (2) quantifying the exclusive breastfeeding discontinuation rate, and (3) identifying which factors are associated with breastfeeding discontinuation. Methods: This was a prospective cohort study of women aged 14 and over, who delivered at the University of Alabama at Birmingham. The primary outcome was mode of infant feeding categorized as exclusive breastfeeding (EBF), combination breastfeeding and formula feeding (CF), and exclusive formula feeding (EFF) at the PPV. Secondary outcome was EBF discontinuation rate. Patients who initiated formula and/or who stopped breastfeeding were asked what influenced their decision. Results: At hospital discharge, 71.1% of the participants were EBF, 21.7% were CF, and 7.2% were EFF. At the PPV, the frequency of the primary outcome of EBF was 31.6% (95% confidence interval: 25.2-38.8); 34.6% (28.0-41.9) were CF, and 33.8% (27.3-41.1) were EFF. Therefore, the EBF absolute and relative discontinuation rates were 39.5% and 55.6%, respectively. No demographic factors, delivery characteristics, or maternal medical morbidities were associated with EBF in the multivariable logistic regression. However, women in the EBF group were more likely to report a workplace environment conducive to breastfeeding and partner and friend support. Conclusion: Significant breastfeeding discontinuation rates occur even among women who deliver at a BFH. Our findings suggest that multifactorial interventions, including a focus on the prevention of formula introduction, are needed in the early postpartum period to achieve higher EBF rates at the PPV.

Euglycemia after antenatal late preterm steroids: a multicenter, randomized controlled trial.

BACKGROUND: Late preterm steroid administration can induce transient maternal and thus fetal hyperglycemia, which can increase production of fetal insulin and C-peptide. Infants delivered in this setting are subsequently at increased risk for hypoglycemia. Although maternal glycemic control before delivery is a key component of care for parturients with diabetes, this intervention has not been studied in the setting of late preterm steroid administration. OBJECTIVE: This study aimed to determine the effect of maternal screening for and treatment of hyperglycemia after late preterm steroid administration on fetal C-peptide levels and other metabolic markers. STUDY DESIGN: This was a multicenter, randomized trial (NCT03076775) of nondiabetic parturients with a singleton gestation receiving betamethasone at 34 0/7 weeks to 36 5/7 weeks for anticipated preterm birth. Participants randomized to maternal glycemic control received fasting and 1-hour postprandial or serial intrapartum capillary blood glucose screening with insulin treatment as indicated. Those randomized to expectant management did not receive any glucose screening or treatment. The primary outcome was fetal C-peptide level measured from umbilical cord blood at delivery. Secondary outcomes included other fetal metabolic markers and neonatal hypoglycemia (glucose level <40 mg/dL). Baseline characteristics and outcomes were compared between the groups. We estimated that we would need a sample size of 144 to provide >90% power to show a 1 ng/mL decrease in C-peptide concentration (±1.5 ng/mL) at ⍺=0.05 using a 2-sample t test and 1 interim analysis. After the interim analysis, the trial was stopped for futility. RESULTS: Of 491 screened parturients, 163 (33%) were deemed eligible and 86 (53%) were randomized to 1 of the treatment groups (June 2017 to February 2021). One person was lost to follow-up because of delivery at another hospital. Baseline characteristics were similar between groups. The median interval from betamethasone administration to delivery was 24 hours (interquartile range, 13-96 hours) and did not differ between groups (P=.82). Most (82%) randomized to maternal glycemic control had hyperglycemia: 80% had at least 1 fasting glucose level >95 mg/dL, 75% had at least one 1-hour postprandial glucose level >140 mg/dL, and 80% had at least 1 intrapartum glucose level >110 mg/dL. In addition, 15% had at least 1 glucose level >180 mg/dL. None had maternal hypoglycemia after insulin treatment. Compared with expectant management, maternal glycemic control did not affect the median fetal C-peptide level (1.02; interquartile range, 0.52-1.85 vs 1.09; interquartile range, 0.61-1.65; P=.97) or other metabolic markers. Maternal glycemic control also did not affect neonatal hypoglycemia (49% vs 51%; P=.83) or other secondary neonatal or maternal outcomes. There was no evidence of effect modification by gestational age or body mass index at randomization, indication for betamethasone, duration from betamethasone to delivery, maternal race or ethnicity, or neonatal sex. In addition, the results were unchanged in a sensitivity analysis using a per-protocol approach. CONCLUSION: Maternal hyperglycemia was observed in most nondiabetic parturients after receiving late preterm betamethasone. However, there was no improvement in fetal metabolic status, neonatal hypoglycemia, or other neonatal or maternal outcomes with maternal glycemic control. Therefore, maternal glucose surveillance and treatment does not seem to be beneficial in nondiabetic parturients receiving late preterm steroids.

Effect of misoprostol on type 3 transformation zone of the cervix among Cameroonian women.

Background: Type 3 transformation zone (TZ) of the cervix has been shown to be associated with a four to five-fold increased risk of missed precancerous/cancerous lesions. The aim of this study was to evaluate the effect of intravaginal misoprostol on the TZ among women with Type 3 TZ in Cameroon. Materials and methods: A single dose of vaginal misoprostol (400 mcg or 600 mcg) was administered as part of the plan of care for women with Type 3 TZ during cervical cancer screening. The primary outcome was successful conversion from Type 3 TZ to Types 1 or 2 TZ. Descriptive analysis was performed using chi-square and Fisher's exact tests. Results: Among the 90 of 107 (84.2%) women who returned for re-evaluation of the cervix, 43 (47.8%, 95% CI: 0.36%-0.60%) had conversion of Type 3 TZ to Types 1 or 2. Women who received misoprostol 600 mcg were more likely to have their Type 3 TZs converted to Types 1 or 2 than women receiving 400 mcg (p = 0.037). Conclusion: Misoprostol converted approximately 50% of Type 3 TZ to Types 1 or 2 in Cameroon. Misoprostol is feasible in converting Type 3 TZ to Types 1 or 2 among Cameroonian women.

HSV-infection-related herpetic anogenital ulcer disease among PLWH in southeastern US: electronic medical record based analysis.

ObjectivesThe southeastern US is a domestic epicentre for incident HIV with high prevalence of herpes simplex virus (HSV) coinfection. We estimated the incidence rates (IR) of symptomatic herpetic anogenital ulcer disease (HAUD) and assessed its associations with demographic and clinical characteristics, specifically with immunological markers using median, nadir and trajectory CD4 counts. METHODS: Electronic medical records (EMR) of over 7000 people living with HIV (PLWH) attending one of the leading HIV clinics in the southeastern US between 2006 and 2018 were reviewed and analysed. IR of HSV-related HAUD were estimated per 10 000 person years. Joinpoint regressions were performed to examine temporal changes in the trends of IR. All IR and trends were stratified by gender and race. Six CD4 trajectory groups were constructed using the group-based trajectory modelling. Multivariable logistic models were conducted to assess the associations of CD4 counts (nadir, median CD4 and newly defined CD4 trajectory), separately with HAUD. RESULTS: Of the 4484 PLWH eligible individuals (3429 men, 1031 women and 24 transgender), we observed 425 patients with HSV-related HAUD. The mean log10viral load was higher in HAUD than HAUD-free groups, whereas the median nadir CD4 count (cells/uL) was higher in the non-cases than the case groups (p<0.05). HAUD were more frequent in women than men. Median CD4 (<200 cell/uL) was associated with HAUD (OR=2.1), but there were no significant associations with nadir CD4. Significant associations with declining and sustained low CD4 counts trajectory patterns were observed with HAUD. CONCLUSIONS: There were significant differences between men and women with incident HAUD among PLWH. EMR-based studies can provide innovative trajectory models that can potentially be helpful in guiding screening and clinical care of HAUD among high-risk PLWH.

How fluoroquinolone preauthorization affects third- and fourth-generation cephalosporin use and resistance in a large academic hospital.

OBJECTIVE: We observed an overall increase in the use of third- and fourth-generation cephalosporins after fluoroquinolone preauthorization was implemented. We examined the change in specific third- and fourth-generation cephalosporin use, and we sought to determine whether there was a consequent change in non-susceptibility of select Gram-negative bacterial isolates to these antibiotics. DESIGN: Retrospective quasi-experimental study. SETTING: Academic hospital. INTERVENTION: Fluoroquinolone preauthorization was implemented in the hospital in October 2005. We used interrupted time series (ITS) Poisson regression models to examine trends in monthly rates of ceftriaxone, ceftazidime, and cefepime use and trends in yearly rates of nonsusceptible isolates (NSIs) of select Gram-negative bacteria before (1998-2004) and after (2006-2016) fluoroquinolone preauthorization was implemented. RESULTS: Rates of use of ceftriaxone and cefepime increased after fluoroquinolone preauthorization was implemented (ceftriaxone RR, 1.002; 95% CI, 1.002-1.003; P < .0001; cefepime RR, 1.003; 95% CI, 1.001-1.004; P = .0006), but ceftazidime use continued to decline (RR, 0.991, 95% CI, 0.990-0.992; P < .0001). Rates of ceftazidime and cefepime NSIs of Pseudomonas aeruginosa (ceftazidime RR, 0.937; 95% CI, 0.910-0.965, P < .0001; cefepime RR, 0.937; 95% CI, 0.912-0.963; P < .0001) declined after fluoroquinolone preauthorization was implemented. Rates of ceftazidime and cefepime NSIs of Enterobacter cloacae (ceftazidime RR, 1.116; 95% CI, 1.078-1.154; P < .0001; cefepime RR, 1.198; 95% CI, 1.112-1.291; P < .0001) and cefepime NSI of Acinetobacter baumannii (RR, 1.169; 95% CI, 1.081-1.263; P < .0001) were increasing before fluoroquinolone preauthorization was implemented but became stable thereafter: E. cloacae (ceftazidime RR, 0.987; 95% CI, 0.948-1.028; P = .531; cefepime RR, 0.990; 95% CI, 0.962-1.018; P = .461) and A. baumannii (cefepime RR, 0.972; 95% CI, 0.939-1.006; P = .100). CONCLUSIONS: Fluoroquinolone preauthorization may increase use of unrestricted third- and fourth-generation cephalosporins; however, we did not observe increased antimicrobial resistance to these agents, especially among clinically important Gram-negative bacteria known for hospital-acquired infections.

What Women Really Think About Breastfeeding and Breast Pumping: A Qualitative Analysis of Women Who Deliver at a Baby-Friendly Hospital.

Introduction: The Baby-Friendly Hospital Initiative has had a positive impact on breastfeeding initiation; however, posthospital exclusive breastfeeding (EBF) rates remain low. We aimed to analyze thoughts and attitudes toward breastfeeding at the postpartum visit among women who deliver at a Baby-Friendly hospital. Methods: Women ≥14 years who delivered a live-born infant at our center were eligible. Participants completed an infant feeding questionnaire at the postpartum visit recording patient and delivery characteristics, antepartum care and infant feeding details, reasons for breastfeeding discontinuation or formula initiation, workplace environment, and cultural beliefs about breastfeeding. Thematic coding via line-by-line analysis of the free responses was performed using NVivo12 by QSR international. Results: Of 263 participants, 110 responded to the open-ended question. Of these, 53 and 46 were negative-toned and positive-toned, respectively. Negative breastfeeding responses related to the mother addressed the need for more support, low milk supply, pressure to breastfeed and feelings of guilt if unsuccessful, maternal health issues, painful breastfeeding, and high time requirements. Negative breastfeeding responses about the baby included concerns about infant health, latching issues, and disinterest. Positive responses focused on the support system, maternal weight loss, health benefits for baby, and mom-baby bonding. Some women (27) commented specifically on pumping. Negative comments noted that pumping led to less milk production, was time consuming, and was too much work. Positive comments about pumping noted that it is a convenient alternative to breastfeeding. Conclusion: Efforts to improve posthospital EBF rates in accordance with national guidelines must acknowledge the complex experience of breastfeeding mothers.

Single Dose of Oral Azithromycin With or Without Amoxicillin to Prevent Peripartum Infection in Laboring, High-Risk Women in Cameroon: A Randomized Controlled Trial.

OBJECTIVE: To compare the effectiveness of single-dose azithromycin, with or without amoxicillin, with placebo to prevent peripartum infection in laboring women. METHODS: We conducted a multicenter, three-group, double-blind randomized controlled trial of women with viable term nonanomalous pregnancies with either prolonged labor of 18 hours or longer or rupture of membranes for 8 hours or longer in Cameroon. Women with chorioamnionitis before randomization, study drug contraindications, or planned cesarean births were excluded. Women were randomized to oral azithromycin 1 g-placebo (group 1), oral azithromycin 1 g-oral amoxicillin 2 g (group 2), or placebo-placebo (group 3). All groups received usual care, including antibiotics given at the health care professional's discretion. The primary outcome was a composite of maternal peripartum infection or death from any cause up to 6 weeks postpartum. Two primary comparisons (group 1 vs group 3 and group 2 vs group 3) were planned. We estimated that 241 women per group (planning for 750 total) would provide 80% power at two-sided α=0.05 (0.025 per comparison) to detect a 50% effect size assuming 20% baseline composite infection rate. RESULTS: From January 6, 2018, to May 15, 2020, 6,531 women were screened, and 756 (253 in group 1, 253 in group 2, and 250 in group 3) were randomized. Baseline characteristics (including body mass index, duration of rupture of membranes or labor, and parity) were balanced across groups, except for maternal age. More than 60% of women in each group received usual-care antibiotics: more than 90% penicillin and approximately 50% for prolonged rupture of membranes across all study groups. Composite outcome incidences were similar in antibiotic groups 1 (6%) and 2 (7%) compared with placebo group 3 (10%) (RR 0.6, 95% CI 0.3-1.2; 0.7, 95% CI 0.4-1.3, respectively). Chorioamnionitis and wound infection were significantly lower in group 2 (3.2% vs 0.4% and 4% vs 0.8% respectively, both P=.02) compared with group 3. There were no differences in other maternal or neonatal outcomes including neonatal infection. CONCLUSION: A single dose of oral azithromycin with or without amoxicillin for prolonged labor or rupture of membranes at term did not reduce maternal peripartum or neonatal infection. Observed lower than expected infection rates and frequent usual-care antibiotic use may have contributed to these findings. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03248297. FUNDING SOURCE: Merck for Mothers Investigator Studies Program grant.