Antimicrobial susceptibility of Gram-negative uropathogens isolated from obstetric patients.

OBJECTIVE: To evaluate the antimicrobial susceptibility of Gram-negative uropathogens isolated from pregnant women. METHODS: We performed a snapshot cohort study of women receiving care in the University of Florida prenatal clinics during March 2000. Subjects with asymptomatic bacteriuria or cystitis were identified and the antimicrobial susceptibility of each pathogen was recorded. Data were analyzed using chi-square, Fisher's exact test and ninety-five percent confidence intervals, as appropriate. RESULTS: Ninety-five positive cultures were identified. Isolates were more often susceptible to trimethoprim-sulfamethoxazole (TMP-SMX) (87%) and nitrofurantoin (89%) than to ampicillin (72%) (p < 0.03). Escherichia coli accounted for 71 (75%) cases and was more often susceptible to nitrofurantoin (100%) than to TMP-SMX (87%) (p < 0.01). Proteus isolates were all susceptible to TMP-SMX and resistant to nitrofurantoin (p < 0.01). CONCLUSIONS: Both TMP-SMX and nitrofurantoin are superior to ampicillin for empiric treatment of lower urinary tract infection in pregnant women. Nitrofurantoin is superior to TMP-SMX for treatment of infections caused by E. coli. For suspected or confirmed cases caused by Proteus organisms, TMP-SMX is the preferred agent

Assessment of the Value of Rescreening for Syphilis in the Third Trimester of Pregnancy

Objectives. Our aim is evaluating the need for repeating tests for syphilis on pregnant women in the third trimester. Study design. A single-center retrospective cohort study was performed on all women delivering 7/03–6/04. Results. During the study interval, 2244 women delivered at our hospital. Of those women having available records and attending at least one prenatal visit, 1940 (98.9%) were screened for syphilis at the first prenatal visit. Of the 1627 women beginning prenatal care prior to 27 weeks and delivering after 32 weeks, 1377 (84.6%) were rescreened in the third trimester. No cases of syphilis were identified with either the initial (upper limit of 95% CI 0.24%) or repeat (upper limit of 95% CI 0.34%) screening. Conclusions. In our obstetric population, syphilis is so uncommon that mandated prenatal screening on more than one occasion seems unjustified and laws requiring repeated screening should be reevaluated

Performance Characteristics of Putative Tests for Subclinical Chorioamnionitis

Objective: To evaluate amniotic fluid glucose, matrix metalloproteinase (MMP)-9, interleukin (IL)-6, and IL-12 for diagnosing subclinical chorioamnionitis in women with preterm labor. Methods: Forty-four women in preterm labor at 22–35 weeks gestation with suspected subclinical chorioamnionitis underwentamniocentesis.Amniotic fluid analysis included Gram stain, culture, and determination of glucose, MMP-9, IL-6, and IL-12 concentrations. Median values of these analytes were compared using the Mann-Whitney U test. Sensitivity, specificity, and positive and negative predictive values were calculated for tests using a positive amniotic fluid culture or delivery within 24 hours as the key outcome variables Results: Amniotic fluid concentrations of glucose, MMP-9, and IL-6 correlated closely with positive culture or delivery within 24 hours. IL-12 concentrations did not correlate with either a positive culture or delivery within 24 hours. Conclusions: Amniotic fluid glucose, MMP-9, and IL-6 reliably predict microbial invasion of the amniotic cavity or imminent delivery. IL-12 values did not correlate with amniotic fluid culture results or imminent delivery

The theory of agency and breastfeeding

Objective: In this paper, we apply psychological agency theory to women’s interviews of their breastfeeding experiences to understand the role of agency in relation to breastfeeding initiation, maintenance and duration. Design: Qualitative, video interviews were collected from 49 women in the UK from a wide range of ethnic, religious, educational and employment backgrounds about their breastfeeding experiences. We undertook secondary analysis of the data focusing on their accounts of vulnerability and agency. Findings: Women’s agency was impacted by a variety of factors including their own vulnerability, knowledge, expectations and experience, the feeding environment and the support of health professionals in sharing decision-making and dealing with uncertainty. Conclusion: Health professionals as co-agents with women are well positioned to maintain, enhance or restore women’s sense of agency. Breastfeeding goals should be included in women’s birth plans. Training related to agency, continuity of care, and staffing and workload management supported by national breastfeeding policies could improve breastfeeding rates and experiences

Is Perioperative Hypothermia a Risk Factor for Post-Cesarean Infection?

Objective: To determine whether hypothermia during Cesarean delivery is a risk factor for postoperative infection. Methods: An historical cohort investigation was conducted on all women delivered by Cesarean at our center during 2001. Initial recovery-room temperature, taken via the oral or axillary route, was used as a surrogate for intraoperative temperature. Adding 0.5(°)C to axillary temperatures generated oral temperature equivalents. Women with chorioamnionitis were excluded, as were those with an initial recovery-room temperature that exceeded 37.9(°)C or was recorded more than 20 minutes after the end of surgery. Prophylactic antibiotics (cefazolin, 1 g) were given during Cesarean delivery. Results: A total of 42 women (7.6%) were diagnosed with postoperative infections. Infections included endometritis (n= 25), wound abscess (n = 7), wound cellulitis (n = 7) and urinary tract infection (UTI) (n = 4). No cases of septic pelvic thrombophlebitis or pelvic abscess occurred. One woman had both endometritis and a UTI. Mean temperatures were higher, rather than lower, for women who subsequently had postoperative infections compared with those who did not (36.4 ± 0.8(°)Cvs. 35.9 ± 0.7(°)C; p < 0.001). Mean temperatures for the various postoperative infections were as follows: endometritis, 36.5 ± 0.8(°)C (p < 0.001 vs. uninfected group); wound abscess 36.0 ± 0.8(°)C (p = 0.63); wound cellulitis, 36.3 ± 0.6(°)C (p = 0.14); UTI, 36.7 ± 0.9(°)C (p = 0.04). Conclusions: Women who develop post-Cesarean infections have higher initial recovery-room temperatures than those who do not develop such infections. This suggests the presence of subclinical infection at the time of Cesarean. Evaluating whether intraoperative warming has any role during Cesarean delivery requires a randomized clinical trial

Intrapartum Antibiotic Prophylaxis and Early-Onset Neonatal Sepsis Patterns

Objective: To compare the relative effects of intrapartum antibiotic prophylaxis regimens on patterns of early-onset neonatal sepsis. Methods: We performed an historical cohort study of 17 187 infants born at our center from September 1993 to February 2000. A risk-based strategy was employed prior to July 1996 and a screening-based strategy was utilized thereafter. Ampicillin was utilized prior to March 1995 and penicillin was used thereafter. Results: There were 75 cases of neonatal sepsis, 34 (4.10/1000) in the risk-based era and 41 (4.63/1000) in the screening-based era (p = 0.62). There were fewer ampicillin-resistant isolates during the risk-based than the screening-based era (32 versus 61%; p = 0.014). The only significant change in organism-specific sepsis rates was an increase in the rate of infection caused by coagulase-negative staphylococci in the screening-based era (0.36 versus 1.46/1000; p = 0.018), but 75% of infants infected with these organisms were not exposed to ß-lactam antibiotics within 72 h prior to delivery. For the risk- and screening-based eras, respectively, the rates of Gram-negative sepsis (1.21 versus 1.46/1000; p = 0.65) and the proportions of Gram-negative pathogens that were ampicillin-resistant (70 versus 77%; p = 1.0) were similar. The drug employed for prophylaxis did not appear to affect the pattern of sepsis cases. Conclusion: In our patient population, coagulase-negative staphylococci have become the most common cause of early-onset neonatal sepsis. The cause of this shift in pathogen prevalence is uncertain and seemingly unrelated to intrapartum antibiotic exposure

Transmission and accumulation of CTL escape variants drive negative associations between HIV polymorphisms and HLA

Human immunodeficiency virus (HIV)-1 amino acid sequence polymorphisms associated with expression of specific human histocompatibility leukocyte antigen (HLA) class I alleles suggest sites of cytotoxic T lymphocyte (CTL)-mediated selection pressure and immune escape. The associations most frequently observed are between expression of an HLA class I molecule and variation from the consensus sequence. However, a substantial number of sites have been identified in which particular HLA class I allele expression is associated with preservation of the consensus sequence. The mechanism behind this is so far unexplained. The current studies, focusing on two examples of “negatively associated” or apparently preserved epitopes, suggest an explanation for this phenomenon: negative associations can arise as a result of positive selection of an escape mutation, which is stable on transmission and therefore accumulates in the population to the point at which it defines the consensus sequence. Such negative associations may only be in evidence transiently, because the statistical power to detect them diminishes as the mutations accumulate. If an escape variant reaches fixation in the population, the epitope will be lost as a potential target to the immune system. These data help to explain how HIV is evolving at a population level. Understanding the direction of HIV evolution has important implications for vaccine development

Interleukin-11 Is the Dominant IL-6 Family Cytokine during Gastrointestinal Tumorigenesis and Can Be Targeted Therapeutically

SummaryAmong the cytokines linked to inflammation-associated cancer, interleukin (IL)-6 drives many of the cancer “hallmarks” through downstream activation of the gp130/STAT3 signaling pathway. However, we show that the related cytokine IL-11 has a stronger correlation with elevated STAT3 activation in human gastrointestinal cancers. Using genetic mouse models, we reveal that IL-11 has a more prominent role compared to IL-6 during the progression of sporadic and inflammation-associated colon and gastric cancers. Accordingly, in these models and in human tumor cell line xenograft models, pharmacologic inhibition of IL-11 signaling alleviated STAT3 activation, suppressed tumor cell proliferation, and reduced the invasive capacity and growth of tumors. Our results identify IL-11 signaling as a potential therapeutic target for the treatment of gastrointestinal cancers

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

Taxonomy of prokaryotic viruses : 2017 update from the ICTV Bacterial and Archaeal Viruses Subcommittee

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