Do antibiotics interfere with the efficacy of oral contraceptives?

Among antibiotics, only rifampin has been demonstrated to interfere with the effectiveness of oral contraceptives (OCs) (strength of recommendation [SOR]: C, limited case series). There is little convincing evidence to show a systematic interaction between other antibiotics and oral contraceptive steroids (SOR: B, based on systematic reviews, case reports, and pharmacologic studies). However, current studies may not have separately evaluated the minority of women whose metabolism of contraceptive steroids makes them more vulnerable to OC failure. Given the significant consequences of unintended pregnancy, some experts recommend a conservative approach, including patient education and backup forms of birth control (SOR: C, expert opinion)

High Frequency of Extra-Pair Paternity in Eastern Kingbirds

Genetic parentage in the socially monogamous and territorial Eastern Kingbird( Tyrannust tyrannus) was examined in a central New York population by multilocus DNA fingerprinting. Extra-pair young were identified in 60% (12 of 20) of nests. Of the 64 nestlings profiled, 42% were sired by extra-pair males, but no cases of conspecific brood parasitism were detected. These results are markedly different from a previous electrophoretic study of the same species in a Michigan population, which reported 39% of nestlings were unrelated to one (typically the mother, quasiparasitismo)r both (conspecificb roodp arasitism) of the putative parents. In the New York population, extra-pairp aternityw as most common among females that returned to breed on a former territory. Among females that were new to a breeding territory, extrapair paternity increased directly with breeding density. Although the power of the tests was low, neither breeding synchrony nor male experience with a breeding territory appeared to be associated with the occurrence of extra-pair young

Fluorescence resonance energy transfer sensors for quantitative monitoring of pentose and disaccharide accumulation in bacteria

<p>Abstract</p> <p>Background</p> <p>Engineering microorganisms to improve metabolite flux requires detailed knowledge of the concentrations and flux rates of metabolites and metabolic intermediates <it>in vivo</it>. Fluorescence resonance energy transfer sensors represent a promising technology for measuring metabolite levels and corresponding rate changes in live cells. These sensors have been applied successfully in mammalian and plant cells but potentially could also be used to monitor steady-state levels of metabolites in microorganisms using fluorimetric assays. Sensors for hexose and pentose carbohydrates could help in the development of fermentative microorganisms, for example, for biofuels applications. Arabinose is one of the carbohydrates to be monitored during biofuels production from lignocellulose, while maltose is an important degradation product of starch that is relevant for starch-derived biofuels production.</p> <p>Results</p> <p>An <it>Escherichia coli </it>expression vector compatible with phage λ recombination technology was constructed to facilitate sensor construction and was used to generate a novel fluorescence resonance energy transfer sensor for arabinose. In parallel, a strategy for improving the sensor signal was applied to construct an improved maltose sensor. Both sensors were expressed in the cytosol of <it>E. coli </it>and sugar accumulation was monitored using a simple fluorimetric assay of <it>E. coli </it>cultures in microtiter plates. In the case of both nanosensors, the addition of the respective ligand led to concentration-dependent fluorescence resonance energy transfer responses allowing quantitative analysis of the intracellular sugar levels at given extracellular supply levels as well as accumulation rates.</p> <p>Conclusion</p> <p>The nanosensor destination vector combined with the optimization strategy for sensor responses should help to accelerate the development of metabolite sensors. The new carbohydrate fluorescence resonance energy transfer sensors can be used for <it>in vivo </it>monitoring of sugar levels in prokaryotes, demonstrating the potential of such sensors as reporter tools in the development of metabolically engineered microbial strains or for real-time monitoring of intracellular metabolite during fermentation.</p

Le Forum, Vol. 43 No. 1

https://digitalcommons.library.umaine.edu/francoamericain_forum/1099/thumbnail.jp

Noncoding deletions reveal a gene that is critical for intestinal function.

Large-scale genome sequencing is poised to provide a substantial increase in the rate of discovery of disease-associated mutations, but the functional interpretation of such mutations remains challenging. Here we show that deletions of a sequence on human chromosome 16 that we term the intestine-critical region (ICR) cause intractable congenital diarrhoea in infants1,2. Reporter assays in transgenic mice show that the ICR contains a regulatory sequence that activates transcription during the development of the gastrointestinal system. Targeted deletion of the ICR in mice caused symptoms that recapitulated the human condition. Transcriptome analysis revealed that an unannotated open reading frame (Percc1) flanks the regulatory sequence, and the expression of this gene was lost in the developing gut of mice that lacked the ICR. Percc1-knockout mice displayed phenotypes similar to those observed upon ICR deletion in mice and patients, whereas an ICR-driven Percc1 transgene was sufficient to rescue the phenotypes found in mice that lacked the ICR. Together, our results identify a gene that is critical for intestinal function and underscore the need for targeted in vivo studies to interpret the growing number of clinical genetic findings that do not affect known protein-coding genes

Developmental Localization and Methylesterification of Pectin Epitopes during Somatic Embryogenesis of Banana (Musa spp. AAA)

The plant cell walls play an important role in somatic embryogenesis and plant development. Pectins are major chemical components of primary cell walls while homogalacturonan (HG) is the most abundant pectin polysaccharide. Developmental regulation of HG methyl-esterification degree is important for cell adhesion, division and expansion, and in general for proper organ and plant development.Developmental localization of pectic homogalacturonan (HG) epitopes and the (1→4)-β-D-galactan epitope of rhamnogalacturonan I (RG-I) and degree of pectin methyl-esterification (DM) were studied during somatic embryogenesis of banana (Musa spp. AAA). Histological analysis documented all major developmental stages including embryogenic cells (ECs), pre-globular, globular, pear-shaped and cotyledonary somatic embryos. Histochemical staining of extracellularly secreted pectins with ruthenium red showed the most intense staining at the surface of pre-globular, globular and pear-shaped somatic embryos. Biochemical analysis revealed developmental regulation of galacturonic acid content and DM in diverse embryogenic stages. Immunodots and immunolabeling on tissue sections revealed developmental regulation of highly methyl-esterified HG epitopes recognized by JIM7 and LM20 antibodies during somatic embryogenesis. Cell walls of pre-globular/globular and late-stage embryos contained both low methyl-esterified HG epitopes as well as partially and highly methyl-esterified ones. Extracellular matrix which covered surface of early developing embryos contained pectin epitopes recognized by 2F4, LM18, JIM5, JIM7 and LM5 antibodies. De-esterification of cell wall pectins by NaOH caused a decrease or an elimination of immunolabeling in the case of highly methyl-esterified HG epitopes. However, immunolabeling of some low methyl-esterified epitopes appeared stronger after this base treatment.These data suggest that both low- and highly-methyl-esterified HG epitopes are developmentally regulated in diverse embryogenic stages during somatic embryogenesis. This study provides new information about pectin composition, HG methyl-esterification and developmental localization of pectin epitopes during somatic embryogenesis of banana

BTN3A2 Expression in Epithelial Ovarian Cancer Is Associated with Higher Tumor Infiltrating T Cells and a Better Prognosis

BTN3A2/BT3.2 butyrophilin mRNA expression by tumoral cells was previously identified as a prognostic factor in a small cohort of high grade serous epithelial ovarian cancer (HG-EOC). Here, we evaluated the prognostic value of BT3.2 at the protein level in specimen from 199 HG-EOC patients. As the only known role of butyrophilin proteins is in immune regulation, we evaluated the association between BT3.2 expression and intratumoral infiltration of immune cells by immunohistochemistry with specific antibodies against BT3.2, CD3, CD4, CD8, CD20, CD68 and CD206. Epithelial BT3.2 expression was significantly associated with longer overall survival and lower risk of disease progression (HR = 0.651, p = 0.006 and HR = 0.642, p = 0.002, respectively) and significantly associated with a higher density of infiltrating T cells, particularly CD4+ cells (0.272, p<0.001). We also observed a strong association between the relative density of CD206+ cells, as evaluated by the ratio of intratumoral CD206+/CD68+ expression, and risk of disease progression (HR = 1.355 p = 0.044, respectively). In conclusion, BT3.2 protein is a potential prognostic biomarker for the identification of HG-EOC patients with better outcome. In contrast, high CD206+/CD68+ expression is associated with high risk of disease progression. While the role of BT3.2 is still unknown, our result suggest that BT3.2 expression by epithelial cells may modulates the intratumoral infiltration of immune cells

Proposed Standards for Medical Education Submissions to the Journal of General Internal Medicine

To help authors design rigorous studies and prepare clear and informative manuscripts, improve the transparency of editorial decisions, and raise the bar on educational scholarship, the Deputy Editors of the Journal of General Internal Medicine articulate standards for medical education submissions to the Journal. General standards include: (1) quality questions, (2) quality methods to match the questions, (3) insightful interpretation of findings, (4) transparent, unbiased reporting, and (5) attention to human subjects’ protection and ethical research conduct. Additional standards for specific study types are described. We hope these proposed standards will generate discussion that will foster their continued evolution

Subsequent Surgery After Revision Anterior Cruciate Ligament Reconstruction: Rates and Risk Factors From a Multicenter Cohort

BACKGROUND: While revision anterior cruciate ligament reconstruction (ACLR) can be performed to restore knee stability and improve patient activity levels, outcomes after this surgery are reported to be inferior to those after primary ACLR. Further reoperations after revision ACLR can have an even more profound effect on patient satisfaction and outcomes. However, there is a current lack of information regarding the rate and risk factors for subsequent surgery after revision ACLR. PURPOSE: To report the rate of reoperations, procedures performed, and risk factors for a reoperation 2 years after revision ACLR. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: A total of 1205 patients who underwent revision ACLR were enrolled in the Multicenter ACL Revision Study (MARS) between 2006 and 2011, composing the prospective cohort. Two-year questionnaire follow-up was obtained for 989 patients (82%), while telephone follow-up was obtained for 1112 patients (92%). If a patient reported having undergone subsequent surgery, operative reports detailing the subsequent procedure(s) were obtained and categorized. Multivariate regression analysis was performed to determine independent risk factors for a reoperation. RESULTS: Of the 1112 patients included in the analysis, 122 patients (11%) underwent a total of 172 subsequent procedures on the ipsilateral knee at 2-year follow-up. Of the reoperations, 27% were meniscal procedures (69% meniscectomy, 26% repair), 19% were subsequent revision ACLR, 17% were cartilage procedures (61% chondroplasty, 17% microfracture, 13% mosaicplasty), 11% were hardware removal, and 9% were procedures for arthrofibrosis. Multivariate analysis revealed that patients aged <20 years had twice the odds of patients aged 20 to 29 years to undergo a reoperation. The use of an allograft at the time of revision ACLR (odds ratio [OR], 1.79; P = .007) was a significant predictor for reoperations at 2 years, while staged revision (bone grafting of tunnels before revision ACLR) (OR, 1.93; P = .052) did not reach significance. Patients with grade 4 cartilage damage seen during revision ACLR were 78% less likely to undergo subsequent operations within 2 years. Sex, body mass index, smoking history, Marx activity score, technique for femoral tunnel placement, and meniscal tearing or meniscal treatment at the time of revision ACLR showed no significant effect on the reoperation rate. CONCLUSION: There was a significant reoperation rate after revision ACLR at 2 years (11%), with meniscal procedures most commonly involved. Independent risk factors for subsequent surgery on the ipsilateral knee included age <20 years and the use of allograft tissue at the time of revision ACLR

Chromosome 3 Anomalies Investigated by Genome Wide SNP Analysis of Benign, Low Malignant Potential and Low Grade Ovarian Serous Tumours

Ovarian carcinomas exhibit extensive heterogeneity, and their etiology remains unknown. Histological and genetic evidence has led to the proposal that low grade ovarian serous carcinomas (LGOSC) have a different etiology than high grade carcinomas (HGOSC), arising from serous tumours of low malignant potential (LMP). Common regions of chromosome (chr) 3 loss have been observed in all types of serous ovarian tumours, including benign, suggesting that these regions contain genes important in the development of all ovarian serous carcinomas. A high-density genome-wide genotyping bead array technology, which assayed >600,000 markers, was applied to a panel of serous benign and LMP tumours and a small set of LGOSC, to characterize somatic events associated with the most indolent forms of ovarian disease. The genomic patterns inferred were related to TP53, KRAS and BRAF mutations. An increasing frequency of genomic anomalies was observed with pathology of disease: 3/22 (13.6%) benign cases, 40/53 (75.5%) LMP cases and 10/11 (90.9%) LGOSC cases. Low frequencies of chr3 anomalies occurred in all tumour types. Runs of homozygosity were most commonly observed on chr3, with the 3p12-p11 candidate tumour suppressor region the most frequently homozygous region in the genome. An LMP harboured a homozygous deletion on chr6 which created a GOPC-ROS1 fusion gene, previously reported as oncogenic in other cancer types. Somatic TP53, KRAS and BRAF mutations were not observed in benign tumours. KRAS-mutation positive LMP cases displayed significantly more chromosomal aberrations than BRAF-mutation positive or KRAS and BRAF mutation negative cases. Gain of 12p, which harbours the KRAS gene, was particularly evident. A pathology review reclassified all TP53-mutation positive LGOSC cases, some of which acquired a HGOSC status. Taken together, our results support the view that LGOSC could arise from serous benign and LMP tumours, but does not exclude the possibility that HGOSC may derive from LMP tumours