Activity of fosfomycin when tested against US contemporary bacterial isolates

Fosfomycin and comparators were susceptibility tested against over 2200 contemporary clinical isolates from US medical centers. Fosfomycin was active against Enterobacterales (MIC_50/90, 4/16?μg/mL), including multidrug-resistant isolates. Potent activity was exhibited against gram-positive organisms, including Staphylococcus aureus (MIC_50/90, 4/8?μg/mL). Fosfomycin may provide a promising alternative option for treatment of infections where resistant bacteria may occur.     

Activity of tedizolid against gram-positive clinical isolates causing infections in Europe and surrounding areas (2014–2015)

Activities of tedizolid and comparators were evaluated against gram-positive isolates responsible for skin and skin structure infections, pneumonia, and bloodstream infections. Non-duplicate gram-positive isolates (8011) were collected from 20 European countries/regions.

Tedizolid (0.12?mg/L) showed similar results of minimum inhibitory concentration required to inhibit the growth of 50% of organisms (MIC₅₀) regardless of pathogen/group or infection type, except for coagulase-negative staphylococci, Enterococcus faecalis, and viridans group streptococci (VGS), against which tedizolid had MIC₅₀ values of 0.06, 0.25, and 0.06?mg/L, respectively. Similar results of tedizolid MIC₅₀ and minimum inhibitory concentration required to inhibit the growth of 90% of organisms (MIC₉₀) (MIC_50/90, 0.12/0.12?mg/L) were obtained against methicillin-resistant Staphylococcus aureus and methicillin-susceptible S. aureus. Tedizolid, linezolid, and daptomycin were active against enterococci. Tedizolid (MIC₉₀, 0.12–0.25?mg/L), ceftaroline (MIC₉₀, 0.12?mg/L), and vancomycin (MIC₉₀, 0.25–0.5?mg/L) had the lowest MIC₉₀ values against Streptococcus pneumoniae and VGS, whereas ceftaroline (MIC₉₀, ≤0.015?mg/L), penicillin (MIC₉₀, ≤0.06?mg/L), ceftriaxone (MIC₉₀, ≤0.06–0.12?mg/L), and tedizolid (MIC₉₀, 0.12?mg/L) were the most potent against β-haemolytic streptococci.

Tedizolid displayed potent activity against gram-positive isolates from Europe, regardless of infection type.     

Breast milk transmission of flaviviruses in the context of Zika virus: A systematic review

Background

Since the Zika virus epidemic in the Americas began in 2015, Zika virus transmission has occurred throughout the Americas. However, limited information exists regarding possible risks of transmission of Zika virus and other flaviviruses through breast feeding and human milk. We conducted a systematic review of the evidence regarding flaviviruses detection in and transmission through milk, specifically regarding Zika virus, Japanese encephalitis virus, tick‐borne encephalitis virus, Powassan virus, West Nile virus, dengue virus, and yellow fever virus.

Methods

Medline, Embase, Global Health, CINAHL , Cochrane Library, Scopus, Popline, Virtual Health Library, and WorldCat were searched through June 2017. Two authors independently screened potential studies for inclusion and extracted data. Human and nonhuman (animal) studies describing: 1) confirmed or suspected cases of mother‐to‐child transmission through milk; or 2) the presence of flavivirus genomic material in milk.

Results

Seventeen studies were included, four animal models and thirteen observational studies. Dengue virus, West Nile virus, and Zika virus viral ribonucleic acid was detected in human milk, including infectious Zika virus and dengue virus viral particles. Human breast‐feeding transmission was confirmed for only yellow fever virus. There was evidence of milk‐related transmission of dengue virus, Powassan virus, and West Nile virus in animal studies.

Conclusions

Because the health advantages of breast feeding are considered greater than the potential risk of transmission, the World Health Organization recommends that mothers with possible or confirmed Zika virus infection or exposure continue to breast feed. This review did not identify any data that might alter this recommendation.

     

Systematic comparison of adeno‐associated virus and biotinylated dextran amine reveals equivalent sensitivity between tracers and novel projection targets in the mouse brain

As an anterograde neuronal tracer, recombinant adeno‐associated virus (AAV) has distinct advantages over the widely used biotinylated dextran amine (BDA). However, the sensitivity and selectivity of AAV remain uncharacterized for many brain regions and species. To validate this tracing method further, AAV (serotype 1) was systematically compared with BDA as an anterograde tracer by injecting both tracers into three cortical and 15 subcortical regions in C57BL/6J mice. Identical parameters were used for our sequential iontophoretic injections, producing injections of AAV that were more robust in size and in density of neurons infected compared with those of BDA. However, these differences did not preclude further comparison between the tracers, because the pairs of injections were suitably colocalized and contained some percentage of double‐labeled neurons. A qualitative analysis of projection patterns showed that the two tracers behave very similarly when injection sites are well matched. Additionally, a quantitative analysis of relative projection intensity for cases targeting primary motor cortex (MOp), primary somatosensory cortex (SSp), and caudoputamen (CP) showed strong agreement in the ranked order of projection intensities between the two tracers. A detailed analysis of the projections of two brain regions (SSp and MOp) revealed many targets that have not previously been described in the mouse or rat. Minor retrograde labeling of neurons was observed in all cases examined, for both AAV and BDA. Our results show that AAV has actions equivalent to those of BDA as an anterograde tracer and is suitable for analysis of neural circuitry throughout the mouse brain. J. Comp. Neurol. 522:1989–2012, 2014. © 2014 Wiley Periodicals, Inc.     

Cellular resolution anatomical and molecular atlases for prenatal human brains

Increasing interest in studies of prenatal human brain development, particularly using new single-cell genomics and anatomical technologies to create cell atlases, creates a strong need for accurate and detailed anatomical reference atlases. In this study, we present two cellular-resolution digital anatomical atlases for prenatal human brain at postconceptional weeks (PCW) 15 and 21. Both atlases were annotated on sequential Nissl-stained sections covering brain-wide structures on the basis of combined analysis of cytoarchitecture, acetylcholinesterase staining, and an extensive marker gene expression dataset. This high information content dataset allowed reliable and accurate demarcation of developing cortical and subcortical structures and their subdivisions. Furthermore, using the anatomical atlases as a guide, spatial expression of 37 and 5 genes from the brains, respectively, at PCW 15 and 21 was annotated, illustrating reliable marker genes for many developing brain structures. Finally, the present study uncovered several novel developmental features, such as the lack of an outer subventricular zone in the hippocampal formation and entorhinal cortex, and the apparent extension of both cortical (excitatory) and subcortical (inhibitory) progenitors into the prenatal olfactory bulb. These comprehensive atlases provide useful tools for visualization, segmentation, targeting, imaging, and interpretation of brain structures of prenatal human brain, and for guiding and interpreting the next generation of cell census and connectome studies.     

ASO Research Letter: Trends in Location of Death for Individuals with Pancreatic Cancer in the United States

Annals of Surgical Oncology -     

Uterine artery pulsatility index and serum BMP-9 predict resistance to methotrexate therapy in gestational trophoblastic neoplasia: A cohort study

Background: Methotrexate is the most common first-line chemotherapy for low-risk gestational trophoblastic neoplasia (GTN). Uterine artery pulsatility index (UAPI) is an ultrasound marker for tumor vascularity that has been associated with an increased risk of methotrexate resistance. The combination of circulating angiogenic factor levels with UAPI data may improve the capacity of this model to predict chemoresistance. Methods: This was a single-center cohort study of women newly diagnosed between January 2008 and June 2012 with low-risk GTN during postmolar surveillance and treated with single-agent methotrexate at Charing Cross Hospital, a UK national center for treatment of gestational trophoblastic disease. Two hundred seventeen women underwent an ultrasound for UAPI measurement prior to initiation of chemotherapy. To examine serologic markers of methotrexate resistance among this cohort, we performed a case-control study using archived serum from 76 patients who could be matched based on prognostic risk score. Serum samples were examined by immunoassay to measure 8 different angiogenic factors (VEGF-A, FGF-basic, PLGF-1, PDGF-BB, EGF, ANGPT2, BMP-9, and ENG). Receiver-operator characteristic area under the curve (AUC) values were calculated for the ability of each analyte to correctly classify patients as methotrexate sensitive (MTX-S) or resistant (MTX-R). Results: Total human chorionic gonadotropin levels were similar between the MTX-S and MTX-R groups. UAPI values were significantly higher in MTX-S (median 1.30 [interquartile range {IQR} = 0.80-1.90]) compared to MTX-R patients (median 0.875 [IQR = 0.60-1.30]; P < 0.0001) with AUC 0.68 (95% confidence interval 0.61-0.76; P < 0.0001). In univariate analysis, only BMP-9 concentrations were significantly different between groups, lower among MTX-S (median of 225 ng/L, IQR = 170-287) compared to MTX-R patients (median 280 ng/L [IQR = 200-339]; P= 0.03). Combining UAPI with BMP-9 concentration improved prediction for chemoresistance with AUC 0.77 (95% confidence interval 0.66-0.88; P < 0.0001). Conclusion: Circulating levels of BMP-9 are elevated in newly diagnosed women with low-risk GTN destined to fail primary methotrexate therapy. A combined test using serum BMP-9 plus UAPI might improve prediction of MTX-R in low-risk GTN.