Intrapartum transperineal ultrasound as a predictor of instrumentation difficulty with vacuum-assisted delivery in primiparous women

Objectives: To assess the capability of different intrapartum transperineal ultrasound parameters to predict the difficulty of vacuum extraction. This is a prospective observational study performed between 04/2012 and 03/2013 on 72 primiparous-women, ≥37-weeks with singleton pregnancies at full dilatation that underwent transperineal ultrasound before vacuum placement for foetal extraction. Working in a transperineal longitudinal plane we evaluated: progression-angle, progression-distance and head direction; in a transverse plane: midline-angle and head-perineum distance. The vacuum extractions were classified as easy-group (EG) (≤3 vacuum pulls), difficult/impossible-group (DG)(≥4 pulls). Occiput-posterior presentations were not assessed.

Results: Fifty-two (52) patients were studied (26 patients per study group). No differences were observed in obstetric, neonatal or intrapartum characteristics between the study groups, with the following exceptions: new-born (NB) weight (3147?g versus 3540?g) and the number of vacuum pulls (1.4 EG versus 4.3 DG; p?<?0.0005). The progression angle was 133.1° (123°–143°) in EG and 109.2° (97.2°–121.2°) in DG (p?<?0.0005); up direction of foetal head was 88% versus 34.5% (p?<?0.0005); progression distance was 37?mm (26.6–47.4) versus 29.9?mm (8.8–51; p?=?0.003); midline angle was 35° (15.4°–54.6°) versus 59.7° (34.5°–84.9°; p?=?0.0005); head-perineum distance was 41.9?mm (35.2–48.6) versus 48.9?mm (40.5–57.3; p?=?0.017). The area under the Receiver Operating Characteristic (ROC) curve for the progression angle was 0.9 (95%CI, 0.82–0.99), and the midline angle was 0.8 (95%CI, 0.67–0.92).

Conclusion: If previous to the placement of the vacuum cup the progression angle is ≤120°, the foetal head direction is horizontal or down, and the midline angle is ≥35°, there is an 85% chance that the delivery will require more than 4 vacuum pulls.     

Identification of Plasmodium falciparum antigens by antigenic analysis of genomic and proteomic data

The recent explosion in genomic sequencing has made available a wealth of data that can now be analyzed to identify protein antigens, potential targets for vaccine development. Here we present, in the context of Plasmodium falciparum, a strategy that rapidly identifies target antigens from large and complex genomes. Sixteen antigenic proteins recognized by volunteers immunized with radiation-attenuated P. falciparum sporozoites, but not by mock immunized controls, were identified. Several of these were more antigenic than previously identified and well characterized P. falciparum-derived protein antigens. The data suggest that immune responses to Plasmodium are dispersed on a relatively large number of parasite antigens. These studies have implications for our understanding of immunodominance and breadth of responses to complex pathogens.     

Reproductive isolation revealed in preliminary crossbreeding experiments using field collected Triatoma dimidiata (Hemiptera: Reduviidae) from three ITS-2 defined groups

Triatoma dimidiata, a Chagas disease vector distributed in Mexico, Central America, Colombia, Venezuela, Peru and Ecuador, has been studied using genetic markers and four groups have been defined by ITS-2 sequences: 1A, 1B, 2 and 3. To gather evidence on the divergence and reproductive isolation among T. dimidiata ITS-2 groups, we carried out 15 crossbreeding experiments with field-collected sylvan and domestic T. dimidiata from Guatemala where three groups are found: 1A, 2 and 3. Reciprocal crosses between individuals from groups 1A and 2, and a cross between group 2 individuals from different habitats, produced an average 129.78 ± 42.29 eggs with hatching success ranging from 31.6 to 90.1%. The offspring of these crosses reached the adult stage, and crosses between F1 insects produced eggs. These results suggest that there are no pre- or post-zygotic reproductive barriers between groups 1A and 2, or within group 2. Crosses between group 3 females and males from groups 1A or 2 produced on average 85.67 ± 30.26 eggs and none of them hatched. These results support the existence of pre-zygotic barriers between T. dimidiata group 3 and groups 1A and 2. The group 3 individuals were collected in sylvatic environments in Yaxha, Peten, Guatemala. Previously, distinct chromosomal characteristics (cytotype 3) were described in individuals from this population. Based on this evidence we suggest that this population is divergent at the species level from other T. dimidiata populations.     

Epidemiology,antibiotic therapy and outcomes of bacteremia caused by drug-resistant ESKAPE pathogens in cancer patients

Purpose

Infection due to the six ESKAPE pathogens has recently been identified as a serious emerging problem. However, there is still a lack of information on bacteremia caused by these organisms in cancer patients. We aimed to assess the epidemiology, antibiotic therapy and outcomes of bacteremia due to drug-resistant ESKAPE pathogens (rESKAPE) in patients with cancer.

Methods

All episodes of bacteremia prospectively documented in hospitalized adults with cancer from 2006 to 2011 were analyzed.

Results

Of 1,148 episodes of bacteremia, 392 (34 %) were caused by ESKAPE pathogens. Fifty-four episodes (4.7 %) were due to rESKAPE strains (vancomycin-resistant Enterococcus faecium 0, methicillin-resistant Staphylococcus aureus (MRSA) 13, extended-spectrum beta-lactamase (ESLB)-producing Klebsiella pneumoniae 7, carbapenem-resistant Acinetobacter baumannii 4, carbapenem- and quinolone-resistant Pseudomonas aeruginosa 18 and derepression chromosomic ß-lactam and ESBL-producing Enterobacter species 12. Risk factors independently associated with rESKAPE bacteremia were comorbidities, prior antibiotic therapy, urinary catheter and urinary tract source. Inappropriate empirical antibiotic therapy was more frequent in patients with rESKAPE bacteremia than in the other cases (55.6 % vs. 21.5 %, p?<?0.001). Persistence of bacteremia (25 % vs. 9.7 %), septic metastasis (8 % vs. 4 %) and early case-fatality rate (23 % vs. 11 %) were more frequent in patients with rESKAPE bacteremia than in patients with other etiologies (p?<?0.05).

Conclusions

Bacteremia due to rESKAPE pathogens in cancer patients occurs mainly among those with comorbidities who have received prior antibiotic therapy and have a urinary tract source. These patients often receive inappropriate empirical antibiotic therapy and have a poor outcome.     

Changes in blood cell membrane properties in HIV type-1-infected patients

To evaluate the possible HIV-1 infection-induced changes in cell membrane properties and in calcium signaling, membrane fluidity, acetylcholinesterase (AChE, a glycosylphosphatidylinositol-anchored protein) activity, and intracellular calcium concentration ([Ca2(+)](int)) were evaluated in lymphocytes and erythrocytes of infected individuals, previous to their engagement in antiretroviral therapy. Membrane fluidity was assessed by fluorescence spectroscopy measurements, using the fluorescence probes 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-[4-(trimethylamino)-phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH). AChE activity was determined by the colorimetric Ellman's method and [Ca2(+)](int) using the fluorescent fura-2 acetoxymethyl ester. When compared with the control group, lymphocytes of infected patients presented significantly decreased membrane fluidity, decreased AChE activity, and increased [Ca2(+)](int). Erythrocytes from HIV-infected patients presented decreased [Ca2(+)](int) when compared with the control group and decreased membrane fluidity near the lipid/water interface. Our data show that HIV-1 infection leads to biochemical and biophysical changes in the membrane itself and in membrane protein activity in lymphocytes (average of infected and noninfected subpopulations) and even in erythrocytes. The present observations are in agreement with a process of facilitated propagation of the infection to new cells, stimulation of virion production, and maintenance of a reservoir of erythrocyte-bound infectious virus.     

Modulation of cardiomyocyte electrical properties using regulated bone morphogenetic protein-2 expression

Because cardiomyocytes lose their ability to divide after birth, any subsequent cell loss or dysfunction results in pathologic cardiac rhythm initiation or impulse conduction. Strategies to restore and control the electrophysiological activity of the heart may, therefore, greatly affect the regeneration of cardiac tissue functionality. Using lentivirus-derived particles to regulate the bone morphogenetic protein-2 (BMP-2) gene expression in a pristinamycin- or gaseous acetaldehyde-inducible manner, we demonstrated the adjustment of cardiomyocyte electrophysiological characteristics. Complementary metal oxide semiconductor-based high-density microelectrode arrays (HD-MEAs) were used to monitor the electrophysiological activity of neonatal rat cardiomyocytes (NRCs) cultured as monolayers (NRCml) or as microtissues (NRCmt). NRCmt more closely resembled heart tissue physiology than did NRCml and could be conveniently monitored using HD-MEAs because of their ability to detect low-signal events and to sub-select the region of interest, namely, areas where the microtissues were placed. Cardiomyocyte-forming microtissues, transduced using lentiviral vectors encoding BMP-2, were capable of restoring myocardial microtissue electrical activity. We also engineered NRCmt to functionally couple within a cardiomyocyte monolayer, thus showing pacemaker-like activity upon local regulation of transgenic BMP-2 expression. The controlled expression of therapeutic transgenes represents a crucial advance for clinical interventions and gene-function analysis.     

Ectopic expression of delta FBJ murine osteosarcoma viral oncogene homolog B mediates transdifferentiation of adipose-like spheroids into osteo-like microtissues

Differentiation and transdifferentiation strategies have a large role in the manipulation of cells in replacing dysfunctional cells and tissues. We developed adipose-like microtissues using gravity-enforced self-assembly of monodispersed human primary preadipocytes to determine their transdifferentiation capacity to form bone-like tissues. Using lentivirus-derived particles to induce ectopic bone morphogenetic protein (BMP)-2 and delta FBJ murine osteosarcoma viral oncogene homolog B (DeltaFosB) gene expression, we demonstrated a time-dependent induction of osteoblast-specific genes and properties such as calcium deposits, bone-like extracellular matrix (ECM), and matrix mineralization. DeltaFosB was able to trigger partial Pref-1-mediated de-differentiation of adipocytes, which also retained their adipocytic cell phenotype. Osteoblast-specific structures could be co-localized in the ECM of lipid-containing cells analyzed using immunofluorescence and transmission electron microscopy when BMP-2 and DeltaFosB were co-expressed, suggesting that differentiated adipocytes are able to transdifferentiate into osteoblasts via a transient hybrid adipocyte-preadipocyte-osteoblast cell phenotype. Microtissues transgenic for BMP-2 and DeltaFosB expression were able to reproduce bone matrix, which occurs to a lesser extent in conventional two-dimensional (2D) cultures but is known to play a decisive role in the development and function of bone in vivo. This demonstrates that ECM-inclusive studies are essential for future characterization assays. Therefore, 3D cultures provide a superior ex vivo system for the improved characterization of phenotypical and functional alterations resulting from interventions directed toward differentiation processes. Precise control of transdifferentiation of adipocytes into osteoblasts in a 3D culture mimicking in vivo tissue conditions as closely as possible will foster important advances in regenerative medicine and tissue engineering.