Changes in Pneumococcal Serotypes and Antimicrobial Resistance after Introduction of the 13-Valent Conjugate Vaccine in the United States

Ongoing surveillance for Streptococcus pneumoniae is needed to assess the impact of the pneumococcal conjugate vaccine introduced in 2010 (PCV13). Forty-two U.S. centers submitted S. pneumoniae isolates between 1 October 2012 and 31 March 2013. Susceptibility testing was performed by use of a broth dilution method as recommended by the Clinical and Laboratory Standards Institute. Serotyping was performed by multiplex PCR and the Quellung reaction. Multidrug resistance (MDR) was defined as nonsusceptibility to penicillin (PNSP; MIC ≥ 0.12 μg/ml) combined with resistance to ≥2 non-β-lactam antimicrobials. Penicillin-resistant S. pneumoniae (PRSP) was defined as a penicillin MIC of ≥2 μg/ml. For the 1,498 isolates collected during 2012-13, the PRSP and MDR rates were 14.2 and 21.0%, respectively. These percentages were lower than rates obtained in a surveillance study conducted 4 years earlier in 2008-09 (17.0 and 26.6%, respectively). The most common serotypes identified in 2012-13 were 3, 35B, and 19A, each representing 9 to 10% of all isolates. The largest percentage of PNSP in 2012-13 were found in serotypes 35B (24.8%), 19A (23.5%), and 15A (10.3%). Predominant PRSP serotypes were 19A (54.5%), 35B (28.2%), and 19F (7.0%). Major MDR serotypes were 19A (38.5%), 15A (16.9%), 6C (8.3%), and 35B (6.4%). The change in prevalence of PCV13 serotypes (43.4 to 27.1%) was primarily due to a decrease in serotype 19A strains, i.e., 22% of all strains in 2008-09 to 10% of all strains in 2012-13. Among the PNSP subset, serotypes showing a proportional increase were 35B, 15B, and 23B. Among MDR strains, the largest proportional increases were observed in serotypes 35B, 15B, and 23A.     

Crack Propagation in As-Extruded and Heat-Treated Mg-Dy-Nd-Zn-Zr Alloy Explained by the Effect of LPSO Structures and Their Micro- and Nanohardness

The investigation of the crack propagation in as-extruded and heat-treated Mg-Dy-Nd-Zn-Zr alloy with a focus on the interaction of long-period stacking-ordered (LPSO) structures is the aim of this study. Solution heat treatment on a hot extruded Mg-Dy-Nd-Zn-Zr (RESOLOY^®) was done to change the initial fine-grained microstructure, consisting of grain boundary blocky LPSO and lamellar LPSO structures within the matrix, into coarser grains of less lamellar and blocky LPSO phases. C-ring compression tests in Ringer solution were used to cause a fracture. Crack initiation and propagation is influenced by twin boundaries and LPSO lamellae. The blocky LPSO phases also clearly hinder crack growth, by increasing the energy to pass either through the phase or along its interface. The microstructural features were characterized by micro- and nanohardness as well as the amount and location of LPSO phases in dependence on the heat treatment condition. By applying nanoindentation, blocky LPSO phases show a higher hardness than the grains with or without lamellar LPSO phases and their hardness decreases with heat treatment time. On the other hand, the matrix increases in hardness by solid solution strengthening. The microstructure consisting of a good balance of grain size, matrix and blocky LPSO phases and twins shows the highest fracture energy.     

An unusual presentation of a common infection

A 40-year-old Ghanaian woman presented with fever and exanthema. She had anemia, leukopenia, increased erythrocyte sedimentation rate (ESR), creatinin kinase, lactate dehydrogenase (LDH), and liver enzymes. She was diagnosed with schistosomiasis and was cured with praziquantel. During the following years, she developed polymyositis, chronic nephritis, and life-threatening perimyocarditis. High numbers of Epstein–Barr virus (EBV)-encoded RNA copies were demonstrated in CD8+ T-lymphocytes from endomyocardial biopsies. There was no evidence of any underlying immunosuppression or an EBV-related malignancy. Chronic active EBV infection was diagnosed, a clinical picture not described in an adult African previously. Interestingly, among all therapy attempts, only rituximab was effective at stabilizing the disease.     

Electrical impedance measurements of cochlear structures using the four-electrode reflection-coefficient technique

In individuals with severe-to-profound hearing loss, cochlear implants (CIs) bypass normal inner ear function by applying electrical current directly into the cochlea, thereby stimulating surviving auditory nerve fibers. Although cochlear implants are able to restore some auditory sensation, they are far from providing normal hearing. It has been estimated that up to 75% of the current injected via a CI is shunted along scala tympani and is not available to stimulate auditory neurons. The path of the injected current and the consequent population of stimulated spiral ganglion cells are dependent upon the positions of the electrode contacts within the cochlea and the impedances of cochlear structures. However, characterization of the current path remains one of the most critical, yet least understood, aspects of cochlear implantation. In particular, the impedances of cochlear structures, including the modiolus, are either unknown or based upon estimates derived from circuit models. Impedance values for many cochlear structures have never been measured. By combining the hemicochlea preparation, a cochlea cut in half along its mid-modiolar plane, and the four-electrode reflection-coefficient technique, impedances can be measured for cochlear tissues in a cochlear cross section including the modiolus. Advantages and disadvantages of the method are discussed in detail and electrical impedance measurements obtained in the gerbil hemicochlea are presented. The resistivity values for the cochlear wall in Ωcm are, 528 (range: 432–708) for scala media 3rd turn, 502 (range: 421–616) for scala tympani 3rd turn and scala vestibuli 2nd turn, 627 (range: 531–759) for scala media 2nd turn, 434 (range: 353–555) for scala tympani 2nd turn and scala vestibuli basal turn, 434 (range: 373–514) for scala media basal turn, and 590 (range: 546–643) for scala tympani basal turn. The resistivity was 455 Ωcm (range: 426–487) for the modiolus.     

Ausscheidung stickstoffhaltiger Substanzen im Urin ehemals hypotroph geborener dystropher Kleinkinder

Zusammenfassung Fragestellung: Etwa 25–30% der Kinder mit intrauteriner Wachstumsretardierung (Hypotrophie) zeigen auch in ihrer weiteren Entwicklung kein Aufholwachstum. Uns interessierte, wie die dystrophen, ehemals hypotroph geborenen Kleinkinder das Nahrungseiwei? utilisieren. Methode: Wir untersuchten die Gesamtstickstoff-, Harnstoff-, α-Amino-Stickstoff- und Ammoniakausscheidung im Urin bei 73 ehemals hypotroph geborenen Kindern im mittlerem Alter von 2,1 Jahren. Das durchschnittliche K?rpergewicht dieser Gruppe wurde mit 8,36 kg bestimmt, das entspricht einem mittleren SDS von –3,02. Ergebnisse: Diese Kinder schieden mit 20,8 mmol/kg KG/24 h nahezu die doppelte Stickstoffmenge aus wie die 37 normalgewichtigen eutroph geborenen Kinder der Vergleichsgruppe (10,6 mmol/kg KG/24 h). Offenbar war die Proteinutilisation bei den dystrophen, ehemals hypotroph geborenen Kindern auch im Alter von 2 Jahren eingeschr?nkt. Schlu?folgerung: Bei diesen Kindern würde eine Anreicherung der Nahrung mit Protein keinen positiven Effekt auf die weitere Entwicklung haben.      

Quantitative grading of a human blastocyst: optimal inner cell mass size and shape

Objective: To investigate the predictive value of quantitative measurements of blastocyst morphology on subsequent implantation rates after transfer.

Design: Prospective observational study.

Setting: Private assisted reproductive technology center.

Patient(s): One hundred seventy-four IVF patients receiving transfers of expanded blastocyst-stage embryos on day 5 (n = 112) or day 6 (n = 62) after oocyte retrieval.

Intervention(s): None.

Main Outcome Measure(s): Blastocyst diameter, number of trophectoderm cells, inner cell mass (ICM) size, ICM shape, and implantation and pregnancy rates.

Result(s): Blastocyst diameter and trophectoderm cell numbers were unrelated to implantation rates. Day 5 expanded blastocysts with ICMs of >4,500 μm² implanted at a higher rate than did those with smaller ICMs (55% vs. 31%). Day 5 expanded blastocysts with slightly oval ICMs implanted at a higher rate (58%) compared with those with either rounder ICMs (7%) or more elongated ICMs (33%). Implantation rates were highest (71%) for embryos with both optimal ICM size and shape. Pregnancy rates were higher for day 5 transfers of optimally shaped ICMs compared with day 5 transfers of optimally sized ICMs.

Conclusion(s): Quantitative measurements of the inner cell mass are highly indicative of blastocyst implantation potential. Blastocysts with relatively large and/or slightly oval ICMs are more likely to implant than other blastocysts.     

Failure to demonstrate postpartum functional iron deficiency using quantitative red blood cell analysis.

OBJECTIVE: The aim of this prospective study was to assess erythropoiesis and test for functional iron deficiency in the postpartum period using quantitative red blood cell analysis. STUDY DESIGN: Parameters were determined on admission for delivery and postpartum from 82 obstetric patients at Zurich University Hospital: full blood count, hypochromic and microcytic red cells, reticulocyte count (including subsets), reticulocyte mean corpuscular volume, reticulocyte mean hemoglobin content and reticulocyte mean corpuscular hemoglobin concentration. RESULTS: Microcytic cells increased from 0.9% prepartum to 1.4% on day 42 postpartum; hypochromic cells decreased from 4.3 to 1.9%; reticulocyte mean corpuscular volume decreased from 134 to 125 fl; reticulocyte mean hemoglobin content was unchanged. CONCLUSION: To our knowledge, this is the first medium scale application of quantitative red blood cell analysis to normal pre- and postpartum women. Our data show no evidence of functional iron deficiency or increased erythropoiesis in the postpartum period.     

Gene transfer improves erythroid development in ribosomal protein S19-deficient Diamond-Blackfan anemia

Diamond-Blackfan anemia (DBA) is a congenital bone marrow failure syndrome characterized by a specific deficiency in erythroid progenitors. Forty percent of the patients are blood transfusion-dependent. Recent reports show that the ribosomal protein S19 (RPS19) gene is mutated in 25% of all patients with DBA. We constructed oncoretroviral vectors containing the RPS19 gene to develop gene therapy for RPS19-deficient DBA. These vectors were used to introduce the RPS19 gene into CD34(+) bone marrow (BM) cells from 4 patients with DBA with RPS19 gene mutations. Overexpression of the RPS19 transgene increased the number of erythroid colonies by almost 3-fold. High expression levels of the RPS19 transgene improved erythroid colony-forming ability substantially whereas low expression levels had no effect. Overexpression of RPS19 had no detrimental effect on granulocyte-macrophage colony formation. Therefore, these findings suggest that gene therapy for RPS19-deficient patients with DBA using viral vectors that express the RPS19 gene is feasible.