Blastocyst development after sperm selection at high magnification is associated with size and number of nuclear vacuoles

Spermatozoa selection at high magnification before intracytoplasmic sperm injection seems to be positively associated with pregnancy rates after day 3 embryo transfers. The aim was to demonstrate an association between the presence of vacuoles in sperm nuclei and the competence of embryos to develop to day 5. Grading of spermatozoa at x 6000-x 12,500 magnification: grade I, no vacuoles; grade II, or=1 large vacuole; grade IV, large vacuoles with other abnormalities. The outcome of embryo development in a group of 25 patients after sibling oocyte injection with the four different grades of spermatozoa showed no significant difference in embryo quality up to day 3. However, the occurrence of blastocyst formation was 56.3 and 61.4% with grade I and II spermatozoa respectively, compared with 5.1% with grade III and 0% with grade IV respectively (P < 0.001). Spermatozoa selection at high magnification using Nomarski interference contrast is useful to identify more precisely the size and the number of nuclear vacuoles that greatly exert a negative effect on embryo development to the blastocyst stage. These observations confirm previous studies pointing to possible 'early and late paternal effects', both of which may have an impact on early embryonic development.     

Mutational spectrum of ATRX aberrations in neuroblastoma and associated patient and tumor characteristics

Neuroblastoma is the most common extracranial solid tumor in children. The chromatin remodeler ATRX is frequently mutated in high‐risk patients with a poor prognosis. Although many studies have reported ATRX aberrations and the associated clinical characteristics in neuroblastoma, a comprehensive overview is currently lacking. In this study, we extensively characterize the mutational spectrum of ATRX aberrations in neuroblastoma tumors reported in previous studies and present an overview of patient and tumor characteristics. We collected the data of a total of 127 neuroblastoma patients and three cell lines with ATRX aberrations originating from 20 papers. We subdivide the ATRX aberrations into nonsense, missense, and multiexon deletions (MEDs) and show that 68% of them are MEDs. Of these MEDs, 75% are predicted to be in‐frame. Furthermore, we identify a missense mutational hotspot region in the helicase domain. We also confirm that all three ATRX mutation types are more often identified in patients diagnosed at an older age, but still approximately 40% of the patients are aged 5 years or younger at diagnosis. Surprisingly, we found that 11q deletions are enriched in neuroblastomas with ATRX deletions compared to a reference cohort, but not in neuroblastomas with ATRX point mutations. Taken together, our data emphasizes a distinct ATRX mutation spectrum in neuroblastoma, which should be considered when studying molecular phenotypes and therapeutic strategies.     

Analysis of Mechanical Properties Related to Fiber Length of Closed-Loop-Recycled Offcuts of a Thermoplastic Fiber Composites (Organo Sheets)

Increasing demand for energy-efficient means of transport has steadily intensified the trend towards lightweight components. Thermoplastic glass fiber composites (organo sheets) play a major role in the production of functional automotive components. Organo sheets are cut, shaped and functionalized by injection molding to produce hybrid components, such as those used in car door modules. The cutting process produces a considerable amount of production waste, which has thus far been thermally recycled. This study develops a closed mechanical recycling process and analyzes the different steps of the process. The offcuts were shredded using two shredding methods and implemented directly in the injection-molding process. Using tensile tests and impact bending tests, the material properties of the recycled materials were compared with the virgin material. In addition, fiber length degradation via the injection-molding process and the influence of the waterjet-cutting process on the mechanical properties are investigated. Recycled offcuts are both comparable to new material in terms of mechanical properties and usability, and are also economically and ecologically advantageous. Recycling polypropylene waste with glass fiber reinforcement in a closed loop is an effective way to reduce industrial waste in a sustainable and economical production process.     

Material differentiation by dual energy CT: initial experience

The aim of this study was to assess the feasibility of a differentiation of iodine from other materials and of different body tissues using dual energy CT. Ten patients were scanned on a SOMATOM Definition Dual Source CT (DSCT; Siemens, Forchheim, Germany) system in dual energy mode at tube voltages of 140 and 80 kVp and a ratio of 1:3 between tube currents. Weighted CT Dose Index ranged between 7 and 8 mGy, remaining markedly below reference dose values for the respective body regions. Image post-processing with three-material decomposition was applied to differentiate iodine or collagen from other tissue. The results showed that a differentiation and depiction of contrast material distribution is possible in the brain, the lung, the liver and the kidneys with or without the underlying tissue of the organ. In angiographies, bone structures can be removed from the dataset to ease the evaluation of the vessels. The differentiation of collagen makes it possible to depict tendons and ligaments. Dual energy CT offers a more specific tissue characterization in CT and can improve the assessment of vascular disease. Further studies are required to draw conclusions on the diagnostic value of the individual applications.     

Adjuvant capecitabine-containing chemotherapy benefit and homologous recombination deficiency in early-stage triple-negative breast cancer patients

Background The addition of adjuvant capecitabine to standard chemotherapy of early-stage triple-negative breast cancer (TNBC) patients has improved survival in a few randomised trials and in meta-analyses. However, many patients did not benefit. We evaluated the BRCA1-like DNA copy number signature, indicative of homologous recombination deficiency, as a predictive biomarker for capecitabine benefit in the TNBC subgroup of the FinXX trial.Methods Early-stage TNBC patients were randomised between adjuvant capecitabine-containing (TX + CEX: capecitabine-docetaxel, followed by cyclophosphamide-epirubicin-capecitabine) and conventional chemotherapy (T + CEF: docetaxel, followed by cyclophosphamide-epirubicin-fluorouracil). Tumour BRCA1-like status was determined on low-coverage, whole genome next-generation sequencing data using an established DNA comparative genomic hybridisation algorithm.Results For 129/202 (63.9%) patients the BRCA1-like status could be determined, mostly due to lack of tissue. During a median follow-up of 10.7 years, 35 recurrences and 32 deaths occurred. Addition of capecitabine appears to improve recurrence-free survival more among 61 (47.3%) patients with non-BRCA1-like tumours (HR 0.23, 95% CI 0.08–0.70) compared to 68 (52.7%) patients with BRCA1-like tumours (HR 0.66, 95% CI 0.24–1.81) (P-interaction = 0.17).Conclusion Based on our data, patients with non-BRCA1-like TNBC appear to benefit from the addition of capecitabine to adjuvant chemotherapy. Patients with BRCA1-like TNBC may also benefit. Additional research is needed to define the subgroup within BRCA1-like TNBC patients who may not benefit from adjuvant capecitabine.Subject terms: Breast cancer, Translational research, Predictive markers, Breast cancer     

Cholera Vaccination in Urban Haiti

Successful and sustained efforts have been made to curtail the major cholera epidemic that occurred in Haiti in 2010 with the promotion of hygiene and sanitation measures, training of health personnel and establishment of treatment centers nationwide. Oral cholera vaccine (OCV) was introduced by the Haitian Ministry of Health as a pilot project in urban and rural areas. This paper reports the successful OCV pilot project led by GHESKIO Centers in the urban slums of Port-au-Prince where 52,357 persons received dose 1 and 90.8% received dose 2; estimated coverage of the at-risk community was 75%. This pilot study demonstrated the effort, community mobilization, and organizational capacity necessary to achieve these results in a challenging setting. The OCV intervention paved the way for the recent launching of a national cholera vaccination program integrated in a long-term ambitious and comprehensive plan to address Haiti''s critical need in water security and sanitation.     

On the variety of cell death pathways in the Lurcher mutant mouse

Apoptosis as well as autophagy have been implicated in the death of cerebellar Purkinje cells (PCs) in the Lurcher (Lc/+) mutant mouse and at least two different apoptotic pathways participate in the transsynaptic death of granule cells (GC) and inferior olivary (IO) neurones. The relative contribution of these pathways can only be assessed from their momentary involvement at any stage of the complete course of neurodegeneration. Here we used quantitative labelling for activated caspase-3 (Casp-3) and Fluoro-Jade B (FJ-B) to investigate the spatio-temporal pattern of neuronal death from P6 to P67 in Lc/+ mutants. Activated Casp-3 was present only in narrow time intervals (P14 to P22 in PCs; P14 to P28 in GCs) and in small subpopulations of PCs, GCs, and IO neurones. FJ-B positive PCs were detected during a broader period (P14 to P28), and outnumbered Casp-3 labelled PCs by a factor exceeding eight. Nevertheless, FJ-B labelling was restricted to PCs and never found in either GC or IO neurones. In conclusion, we present the first complete time course and extent of Casp-3 activation in Lc/+ mutants and show that the majority of dying neurones in Lc/+ mutants undergo Casp-3 independent cell death. The cellular overload produced by the initial gene defect in Lc/+ mutants apparently activates a variety of apoptotic and non-apoptotic pathways within the same neuronal population. Moreover, we present the first evidence for the ability of FJ-B to selectively label a discrete population of dying PCs, implying a higher selectivity of FJ-B than previously supposed.     

Could metabolic liver function tests predict mortality on waiting list for liver transplantation? A study on 560 patients

Ecochard M, Boillot O, Guillaud O, Roman S, Adham M, Mion F, Dumortier J. Could metabolic liver function tests predict mortality on waiting list for liver transplantation? A study on 560 patients.
Clin Transplant 2011: 25: 755–765. © 2010 John Wiley & Sons A/S. Abstract: Background: Allocation of graft in liver transplantation (LT) depends mainly on Model for End Stage Liver Disease (MELD) score. We studied the prognostic ability of three metabolic liver function tests in 560 cirrhotic patients listed for transplantation, in comparison with MELD and Child–Turcotte–Pugh (CTP) scores. Methods: Indocyanine green retention rate (ICG), aminopyrine breath test (ABT), and galactose elimination capacity were performed at the time of listing in addition to standard biological parameters. Seventy‐three patients died on waiting list, 438 were transplanted, and 73 died after LT. Cox regression analysis and receiver operating characteristic curves with c‐statistics were calculated after stratification according to CTP and MELD score. Results: For the mortality before transplantation, c‐statistics showed that ICG and ABT had a slightly better prognostic ability (0.73 and 0.68, respectively) than MELD score (0.66), and similar to CTP score (0.70). ABT’s prognostic ability remained significant once the MELD score (below and above 20) had already been taken into account. Only ICG had a prognostic ability to predict the survival after LT, even after stratification according to MELD and CTP score. Conclusions: Our results strongly support that ABT and ICG may be useful in the ranking of the patients in LT list, adding prognosis information in association with MELD score.