Predator and restraint stress during gestation facilitates pilocarpine-induced seizures in prepubertal rats

Stress during gestation can result in early and long-term developmental aberrations. This study aimed to assess the impact of prenatal restraint or predator stress on pilocarpine-induced epileptic behavior. Pregnant rats were exposed to stressors on gestational days 15, 16, and 17. Restraint stress consisted of daily restraint of the dam. During predator stress, caged rats were exposed to a cat in a cage. On postnatal day 25, male pups were injected with pilocarpine and the behavior of each rat was observed. Prenatal stress led to low birth weight and increased blood corticosterone levels. Both stressors significantly potentiated pilocarpine-induced seizures. Predator-stressed pups exhibited significantly severe tonic-clonic seizures compared with restraint-stressed animals. These data emphasize the impact of prenatal stress on fetal growth, and neural and endocrine function. The results also suggest that psychosocial stressors have a greater impact on neural and endocrine function than physical stressors do.     

Dual-energy contrast-enhanced breast tomosynthesis: optimization of beam quality for dose and image quality

Dual-energy contrast-enhanced breast tomosynthesis is a promising technique to obtain three-dimensional functional information from the breast with high resolution and speed. To optimize this new method, this study searched for the beam quality that maximized image quality in terms of mass detection performance. A digital tomosynthesis system was modeled using a fast ray-tracing algorithm, which created simulated projection images by tracking photons through a voxelized anatomical breast phantom containing iodinated lesions. The single-energy images were combined into dual-energy images through a weighted log subtraction process. The weighting factor was optimized to minimize anatomical noise, while the dose distribution was chosen to minimize quantum noise. The dual-energy images were analyzed for the signal difference to noise ratio (SdNR) of iodinated masses. The fast ray-tracing explored 523?776 dual-energy combinations to identify which yields optimum mass SdNR. The ray-tracing results were verified using a Monte Carlo model for a breast tomosynthesis system with a selenium-based flat-panel detector. The projection images from our voxelized breast phantom were obtained at a constant total glandular dose. The projections were combined using weighted log subtraction and reconstructed using commercial reconstruction software. The lesion SdNR was measured in the central reconstructed slice. The SdNR performance varied markedly across the kVp and filtration space. Ray-tracing results indicated that the mass SdNR was maximized with a high-energy tungsten beam at 49 kVp with 92.5 μm of copper filtration and a low-energy tungsten beam at 49 kVp with 95 μm of tin filtration. This result was consistent with Monte Carlo findings. This mammographic technique led to a mass SdNR of 0.92 ± 0.03 in the projections and 3.68 ± 0.19 in the reconstructed slices. These values were markedly higher than those for non-optimized techniques. Our findings indicate that dual-energy breast tomosynthesis can be performed optimally at 49 kVp with alternative copper and tin filters, with reconstruction following weighted subtraction. The optimum technique provides best visibility of iodine against structured breast background in dual-energy contrast-enhanced breast tomosynthesis.     

Do men with normal testosterone–oestradiol ratios benefit from letrozole for the treatment of male infertility?

Research question

Previous studies of aromatase inhibitors on male infertility have focused on men with low testosterone–oestradiol ratio of less than 10. Can aromatase inhibitors improve spermatogenesis in men with idiopathic male infertility with normal testosterone–oestradiol ratio?

Staging Systems for Newly Diagnosed Myeloma Patients Undergoing Autologous Hematopoietic Cell Transplantation: The Revised International Staging System Shows the Most Differentiation between Groups

The Revised International Staging System (R-ISS) and the International Myeloma Working Group 2014 (IMWG 2014) are newer staging systems used to prognosticate multiple myeloma (MM) outcomes. We hypothesized that these would provide better prognostic differentiation for newly diagnosed multiple myeloma (MM) compared with ISS. We analyzed the Center for International Blood and Marrow Transplant Research database from 2008 to 2014 to compare the 3 systems (N?=?628) among newly diagnosed MM patients undergoing upfront autologous hematopoietic cell transplantation (AHCT). The median follow-up of survivors was 48 (range, 3 to 99) months. The R-ISS provided the greatest differentiation between survival curves for each stage (for overall survival [OS], the differentiation was 1.74 using the R-ISS, 1.58 using ISS, and 1.60 using the IMWG 2014) . Univariate analyses at 3 years for OS showed R-ISS I at 88% (95% confidence interval [CI], 83% to 93%), II at 75% (95% CI, 70% to 80%), and III at 56% (95% CI, 3% to 69%; P < .001). An integrated Brier score function demonstrated the R-ISS had the best prediction for PFS, though all systems had similar prediction for OS. Among available systems, the R-ISS is the most optimal among available prognostic tools for newly diagnosed MM undergoing AHCT. We recommend that serum lactate dehydrogenase and cytogenetic data be performed on every MM patient at diagnosis to allow accurate prognostication.     

A humanized tissue-engineered in vivo model to dissect interactions between human prostate cancer cells and human bone

Currently used xenograft models for prostate cancer bone metastasis lack the adequate tissue composition necessary to study the interactions between human prostate cancer cells and the human bone microenvironment. We introduce a tissue engineering approach to explore the interactions between human tumor cells and a humanized bone microenvironment. Scaffolds, seeded with human primary osteoblasts in conjunction with BMP7, were implanted into immunodeficient mice to form humanized tissue engineered bone constructs (hTEBCs) which consequently resulted in the generation of highly vascularized and viable humanized bone. At 12 weeks, PC3 and LNCaP cells were injected into the hTEBCs. Seven weeks later the mice were euthanized. Micro-CT, histology, TRAP, PTHrP and osteocalcin staining results reflected the different characteristics of the two cell lines regarding their phenotypic growth pattern within bone. Microvessel density, as assessed by vWF staining, showed that tumor vessel density was significantly higher in LNCaP injected hTEBC implants than in those injected with PC3 cells (p < 0.001). Interestingly, PC3 cells showed morphological features of epithelial and mesenchymal phenotypes suggesting a cellular plasticity within this microenvironment. Taken together, a highly reproducible humanized model was established which is successful in generating LNCaP and PC3 tumors within a complex humanized bone microenvironment. This model simulates the conditions seen clinically more closely than any other model described in the literature to date and hence represents a powerful experimental platform that can be used in future work to investigate specific biological questions relevant to bone metastasis.     

Emergence of mupirocin-resistant MRSA among Iranian clinical isolates

Mupirocin is a topical antimicrobial agent which is increasingly used for the treatment and eradication of Staphylococcus aureus colonization from the noses of patients and hospital staff. However, the extensive use of this antibiotic has given rise to mupirocin resistance in S. aureus. The present study evaluated the rate of mupirocin resistance in S. aureus clinical isolates from burns patients. A total of 125 S. aureus nonduplicate consecutive clinical isolates were collected from the burns patients in Iranian Burns Hospital, and the presence of mecA and mupA genes was assessed through polymerase chain reaction. From the 125 isolates, 107 (85.6 %) and 40 (32 %) had the mecA and mupA genes, respectively. The high prevalence of mupirocin-resistant S. aureus in this burns hospital in comparison with other general hospitals in Iran requires revision in the current mupirocin therapy strategies. In tandem with other countries, the rate of mupirocin resistance is increasing in Iran, which necessitates regular monitoring.     

Carbon Nanotube–Poly(lactide-co-glycolide) Composite Scaffolds for Bone Tissue Engineering Applications

Despite their indisputable clinical value, current tissue engineering strategies face major challenges in recapitulating the natural nano-structural and morphological features of native bone. The aim of this study is to take a step forward by developing a porous scaffold with appropriate mechanical strength and controllable surface roughness for bone repair. This was accomplished by homogenous dispersion of carbon nanotubes (CNTs) in a poly(lactide-co-glycolide) (PLGA) solution followed by a solvent casting/particulate leaching scaffold fabrication. Our results demonstrated that CNT/PLGA composite scaffolds possessed a significantly higher mechanical strength as compared to PLGA scaffolds. The incorporation of CNTs led to an enhanced surface roughness and resulted in an increase in the attachment and proliferation of MC3T3-E1 osteoblasts. Most interestingly, the in vitro osteogenesis studies demonstrated a significantly higher rate of differentiation on CNT/PLGA scaffolds compared to the control PLGA group. These results all together demonstrate the potential of CNT/PLGA scaffolds for bone tissue engineering as they possess the combined effects of mechanical strength and osteogenicity.     

A genetic and clinical study of individuals with nonsyndromic retinopathy consequent upon sequence variants in HGSNAT,the gene associated with Sanfilippo C mucopolysaccharidosis

Pathogenic variants in the gene HGSNAT (heparan‐α‐glucosaminide N‐acetyltransferase) have been reported to underlie two distinct recessive conditions, depending on the specific genotype, mucopolysaccharidosis type IIIC (MPSIIIC)—a severe childhood‐onset lysosomal storage disorder, and adult‐onset nonsyndromic retinitis pigmentosa (RP). Here we describe the largest cohort to‐date of HGSNAT‐associated nonsyndromic RP patients, and describe their retinal phenotype, leukocyte enzymatic activity, and likely pathogenic genotypes. We identified biallelic HGSNAT variants in 17 individuals (15 families) as the likely cause of their RP. None showed any other symptoms of MPSIIIC. All had a mild but significant reduction of HGSNAT enzyme activity in leukocytes. The retinal condition was generally of late‐onset, showing progressive degeneration of a concentric area of paramacular retina, with preservation but reduced electroretinogram responses. Symptoms, electrophysiology, and imaging suggest the rod photoreceptor to be the cell initially compromised. HGSNAT enzymatic testing was useful in resolving diagnostic dilemmas in compatible patients. We identified seven novel sequence variants [p.(Arg239Cys); p.(Ser296Leu); p.(Phe428Cys); p.(Gly248Ala); p.(Gly418Arg), c.1543‐2A>C; c.1708delA], three of which were considered to be retina‐disease‐specific alleles. The most prevalent retina‐disease‐specific allele p.(Ala615Thr) was observed heterozygously or homozygously in 8 and 5 individuals respectively (7 and 4 families). Two siblings in one family, while identical for the HGSNAT locus, but discordant for retinal disease, suggest the influence of trans‐acting genetic or environmental modifying factors.     

An experimental comparison of detector performance for direct and indirect digital radiography systems

Current flat-panel detectors either directly convert x-ray energy to electronic charge or use indirect conversion with an intermediate optical process. The purpose of this work was to compare direct and indirect detectors in terms of their modulation transfer function (MTF), noise power spectrum (NPS), and detective quantum efficiency (DQE). Measurements were made on three flat-panel detectors, Hologic Direct-Ray DR-1000 (DRC), GE Revolution XQ/i (XQ/i), and Philips Digital Diagnost (DiDi) using the IEC-defined RQA5 (approximately 74 kVp, 21 mm Al) and RQA9 (approximately 120 kVp, 40 mm Al) radiographic techniques. The presampled MTFs of the systems were measured using an edge method [Samei et al., Med. Phys. 25, 102 (1998)]. The NPS of the systems were determined for a range of exposure levels by two-dimensional (2D) Fourier analysis of uniformly exposed radiographs [Flynn and Samei, Med. Phys. 26, 1612 (1999)]. The DQEs were assessed from the measured MTF, NPS, exposure, and estimated ideal signal-to-noise ratios. For the direct system, the MTF was found to be significantly higher than that for the indirect systems and very close to an ideal function associated with the detector pixel size. The NPS for the direct system was found to be constant in relation to frequency. For the XQ/i and DRC systems, the DQE results reflected expected differences based on the absorption efficiency of the different detector materials. Using RQA5, the measured DQE values in the diagonal (and axial) direction(s) at spatial frequencies of 0.15 mm(-1) and 2.5 mm(-1) were 64% (64%) and 20% (15%) for the XQ/i system, and 38% (38%) and 20% (20%) for the DRC, respectively. The DQE results of the DiDi system were difficult to interpret due to additional preprocessing steps in that system.