In vivo characterization of early-stage radiation skin injury in a mouse model by two-photon microscopy

Ionizing radiation (IR) injury is tissue damage caused by high energy electromagnetic waves such as X-ray and gamma ray. Diagnosis and treatment of IR injury are difficult due to its characteristics of clinically latent post-irradiation periods and the following successive and unpredictable inflammatory bursts. Skin is one of the many sensitive organs to IR and bears local injury upon exposure. Early-stage diagnosis of IR skin injury is essential in order to maximize treatment efficiency and to prevent the aggravation of IR injury. In this study, early-stage changes of the IR injured skin at the cellular level were characterized in an in vivo mouse model by two-photon microscopy (TPM). Various IR doses were applied to the mouse hind limbs and the injured skin regions were imaged daily for 6 days after IR irradiation. Changes in the morphology and distribution of the epidermal cells and damage of the sebaceous glands were observed before clinical symptoms. These results showed that TPM is sensitive to early-stage changes of IR skin injury and may be useful for its diagnosis.1194Ysciescopu

Evaluation of 3D printed PCL/PLGA/beta-TCP versus collagen membranes for guided bone regeneration in a beagle implant model

Here, we compared 3D-printed polycaprolactone/poly(lactic-co-glycolic acid)/beta-tricalcium phosphate (PCL/PLGA/beta-TCP) membranes with the widely used collagen membranes for guided bone regeneration (GBR) in beagle implant models. For mechanical property comparison in dry and wet conditions and cytocompatibility determination, we analyzed the rate and pattern of cell proliferation of seeded fibroblasts and preosteoblasts using the cell counting kit-8 assay and scanning electron microscopy. Osteogenic differentiation was verified using alizarin red S staining. At 8 weeks following implantation in vivo using beagle dogs, computed tomography and histological analyses were performed after sacrifice. Cell proliferation rates in vitro indicated that early cell attachment was higher in collagen than in PCL/PLGA/beta-TCP membranes; however, the difference subsided by day 7. Similar outcomes were found for osteogenic differentiation, with approximately 2.5 times greater staining in collagen than PCL/PLGA/beta-TCP, but without significant difference by day 14. In vivo, bone regeneration in the defect area, represented by new bone formation and bone-to-implant contact, paralleled those associated with collagen membranes. However, tensile testing revealed that whereas the PCL/PLGA/beta-TCP membrane mechanical properties were conserved in both wet and dry states, the tensile property of collagen was reduced by 99% under wet conditions. Our results demonstrate in vitro and in vivo that PCL/PLGA/beta-TCP membranes have similar levels of biocompatibility and bone regeneration as collagen membranes. In particular, considering that GBR is always applied to a wet environment (e.g. blood, saliva), we demonstrated that PCL/PLGA/beta-TCP membranes maintained their form more reliably than collagen membranes in a wet setting, confirming their appropriateness as a GBR membrane.11109Ysciescopu

A One Health Framework for the Evaluation of Rabies Control Programmes: A Case Study from Colombo City, Sri Lanka

<div><p>Background</p><p>One Health addresses complex challenges to promote the health of all species and the environment by integrating relevant sciences at systems level. Its application to zoonotic diseases is recommended, but few coherent frameworks exist that combine approaches from multiple disciplines. Rabies requires an interdisciplinary approach for effective and efficient management.</p><p>Methodology/Principal Findings</p><p>A framework is proposed to assess the value of rabies interventions holistically. The economic assessment compares additional monetary and non-monetary costs and benefits of an intervention taking into account epidemiological, animal welfare, societal impact and cost data. It is complemented by an ethical assessment. The framework is applied to Colombo City, Sri Lanka, where modified dog rabies intervention measures were implemented in 2007. The two options included for analysis were the control measures in place until 2006 (“baseline scenario”) and the new comprehensive intervention measures (“intervention”) for a four-year duration. Differences in control cost; monetary human health costs after exposure; Disability-Adjusted Life Years (DALYs) lost due to human rabies deaths and the psychological burden following a bite; negative impact on animal welfare; epidemiological indicators; social acceptance of dogs; and ethical considerations were estimated using a mixed method approach including primary and secondary data. Over the four years analysed, the intervention cost US $1.03 million more than the baseline scenario in 2011 prices (adjusted for inflation) and caused a reduction in dog rabies cases; 738 DALYs averted; an increase in acceptability among non-dog owners; a perception of positive changes in society including a decrease in the number of roaming dogs; and a net reduction in the impact on animal welfare from intermediate-high to low-intermediate.</p><p>Conclusions</p><p>The findings illustrate the multiple outcomes relevant to stakeholders and allow greater understanding of the value of the implemented rabies control measures, thereby providing a solid foundation for informed decision-making and sustainable control.</p></div

Detectability of colorectal neoplasia with fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography and computed tomography (FDG-PET/CT)

The purpose of this study was to analyze the detectability of colorectal neoplasia with fluorine-18-2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT). Data for a total of 492 patients who had undergone both PET/CT and colonoscopy were analyzed. After the findings of PET/CT and colonoscopy were determined independently, the results were compared in each of the six colonic sites examined in all patients. The efficacy of PET/CT was determined using colonoscopic examination as the gold standard. In all, 270 colorectal lesions 5 mm or more in size, including 70 pathologically confirmed malignant lesions, were found in 172 patients by colonoscopy. The sensitivity and specificity of PET/CT for detecting any of the colorectal lesions were 36 and 98%, respectively. For detecting lesions 11 mm or larger, the sensitivity was increased to 85%, with the specificity remaining consistent (97%). Moreover, the sensitivity for tumors 21 mm or larger was 96% (48/50). Tumors with malignant or high-grade pathology were likely to be positive with PET/CT. A size of 10 mm or smaller [odds ratio (OR) 44.14, 95% confidence interval (95% CI) 11.44-221.67] and flat morphology (OR 7.78, 95% CI 1.79-36.25) were significant factors that were associated with false-negative cases on PET/CT. The sensitivity of PET/CT for detecting colorectal lesions is acceptable, showing size- and pathology-dependence, suggesting, for the most part, that clinically relevant lesions are detectable with PET/CT. However, when considering PET/CT for screening purposes caution must be exercised because there are cases of false-negative results

Fulvestrant and the sequential endocrine cascade for advanced breast cancer

Following relapse on endocrine therapy for advanced, hormone receptor-positive breast cancer, it is common for patients to experience responses to alternative endocrine agents. Fulvestrant (‘Faslodex’) is a new type of endocrine treatment – an oestrogen receptor (ER) antagonist with no agonist effects. Fulvestrant downregulates cellular levels of the ER resulting in decreased expression of the progesterone receptor. This unique mode of action means that it is important that fulvestrant is placed optimally within the sequence of endocrine therapies to ensure that patients gain maximum benefit. Fulvestrant has shown efficacy when used after progression on tamoxifen or anastrozole in postmenopausal women with advanced breast cancer. After progression on fulvestrant, subsequent endocrine treatments can produce responses in many patients, demonstrating that fulvestrant does not lead to crossresistance with other endocrine therapies. Responses to fulvestrant have also been observed in patients heavily pretreated with prior endocrine therapy. Fulvestrant is a versatile endocrine agent that may be integrated into the therapeutic sequence prior to, or subsequent to, other hormonal therapies, and represents a valuable additional antioestrogen for the treatment of postmenopausal women with advanced breast cancer

Simultaneous expression of Oct4 and genes of three germ layers in single cell-derived multipotent adult progenitor cells

Future application of adult stem cells in clinical therapies largely depends on the successful isolation of homogeneous stem cells with high plasticity. Multipotent adult progenitor cells (MAPCs) are thought to be a more primitive stem cell population capable of extensive in vitro proliferation with no senescence or loss of differentiation capability. The present study was aimed to find a less complicated and more economical protocol for obtaining single cell-derived MAPCs and understand the molecule mechanism of multi-lineage differentiation of MAPCs. We successfully obtained a comparatively homogeneous population of MAPCs and confirmed that single cell-derived MAPCs were able to transcribe Oct4 and genes of three germ layers simultaneously, and differentiate into multiple lineages. Our observations suggest that single cell-derived MAPCs under appropriate circumstances could maintain not only characteristics of stem cells but multi-lineage differentiation potential through quantitative modulation of corresponding regulating gene expression, rather than switching on expression of specific genes

Pine cone scale-inspired motile origami

Stimuli-sensitive hydrogels have received attention because of their potential applications in various fields. Stimuli-directed motion offers many practical applications, such as in drug delivery systems and actuators. Directed motion of asymmetric hydrogels has long been designed; however, few studies have investigated the motion control of symmetric hydrogels. We designed a pine cone scale-inspired movable temperature-sensitive symmetric hydrogel that contains Fe3O4. Alignment of Fe3O4 along the magnetic force is key in motion control in which Fe3O4 acts like fibers in a pine cone scale. Although a homogeneous temperature-sensitive hydrogel cannot respond to a temperature gradient, the Fe3O4-containing hydrogel demonstrates considerable bending motion. Varying degrees and directions of motion are easily facilitated by controlling the amount and alignment angle of the Fe3O4. The shape of the hydrogel layer also influences the morphological structure. This study introduced facile and low-cost methods to control various bending motions. These results can be applied to many fields of engineering, including industrial engineering.111Ysciescopu

Relationship between human tumour angiogenic profile and combretastatin-induced vascular shutdown: an exploratory study

Combretastatin-A4-phosphate (CA4P) acts most effectively against immature tumour vasculature. We investigated whether histological angiogenic profile can explain the differential sensitivity of human tumours to CA4P, by correlating the kinetic changes demonstrated by dynamic MRI (DCE-MRI) in response to CA4P, with tumour immunohistochemical angiogenic markers. Tissue was received from 24 patients (mean age 59, range 32–73, 18 women, 6 men). An angiogenic profile was performed using standard immunohistochemical techniques. Dynamic MRI data were obtained for the same patients before and 4 h after CA4P. Three patients showed a statistically significant fall in Ktrans following CA4P, and one a statistically significant fall in IAUGC60. No statistically significant correlations were seen between the continuous or categorical variables and the DCE-MRI kinetic parameters other than between ang-2 and Ktrans (P=0.044). In conclusion, we found no strong relationships between changes in DCE-MRI kinetic variables following CA4P and the immunohistochemical angiogenic profile

Genetic Polymorphism in a VEGF-Independent Angiogenesis Gene ANGPT1 and Overall Survival of Colorectal Cancer Patients after Surgical Resection

Background The VEGF-independent angiogenic signaling plays an important role in the development of colorectal cancer (CRC). However, its implication in the clinical outcome of CRC has not been reported. This study aimed to investigate the association between genetic variations in several major VEGF-independent signaling pathway genes and the overall survival of CRC patients. Methods Seven single nucleotide polymorphisms (SNPs) in four important VEGF-independent angiogenic genes (ANGPT1, AMOT, DLL4 and ENG) were genotyped in a Chinese population with 408 CRC patients. Results One SNP, rs1954727 in ANGPT1, was significantly associated with CRC overall survival. Compared to patients with the homozygous wild-type genotype of rs1954727, those with heterozygous and homozygous variant genotypes exhibited a favorable overall survival with a hazard ratio (HR) of 0.89 (95% confidence interval [CI] 0.55–1.43, P = 0.623), and 0.32 (95% CI 0.15–0.71, P = 0.005), respectively (P trend = 0.008). In stratified analysis, this association remained significant in patients receiving chemotherapy (P trend = 0.012), but not in those without chemotherapy. We further evaluated the effects of chemotherapy on CRC survival that was stratified by rs1954727 genotypes. We found that chemotherapy resulted in a significantly better overall survival in the CRC patients (HR = 0.44, 95% CI 0.26–0.75, P = 0.002), which was especially prominent in those patients with the heterozygous genotype of rs1954727 (HR = 0.45, 95%CI 0.22–0.92, P = 0.028). Conclusion Our data suggest that rs1954727 in ANGPT1 gene might be a prognostic biomarker for the overall survival of CRC patients, especially in those receiving chemotherapy, a finding that warrants validation in larger independent populations