Real‐time optical spectroscopic monitoring of nonirrigated lesion progression within atrial and ventricular tissues

Despite considerable advances in guidance of radiofrequency ablation (RFA) therapy for the treatment of cardiac arrhythmias, success rates have been hampered by a lack of tools for precise intraoperative evaluation of lesion extent. Near‐infrared spectroscopic (NIRS) techniques are sensitive to tissue structural and biomolecular properties, characteristics that are directly altered by radiofrequency (RF) treatment. In this work, a combined NIRS‐RFA catheter is developed for real‐time monitoring of tissue reflectance during RF energy delivery. An algorithm is proposed for processing NIR spectra to approximate nonirrigated lesion depth in both atrial and ventricular tissues. The probe optical geometry was designed to bias measurement influence toward absorption enabling enhanced sensitivity to changes in tissue composition. A set of parameters termed “lesion optical indices” are defined encapsulating spectral differences between ablated and unablated tissue. Utilizing these features, a model for real‐time tissue spectra classification and lesion size estimation is presented. Experimental validation conducted within freshly excised porcine cardiac specimens showed strong concordance between algorithm estimates and post‐hoc tissue assessment.      

Cloning and expression of neuron-specific enolase in the corpus luteum of dairy goats

Neuron-specific enolase (NSE) is the key molecular marker for diffuse neuroendocrine system (DNES) cells, its expression in the pregnant corpus luteum (CL) of dairy goats was studied by the immunofluorescence method and the ultra structural characteristics of luteal cells were detected by the electron microscopy to identify the existence of DNES cells in the pregnant CL of dairy goats. Besides, the coding sequence of dairy goats NSE gene was cloned and its biological information was analyzed. Results revealed that NSE immunopositive cells exhibited widespread cytoplasmic staining throughout the whole pregnant CL. In addition, these cells showed typical characteristics of DNES cells in the electron microscopy. These results suggested that many DNES cells exist in the pregnant CL of dairy goats. Meanwhile, we identified the coding sequence of dairy goats NSE (GenBank Accession No. JN887466). Its nucleotide sequence homology was found to be 97.9%, 89.3%, 90% and 92.6%, respectively, compared with that of Bos taurus, Rattus norvegicus, Mus musculus and Homo sapiens, while the amino acid sequence homology was 99.1%, 97%, 97.2% and 98.2% respectively. These results first showed that the functional amino acids coded by the NSE gene were highly conserved in Caprine, B. taurus, R. norvegicus, M. musculus and H. sapiens. It was implied that the gene NSE in dairy goats had close homology to that of NSE of other species. Our findings demonstrated the possible existence of DNES cells in pregnant CL, providing new clue for further understanding of interactions between the neuroendocrine and reproductive systems. Characterization of gene sequence of dairy goats NSE will enable us to synthesize interference RNA for further study on the role of NSE on the formation, function and apoptosis of pregnant CL in dairy goats.     

16q22.1 microdeletion detected by array-CGH in a family with mental retardation and lobular breast cancer

We describe the case of a boy with psychomotor delay and dysmorphic features, with a germline 16q22.1 microdeletion identified by array-CGH. The deletion spans 0.24Mb and encompasses three genes (ZFP90, CDH3 and CDH1). The deletion has been demonstrated to be inherited from his mother who was affected by lobular breast cancer (LBC) without any other apparently phenotypic features. We suppose that the microdeletion, in particular ZFP90 which is cerebrally expressed, is causative for the boy's phenotype. Mental retardation in the affected boy can recognize several mechanisms such as variable expressivity, non-penetrance, multifactorial/polygenic inheritance, recessive inheritance, a second rearrangement event and epigenetics. Furthermore, we suggest that the deletion of the CDH1, a tumor suppressor gene, involved in hereditary diffuse gastric cancer (HDGC) and LBC predisposed the mother to the carcinoma.     

A687V EZH2 is a gain-of-function mutation found in lymphoma patients

Heterozygous point mutations at Y641 and A677 in the EZH2 SET domain are prevalent in about 10-24% of Non-Hodgkin lymphomas (NHL). Previous studies indicate that these are gain-of-function mutations leading to the hypertrimethylation of H3K27. These EZH2 mutations may drive the proliferation of lymphoma and make EZH2 a molecular target for patients harboring these mutations. Here, another EZH2 SET domain point mutation, A687V, occurring in about 1-2% of lymphoma patients, is also shown to be a gain-of-function mutation that greatly enhances its ability to perform dimethylation relative to wild-type EZH2 and is equally proficient at catalyzing trimethylation. We propose that A687V EZH2 also leads to hypertrimethylation of H3K27 and may thus be a driver mutation in NHL.     

In vivo measurements of diffuse reflectance and time‐resolved autofluorescence emission spectra of basal cell carcinomas

We present a clinical investigation of diffuse reflectance and time‐resolved autofluorescence spectra of skin cancer with an emphasis on basal cell carcinoma. A total of 25 patients were measured using a compact steady‐state diffuse reflectance/fluorescence spectrometer and a fibre‐optic‐coupled multispectral time‐resolved spectrofluorometer. Measurements were performed in vivo prior to surgical excision of the investigated region. Singular value decomposition was used to reduce the dimensionality of steady state diffuse reflectance and fluorescence spectra. Linear discriminant analysis was then applied to the measurements of basal cell carcinomas (BCCs) and used to predict the tissue disease state with a leave‐one‐out methodology. This approach was able to correctly diagnose 87% of the BCCs. With 445 nm excitation a decrease in the spectrally averaged fluorescence lifetime was observed between normal tissue and BCC lesions with a mean value of 886 ps. Furthermore, the fluorescence lifetime for BCCs was lower than that of the surrounding healthy tissue in all cases and statistical analysis of the data revealed that this decrease was significant (p = 0.002). (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Hemoglobin plus myoglobin concentrations and near infrared light pathlength in phantom and pig hearts determined by diffuse reflectance spectroscopy

To noninvasively determine absolute concentrations of hemoglobin (Hb) plus myoglobin (Mb) in cardiac tissue by means of regular near infrared (NIR) light diffuse reflectance measurements, a first derivative approach was applied. The method was developed to separately calculate oxygenated and deoxygenated [Hb + Mb] as well as an effective pathlength, which NIR light passes through in the tissue between optodes. Applying a cotton wool-based phantom, which mimics muscle tissue, it was shown that the intensity of the pseudo-optical density first derivative depends linearly on both oxygenated and deoxygenated Hb concentration, thereby validating the Lambert-Beer law in the range of 0 to 0.25 mM tetrameric Hb. A high correlation (R = 0.995) was found between concentrations of Hb loaded onto the phantom and those determined spectrophotometrically, thereby verifying the first derivative method validity. The efficiency of the method was tested using in vivo pig hearts prior to and after ischemia initiated experimentally by left anterior descending artery branches occlusion. The results showed that the total [Hb + Mb] was 0.9-1.2 mM heme, the average tissue oxygen saturation was approximately 70% (which reduced to nearly 0% after occlusion), and the NIR (700-965 nm) light pathlength was 2.3 mm (differential pathlength factor [DPF] = 2.7-2.8) in a living heart tissue.     

A method for monitoring of oxygen saturation changes in brain tissue using diffuse reflectance spectroscopy

Continuous measurement of local brain oxygen saturation (SO₂) can be used to monitor the status of brain trauma patients in the neurocritical care unit. Currently, micro‐oxygen‐electrodes are considered as the “gold standard” in measuring cerebral oxygen pressure (pO₂), which is closely related to SO₂ through the oxygen dissociation curve (ODC) of hemoglobin, but with the drawback of slow in response time. The present study suggests estimation of SO₂ in brain tissue using diffuse reflectance spectroscopy (DRS) for finding an analytical relation between measured spectra and the SO₂ for different blood concentrations. The P₃ diffusion approximation is used to generate a set of spectra simulating brain tissue for various levels of blood concentrations in order to estimate SO₂. The algorithm is evaluated on optical phantoms mimicking white brain matter (blood volume of 0.5–2%) where pO₂ and temperature is controlled and on clinical data collected during brain surgery. The suggested method is capable of estimating the blood fraction and oxygen saturation changes from the spectroscopic signal and the hemoglobin absorption profile.

     

生物组织的折射率对漫反射光分布的影响

采用杂合算法,讨论了折射率对不同吸收系数的生物组织漫反射光分布的影响。计算结果表明,在近源处生物组织的折射率越小,漫反射光模拟计算的相对误差越小;而在远离源处,其相对误差随折射率的增大而减小。同时也说明杂合模型不太适合模拟吸收生物组织的漫反射光分布。     

Multiple herbivores and coevolutionary interactions in an Ipomopsis hybrid swarm

Studies focusing on pairwise interactions between plants and herbivores may not give an accurate picture of the overall selective effect of herbivory, given that plants are often eaten by a diverse array of herbivore species. The outcome of such interactions may be further complicated by the effects of plant hybridization. Hybridization can lead to changes in morphological, phenological and chemical traits that could in turn alter plant–herbivore interactions. Here we present results from manipulative field experiments investigating the interactive effects of multiple herbivores and plant hybridization on the reproductive success of Ipomopsis aggregata formosissima X I. tenuituba. Results showed that ungulate herbivores alone had a net positive effect on plant relative fitness, increasing seed production approximately 2-fold. Caterpillars had no effect on plant relative fitness when acting alone, with caterpillar-attacked plants producing the same number of flowers, fruits and seeds as the uneaten controls. Caterpillars, however, significantly reduced flower production of ungulate browsed plants. Flower production in these plants, however, was still significantly greater (approximately 1.7-fold greater) than uneaten controls, likely leading to an increase in reproductive success through the paternal component of fitness given that fruit and seed production was not significantly different from that of herbivore-free controls. Although results suggest that herbivore imposed selection is pairwise, ungulates likely have a large influence on the abundance of, and hence the amount of damage caused by, caterpillar herbivores. Thus, because of the ecological interactions between ungulates and caterpillars, selection on Ipomopsis may be diffuse rather than pairwise, assuming such interactions translate into differential effects on plant fitness as herbivore densities vary. Plant hybridization had no significant effect on patterns of ungulate or caterpillar herbivory; i.e., no significant interactions were detected between herbivory and plant hybridization for any of the fitness traits measured in this study nor did plant hybridization have any significant effect on host preference. These results may be due to patterns of introgression or the lack of species-specific differences between I. aggregate formosissima and I. tenuituba. Plant hybridization per se resulted in lowered reproductive success of white colored morphs due in part to the effects of pollination. Although it appears that there would be strong directional selection favoring darker flower colors due to the lower reproductive success of the white colored morphs in the short run, the natural distribution of hybrids suggest that over the long run selection either tends to average out or there are no fitness differences among morphs in most years due to the additive fitness effects of hawkmoth and hummingbird pollinators.