The role of exercise echocardiography in the management of mitral valve disease

Purpose

Exercise echocardiography can assess the dynamic component of mitral valve (MV) disease and may therefore be helpful for the clinical decision-making by the heart team. The purpose of this study is to determine the role of exercise echocardiography in the management of disproportionately symptomatic or otherwise atypical patients with mitral regurgitation (MR) and stenosis (MS) in clinical practice.

Methods

Data of 14 MR and 14 MS patients, including echocardiograms at rest, were presented retrospectively to an experienced heart team to determine treatment strategy. Subsequently, exercise echo data were provided whereupon once again the treatment strategy was determined. This resulted in: value of exercise echo by means of 1) alteration or 2) confirmation of treatment strategy or 3) no additional value.

Results

During exercise the echocardiographic severity of MV disease increased in 9 (64 %) MR and 8 (57 %) MS patients. Based upon alteration or confirmation of the treatment strategy, the value of exercise echocardiography in the management of MR and MS was 86 % and 57 %, respectively.

Conclusion

This study showed that physical exercise echo can have an important role in the clinical decision-making of challenging patients with MV disease. Exercise echocardiography had additional value to the treatment strategy in 71 % of these patients.     

Mapping the spatial variation of mitral valve elastic properties using air-pulse optical coherence elastography

The mitral valve is a highly heterogeneous tissue composed of two leaflets, anterior and posterior, whose unique composition and regional differences in material properties are essential to overall valve function. While mitral valve mechanics have been studied for many decades, traditional testing methods limit the spatial resolution of measurements and can be destructive. Optical coherence elastography (OCE) is an emerging method for measuring viscoelastic properties of tissues in a noninvasive, nondestructive manner. In this study, we employed air-pulse OCE to measure the spatial variation in mitral valve elastic properties with micro-scale resolution at 1 mm increments along the radial length of the leaflets. We analyzed differences between the leaflets, as well as between regions of the valve. We found that the anterior leaflet has a higher elastic wave velocity, which is reported as a surrogate for stiffness, than the posterior leaflet, most notably at the annular edge of the sample. In addition, we found a spatial elastic gradient in the anterior leaflet, where the annular edge was found to have a greater elastic wave velocity than the free edge. This gradient was less pronounced in the posterior leaflet. These patterns were confirmed using established uniaxial tensile testing methods. Overall, the anterior leaflet was stiffer and had greater heterogeneity in its mechanical properties than the posterior leaflet. This study measures differences between the two mitral leaflets with greater resolution than previously feasible and demonstrates a method that may be suitable for assessing valve mechanics following repair or during the engineering of synthetic valve replacements.     

Stress–strain behavior of mitral valve leaflets in the beating ovine heart

Excised anterior mitral leaflets exhibit anisotropic, non-linear material behavior with pre-transitional stiffness ranging from 0.06 to 0.09 N/mm² and post-transitional stiffness from 2 to 9 N/mm². We used inverse finite element (FE) analysis to test, for the first time, whether the anterior mitral leaflet (AML), in vivo, exhibits similar non-linear behavior during isovolumic relaxation (IVR). Miniature radiopaque markers were sewn to the mitral annulus, AML, and papillary muscles in 8 sheep. Four-dimensional marker coordinates were obtained using biplane videofluoroscopic imaging during three consecutive cardiac cycles. A FE model of the AML was developed using marker coordinates at the end of isovolumic relaxation (when pressure difference across the valve is approximately zero), as the reference state. AML displacements were simulated during IVR using measured left ventricular and atrial pressures. AML elastic moduli in the radial and circumferential directions were obtained for each heartbeat by inverse FEA, minimizing the difference between simulated and measured displacements. Stress–strain curves for each beat were obtained from the FE model at incrementally increasing transmitral pressure intervals during IVR. Linear regression of 24 individual stress–strain curves (8 hearts, 3 beats each) yielded a mean (±SD) linear correlation coefficient (r²) of 0.994±0.003 for the circumferential direction and 0.995±0.003 for the radial direction. Thus, unlike isolated leaflets, the AML, in vivo, operates linearly over a physiologic range of pressures in the closed mitral valve.     

Double blind clinical trial of a remineralizing dentifrice in the prevention of caries in a radiation therapy population

Objectives: The purpose of this study is to determine the efficacy and safety of a specially formulated remineralizing toothpaste in controlling caries in a group of high risk, head and neck radiation patients. Design: The study compares the performance of the remineralizing toothpaste with a leading conventional fluoride dentifrice using double-blind randomization. Test Products The products compared both contain equivalent quantities of fluoride (1150ppm). The remineralizing toothpaste also delivers soluble calcium and phosphate ions, the essential components of teeth. Subjects: On completion, 50 subjects who received >50 Gy of radiation to the head and neck. Measurements: Examinations include coronal and root caries using the Pitts Diagnostic Criteria, salivary flow rate, plaque and gingival indices and microbiological counts over one year. Results: At this point subjects are enrolled in the study at various phases. However, the current average for the net increment per month per subject is −0.12 (±1.30) for coronal caries and 0.06 (±0.73) for root caries in subjects using the remineralizing toothpaste and 0.53 (±1.62) for coronal caries and 0.45 (±0.98) for root caries in subjects using the conventional fluoride dentifrice. Non-parametric analysis of rank scores for net root surface increments/month was statistically significant (p=0.02), suggesting lower net root surface increment/month for the remineralizing toothpaste relative to the conventional toothpaste. No significant differences were noted on coronal surfaces. Conclusions: The results to date indicate that the remineralizing toothpaste is significantly superior to the conventional fluoride dentifrice in preventing root caries in high risk patients.     

经皮椎体成形术治疗骨质疏松性椎体压缩骨折的临床疗效及术后邻近椎体骨折的危险因素分析

摘要 目的：观察骨质疏松性椎体压缩骨折（OVCFs）患者以经皮椎体成形术（PVP）治疗后的临床疗效,并分析术后邻近椎体骨折的危险因素。方法：选取我院2018年6月~2020年9月期间收治的OVCFs患者180例,给予PVP治疗,观察其治疗效果、骨水泥渗漏情况、术后邻近椎体骨折发生情况,采用单因素及多因素Logistic回归分析术后邻近椎体骨折的危险因素。结果：OVCFs患者术前~术后6个月功能障碍指数（ODI）、疼痛视觉模拟评分（VAS）、活动能力评分（LAS）均呈降低趋势（P＜0.05）。随访期间,180例患者中,15例（8.33%）出现了骨水泥渗漏,但均不需要进一步处理。32例（17.78%）出现了术后邻近椎体骨折,148例未出现术后邻近椎体骨折,并以此进行分组。再骨折组、未再骨折组在年龄、骨折病史、骨密度、Cobb角、椎体高度恢复、骨水泥渗漏情况、使用抗骨质疏松药物方面对比有明显差异（P<0.05）。年龄>70岁、骨水泥渗漏、骨密度<-2.5SD、未使用抗骨质疏松药物、Cobb角<15°、椎体高度恢复率>87%均是PVP术后邻近椎体骨折的危险因素（P<0.05）。结论：PVP治疗OVCFs疗效较好,可缓解患者疼痛、减轻功能障碍、改善活动能力,术后邻近椎体骨折的发生受年龄、骨密度、Cobb角等多种因素影响,临床可针对这些因素给予对应的干预措施。     

Early mitral valve repair versus watchful waiting in patients with severe asymptomatic organic mitral regurgitation; rationale and design of the Dutch AMR trial, a multicenter, randomised trial

Background

Asymptomatic severe mitral valve (MV) regurgitation with preserved left ventricular function is a challenging clinical entity as data on the recommended treatment strategy for these patients are scarce and conflicting. For asymptomatic patients, no randomised trial has been performed for objectivising the best treatment strategy.

Methods

The Dutch AMR (Asymptomatic Mitral Regurgitation) trial is a multicenter, prospective, randomised trial comparing early MV repair versus watchful waiting in asymptomatic patients with severe organic MV regurgitation. A total of 250 asymptomatic patients (18–70 years) with preserved left ventricular function will be included. Intervention will be either watchful waiting or MV surgery. Follow-up will be 5 years. Primary outcome measures are all-cause mortality and a composite endpoint of cardiovascular mortality, congestive heart failure, and hospitalisation for non-fatal cardiovascular and cerebrovascular events. Secondary outcome measures are total costs, cost-effectiveness, quality of life, echocardiographic and cardiac magnetic resonance parameters, exercise tests, asymptomatic atrial fibrillation and brain natriuretic peptide levels. Additionally, the complication rate in the surgery group and rate of surgery in the watchful waiting group will be determined.

Implications

The Dutch AMR trial will be the first multicenter randomised trial on this topic. We anticipate that the results of this study are highly needed to elucidate the best treatment strategy and that this may prove to be an international landmark study.     

Assessing the impacts of reservoir expansion using a population model for a threatened riverine fish

Increasing demand for water and a desire for greater human water security has facilitated the global expansion of dams, with river regulation acknowledged as the leading cause of biodiversity decline in rivers. Native biota within these stressed systems are also impacted by reductions in habitat availability, decreased hydraulic diversity, increased sedimentation, movement barriers, invasive species and altered flows that may profoundly change the character and functioning of rivers. Construction or enlargement of reservoirs is continuing, and whilst downstream impacts are often considered, upstream impacts receive far less attention. We develop a population model to examine the impacts of reservoir expansion on a threatened riverine species in South Eastern Australia: the two-spined blackfish. We examined two processes, loss of breeding habitat and increased predation, directly linked to reservoir expansion as well as a broader threat of recruitment failure due to sedimentation. These threatening processes were assessed using the expected minimum population size as an indicator of risk. As is often the case for threatened species, limited data were used to parameterise the model and sensitivity analysis performed to assess the appropriateness of the model parameterisation. The outcomes indicate that the two-spined blackfish population is vulnerable to the loss of breeding habitat particularly if two-spined blackfish are unable to spawn in the larger dam, although this vulnerability is ameliorated if the whole river is accounted for. Including possible impacts from the resident trout population for the whole river, indicates the two-spined blackfish to be vulnerable to low level predation particularly if the trout population have a high growth rate. Population modelling has rarely been used to predict the consequences of dam construction on aquatic species/communities. The example here shows it to be a powerful tool to visualise and quantify potential biodiversity outcomes.     

Characterisation of the digital dermatoglyphic in a berber population of the high Atlas (Marrakesh, Morrocco)

With an aim of characterising the genetic structure of the Berber population, of the Western High Atlas (Marrakesh), and of locating it compared to the other known populations, a preliminary study of the digital dermatoglyphes relating to a sample of 100 individuals (50 men and 50 women) non related taken at random in the population of the commune of Asni (Wilaya de Marrakesh) was carried out. The frequencies of the digital figures obtained in this population are respectively 50.2% of the ulnar loops, 40.6% of the whorls, 7.7% of the archs and 1.5% of the radial loops. No significant difference between the two sexes has been observed. Compared with other Moroccan populations, while basing, oneself on the relatively frequency of the arch, one raises more resemblance of our population (9.2% among women and 6.2% among the men) to the Arab population of the region of Doukkala (8.85% at the men and 7.2% among women) that with the Berber population of the Middle Atlas (5.26% at the men and 5.63% among women). Compared with other Mediterranean populations, the Berber of the High-Atlas remain among the populations which present a higher arch percentage. The analysis of affinities of the digital figures between the population object, of the study and those of the Mediterranean by the Euclidean distances show that this one presents characteristics which differentiates, it from the other populations. One can not however, that conversely with other Moroccan populations analysed, the one becomes attached more to the group, of populations of south of the Mediterranean (Arab and Berber) than to the group of the north populations of mediterranean area (Spain, France and Italy).     

Maternal PCMT1 gene polymorphisms and the risk of neural tube defects in a Chinese population of Lvliang high-risk area

Protein-L-isoaspartate (D-aspartate) O-methyltransferase 1 (PCMT1) gene encodes for the protein repair enzyme L-isoaspartate (D-aspartate) O-methyltransferase (PIMT), which is known to protect certain neural cells from Bax-induced apoptosis. Previous study has shown that PCMT1 polymorphisms rs4552 and rs4816 of infant are associated with spina bifida in the Californian population. The association between maternal polymorphism and neural tube defects is still uncovered. A case-control study was conducted to investigate a possible association between maternal PCMT1 and NTDs in Lvliang high-risk area of Shanxi Province in China, using a high-resolution DNA melting analysis genotyping method. We found that increased risk for anencephaly in isolated NTDs compared with the normal control group was observed for the G (vs. A) allele (p=0.034, OR=1.896, 95% CI, 1.04-3.45) and genotypes GG+GA (p=0.025, OR=2.237, 95% CI, 1.09-4.57). Although the significance was lost after multiple comparison correction, the results implied that maternal polymorphisms in PCMT1 might be a potential genetic risk factor for isolated anencephaly in this Chinese population.     

Polymorphisms of the DNA repair gene EXO1 modulate cognitive aging in old adults in a Taiwanese population

Evidence indicates that the age-related neuropathological mechanisms associated with DNA repair genes may contribute to cognitive aging and Alzheimer’s disease. In this study, we hypothesize that single nucleotide polymorphisms (SNPs) within 155 DNA repair genes may be linked to cognitive aging independently and/or through complex interactions in an older Taiwanese population. A total of 3,730 Taiwanese subjects aged over 60 years from the Taiwan Biobank were analyzed. Mini-Mental State Examination (MMSE) was administered to all subjects, and MMSE scores were used to measure cognitive functions. Our data showed that out of 1,652 SNPs, the rs1776181 (P = 1.47 × 10⁻⁵), rs1776177 (P = 8.42 × 10^-7), rs1635510 (P = 7.97 × 10^-6), and rs2526698 (P = 7.06 × 10^-6) SNPs in the EXO1 gene were associated with cognitive aging. The association with these SNP remained significant after performing Bonferroni correction. Additionally, we found that interactions between the EXO1 and RAD51C genes influenced cognitive aging (P = 0.002). Finally, we pinpointed the influence of interactions between EXO1 and physical activity (P < 0.001) as well as between DCLRE1C and physical activity (P < 0.001). Our study indicated that DNA repair genes may contribute to susceptibility in cognitive aging independently as well as through gene-gene and gene-physical interactions.     

Methodological issues of assessing the risk of a second cancer occurring in the same site as a first cancer using registry data

ObjectiveTo present methodological issues that can arise with the assessment of the risk of a second primary cancer (SPC) occurring in the same site as a first cancer using registry data.Material and methodsData from ten French cancer registries were used, including data for patients with a first prostate cancer (in males), breast cancer (in females), and colon, lung and kidney cancer (in both sexes) diagnosed between 1989 and 2004. Standardized incidence ratios (SIRs) of SPC were computed by excluding, or not, the risk of an SPC at the same site.ResultsFor prostate cancer, the SIR dropped from 1.11 to 0.72 when the risk of SPC of the prostate was included. SIRs increased from 1.36 to 1.45, from 1.14 to 1.21, from 1.57 to 2.01, and from 1.37 to 1.51 for breast, colon, lung, and kidney respectively.ConclusionThe inclusion, or not, of an SPC at the same site can impact on SPC risk estimates.     

Impact of genetic polymorphisms in base excision repair genes on the risk of breast cancer in a Korean population

The contribution of single nucleotide polymorphisms (SNPs) in base excision repair (BER) genes to the risk of breast cancer (BC) was evaluated by focusing on two key genes: apurinic/apyrimidinic endonuclease 1 (APEX1) and 8-oxoguanine DNA glycosylase (OGG1). Genetic variations in the genes encoding these DNA repair enzymes may alter their functions and increase susceptibility to carcinogenesis. The aim of this study was to analyze polymorphisms in two BER genes, exploring their associations and particularly the combined effects of these variants on BC risk in a Korean population. Three SNPs of two BER genes were genotyped using the Illumina GoldenGate™ method. In total, 346 BC patients and 361 cancer-free controls were genotyped for these BER gene polymorphisms and analyzed for their correlation with BC risk in multiple logistic regression models. Multiple logistic regression models adjusted for age, family history of BC, and body mass index were used. The APEX1 Asp148Glu polymorphism was weakly associated with BC risk. The combined analysis among the BER genes, however, showed significant effects on BC risk. The APEX1 Asp148Glu carrier, in combination with OGG1 rs2072668 and OGG1 Ser326Cys, was strongly associated with an increased risk of BC. Moreover, the combination of the C–C haplotype of OGG1 with the APEX1 Asp148Glu genotype was also associated with an additive risk effect of BC [ORs = 2.44, 2.87, and 3.50, respectively]. The combined effect of APEX1 Asp148Glu was found to be associated with an increased risk of BC. These results suggest that the combined effect of different SNPs within BER genes may be useful in predicting BC risk.     

A tentative evaluation for population establishment of Bactrocera dorsalis (Diptera: Tephritidae) by its population modeling: Considering the temporal distribution of host plants in a selected area in Jeju,Korea

The Oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae) is a destructive fruit pest in a wide range of cultivated fruit crops and wild plants. This species is a potentially highly invasive fruit fly to Jeju area of Korea. This study was conducted to evaluate the effect of host plants distributed temporally on the population development of B. dorsalis. The temperature-dependent bionomic data for a synonymous group of B. dorsalis, including B. philippinensis, B. papayae, and B. invadens were collected from previous publications and combined to construct a population model of this pest and its thermal constant. We developed a stage-transition model of eggs, larvae and pupae, and an oviposition model for basic population modeling of the four common strains. We investigated the abundance of the host plants of B. dorsalis in a selected site in Jeju and parameterized them in terms of temporal availability to incorporate into the population model. The contribution of host plants for the population growth of B. dorsalis in the selected site was different according to the group of host plants. For example, B. dorsalis populations largely decreased by 93%, when host plants belong to Moraceae (mainly Ficus sp.) were removed in the simulation. Also, we found that the host plants of Prunus persica, Ficus carica, P. mume, Eriobotrya japonica in this order contributed greatly to population abundance of B. dorsalis in the selected area, which was important in terms of mid-season host plants connecting the early adult population of B. dorsalis to citrus plants in the late season. Finally, we discussed a seasonal management strategy against B. dorsalis while considering the availability of host plants and the biology of this fruit fly in an invaded area.     

Screening of edentulous patients in a dental school population using the prosthodontic diagnostic index

doi:10.1111/j.1741‐2358.2009.00317.x
Screening of edentulous patients in a dental school population using the prosthodontic diagnostic index Purpose: The aim of this study was to classify a number of completely or partially edentulous patients who attended undergraduate clinics at the Dental School of Athens using the prosthodontic diagnostic index (PDI) to identify the complexity of the cases treated by the students. Background: There is a scarcity of studies, concerning prosthodontic patients and screening them according to a classification system such as the PDI. Material and methods: The survey was conducted on 181 patients who attended the clinics for treatment. The PDI categorised the patients into four classes (Class I–IV) according to the severity of certain diagnostic findings. Results: From the 110 completely edentulous patients, 27 patients were in Class I, 21 in Class II, 15 in Class III and 47 in Class IV. From the 71 partially edentulous patients, two were in Class I, 17 in Class II, 29 in Class III and 23 in Class IV. Conclusion: Our results showed that the majority of patients were categorised in Class III (partially edentulous) and IV (completely edentulous). This indicates the need to introduce a proper screening tool, such as the PDIs, during the initial examination, to achieve a successful treatment.     

Estimation of genetic variability of the founder population in a conservation scheme using microsatellites

In a conservation programme with genealogical records it is possible to estimate the amount of variability of the founder population from a measure of the similarity among the individuals in the current population based on microsatellite markers. Here we compare three available methods and we shown that the one based on the molecular coancestry coefficient should be preferred.     

Evaluation of premeiotic activity in the developing rabbit testis using a modified squash technique

Germ cells in the developing rabbit testis were studied using a modified squash technique. Preleptotene figures present in the postnatal testis were examined and compared with corresponding stages in ovarian germ cells. The findings indicated differences in the pattern of preleptotene changes in the developing ovary and testis.     

The identification of sex in the starling Sturnus vulgaris using a molecular DNA technique

Female birds can be identified through the presence of a W-chromosome. We describe a procedure for amplifying a W-linked DNA marker in the starling (Sturnus vulgaris) by the polymerase chain reaction (PCR) so allowing the diagnosis of sex in this species. The technique is sensitive, allowing even the smallest chicks to be sexed from a blood sample. The method possesses a positive internal control to ensure accuracy. It is also applicable to the spotless starling (S. unicolor) but not to two bird species outside the genus. The nucleotide sequence of the female-specific PCR product is given.     

Identification of metastasis-associated proteins in a human tumor metastasis model using the mass-mapping technique

For most cancer cell types, the acquisition of metastatic ability leads to clinically incurable disease. The identification of molecules whose expression is specifically correlated with the metastatic spread of cancer would facilitate the design of therapeutic interventions to inhibit this lethal process. In order to facilitate metastasis gene discovery we have previously characterized a pair of monoclonal cell lines from the human breast carcinoma cell line MDA-MB-435 that have different metastatic phenotypes in immune-compromised mice. In this study, serum-free conditioned media was collected from the cultured monoclonal cell lines and a mass mapping technique was applied in order to profile a component of each cell line proteome. We utilized chromatofocusing in the first dimension to obtain a high resolution separation based on protein pI, and nonporous silica reverse-phase high performance liquid chromatography was used for the second dimension. Selected proteins were identified on the basis of electrospray ionization time of flight mass spectrometry (ESI-TOF MS) intact protein mapping and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) peptide mass fingerprinting. Using this approach we were able to map over 400 proteins and plot them as a 2-D map of pI versus accurate M(r). This was performed over a pI range of 4.0-6.2, and a mass range of 6-80 kDa. ESI-TOF MS data and further analysis using MALDI-TOF MS confirmed and identified 27 differentially expressed proteins. Proteins associated with the metastatic phenotype included osteopontin and extracellular matrix protein 1, whereas the matrix metalloproteinase-1 and annexin 1 proteins were associated with the non-metastatic phenotype. These findings demonstrate that the mass mapping technique is a powerful tool for the detection and identification of proteins in complex biological samples and which are specifically associated with a cellular phenotype.