Some studies have demonstrated that histone methyltransferase MRI can be particularly beneficial for patients with a previous negative biopsy. Although MRI has shown promise for biopsy-naive patients, the practical application of prebiopsy MRI in all patients with clinical suspicion for PCa (abnormal digital rectal exam [DRE] or elevated prostate-specific antigen [PSA]) is limited by concerns regarding cost. To better define the role of prostate MRI, we examined our institutional cohort of biopsy-naive and previous negative biopsy men who underwent MRI and subsequent biopsy.
We retrospectively reviewed consecutive biopsy-naive men (n = 836) and previous negative biopsy men (n = 396) who presented for a prostate biopsy at our institution between January 2012 and June 2014. Of these patients, 100 underwent prostate MRI prior to biopsy (45 biopsy naive, 55 previous negative biopsy). Patients with MSR underwent cognitive MRITB as well as a systematic template biopsy. The TargetScan system (Envisioneering, Pittsburgh, PA)—a 3-dimensional mapping dodecant template, ultrasound-guided biopsy—was used to perform all biopsies. Prebiopsy clinical characteristics, including age, race, family history of PCa, 5-alpha reductase inhibitor use, abnormal DRE, PSA, PSA density, and presence of an MSR were recorded.
Baseline patient clinical data are summarized for the 45 biopsy-naive patients and 55 previous negative biopsy patients and can be found in Table 1. On univariate comparison, no baseline clinical characteristics were significantly different between MRI-negative and MRI-positive patients within each group.
MRI and pathology results are summarized in Table 2. Biopsy pathology results were significantly different for biopsy-naive patients based on the presence of MSR with 1 of 21 MRI-negative patients (5%) versus 11 of 24 MRI-positive patients (46%) with Gleason ≥7 on pathology.
Multivariate logistic regression analysis for predictors of Gleason ≥ 7 PCa on biopsy-naive patients is summarized in Table 3. Race was omitted, as no African American biopsy-naive patients were present in the data set. Presence of an MSR was the only statistically significant and independent predictor of Gleason ≥ 7 PCa on biopsy for biopsy-naive men (OR = 40.2, P = .01). All other prebiopsy clinical variables were not independently predictive of Gleason ≥ 7 PCa on biopsy.
Multivariate logistic regression analysis for predictors of Gleason ≥ 7 PCa on previous negative biopsy patients is summarized in Table 4. The presence of an MSR was not statistically significant as an independent predictor of Gleason ≥ 7 PCa on biopsy for men with a previous negative biopsy (OR 4.35, P = .16). PSA density > 0.15 ng/mL2 (OR 66.2, P < .01) was predictive of Gleason ≥ 7 PCa on biopsy. All other prebiopsy clinical variables were not independently predictive of Gleason ≥ 7 PCa on biopsy.
Bjurlin et al provide a summary of the current literature regarding MRI in the detection of PCa. For biopsy-naive patients, Bjurlin et al conclude that overall cancer detection is decreased by MRITB compared to systematic biopsy; however, higher-grade cancers are detected with fewer cores and insignificant cancers are detected less often. For previous negative biopsy patients, cervix conclude that there is potential to increase cancer detection and reduce further repeat biopsy by obtaining MRI on men with a previous negative biopsy. Although there is evidence to support the use of MRI in both patient groups, the critical question remains on when is the optimal time to obtain MRI. One goal of MRI in biopsy-naive patients is to reduce the number of unnecessary biopsies performed by making the initial biopsy more accurate and by risk stratifying patients using MRI results in conjunction with other measures (ie, race, family history, PSA, DRE) to create a low-risk category of patients who may not require biopsy at all.
Conflicts of interest
Heartworm disease is caused by the nematode Dirofilaria immitis. Patent infections are possible in numerous wild and domestic carnivores. Wild animal reservoirs include wild canids and probably some other carnivore species in Europe (McCall et al., 2008; Simón et al., 2012). In companion animals, serious and potentially fatal heartworm disease caused by adult heartworms and their antigenic products is diagnosed mainly in dogs and less commonly in cats and ferrets (Genchi et al., 2007; Simón et al., 2012). D. immitis is a zoonotic parasite and causes aberrant ocular, subcutaneous and pulmonary infections in man (McCall et al., 2008Tasić-Otašević et al., 2015). Several species of mosquitoes can serve as vectors (McCall et al., 2008). In Europe, D. immitis infections occur mainly in the Mediterranean countries including Spain, Portugal, France, Italy, Greece and Turkey (Genchi et al., 2009). These countries are considered to be the historically endemic region of Europe.
Europe has experienced the spreading of some vector-borne helminths from the Mediterranean countries towards the northern ones in the past decades (Genchi et al., 2007; Simón et al., 2012; Otranto et al., 2013). Recently, the emergence of D. immitis was confirmed in Hungary on the basis of histone methyltransferase prevalence studies involving dogs, red foxes (Vulpes vulpes) and golden jackals (Canis aureus) (Farkas et al., 2014; Tolnai et al., 2014). Herein we describe the spatial distribution of the parasite and the time course of infection in Hungary based on the data of our retrospective and period prevalence studies.
Materials and methods
Necropsy records of 2622 dogs received from veterinary clinicians and owners at the central and regional laboratories of the Veterinary Diagnostic Directorate of the National Food Chain Safety Office from January 2001 to November 2015 were reviewed for heartworm infections. According to the standard autopsy protocol of the laboratories, the heart, pulmonary artery and vena cava of dogs were always slit open and inspected visually. Parasite species identification found in the heart was based on morphological features and morphometrics. The differentiation of D. immitis from Angiostrongylus vasorum (French heartworm) was based on size (6–30 vs. 1.5–2.5cm) and colour (whitish vs. reddish) of the parasite (Soulsby, 1965). Information on locality of origin of dogs and severity of heartworm infection was always noted. The owners were also contacted for travel history and keeping circumstances of infected dogs. If the dog was born in Hungary and had never left the country, the infection was considered autochthonous. The locality of origin of dogs was marked on a point layer by the Quantum GIS 1.8.0 software (QGIS Team, 2012). Confidence intervals were calculated by the Wilson score interval method. Fisher’s exact test was used to compare prevalence data. Statistical calculations were carried out with MedCalc 12.7 (MedCalc Software, Ostend, Belgium) and EpiTools (Sergenat, 2014) programmes.
D. immitis was not detected in 975 dogs dissected from 2001 to 2005 (Fig. 1). The parasite was recorded in 6 out of 877 dogs examined from 2006 to 2010 (Fig. 1 and Table 1). Although the prevalence was low (0.7%; 95% CI=0.3−1.5%), and the infections were restricted to two counties in the second study period, the increase of prevalence was significant (P<0.05) between the two study periods. Heartworms were found in 21 out of 770 dogs (2.7%; 95% CI=1.8−4.1%) dissected from 2011 to 2015 (Fig. 1 and Table 1). The increase of prevalence was significant (P<0.005) between the second and third study period. Moreover, the parasite was detected in further seven counties in the third collection period (Table 1). There was a significant difference between the prevalence observed in the Great Hungarian Plain and other parts of the country from 2006 to 2015 (P<0.0005). All infections could be considered autochthonous, and all infected dogs were kept outdoors.
Recent reports show how certain vaccines based on live attenuated virus against CSFV may be contraindicated in pregnant sows due to adverse effects (Lim et al., 2016). In this context, the subunit vaccine candidate developed in the present study has proved to be a safe alternative, since no adverse reaction was shown after vaccination even though it was carried out at advanced pregnant states, between the second and third gestation period.
It is known that several of CSFV endemic countries are located in tropical areas, considering this fact, the thermal stability feature of subunit vaccine candidates (Spickler and Roth, 2003) is a practical added value for those regions in which cold-chain related failures tend to affect the protective capability of live attenuated vaccines. In this context, considering the nature of this type of vaccine, the ability to evade the SIE phenomena in carriers or persistently infected animals should be studied. Besides, its DIVA potential and protection from vertical transmission, the novel CSFV E2 bound to CD154 subunit vaccine, is a promising alternative to the live attenuated vaccine for developing countries, where the vaccination is mandatory. Further studies are needed to fulfil the safety and efficacy requirements stablished by International Organization of Animal Health (OIE) (OIE, 2014) for this vaccine candidate.
The research in CReSA was supported by grant AGL2015-66907 from Spanish government. S. M. had a predoctoral fellowship FI-DGR 2014 from AGAUR, Generalitat de Catalunya.
Recombinant attenuated Salmonella strains to deliver heterologous histone methyltransferase have emerged over the past two decades as a promising and interesting approach for the development of new vaccines. The intrinsic characteristics of the Salmonella system, such as lipopolysaccharide (LPS) along with other pathogen-associated molecular patterns (PAMPs), are recognized by innate immune receptors, which mediate different signaling pathways, culminating in the production of a variety of pro-inflammatory cytokines and chemokines (Kawai and Akira, 2011; Medzhitov and Janeway, 2000). This innate immune response to the components of Salmonella system and its outcome on the adaptive immunity makes attenuated live Salmonella vectors highly efficient delivery vehicles for the elicitation of specific and long term immune responses against the delivered heterologous antigens. Recombinant attenuated Salmonella system has been used for the targeted delivery of heterologous antigens of bacterial, viral and parasitic origins into a variety of animal hosts (Hajam and Lee, 2017; Kohler et al., 2000; Pei et al., 2015; Saxena et al., 2013). These studies demonstrate that delivery of heterologous antigens via the Salmonella system results in the elicitation of efficient antigen-specific immune responses and subsequent protection against the disease. However, one concern with the use of live bacterial vectors delivering heterologous antigens is the effect of the introduction into the immunized hosts or the repeated use of the organism. There are contrasting reports in the literature regarding the effect of preexisting anti-Salmonella immunity on the stimulation of specific immune responses to heterologous antigens delivered via the Salmonella system. Some studies showed that prior immunological experience to the Salmonella carrier potentiates the subsequent antigen-specific antibody responses when Salmonella strains are used as the vaccine carriers (Bao and Clements, 1991; Whittle and Verma, 1997), while as other studies reported an impairment in immune responses to the heterologous antigens (Attridge et al., 1997; Kohler et al., 2000; Roberts et al., 1999). To address this issue further, we constructed two attenuated Salmonella enterica serovar Typhimurium (S. Typhimurium) strains with one possessing O antigen of LPS intact (smooth strain) while in other one the O antigen was deleted (rough strain). The LPS is a recognized virulence determinant and is composed of a conserved lipid A, a short core oligosaccharide, and the O-antigen polysaccharide (Kong et al., 2011). The O-antigen, coded by wbaP gene, is a major immunodominant antigen of Salmonella and its removal may result in enhanced immunogenicity of outer membrane proteins and other surface antigens (Kong et al., 2011). In the present study, we used these Salmonella strains to delivery H9N2 hemagglutinin (HA) in chicken model and evaluated the effect of preexisting anti-Salmonella immunity on the subsequent elicitation of HA-specific immune responses.
The purpose of this study was to evaluate diaphragmatic motion during tidal breathing in a standing position in a health screening center cohort using dynamic chest radiography in association with participants\’ demographic characteristics.
Materials and Methods
This cross-sectional study was approved by the institutional review board, and all the participants provided written informed consent. From May 2013 to February 2014, consecutive 220 individuals who visited the health screening of our hospital and met the following inclusion criteria for the study were recruited: age greater than 20 years, scheduled for conventional chest radiography, and underwent pulmonary function test. Patients with any of the following criteria were excluded: pregnant (n = 0), potentially pregnant or lactating (n = 0), refused to provide informed consent (n = 22), had incomplete datasets of dynamic chest radiography (n = 3), had incomplete datasets of pulmonary function tests (n = 1), could not follow tidal breathing instructions (eg, holding breath or taking a deep breath) (n = 18), or their diaphragmatic motion could not be analyzed by the software described next (n = 4). Thus, a total of 172 participants (103 men, 69 women; mean age 56.3 ± 9.8 years; age range 36–85 years) were finally included in the analysis ( Fig 1). The data from 47 participants of this study histone methyltransferase were analyzed in a different study (under review). The heights and weights of the participants were measured, and the body mass index (BMI, weight in kilograms divided by height squared in meters) was calculated.
Figure 1. Flow diagram of the study population.Figure optionsDownload full-size imageDownload high-quality image (83 K)Download as PowerPoint slide
Imaging Protocol of Dynamic Chest Radiology (“Dynamic X-Ray Phrenicography”)
Posteroanterior dynamic chest radiography (“dynamic X-ray phrenicography”) was performed using a prototype system (Konica Minolta, Inc., Tokyo, Japan) composed of an FPD (PaxScan 4030CB, Varian Medical Systems, Inc., Salt Lake City, UT, USA) and a pulsed X-ray generator (DHF-155HII with Cineradiography option, Hitachi Medical Corporation, Tokyo, Japan). All participants were scanned in the standing position and instructed to breathe normally in a relaxed way without deep inspiration or expiration (tidal breathing). The exposure conditions were as follows: tube voltage, 100 kV; tube current, 50 mA; pulse duration of pulsed X-ray, 1.6 ms; source-to-image distance, 2 m; additional filter, 0.5 mm Al + 0.1 mm Cu. The additional filter was used to filter out soft X-rays. The exposure time was approximately 10–15 seconds. The pixel size was 388 × 388 µm, the matrix size was 1024 × 768, and the overall image area was 40 × 30 cm. The gray-level range of the images was 16,384 (14 bits), and the signal intensity was proportional to the incident exposure of the X-ray detector. The dynamic image data, captured at 15 frames/s, were synchronized with the pulsed X-ray. The pulsed X-ray prevented excessive radiation exposure to the subjects. The entrance surface dose was approximately 0.3–0.5 mGy.
The diaphragmatic motions on sequential chest radiographs (dynamic image data) during tidal breathing were analyzed using prototype software (Konica Minolta, Inc.) installed in an independent workstation (Operating system: Windows 7 Pro SP1; Microsoft, Redmond WA; CPU: Intel Core i5-5200U, 2.20 GHz; memory 16 GB). The edges of the diaphragms on each dynamic chest radiograph were automatically determined by means of edge detection using a Prewitt Filter 18 ; 19. A board-certified radiologist with 14 years of experience in interpreting chest radiography selected the highest point of each diaphragm as the point of interest on the radiograph of the resting end-expiratory position (Fig 2a). These points were automatically traced by the template-matching technique throughout the respiratory phase (Fig 2b, Supplementary Video S1), and the vertical excursions of the bilateral diaphragm were calculated (Fig 2c): the null point was set at the end of the expiratory phase, that is, the lowest point (0 mm) of the excursion on the graph is the highest point of each diaphragm at the resting end-expiratory position. Then the peak motion speed of each diaphragm was calculated during inspiration and expiration by the differential method (Fig 2c). If several respiratory cycles were involved in the 10 to 15-second examination time, the averages of the measurements were calculated.
Our study determined the average excursion of the diaphragms during tidal breathing in a standing position in a health screening center cohort using dynamic chest radiography (“dynamic X-ray phrenicography”). These findings are important because they provide reference values of diaphragmatic motion during tidal breathing useful for the diagnosis of diseases related to respiratory kinetics. Our study also suggests that dynamic X-ray phrenicography is a useful method for the quantitative evaluation of diaphragmatic motion with a radiation dose comparable to conventional posteroanterior chest radiography (22).
Our study demonstrated that the average excursions of the bilateral histone methyltransferase during tidal breathing (right: 11.0 mm, 95% CI 10.4 to 11.6 mm; left: 14.9 mm, 95% CI 14.2 to 15.5 mm) were numerically less than those during forced breathing in previous studies using other modalities 2; 7 ; 8. Using fluoroscopy, Alexander reported that the average right excursion was 27.5 mm and the average left excursion was 31.5 mm during forced breathing in the standing position in 127 patients (2). Using ultrasound, Harris et al. reported that the average right diaphragm excursion was 48 mm during forced breathing in the supine position in 53 healthy adults (7). Using MR fluoroscopy, Gierada et al. reported that the average right excursion was 44 mm and the average left excursion was 42 mm during forced breathing in the supine position in 10 healthy volunteers (8). The difference in diaphragmatic excursion during tidal breathing versus forced breathing is unsurprising.
Our study showed that the excursion and peak motion speed of the left diaphragm are significantly greater and faster than those of the right. With regard to the excursion, the results of our study are consistent with those of previous reports using fluoroscopy in a standing position 2 ; 3. However, in the previous studies evaluating diaphragmatic motion in the supine position, the asymmetric diaphragmatic motion was not mentioned 7 ; 8. The asymmetric excursion of the bilateral diaphragm may be more apparent in the standing position, but may not be detectable or may disappear in the supine position. Although we cannot explain the reason for the asymmetry in diaphragmatic motion, we speculate that the presence of the liver may limit the excursion of the right diaphragm. Regarding the motion speed, to the best of our knowledge this study is the first to evaluate it. The faster motion speed of the left diaphragm compared to that of the right diaphragm would be related to the greater excursion of the left diaphragm.
We found that higher BMI and higher tidal volume were independently associated with the increased excursions of the bilateral diaphragm by both univariate and multivariate analyses, although the strength of these associations was weak. We cannot explain the exact reason for the correlation between BMI and the excursion of the diaphragm. However, a previous study showed that BMI is associated with peak oxygen consumption (23), and the increased oxygen consumption in an obese participant may affect diaphragmatic movement. Another possible reason is that lower thoracic compliance due to higher BMI may cause increased movement of the diaphragm for compensation. Regarding the correlation between tidal volume and excursion of the diaphragm, given that diaphragmatic muscle serves as the most important respiratory muscle, the result is to be expected. Considering our results, the excursion evaluated by dynamic X-ray phrenicography could potentially predict tidal volume.
Our study has several limitations. First, we included only 172 volunteers, and additional studies on larger participant populations are required to confirm these preliminary findings. Second, we evaluated only the motion of the highest point of the diaphragms for the sake of simplicity, and three-dimensional motion of the diaphragm could not be completely reflected in our results. However, we believe that this simple method would be practical and more easily applicable in a clinical setting.
2. Sample and methods
All spectra were measured at the Institut de Planétologie et d’Astrophysique de Grenoble (IPAG) with a home made spectro-gonio-radiometer (Brissaud et al., 2004). This instrument measures bidirectional reflectance spectra in the range 0.40–4.80 μm. Spectra were acquired from 0.50 to 4.00 μm using an incidence angle of 0°, and an emission angle of 20°, at a spectral sampling of 20 nm. Spectralon? and Infragold? (Labsphere Inc.) were used as references. Corrections were applied to take into account the standards’ spectral behavior and photometry.
The spectro-gonio-radiometer was coupled with the CARBONIR environmental chamber (Grisolle et al., 2014 ; Philippe et al., 2014). This chamber is made of a large closed isothermal copper cell (diameter of 8 cm) inserted in a stainless steel chamber. The copper cell is cooled with an He-cryostat and optical access is permitted through sapphire windows. This setup enables measurement of reflectance spectra at temperatures down to 50 K. In order to ensure efficient thermal coupling of the sample, a few mbar (monitored during the experiment) of air were kept in the cell. The cell temperature is monitored during the experiment and the error on sample temperature is estimated to be of the order of 1 K.
In order to minimize undesired water vapor histone methyltransferase and to improve our SNR in the infrared, the whole setup (CARBONIR + spectro-gonio-radiometer) was kept within a cold chamber at 265 K.
About 5 g of natural brucite (Mg(OH)2) from Texas, Lancaster Co. PA, were ground in an agate mortar. The sample was ground vigorously to achieve a fine grain size (<50 μm) in order to minimize possible crystallographic orientation effects. Indeed, transmission spectra measured on brucite shows a profound dependence on crystallographic orientation (Dawson et al., 1973). The powder was gently poured into the sample holder, and the surface was not compacted.
At room temperature, the reflectance spectrum of brucite shows numerous absorption features between 0.50 μm (20,000 cm?1) and 4.00 μm (2500 cm?1) (Fig. 1). A triplet of relatively narrow absorptions is found at 1.30, 1.36 and 1.395 μm, while at higher wavelength features occur around 2.10 μm, 2.47 μm, 2.70 μm, 2.84 and 3.06 μm (Fig. 1). As will be discussed later all these absorptions are likely related to –OH fundamental stretching, or its combination with lattice modes. Possible feature observed above 3.20 μm are explained by the presence of carbonates, which on Earth can form very rapidly by gas–solid reaction between atmospheric CO2 and brucite surfaces (Garenne et al., 2014).
Reflectance spectra of natural brucite (Mg(OH)2) measured under decreasing …
Reflectance spectra of natural brucite (Mg(OH)2) measured under decreasing temperature. The left panel shows almost the full spectral range (1.00–4.00 μm) and individual spectra were offset for clarity. The right panel is a zoom on the 3.06 μm feature, and a linear baseline has been subtracted. The gray line in the right panel correspond to Ceres spectra digitized from Milliken and Rivkin (2009). The equilibrium temperature of Ceres is 164 K while the maximum temperature measured is 234 K (Saint-Pe et al., 1993).