Apparent Blood Research Articles

Dysregulation of TET2 in hematologic malignancies.

The TET dioxygenases, TET1, TET2, and TET3, catalyze transfer of an oxygen atom to the methyl group of 5-methylcytocine (5-mC), converting it to 5-hydroxymethylcytocine (5-hmC). Among the genes encoding these enzymes, ten-eleven translocation 2 (TET2) is frequently mutated somatically in both myeloid and lymphoid malignancies. Because these TET2 mutations result in the impairment of the dioxygenase activity of TET2, it is thought that these mutations interfere with 5-mC to 5-hmC conversion. There is ample evidence indicating that TET2 mutations are a driver of tumorigenesis in blood cells and that TET2 mutations are often acquired at the hematopoietic stem/early progenitor cell stage. In addition, TET2 is the second-most frequently mutated gene in clonal hematopoiesis in individuals with no apparent blood cancers, suggesting that while TET2 mutations alone are insufficient to cause hematologic malignancy, they represent an early event during tumorigenesis. A number of questions, including the precise target genome regions of TET2, and the importance of the balance of 5-mC and 5-hmC in the regulatory regions in transcriptional control, remain.

Effects of dietary onion (Allium cepa) extract supplementation on performance, apparent total tract retention of nutrients, blood profile and meat quality of broiler chicks.

ObjectiveThis study was conducted to investigate the effect of dietary onion (Allium cepa) extract (OE) supplementation on growth performance, apparent total tract retention (ATTR), blood profile, carcass characteristics and meat quality in broilers.MethodsFour hundred male broiler chicks (Ross 308, 3-d old) were randomly allocated to four dietary treatments for 28 d feeding trial. Each treatment has five replications with 20 birds each. Four dietary treatments were designated according to the OE supplementation levels (0 as control, 5, 7.5, and 10 g of OE per kg of basal diet respectively). On d 28, a total of 20 birds from each treatment were subjected for ATTR, serum biochemical assay, carcass characteristic and organ weight measurement.ResultsOverall weight gain of OE 7.5 g/kg group was higher (p = 0.04) than control group. The ATTRs of dietary energy (p<0.01) and ether extract (p = 0.04) linearly increased with increasing levels of dietary OE. However, no difference in ATTR of dry matter and crude protein was evident. Furthermore, serum IgG concentration increased linearly (p<0.01) and quadratically (p = 0.03) with increasing OE supplementation. No differences in carcass dressing weight and amount of abdominal fat by treatments were observed. Also, the weight of organ including immune organ was not different among the treatments. The TBARS values of 10 d stored breast meat decreased linearly (p<0.01) and quadratically (p<0.01) with increasing dietary OE levels. The meat color was also affected, with lower (p<0.01) redness score in meats from OE supplemented groups. This study showed that dietary OE improved broiler weight gain presumably by increasing feed intake and ATTR of both energy and ether extract. The dietary OE increased serum IgG level and meat anti-oxidation capacity.ConclusionThis study implies that the recommended level of dietary OE supplementation could be beneficial for improving broiler performance and meat quality.

NIMG-22. MRI CHANGES IN NEWLY DIAGNOSED GLIOBLASTOMA DURING CHEMORADIATION AND ADJUVANT TEMOZOLOMIDE

Characterize anatomic and functional MRI changes in patients with newly diagnosed glioblastoma (nGBM) to more accurately measure impact of treatment. The standard of care for nGBM is maximal safe resection, six weeks of concurrent chemoradiation (CRT), followed by adjuvant monthly temozolomide. FLAIR and T1 post-contrast sequences are frequently used to assess treatment response but poorly reflect underlying tumor behavior with respect to tumor cellularity, vascular permeability, and perfusion. Following IRB approval, patients with nGBM underwent MR imaging before treatment, during week 6 of CRT, four weeks post-CRT, and before cycle 2 of adjuvant temozolomide (“pre-cycle 2”). We measured FLAIR and contrast-enhancing (CE) volumes, apparent diffusion coefficient (ADC; reflecting tumor cellularity), Ktrans (reflecting vascular permeability), and relative cerebral blood volume (rCBV) and flow (rCBF; reflecting perfusion) on spin echo (SE) and gradient echo (GE) sequences (rCBVSE, rCBFSE, rCBVGE, rCBFGE, respectively). Fourteen patients were included. Percent changes during treatment were compared to pre-treatment values. Within the CE region of interest (ROI), the respective median percent changes during CRT, post-CRT, and pre-cycle 2 were: CE volume -0.75%, 19.98%, 5.93%; ADC 10.15%, 18.03%, 27.21%; Ktrans 32.05%, 22.48%, 7.06%; rCBVSE -18.82%, -33.21%, -32.86%; rCBFSE -11.42%, -28.80%, -26.99%; rCBVGE -17.05%, -23.92%, -30.39%; and rCBFGE -21.98%, -24.29%, -32.12%. Within the peri-tumoral FLAIR ROI, the respective median percent changes during CRT, post-CRT, and pre-cycle 2 were: FLAIR volume 20.36%, 80.29%, 69.36%; ADC -3.63%, 6.59%, 11.51%; Ktrans 5.88%, -7.40%, -31.45%; rCBVSE -11.62%, -34.60%, -20.18%; rCBFSE -0.31%, -22.42%, -25.23%; rCBVGE -0.80%, -13.05%, -22.32%; and rCBFGE 6.30%, -6.25%, -19.57%. Chemoradiation in nGBM results in increased edema and permeability early during treatment, likely related to tumoral and peri-tumoral inflammation; decreased tumor cellularity, reflected by increased ADC; and decreased perfusion. ADC, Ktrans, and perfusion parameters are thus helpful in better characterizing tumor microenvironment during treatment.

The influence of oxygen tension on the local regulation of blood flow by shear stress

Introduction and purpose. Vascular response to mechanical stimuli, namely transmural pressure (Bayliss effect) and wall shear stress (response to blood flow), play an important role in regulation of vascular tone. The purpose of the work was to study an influence of hypoxia on the vessel radius and blood flow control by response to shear stress. Methodology/approach. Mathematical simulation was used. The model is based on published data of experiments on small cerebral arteries of rats. The main assumptions of the model are: 1) the vessel is a thin wall cylinder; 2) the radius is controlled by two parameters: concentration of free calcium ions in the cytoplasm of the smooth muscle cells and concentration of nitric oxide (NO) in the smooth muscle layer; 3) the rate of NO production by endothelium is proportional to modulus of shear stress on the vessel wall. The apparent blood viscosity is calculated using the solution of the problem of two-layer flow. The numerical experiments were performed in Turbo Pascal. The main results and discussion. The dependence of vessel tone regulation by response to altered shear stress on oxygen tension is caused by dependence of NO synthesis in endothelium and NO consumption on oxygen concentration. As it follows from mathematical simulation, hypoxia reduces the role of mechanogenic regulation, and the increase of the wall sensitivity to NO makes this effect more appreciable. Calculations performed for typical value of cerebral vessel response to shear stress, show that the fall in oxygen tension from 100 to 30 per cent leads to decrease in diameter by 6 %, in blood flow rate by 11 %. The rheological factors prevent flow rate diminution, but their contribution is very small: less than 3 %. The fall in oxygen tension reduces NO production rate by endothelial cells and NO concentration in the vessel wall. At strong hypoxia (reduction in oxygen tension from 100 to 30 % and less) NO concentration in smooth muscle layer drops by more than 15 %. Conclusions. Hypoxia decreases NO-dependent vessel response to altered shear rate. This effect increases with the value of vessel response to shear stress. The rheological factors impede the decrease of this response.

The role of diffusion tensor imaging and dynamic susceptibility perfusion MRI in the evaluation of meningioma grade and subtype

PurposeWe prospectively investigated the relationship between diffusion tensor imaging (DTI), dynamic susceptibility perfusion (DSP) MRI metrics and grade, subtype and Ki-67 labelling index of meningiomas. Materials and ΜethodsThirty-nine patients operated for meningioma were included in the study. DTI and DSP were performed within a week prior to surgical excision. Lesion/normal (L/N) tissue ratios and peritumoral area/normal tissue (P/N) ratios were calculated for the apparent diffusion coefficient (ADC), fractional anisotropy (FA) and relative cerebral blood volume (rCBV). In the tumor specimens Ki-67 antigen expression was evaluated by the MIB-1 immunostaining method. ResultsThere were 31 grade I, 7 grade II and one grade III meningiomas. Grade I meningiomas had a significantly lower L/N rCBV ratios than grade II/III meningiomas (median 5.1 vs 6.4, p=0.031). Grade I meningiomas revealed significantly lower P/N rCBV ratios than grade II/III meningiomas (median 0.78 vs 1.1, p=0.0077). Grade I meningiomas had significantly higher FA ratios than grade II/III meningiomas (median 0.5 vs 0.31, p=0.012). Meningiomas of meningothelial type had a significantly higher L/N rCBV ratio than other grade I meningiomas (median 5.4 vs 3.8, p=0.0136). There was no significant correlation between rCBV, ADC, FA and Ki-67 index. ConclusionDynamic susceptibility perfusion indexes in lesion/normal and peritumoral/normal tissue ratios are useful for the differentiation grade I from grade II/III menigiomas. Meningothelial meningiomas showed higher lesion/normal tissue rCBV ratios from the other benign meningioma subtypes.

Assessment of Glioma Response to Radiotherapy Using Multiple MRI Biomarkers with Manual and Semiautomated Segmentation Algorithms.

Multimodality magnetic resonance imaging (MRI) can provide complementary information in the assessment of brain tumors. We aimed to segment tumor in amide proton transfer-weighted (APTw) images and to investigate multiparametric MRI biomarkers for the assessment of glioma response to radiotherapy. For tumor extraction, we evaluated a semiautomated segmentation method based on region of interest (ROI) results by comparing it with the manual segmentation method. Thirteen nude rats injected with U87 tumor cells were irradiated by an 8-Gy radiation dose. All MRI scans were performed on a 4.7-T animal scanner preradiation, and at day 1, day 4, and day 8 postradiation. Two experts performed manual and semiautomated methods to extract tumor ROIs on APTw images. Multimodality MRI signals of the tumors, including structural (T2 and T1 ), functional (apparent diffusion coefficient and blood flow), and molecular (APTw and magnetization transfer ratio or MTR), were calculated and compared quantitatively. The semiautomated method provided more reliable tumor extraction results on APTw images than the manual segmentation, in less time. A considerable increase in the ADC intensities of the tumor was observed during the postradiation. A steady decrease in the blood flow values and in the APTw signal intensities were found after radiotherapy. The semiautomated method of tumor extraction showed greater efficiency and stability than the manual method. Apparent diffusion coefficient, blood flow, and APTw are all useful biomarkers in assessing glioma response to radiotherapy.

Influence of low or high density corn and soybean meal-based diets and protease supplementation on growth performance, apparent digestibility, blood characteristics and noxious gas emission of finishing pigs

This study was conducted to evaluate the influence of dietary supplementation of high and low nutrient density diets and protease on growth performance, apparent nutrient digestibility, blood metabolites, and excreta noxious gas emission in finishing pigs. A total of 140 pigs [(Landrace×Yorkshire)×Duroc] with an initial average body weight (BW) of 50.69±1.91kg were used in a 12-week trial. Pigs were blocked and stratified based on sex and body weight in a 2×2 factorial design with the following factors: 1) low or high nutrient density diet and 2) with or without Protease, 125g/t (Prot). Each treatment consisted of 7 replicate pens with 5 pigs (3 barrows and 2 gilts) per pen. Supplementation of protease significantly increased (P<0.05) ADG and G: F ratio during week 6 to12 and the G: F ratio was also significantly increased (P<0.05) overall. Trends in increased (P=0.08, 0.09 and 0.08) ADG was observed in pigs fed high density diet compared with low density diet during weeks 0–6, 6 to12 and overall respectively. Likewise, feed efficiency was significantly increased (P<0.05) in pigs fed high density diets compared with low density diets. A trend in interactive effect between diets and protease was observed for feed efficiency during wk 6–12. The co-efficient of apparent digestibility (CATTD) of DM, N and Energy was significantly higher (P<0.05) in pigs fed protease supplemented diet during wk 12. Nitrogen digestibility tended to increase (P=0.06) in high density diet than low density diet during wk 6. The supplementation of protease in the diet led to significantly higher (P<0.05) level of creatinine during wk 6 and lower (P<0.05) levels of cortisol and epinephrine in blood serum during wk 12. The concentration of creatinine tended (P=0.08) to be higher in high than low density diets during wk 12. The noxious gases were not affected (P>0.05) by density diets and protease. No interactions were observed between the diets and protease for nutrient digestibility, blood profiles and noxious gases emission.In conclusion, dietary supplementation with 125g/t of protease has beneficial effects on growth performance and CATTD. The stress related hormones were also reduced in pigs fed protease supplemented diets. In addition to tendency in weight gain, feed efficiency was improved in pigs fed high density diets than low density diets.

Effects of fenugreek seed extract supplementation on growth performance, nutrient digestibility, diarrhoea scores, blood profiles, faecal microflora and faecal noxious gas emission in weanling piglets.

This study was conducted to evaluate the effect of dietary fenugreek seed extract (FSE) on growth performance, apparent total tract digestibility (ATTD), diarrhoea scores, blood profiles, faecal microflora and faecal gas emission in weanling pigs. A total of 135 weanling pigs [(Yorkshire×Landrace) ×Duroc] with an average BW of (7.96±1.03kg; 28 days of age) were used in a 42-day study. Piglets were randomly allotted to three experimental diets with nine replicate pens and five pigs per pen. Dietary treatments were as follows: CON, basal diet; FSE1, basal diet+0.1% FSE; FSE2, basal diet+0.2% FSE. Pigs were fed with phase 1 (0-14 days) and phase 2 (14-42 days) diets in the form of mash. Average daily gain (ADG) was linearly increased (p=0.031) by FSE supplementation compared with CON diet during days 0-14. From days 14-42, FSE2 diet had increased ADG and growth efficiency (G/F) compared with the CON diet (p=0.014 and 0.026 respectively). Moreover, ADG and G/F were increased by FSE supplementation during days 0-42 (linear, p=0.037 and 0.014 respectively). Energy digestibility was higher (linear, p=0.030) by FSE supplementation at 6weeks. On day 42, dietary supplementation of FSE linearly increased red blood cells (RBC) and immunoglobulin G (IgG) concentration (p=0.042 and 0.038 respectively). Piglets fed FSE2 diet had higher (linear, p=0.025) serum high-density lipoprotein cholesterol (HDL-C) concentration compared with those fed CON diet. However, piglets fed FSE2 diet had linearly reduced faecal ammonia (NH3 ) and hydrogen sulphide (H2 S) gas emission compared with those fed the CON diet (p=0.018 and 0.010 respectively). In conclusion, FSE supplementation increased the performance and reduced faecal gas emission in weanling pigs.

Lessons learned? Ebola, dietary salt reduction and epigenetics.

TIME Persons of the Year 2014 were the Ebola fighters who worked with few resources at considerable personal risk and saved lives. Jeremy Farrar, director of the Wellcome Trust, wrote of Ebola in 2014, ‘It is still a matter of quarantine and safe funerary practices: shut you away and bury you nicely. These remain the most effective public health tools we have, but also the bluntest and most brutal. Can it be right to rely on them still?’ A year later, he announced in triumph the news of an effective Ebola vaccine. Developing and mounting a vaccine trial during the worst-ever Ebola outbreak is a staggering achievement itself—and an efficacy of 100% is truly remarkable. More reliable estimates using complete data and per-protocol analyses will be published in due course. A systematic review of risk factors for transmission of Ebola published in this issue found that caring for a case in the community, especially until death, and participation in traditional funeral rites were strongly associated with acquiring disease. These findings provide support for the current Ebola vaccination strategy used in Guinea. There is no shortage of lessons learned from the recent Ebola epidemic—including the need for reforms in rapid response capability, research, leadership and better governance. But the importance of disease mapping appears to have been overlooked in the dialogue on Ebola. In this issue, Tom Koch, medical cartographer, poses this question: ‘How did many of the best minds in infectious disease, epidemiology and disaster medicine miss the early spread of the filovirus from a remote village in Guinea until its presence became regionally epidemic?’ The answer is that people living in remote villages where Ebola was first diagnosed are highly mobile. Quarantine measures— the only effective prevention strategy—were not used in villages and towns linked by patterns of travel to Ebola villages. Early proposals for containing the Ebola epidemic made no mention of mapping, and mathematic models assessing outbreak potential ignored the spatial dimension, assuming ‘that hosts mixed randomly both in the community and hospital’. Mapping of Ebola focused largely on producing incidence maps which were site specific and could not give predictive information on likelihood of spread to other places. Koch makes several proposals, including use of origin-destination maps of travel patterns of exposed and sick people, augmented with vector environmental factors where feasible, to assess the risk of spread and possible quarantine of villages and towns: essential reading for planning responses to the next viral epidemic. Lessons can be learned from a review of the evidence for and against population-wide reductions in dietary salt— sometimes dramatically termed ‘salt wars’. Trinquart and colleagues conducted a ‘meta-knowledge’ analysis—a twostep process: first, examining the patterns of citation in relevant reports; and second, assessing the agreement in primary study selection in systematic reviews. The authors’ aim was to understand how the salt controversy has been sustained (over two decades) and explore how the beliefs or prejudices shape knowledge production. The idea of exploring citation bias is not new. Studies reporting small effects of salt reduction on blood pressure were cited much less often than one that demonstrated effects about 10 times greater (see Figure 1). This review included non-randomized studies, which exaggerated the apparent blood pressure reduction. Over the longer term, this citation bias has weakened (see Figure 2) but it is notable that this review is still being cited, probably because it was published in the British Medical Journal, perhaps taken to suggest higher quality research and being easy to find.

Effects of a specific blend of essential oils on apparent nutrient digestion, rumen fermentation and rumen microbial populations in sheep fed a 50:50 alfalfa hay:concentrate diet.

ObjectiveAn experiment was conducted to investigate the effects of a specific mixture of essential oils (MEO), containing thyme, clove and cinnamon EO, on rumen microbial fermentation, nutrient apparent digestibility and blood metabolites in fistulated sheep.MethodsSix sheep fitted with ruminal fistulas were used in a repeated measurement design with two 24-d periods to investigate the effect of adding MEO at 0 (control), 0.8, and 1.6 mL/d on apparent nutrient digestibility, rumen fermentation characteristics, rumen microbial population and blood chemical metabolites. Animals were fed with a 50:50 alfalfa hay:concentrate diet.ResultsRuminal pH, total volatile fatty acids (VFA) concentration, molar proportion of individual VFA, acetate: propionate ratio and methane production were not affected with MEO. Relative to the control, Small peptides plus amino acid nitrogen and large peptides nitrogen concentration in rumen fluid were not affected with MEO supplementation; while, rumen fluid ammonia nitrogen concentration at 0 and 6 h after morning feeding in sheep fed with 1.6 mL/d of MEO was lower (p<0.05) compared to the control and 0.8 mL/d of MEO. At 0 h after morning feeding, ammonia nitrogen concentration was higher (p<0.05) in sheep fed 0.8 mL/d of MEO relative to 1.6 mL/d and control diet. Ruminal protozoa and hyper ammonia producing (HAP) bacteria counts were not affected by addition of MEO in the diet. Relative to the control, no changes were observed in the red and white blood cells, hemoglobin, hematocrit, glucose, beta-hydroxybutyric acid, cholesterol, total protein, albumin, blood urea nitrogen and aspartate aminotransferase and alanine aminotransferase concentration. Apparent total tract digestibility of dry matter, crude proten, organic matter, and neutral detergent fiber were not influenced by MEO supplementation.ConclusionThe results of the present study suggested that supplementation of MEO may have limited effects on apparent nutrient digestibility, ruminal fermentation and protozoa and HAP bacteria count, blood cells and metabolites.

Effect of dietary cation–anion difference on ruminal metabolism, total apparent digestibility, blood and renal acid–base regulation in lactating dairy cows

The present study aimed to evaluate the effect of dietary cation–anion difference (DCAD) on ruminal fermentation, total apparent digestibility, blood and renal metabolism of lactating dairy cows. Sixteen Holstein cows were distributed in four contemporary 4×4 Latin Square designs, which consisted of four periods of 21 days and four treatments according to DCAD: +290; +192; +98 and −71 milliequivalent (mEq)/kg dry matter (DM). Ruminal pH and concentrations of acetic and butyric acid increased linearly according to the increase of DCAD. Similarly, NDF total apparent digestibility linearly increased by 6.38% when DCAD increased from −71 to 290 mEq/kg DM [Y=65.90 (SE=2.37)+0.0167 (SE=0.0068)×DCAD (mEq/kg DM)]. Blood pH was also increased according to DCAD, which resulted in reduction of serum concentrations of Na, K and ionic calcium (iCa). To maintain the blood acid–base homeostasis, renal metabolism played an important role in controlling serum concentrations of Na and K, since the Na and K urinary excretion increased linearly by 89.69% and 46.06%, respectively, from −71 to 290 mEq/kg DM. Changes in acid–base balance of biological fluids may directly affect the mineral composition of milk, as milk concentrations of Na, K, iCa and chlorides were reduced according to blood pH increased. Thus, it can be concluded that the increase of DCAD raises the pH of ruminal fluid, NDF total apparent digestibility, and blood pH, and decreases the milk concentration of cationic minerals, as well as the efficiency of Na utilization to milk production.

Defatted maize germ in equine diets

This study investigated the inclusion levels of defatted maize germ (DMG) in the diet of horses by determining the apparent digestibility coefficients of the nutrients, and the physicochemical parameters of feaces and blood samples. Four adult horses, weighing 483.3 ± 27.5 kg average, arranged in 4x4 Latin square were used. The energy provided by the diets came from hay, 50% (Jiggs hay), and from the concentrate, 50%, with increasing DMG levels (0, 10, 20 and 30%). Digestibility was determined using samples from total feaces collection. The characteristics of color, consistency, pH and buffering capacity (BC) 5 and 6 of the feaces were determined daily during the collection days. The blood samples were collected by venipuncture of the jugular, with vacuum tubes, to determine the concentration of glucose, triglycerides, cholesterol and insulin using biochemical kits and the concentration of short-chain fatty acids, by gas chromatography. The diets did not affect significantly (P> 0.05) the digestibility of nutrients, fecal pH (mean 6.7), buffering capacity at pH 5 (22.7) and pH 6 (6.9), and fecal concentration of short-chain fatty acids. Likewise, diets did not affect significantly (P> 0.05) the blood concentrations of glucose, insulin, cholesterol, and total short-chain fatty acids. However, diets changed significantly (P <0.05) the blood concentrations of triglycerides, described by the equation ŷ = 30.62 + 0.26x. The triglycerides, glucose and insulin variables also changed significantly (P <0.05) over time, according to the following equations: ŷ = 32.30 + 0.87x; ŷ = 85.93 + 3.17x – 0.61x²; and y = 3.19 + 1.38x – 0.22x², respectively. The defatted maize germ can be included up to 30% of the concentrate (up to 9.6% of the diet) without changing the diet apparent digestibility coefficient, and feaces and blood physicochemical parameters. This ingredient can be an alternative for high fiber diets and can contribute to formulating diets with lower glycemic and insulinemic indexes.

Quantitative Measurement of Cerebral Perfusion with Intravoxel Incoherent Motion in Acute Ischemia Stroke: Initial Clinical Experience.

Background:Intravoxel incoherent motion (IVIM) has the potential to provide both diffusion and perfusion information without an exogenous contrast agent, its application for the brain is promising, however, feasibility studies on this are relatively scarce. The aim of this study is to assess the feasibility of IVIM perfusion in patients with acute ischemic stroke (AIS).Methods:Patients with suspected AIS were examined by magnetic resonance imaging within 24 h of symptom onset. Fifteen patients (mean age was 68.7 ± 8.0 years) who underwent arterial spin labeling (ASL) and diffusion-weighted imaging (DWI) were identified as having AIS with ischemic penumbra were enrolled, where ischemic penumbra referred to the mismatch areas of ASL and DWI. Eleven different b-values were applied in the biexponential model. Regions of interest were selected in ischemic penumbras and contralateral normal brain regions. Fast apparent diffusion coefficients (ADCs) and ASL cerebral blood flow (CBF) were measured. The paired t-test was applied to compare ASL CBF, fast ADC, and slow ADC measurements between ischemic penumbras and contralateral normal brain regions. Linear regression and Pearson's correlation were used to evaluate the correlations among quantitative results.Results:The fast ADCs and ASL CBFs of ischemic penumbras were significantly lower than those of the contralateral normal brain regions (1.93 ± 0.78 μm2/ms vs. 3.97 ± 2.49 μm2/ms, P = 0.007; 13.5 ± 4.5 ml·100 g-1·min-1 vs. 29.1 ± 12.7 ml·100 g-1·min-1, P < 0.001, respectively). No significant difference was observed in slow ADCs between ischemic penumbras and contralateral normal brain regions (0.203 ± 0.090 μm2/ms vs. 0.198 ± 0.100 αμm2/ms, P = 0.451). Compared with contralateral normal brain regions, both CBFs and fast ADCs decreased in ischemic penumbras while slow ADCs remained the same. A significant correlation was detected between fast ADCs and ASL CBFs (r = 0.416, P < 0.05). No statistically significant correlation was observed between ASL CBFs and slow ADCs, or between fast ADCs and slow ADCs (r = 0.111, P = 0.558; r = 0.200, P = 0.289, respectively).Conclusions:The decrease in cerebral blood perfusion primarily results in the decrease in fast ADC in ischemic penumbras; therefore, fast ADC can reflect the perfusion situation in cerebral tissues.

Effects of a multi-strain Bacillus species-based direct-fed microbial on growth performance, nutrient digestibility, blood profile, and gut health in nursery pigs fed corn-soybean meal-based diets.

This experiment was conducted to investigate the effect of a spp.-based direct-fed microbial (DFM) on growth performance, apparent total tract digestibility (ATTD), blood profile, intestinal histomorphology, and fecal gas emission in piglets fed corn and soybean meal-based diets. The DFM product was based on 1 strain of and 2 strains of and formulated to supply 1.5 × 10 cfu/g of feed. A total of 128 piglets ([Yorkshire × Landrace] × Duroc; 6.8 ± 0.6 kg BW; weaning age: 24 d) were housed in groups (4 pigs/pen, 2 barrows and 2 gilts) and fed diets ( = 16) without or with DFM in a 2-phase feeding program: d 0 to 14 (phase I) and 15 to 42 (phase II). Feed intake and BW were measured weekly. At the end of each phase, samples for blood urea nitrogen (BUN), blood creatinine, ATTD, and fecal noxious gas emission were taken. At termination, 12 piglets per treatment were killed to access intestinal tissues for histomorphology. Overall, pigs fed DFM had a greater ( < 0.05) G:F than pigs fed the control diet. In phase I, pigs fed DFM showed a greater ( < 0.05) ADG and lower ( < 0.05) concentration of BUN and fecal ammonia emission than the control group. In phase II, a greater ( < 0.05) ATTD of nitrogen and longer ( < 0.05) duodenum and jejunum villi were observed in pigs fed the DFM diet compared with the control group. In conclusion, inclusion of DFM improved growth performance and villi length of the duodenum and jejunum in nursery pigs. Furthermore, DFM enhanced protein utilization as demonstrated by increased nitrogen digestibility, lower BUN, and lower fecal ammonia release.

Development of a Multiparametric Voxel-Based Magnetic Resonance Imaging Biomarker for Early Cancer Therapeutic Response Assessment

Quantitative magnetic resonance imaging (MRI)-based biomarkers, which capture physiological and functional tumor processes, were evaluated as imaging surrogates of early tumor response following chemoradiotherapy in glioma patients. A multiparametric extension of a voxel-based analysis, referred as the parametric response map (PRM), was applied to quantitative MRI maps to test the predictive potential of this metric for detecting response. Fifty-six subjects with newly diagnosed high-grade gliomas treated with radiation and concurrent temozolomide were enrolled in a single-site prospective institutional review board-approved MRI study. Apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) maps were acquired before therapy and 3 weeks after therapy was initiated. Multiparametric PRM (mPRM) was applied to both physiological MRI maps and evaluated as an imaging biomarker of patient survival. For comparison, single-biomarker PRMs were also evaluated in this study. The simultaneous analysis of ADC and rCBV by the mPRM approach was found to improve the predictive potential for patient survival over single PRM measures. With an array of quantitative imaging parameters being evaluated as biomarkers of therapeutic response, mPRM shows promise as a new methodology for consolidating physiologically distinct imaging parameters into a single interpretable and quantitative metric.

Improved black-blood imaging using DANTE-SPACE for simultaneous carotid and intracranial vessel wall evaluation.

The purpose of this study was to develop a three-dimensional black blood imaging method for simultaneously evaluating the carotid and intracranial arterial vessel walls with high spatial resolution and excellent blood suppression with and without contrast enhancement. The delay alternating with nutation for tailored excitation (DANTE) preparation module was incorporated into three-dimensional variable flip angle turbo spin echo (SPACE) sequence to improve blood signal suppression. Simulations and phantom studies were performed to quantify image contrast variations induced by DANTE. DANTE-SPACE, SPACE, and two-dimensional turbo spin echo were compared for apparent signal-to-noise ratio, contrast-to-noise ratio, and morphometric measurements in 14 healthy subjects. Preliminary clinical validation was performed in six symptomatic patients. Apparent residual luminal blood was observed in five (pre-contrast) and nine (post-contrast) subjects with SPACE and only two (post-contrast) subjects with DANTE-SPACE. DANTE-SPACE showed 31% (pre-contrast) and 100% (post-contrast) improvement in wall-to-blood contrast-to-noise ratio over SPACE. Vessel wall area measured from SPACE was significantly larger than that from DANTE-SPACE due to possible residual blood signal contamination. DANTE-SPACE showed the potential to detect vessel wall dissection and identify plaque components in patients. DANTE-SPACE significantly improved arterial and venous blood suppression compared with SPACE. Simultaneous high-resolution carotid and intracranial vessel wall imaging to potentially identify plaque components was feasible with a scan time under 6 min. Magn Reson Med 75:2286-2294, 2016. © 2015 Wiley Periodicals, Inc.

Magnitude of blood pressure reduction in the placebo arms of modern hypertension trials: implications for trials of renal denervation.

Early phase studies of novel interventions for hypertension, such as renal sympathetic denervation, are sometimes single-armed (uncontrolled). We explored the wisdom of this by quantifying the blood pressure fall in the placebo arms of contemporary trials of hypertension. We searched Medline up to June 2014 and identified blinded, randomized trials of hypertension therapy in which the control arm received placebo medication or a sham (placebo) procedure. For nonresistant hypertension, we have identified all such trials of drugs licensed by the US Food and Drug Administration since 2000 (5 drugs). This US Food and Drug Administration-related restriction was not applied to resistant hypertension trials. This produced 7451 patients, who were allocated to a blinded control from 52 trials of nonresistant hypertension and 694 patients from 8 trials of resistant hypertension (3 drugs and 2 interventions). Systolic blood pressure fell by 5.92 mm Hg (95% confidence interval, 5.14-6.71; P<0.0001) in the nonresistant cohort and by 8.76 mm Hg (95% confidence interval, 4.83-12.70; P<0.0001) in the resistant cohort. Using metaregression, the falls were larger in trials that did not use ambulatory blood pressure monitoring as an inclusion criterion (z=2.84; P=0.0045), in those with higher baseline blood pressures (z=-0.3; P=0.0001), and in those where the patients were prescribed a continuous background of antihypertensives (z=-2.72; P=0.0065). The nontrivial magnitude of these apparent blood pressure reductions with perfectly ineffective intervention (placebo) illustrates that efficacy explorations of novel therapies for hypertension, once safety is established, should be performed with a randomized, appropriately controlled, and blinded design.

Acute vocal fold dystonic reaction to propofol: a case report

A 67-year old male underwent uneventful robotic-assisted thoracoscopic resection of a solitary pulmonary fibrous tumor. Immediately following extubation at the completion of the surgical procedure, the patient developed respiratory distress that did not resolve with treatment. Benadryl provided only temporary relief. Midazolam and hydromorphone were given for anxiolysis and analgesia respectively, which provided transient relief of symptoms. Propofol was given to decrease upper airway reflexes. Adequate reversal from nondepolarizing neuromuscular blockade was confirmed with nerve stimulator. A flexible laryngoscope was introduced nasally to visualize the vocal cords, which revealed intermittent tremulousness of the vocal cords, adduction of bilateral vocal cords to the midline, and minimal to absent opening with inspiration, without any apparent injury or blood, saliva, or vomit noted in or around the glottic opening. The patient was then given diazepam and reintubated. Given the patient's history of difficulty breathing after previous surgery and the lack of vocal cord movement, dystonic reaction to propofol was suspected. The patient remained intubated for two hours in the post-anesthesia care unit before being extubated uneventfully.

NI-25 * PHYSIOLOGIC IMAGING IN PATIENTS WITH BRAIN METASTASES; HETEROGENEITY BASED UPON PRIMARY TUMOR SUBTYPE

BACKGROUND: Structural and biologic tissue characteristics prior to and following radiosurgery (SRS) can be quantified by analyzing physiologic imaging sequences including diffusion and perfusion weighted imaging (DWI, PWI) and considering their derived parameters including apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV). Increasingly in neuro-oncology, these types of imaging sequences are being considered as prognostic and diagnostic markers. Patients' primary tumor type may impact these imaging values, and an understanding of how baseline DWI and PWI measures depend upon primary tumor type is necessary in order to consider how these markers may impact therapeutic response or when considering diagnostic possibilities such as radiation necrosis. METHODS: 78 patients with 187 brain metastases were identified retrospectively from a cohort of patients who underwent SRS between August, 2011 and March 2014 at two institutions. Included subjects had undergone MRI with physiologic (DWI and PWI) imaging prior to SRS. The physiologic sequences were processed and co-registered to anatomic sequences acquired on the day of treatment. Lesions were segmented and ROIs were generated for image analysis using the T1 + Gd sequence. Quantitative measures included rCBV, rCBF, ADC and tumor volume for each lesion. Tumor subtypes included breast, lung, colon, melanoma, renal cell, ovarian, and “other”. RESULTS AND CONCLUSIONS: There was no significant difference in tumor volume based upon tumor type, although there was a trend toward larger tumors at diagnosis for colon and ovarian primaries. There was no significant difference in ADC between tumor type; a significant elevation in rCBV was seen for renal cell and ovarian primary tumors (2.51 and 2.46) when compared with breast, colon, melanoma and lung primary tumors (1.18, 1.24, 1.38, 1.27, respectively). When considering questions of diagnostic specificity, it is important to recognize the relatively low rCBV in many active brain metastases, particularly as compared with primary brain tumors.

Is there a place for microsurgical vascular decompression of the brainstem for apparent essential blood hypertension? a review.

There are anatomical and physiological evidences that the ventrolateral (VL) region of the medulla plays an important role in blood pressure regulation and that dysfunction at this level may generate hypertension (HT). Vascular compression by a megadolicho-artery from the vertebrobasilar arterial system at the root entry/exit zone (REZ) of the glossopharyngeal (IXth) and vagal (Xth) cranial nerves (CNs) and the adjacent VL aspect of the medulla has been postulated as a causal factor for HT from neurogenic origin. The first attempts at microvascular decompression (MVD) of the IX-Xth CNs together with the neighbouring VL brainstem was revealed promising. These surgical attempts, as well as the numerous MRI studies, with the goal to detect and identify likely responsible neurovascular conflicts (NVC), are reviewed. Established criteria for indication of MVD as an aetiological treatment of apparent essential HT are still needed.