Technical Aspects of Fecal Microbial Transplantation (FMT).

PURPOSE OF REVIEW: Fecal microbial transplantation (FMT) has become established as an effective therapeutic modality in the treatment of antibiotic-refractory recurrent Clostridium difficile colitis. A number of formulations and methods of delivery of FMT are currently available, each with distinct advantages. This review aims to review donor and patient selection for FMT as well as procedural aspects of FMT to help guide clinical practice. RECENT FINDINGS: FMT can be obtained in fresh, frozen, lyophilized, and capsule-based formulations for delivery by oral ingestion, nasoenteric tube, colonoscopy, or enema (depending on the formulation used). Choosing the optimal method relies heavily on patient-related factors, including underlying pathology and severity of illness. As potential applications for FMT expand, careful donor screening and patient selection are critical to minimizing risk to patients and physicians. FMT represents an excellent therapeutic option for treatment of recurrent Clostridium difficile colitis and holds promise as a possible treatment modality in a variety of other conditions. The wide array of delivery methods allows for its application in various disease states in both the inpatient and outpatient setting.

A system for detecting high impact-low frequency mutations in primary tumors and metastases.

Tumor complexity and intratumor heterogeneity contribute to subclonal diversity. Despite advances in next-generation sequencing (NGS) and bioinformatics, detecting rare mutations in primary tumors and metastases contributing to subclonal diversity is a challenge for precision genomics. Here, in order to identify rare mutations, we adapted a recently described epithelial reprograming assay for short-term propagation of epithelial cells from primary and metastatic tumors. Using this approach, we expanded minor clones and obtained epithelial cell-specific DNA/RNA for quantitative NGS analysis. Comparative Ampliseq Comprehensive Cancer Panel sequence analyses were performed on DNA from unprocessed breast tumor and tumor cells propagated from the same tumor. We identified previously uncharacterized mutations present only in the cultured tumor cells, a subset of which has been reported in brain metastatic but not primary breast tumors. In addition, whole-genome sequencing identified mutations enriched in liver metastases of various cancers, including Notch pathway mutations/chromosomal inversions in 5/5 liver metastases, irrespective of cancer types. Mutations/rearrangements in FHIT, involved in purine metabolism, were detected in 4/5 liver metastases, and the same four liver metastases shared mutations in 32 genes, including mutations of different HLA-DR family members affecting OX40 signaling pathway, which could impact the immune response to metastatic cells. Pathway analyses of all mutated genes in liver metastases showed aberrant tumor necrosis factor and transforming growth factor signaling in metastatic cells. Epigenetic regulators including KMT2C/MLL3 and ARID1B, which are mutated in >50% of hepatocellular carcinomas, were also mutated in liver metastases. Thus, irrespective of cancer types, organ-specific metastases may share common genomic aberrations. Since recent studies show independent evolution of primary tumors and metastases and in most cases mutation burden is higher in metastases than primary tumors, the method described here may allow early detection of subclonal somatic alterations associated with metastatic progression and potentially identify therapeutically actionable, metastasis-specific genomic aberrations.

Are low sun exposure and/or vitamin D risk factors for type 1 diabetes?

The global variation in type 1 diabetes (T1D) incidence rates is one of the most significant observed for any non-communicable disease. Geographical patterns in incidence suggest that low sun exposure may contribute to the wide disparity, with incidence rates generally increasing with distance from the Equator. T1D development is associated with hyperactivity of the adaptive immune system leading to autoimmune destruction of insulin-secreting pancreatic ß cells. Both exposure to ultraviolet radiation (UVR) and vitamin D, with their known immunosuppressive effects, have the potential to delay or inhibit the disease. Efforts to confirm the role of UVR by vitamin D dependent and independent pathways in the pathogenesis of T1D have been challenged by inconsistent results among studies. Human observational studies and animal and in vitro experiments indicate that at least some of the benefits of sun exposure come from improved vitamin D status. There is no evidence of benefit for T1D risk of vitamin D supplementation during pregnancy at current recommended levels (400 IU per day); but some evidence supports that higher sun exposure and/or vitamin D sufficiency in pregnancy, or supplementation in early life, decreases T1D risk. Further research is required to confirm an association between UVR exposure and T1D and clarify the mechanisms involved.

Interaction between supplemental zinc oxide and zilpaterol hydrochloride on growth performance, carcass traits, and blood metabolites in feedlot steers.

Interactive effects of supplemental Zn and zilpaterol hydrochloride (ZH) were evaluated in feedlot steers ( = 40; 652 kg ± 14 initial BW) to determine their impact on feedlot performance, blood constituents, and carcass traits. The study was conducted as a randomized complete block design with a 2 × 2 factorial treatment arrangement. Steers were blocked by BW and randomly assigned to treatments. Factors consisted of supplemental Zn (60 or 300 mg/kg diet DM) and ZH (0 or 8.33 mg/kg) in the diets. For diets supplemented with 300 mg Zn/kg DM, 60 mg Zn/kg was supplemented as zinc sulfate and 240 mg Zn/kg was supplemented as zinc oxide, and the diet was fed for 24 d. Zilpaterol hydrochloride was fed for 21 d followed by a 3-d withdrawal. Cattle were housed in partially covered individual feeding pens equipped with automatic waterers and fence-line feed bunks and were fed once daily for ad libitum intake. Plasma samples were collected on d 0 and 21 to assess changes in Zn, plasma urea nitrogen (PUN), glucose, and lactate concentrations, and serum samples were collected on d 21 to assess IGF-1 concentration. On d 25, cattle were weighed and transported 450 km to a commercial abattoir for harvest; HCW and incidence of liver abscesses were recorded. Carcass data were collected after 36 h of refrigeration. Data were analyzed as a mixed model with Zn, ZH, and Zn × ZH as fixed effects; block as a random effect; and steer as the experimental unit. No interaction or effects of Zn or ZH were observed for IGF-1 concentration, plasma glucose, or lactate concentrations ( ≥ 0.25). No interaction between Zn and ZH was observed for PUN concentration, but PUN decreased with ZH ( < 0.01). There were no effects of ZH or Zn on ADG, DMI, final BW, feed efficiency, HCW, back fat, KPH, quality grade, or incidence of liver abscesses ( > 0.05). Zinc supplementation tended ( = 0.08) to improve the proportion of carcasses grading USDA Choice. Feeding ZH decreased yield grade ( = 0.05) and tended to increase LM area ( = 0.07). In conclusion, increasing dietary concentrations of Zn does not impact response to ZH, but feeding ZH altered circulating concentrations of PUN.

Effects of crystalline menthol on blood metabolites in Holstein steers and in vitro volatile fatty acid and gas production.

Fifty-two Holstein steers (573 ± 9.92 kg BW) were used to determine if oral administration of crystalline menthol would induce changes in endogenous secretions of IGF-1 and circulating concentrations of glucose, lactate, and plasma urea nitrogen (PUN). Steers were blocked by BW and assigned within block to treatment. Treatments consisted of 0, 0.003, 0.03, or 0.3% crystalline menthol (DM basis) added to the diet. Animals were housed in individual, partially covered pens equipped with feed bunks and automatic water fountains. On d 1 of the experiment, blood samples were obtained via jugular venipuncture at 0, 6, 12, 18, and 24 h after feeding. Treatment administration commenced on d 2, and blood samples were again drawn at 0, 6, 12, 18, and 24 h after feeding. This blood-sampling schedule was repeated on d 9, 16, 23, and 30. Plasma was analyzed for PUN, glucose, and lactate concentrations. Serum was used to analyze IGF-1 concentration. Body weights were measured on d 1, 9, 16, 23, and 30. To accompany the live animal phase, in vitro fermentations were performed using ruminal fluid cultures. Measurements included VFA concentrations and fermentative gas production for cultures containing crystalline menthol at 0, 0.003, 0.03, or 0.3% of substrate DM. Addition of menthol to the diet of steers resulted in a treatment × day interaction ( < 0.01) for concentrations of IGF-1, PUN, and plasma glucose. Cattle fed 0 and 0.003% menthol had greater serum IGF-1 concentrations on d 2 compared with steers fed 0.03% menthol. Steers fed 0% menthol had greater serum IGF-1 concentrations on d 9 compared with steers fed 0.03 and 0.3% menthol, whereas no differences were observed on d 23 or 30. Plasma glucose was similar among treatments until d 23, when steers supplemented with 0.03% menthol had lower glucose concentrations. Plasma urea nitrogen concentrations were not different among treatments; however, PUN concentrations varied by day. A linear response was detected for BW ( = 0.03), with steers consuming 0% menthol having the greatest BW and steers that consumed 0.3% menthol having the lightest BW until d 30. A menthol × day interaction was observed for daily feed deliveries ( < 0.01): cattle fed 0.3% menthol consumed less feed from d 5 through 12. Furthermore, in vitro gas production and VFA concentrations were unaffected by addition of menthol ( > 0.21). In conclusion, menthol supplementation minimally affected blood parameters associated with growth or ruminal fermentative activity.

Dentatorubrothalamic tract localization with postmortem MR diffusion tractography compared to histological 3D reconstruction.

Diffusion-weighted imaging (DWI) tractography is a technique with great potential to characterize the in vivo anatomical position and integrity of white matter tracts. Tractography, however, remains an estimation of white matter tracts, and false-positive and false-negative rates are not available. The goal of the present study was to compare postmortem tractography of the dentatorubrothalamic tract (DRTT) by its 3D histological reconstruction, to estimate the reliability of the tractography algorithm in this specific tract. Recent studies have shown that the cerebellum is involved in cognitive, language and emotional functions besides its role in motor control. However, the exact working mechanism of the cerebellum is still to be elucidated. As the DRTT is the main output tract it is of special interest for the neuroscience and clinical community. A postmortem human brain specimen was scanned on a 7T MRI scanner using a diffusion-weighted steady-state free precession sequence. Tractography was performed with PROBTRACKX. The specimen was subsequently serially sectioned and stained for myelin using a modified Heidenhain-Woelke staining. Image registration permitted the 3D reconstruction of the histological sections and comparison with MRI. The spatial concordance between the two modalities was evaluated using ROC analysis and a similarity index (SI). ROC curves showed a high sensitivity and specificity in general. Highest measures were observed in the superior cerebellar peduncle with an SI of 0.72. Less overlap was found in the decussation of the DRTT at the level of the mesencephalon. The study demonstrates high spatial accuracy of postmortem probabilistic tractography of the DRTT when compared to a 3D histological reconstruction. This gives hopeful prospect for studying structure-function correlations in patients with cerebellar disorders using tractography of the DRTT.

Effects of flaxseed encapsulation on biohydrogenation of polyunsaturated fatty acids by ruminal microorganisms: feedlot performance, carcass quality, and tissue fatty acid composition.

The objective of this study was to evaluate the efficacy of protecting PUFA within ground flaxseed against ruminal biohydrogenation by encapsulating them in a matrix consisting of a 1:1 blend of ground flaxseed and dolomitic lime hydrate (L-Flaxseed). Crossbreed heifers ( = 462, 346 ± 19 kg) were blocked by weight and randomly assigned to pens. Pens were assigned to 1 of 6 dietary treatments in a randomized complete block design. Treatment 1 consisted of a combination of 54.6% steam-flaked corn (SFC), 30.0% wet corn gluten feed, 8.0% roughage, and supplement (0% flaxseed). In treatments 2 and 3, a proportion of SFC was replaced with 3 and 6% flaxseed, respectively; in treatments 4, 5, and 6, SFC was replaced with 2, 4, or 6% L-Flaxseed, respectively. Cattle were fed for 140 or 168 d and then harvested in a commercial abattoir where carcass data were collected. Approximately 24 h after harvest, carcasses were evaluated for 12th-rib fat thickness, KPH, LM area, marbling score, and USDA yield and quality grades. Samples of LM were also obtained for determination of long-chain fatty acid profiles. Cattle that were fed diets with 4 and 6% L-Flaxseed consumed less feed than other treatments ( < 0.05), which adversely affected ADG. Compared with cattle fed 0% flaxseed, cattle in these treatments had lower final BW (18 and 45 kg less for the 4 and 6% L-Flaxseed treatments, respectively), less ADG (0.16 and 0.48 kg/day less for the 4 and 6% L-Flaxseed treatments, respectively), and lower carcass weights, dressing percentages, LM areas, backfat thicknesses, and marbling scores ( < 0.05). The addition of flaxseed or 2% L-Flaxseed did not affect performance or carcass traits ( > 0.05). Supplementation with flaxseed increased ( < 0.05) the concentration of α-linolenic acid (ALA) in meat (0.173, 0.482, 0.743 mg/g for 0, 3, and 6% flaxseed, respectively). Furthermore, proportionate increases in the ALA content of muscle tissue were 47% greater when flaxseed was encapsulated within the dolomitic lime hydrate matrix (0.288, 0.433, 0.592 mg/g for 2, 4, and 6% L-Flaxseed, respectively). Both products showed a linear response in ALA concentration ( > 99%; increases for Flaxseed and L-Flaxseed of 0.095 and 0.140 mg of ALA/g of tissue for each percentage of flaxseed added). This study indicates that a matrix consisting of dolomitic lime hydrate is an effective barrier to ruminal biohydrogenation of PUFA; however, adverse effects on DMI limit the amounts that can be fed.

Manipulation of dietary calcium concentration to potentiate changes in tenderness of beef from heifers supplemented with zilpaterol hydrochloride.

Dietary Ca concentrations were manipulated during supplementation of zilpaterol hydrochloride (ZH) to evaluate impact on feedlot performance, carcass characteristics, and beef tenderness using 96 heifers (BW 392 kg ± 3.2). We hypothesized that temporary depletion followed by repletion of dietary Ca before harvest would increase intracellular Ca concentrations, thus stimulating postmortem activity of Ca-dependent proteases to effect changes in tenderness. Heifers were stratified by initial BW and randomly assigned, within strata (block), to treatments consisting of a finishing diet in which Ca was added in the form of limestone (+Ca) or removed (-Ca) during ZH supplementation. Cattle were fed a common diet, including limestone, before ZH supplementation, and 28 d before slaughter, ZH was added to the diet with and without supplemental Ca. Calcium content of the diets during ZH supplementation was 0.74% or 0.19% (diet DM) for +Ca and -Ca, respectively. Zilpaterol hydrochloride was fed for 25 d then removed from the diet 3 d before harvest. The final 3 d before harvest, all cattle were fed Ca at 0.74% of diet DM. Heifers were housed in concrete-surfaced pens with 8 animals/pen (6 pens/treatment). At the end of the finishing phase, animals were weighed and transported to an abattoir in Holcomb, KS. Severity of liver abscesses and HCW were collected the day of harvest, and after 48 h of refrigeration, USDA yield and quality grades, KPH, LM area, and 12th-rib subcutaneous fat thickness were determined. Boneless loin sections were also collected for Warner-Bratzler shear force determination. Removal of Ca did not affect Warner-Bratzler shear force values (P = 0.64). In addition, ADG, DMI, final BW, and feed efficiency were unaffected by treatment (P > 0.05). Carcass measurements also were unaffected by the temporary decrease in dietary Ca (P > 0.05). In conclusion, temporary depletion of dietary Ca during ZH supplementation did not alter beef tenderness, live animal performance, or carcass measurements.

Effects of zilpaterol hydrochloride on growth performance, blood metabolites, and fatty acid profiles of plasma and adipose tissue in finishing steers.

The effects of zilpaterol hydrochloride (ZH) on blood metabolites and fatty acid profiles of plasma and adipose tissue were evaluated in crossbred finishing steers (n = 18, BW 639 ± 12.69 kg) that were stratified by BW and randomly assigned, within strata (block), to receive 0 (control) or 8.33 mg/kg diet DM ZH. Cattle were fed once daily ad libitum in individual feeding pens (9 pens/treatment). Zilpaterol hydrochloride was fed for 23 d and withdrawn 3 d before harvest. Blood samples and measures of BW were taken on d 0, 7, 14, and 21. Concentrations of ß-hydroxybutyrate (BHB), glucose, and lactate were determined from whole blood. Nonesterified fatty acids, urea nitrogen (PUN), glucose, lactate, and long-chain fatty acid (LCFA) concentrations were analyzed from plasma. Postharvest, adipose tissue samples (approximately 20 g) from subcutaneous fat covering the lumbar vertebrae were collected after 48 h of refrigeration and analyzed for LCFA profiles. Feeding ZH decreased DMI by 8% (P = 0.03) but did not affect BW gain or efficiency (P = 0.83 and P = 0.56, respectively). Addition of ZH resulted in greater HCW, dressing percentage, and LM area ( P = 0.02, P = 0.08, and P = 0.07, respectively) but did not influence other carcass traits (P > 0.10). A ZH × d interaction was observed for PUN and whole-blood glucose concentrations (P = 0.06), in which concentrations decreased in cattle receiving ZH. Nonesterified fatty acids, BHB, plasma glucose, whole-blood, and plasma lactate concentrations were unaffected by ZH (P > 0.10). Zilpaterol hydrochloride increased plasma concentrations of elaidic (P = 0.03), vaccenic (P = 0.006), and docosapentaenoic acids ( P= 0.08), but LCFA concentrations of adipose tissue were unaffected ( P> 0.10), suggesting no preferential oxidation of specific fatty acids. In conclusion, ZH supplementation decreased PUN concentration possibly due to decreased muscle catabolism, but components of blood related to lipid oxidation were unaffected.

Effects of the Programmed Nutrition Beef Program on feedlot performance and carcass characteristics.

The objective of this study was to examine the effects of alternative finishing strategies on feedlot performance and carcass characteristics. Beef steers (64 pens; 8 steers/pen) were allocated to a randomized complete block design with a 2 × 2 factorial treatment arrangement. Factor 1 consisted of diet, with cattle fed a conventional (CON) diet or a diet consisting of Programmed Nutrition Beef Program (PN) supplements. The PN treatment included Programmed Nutrition Beef Receiver fed from d 1 through 20 of feeding and Programmed Nutrition Beef Finisher fed from d 21 to harvest. Factor 2 evaluated the presence (EGP+) or absence (EGP-) of exogenous growth promotants (ExGP) in the production system. Steers in the EGP+ treatments were initially implanted with Component E-S, reimplanted with Component TE-IS, and fed 400 mg·animal·dof ractopamine hydrochloride for the final 28 d before harvest. Steers were harvested on d 175, and strip loins were removed from 2 carcasses selected at random from each pen for transport to Kansas State University. One 1.27-cm-thick steak was removed from the anterior face for proximate and long-chain fatty acid analysis. There were no diet × ExGP interactions ( > 0.10) for feedlot performance except for DMI ( = 0.02). Steers in the PN/EGP+ treatment consumed more feed than all other treatments ( < 0.05). Both diet and ExGP affected DMI ( < 0.05), with PN and EGP+ steers consuming more feed than their contemporaries. Gain:feed and ADG were unaffected ( > 0.10) by diet, but ExGP improved these measures ( < 0.01). There were no diet × ExGP interactions for carcass characteristics except KPH fat and percentages of yield grade 3 and 4 carcasses ( < 0.05). Diet affected total incidence of liver abscesses because PN steers had a greater ( = 0.05) incidence of liver abscesses than steers in the CON treatment. Diet did not affect the other carcass characteristics ( > 0.10). Use of ExGP increased ( < 0.05) HCW, LM area, and 12th-rib fat but did not affect ( > 0.10) marbling score. Using ExGP reduced the percentage carcasses grading Premium Choice ( < 0.05). No diet × ExGP interactions or diet effects were detected for long-chain fatty acid profiles ( > 0.10). Use of ExGP increased ( < 0.05) the ratio of saturated:unsaturated fatty acids. In summary, the alternative feeding strategy presented in this study produced similar feedlot performance and carcass characteristics compared with a conventional feedlot system.

Replacing stressful challenges with positive coping strategies: a resilience program for clinical placement learning.

Clinical education is foundational to health professional training. However, it is also a time of increased stress for students. A student's perception of stressors and their capacity to effectively manage them is a legitimate concern for educators, because anxiety and decreased coping strategies can interfere with effective learning, clinical performance and capacity to care for patients. Resilience is emerging as a valuable construct to underpin positive coping strategies for learning and professional practice. We report the development and evaluation of a psycho-education resilience program designed to build practical skills-based resilience capacities in health science (physiotherapy) students. Six final year undergraduate physiotherapy students attended four action research sessions led by a clinical health psychologist. Resilience strategies drawn from cognitive behavioural therapy, and positive and performance psychology were introduced. Students identified personal learning stressors and their beliefs and responses. They chose specific resilience-based strategies to address them, and then reported their impact on learning performance and experiences. Thematic analysis of the audio-recorded and transcribed action research sessions, and students' de identified notes was conducted. Students' initial descriptions of stressors as 'problems' outside their control resulting in poor thinking and communication, low confidence and frustration, changed to a focus on how they managed and recognized learning challenges as normal or at least expected elements of the clinical learning environment. The research suggests that replacing stressful challenges with positive coping strategies offers a potentially powerful tool to build self-efficacy and cognitive control as well as greater self-awareness as a learner and future health practitioner.

Effects of feeding diets rich in α-linolenic acid and copper on performance, carcass characteristics, and fatty acid profiles of feedlot heifers.

Our objective was to evaluate whether feeding elevated Cu concentrations in conjunction with Linpro, a co-extruded blend of field peas and flaxseed, affected in vitro fermentation, performance, and plasma lipid profiles of fattening beef heifers. In study 1, 2 in vitro trials were conducted as randomized complete experiments with a 2×2 factorial treatment arrangement (10 or 100 mg/kg added Cu and 0 or 10% Linpro, DM basis) to determine VFA/gas production and IVDMD. Linpro contains 12% α-linolenic acid and added vitamins and minerals. In study 2, a randomized complete block experiment with a 2×2 factorial treatment arrangement was conducted with the same previously described treatment. Crossbred yearling heifers (n=261; 351±23 kg initial BW) were blocked by weight into heavy and light groups and randomly assigned to experimental pens containing 10 or 11 heifers each. In study 1, no interactions between levels of Cu and Linpro were observed. Copper concentration did not affect IVDMD (P>0.2) but increased (P<0.05) by 1.2% when Linpro was included. Final pH was not effected by added Cu (P>0.05), but pH increased when Linpro was added (P<0.05). Total VFA were greater in high-Cu treatments (P=0.038) and molar proportions were not affected (P>0.34). Linpro had no effect on total VFA (P=0.46) and molar proportions of propionate and isobutyrate increased whereas acetate and the acetate:propionate ratio decreased (P<0.01). Linpro increased the production of H2S (30% higher; P=0.05), and Cu inclusion slightly increased CO2 proportion (64.06 vs. 67.58% for Linpro vs. Cu treatments, respectively). In study 2, there were no interactions between levels of Linpro and supplemental Cu except for plasma n-6:n-3 ratio (P<0.01). Final BW were similar for cattle fed 0 and 10% Linpro (581 vs. 588 kg; P>0.20), but cattle fed diets with Linpro consumed less feed (14.08 vs. 13.59 kg/d; P<0.05) and were therefore more efficient (0.129 vs. 0.137 for 0 vs. 10% Linpro, respectively; P<0.01). Carcass traits were not affected by treatment. Feeding elevated levels of Cu did not appreciably alter PUFA proportions in plasma and LM. Plasma and LM concentrations of omega-3 fatty acids, including C18:3, C20:5, and C22:5, were greater for heifers fed Linpro (P<0.05). Increasing dietary Cu was not effective as a strategy for decreasing ruminal biohydrogenation and subsequent tissue deposition of PUFA.

Effects of the Programmed Nutrition Beef Program on meat quality characteristics.

The objective of this study was to examine the effects of alternative finishing strategies on beef steak color and cooked meat characteristics. Beef steers (n = 64 pens; 8 steers/pen) were allocated to a randomized complete block design with a 2 × 2 factorial treatment arrangement and initial body weight serving as the blocking factor. Factor 1 consisted of dietary treatment with cattle either being fed a conventional feedlot diet (CON) or a diet that included Programmed Nutrition Beef Program supplements. Cattle in the Programmed Nutrition (PN) treatments were fed in two-stages: 1) the basal diet with Programmed Nutrition Beef Receiver from d 1 to 20 and the basal diet with Programmed Nutrition Beef Finisher from d 21 to harvest. Factor 2 consisted of the inclusion (EGP+) or absence (EGP-) of an exogenous growth promoting program. Steers in the EGP+ treatments were implanted initially with Component E-S, reimplanted with Component TE-IS, and fed 400 mg · d(-1) · steer(-1) of ractopamine hydrochloride for the final 28 d before harvest. Steers were harvested on d 175 of feeding and 1 strip loin was removed from 2 carcasses selected at random from each pen for transport to Kansas State University. After 14 d of aging, loins were fabricated into 2.54-cm thick steaks for objective and trained sensory panel measurement of cooked meat characteristics and objective color measurements during 7 d retail display. There were no interactions (P > 0.10) between feeding strategy and exogenous growth promotants for all objective measures of color and cooked meat characteristics. Throughout the display period, PN steaks were darker (P = 0.02) than CON steaks, but surface percentages of oxymyoglobin and metmyoglobin and metmyoglobin reducing ability were unaffected by feeding strategy (P > 0.10). Loins and steaks from PN cattle possessed decreased moisture loss during aging and cooking (P < 0.01). Trained sensory panel evaluation of cooked meat revealed a dietary program × growth promotant interaction for myofibrillar tenderness, connective tissue amount, and overall tenderness (P = 0.01). Compared to the CON/EGP- and PN/EGP- treatments, steaks from the CON/EGP+ and PN/EGP+ treatments were evaluated by panelists as being less myofibrillar and overall tender (P < 0.05). The alternative feeding strategies presented in this study can favorably impact water-holding capacity without negatively compromising retail display discoloration.

[High-intensity focussed ultrasound in low-risk prostate cancer - oncological outcome and postinterventional quality of life of an inexperienced therapy centre in comparison with an experienced therapy centre]. / Hochintensiver fokussierter Ultraschall bei Low-Risk Prostatakarzinom - Onkologisches Outcome und postinterventionelle Lebensqualität im direkten Vergleich eines erfahrenen und unerfahrenen Therapiezentrums.

BACKGROUND: In patients with low-risk prostate cancer (PCa) the standard therapies carry a risk of overtreatment with potentially preventable side effects whereas restrained therapeutic strategies pose a risk of underestimation of the individual cancer risk. Alternative treatment options include thermal ablation strategies such as high-intensity focused ultrasound (HIFU). PATIENTS AND METHODS: 96 patients with low-risk PCa (D'Amico) were treated at 2 HIFU centres with different expertise (n=48, experienced centre Lyon/France; n=48 inexperienced centre Charité Berlin/Germany). Matched pairs were formed and analysed with regard to biochemical disease-free survival (BDFS) as well as postoperative functional parameters (micturition, erectile function). The matched pairs were discriminated as to whether they had received HIFU treatment alone or a combination of HIFU with transurethral resection of the prostate (TURP). Patients of the Lyon group were retrospectively matched through the @-registry database whereas patients of the Berlin group were prospectively evaluated. In the latter patients quality of life assessment was additionally inquired. RESULTS: Postoperative PSA-Nadir was lower in the Berlin group for patients with HIFU only (0.007 vs. Lyon 0.34 ng/ml; p=0.037) and HIFU+TURP (0.25 vs. Lyon 0.42 ng/ml; p=0.003). BDFS was comparable in both groups for HIFU only (Berlin 4.77, Lyon 5.23 years; p=0.741) but patients with combined HIFU+TURP in the Berlin group showed an unfavourable BDFS as compared to the Lyon group (Berlin 3.02, Lyon 4.59 years; p=0.05). In an analysis of Berlin subgroups especially patients who had received HIFU and TURP (n=4) within the same narcosis had an unfavourable BDFS (p=0.009). Median follow-up was 3.36 years for HIFU only and 2.26 years for HIFU+TURP. Neither HIFU only (p=0.117) nor HIFU+TURP (p=0.131) showed an impact on postoperative micturition. Erectile function was negatively influenced (HIFU: p=0.04; HIFU+TURP: p=0.036). There was no measurable change in quality of life after the treatment. CONCLUSION: The 4-year BDFS after HIFU and HIFU+TURP is comparable to that of the standard therapies. The erectile function is sustainably negatively influenced whereas postoperative micturition and quality of life were not affected by HIFU or HIFU+TURP. These results are strongly limited by the low patient count and the short follow-up period and require validation in prospective multicentre studies with higher number of cases.

Transient and state modulation of beta power in human subthalamic nucleus during speech production and finger movement.

Signs of Parkinson's disease (PD) are augmented by speech and repetitive motor tasks. The neurophysiological basis for this phenomenon is unknown, but may involve augmentation of ß (13-30 Hz) oscillations within the subthalamic nucleus (STN). We hypothesized that speech and motor tasks increase ß power in STN and propose a mechanism for clinical observations of worsening motor state during such behaviors. Subjects undergoing deep brain stimulation (DBS) surgery performed tasks while STN local field potential (LFP) data were collected. Power in the ß frequency range was analyzed across the entire recording to observe slow shifts related to block design and during time epochs synchronized to behavior to evaluate immediate fluctuations related to task execution. Bilaterally symmetric ß event related desynchronization was observed in analysis time-locked to subject motor and speech tasks. We also observed slow shifts of ß power associated with blocks of tasks. Repetitive combined speech and motor, and isolated motor blocks were associated with the highest bilateral ß power state. Overt speech alone and imagined speech were associated with a low bilateral ß power state. Thus, changing behavioral tasks is associated with bilateral switching of ß power states. This offers a potential neurophysiologic correlate of worsened PD motor signs experienced during clinical examination with provocative tasks: switching into a high ß power state may be responsible for worsening motor states in PD patients when performing unilateral repetitive motor tasks and combined speech and motor tasks. Beta state changes could be chronically measured and potentially used to control closed loop neuromodulatory devices in the future.

[Introduction of interdisciplinary prostate cancer centers based on the recommendations of the German Cancer Society. A cost-benefit analysis 3 years after accreditation]. / Etablierung von interdisziplinären Prostatakrebszentren nach den Empfehlungen der DKG. Eine Kosten-Nutzen-Analyse 3 Jahre nach Zertifizierung.

The introduction of prostate cancer treatment centers according to the criteria of the German Cancer Society ("Deutsche Krebsgesellschaft", DKG) aims at improving the quality of care for patients with prostate cancer. Systematic analyses of the effects and costs are lacking as yet. Three years after certification of the Interdisciplinary Prostate Cancer Center at the Charité Hospital Berlin we observed a decrease in the rate of positive surgical margins (tumor stage pT2), but other parameters of treatment quality including patient satisfaction remained unchanged. A survey among urologists of the region showed a high acceptance of prostate cancer centers in general. The majority of participating urologists appreciated the work of the Charité center, in particular the treatment recommendations given by the center were mostly followed and the majority of urologists regularly use educational activities of the center. However, only 30% of the participating urologists confirmed short-term improvements in the quality of patient care. Yearly additional costs for the Charité prostate cancer center are estimated at 205,000 euro (precertification phase and certification) and 138,000 euro (monitoring phase), despite the initial drop in mean treatment costs per case (radical prostatectomy). The introduction of prostate cancer treatment centers certified by the DKG is cost intensive, increases in treatment efficiency notwithstanding. Short-term improvements in quality of care cannot be unequivocally demonstrated. Prostate cancer centers serve an important role in counseling and medical education and may thus help disseminate evidence-based treatment strategies.

[Interdisciplinary recommendations for the treatment of metastatic renal cell carcinoma]. / Interdisziplinäre Empfehlungen zur Behandlung des metastasierten Nierenzellkarzinoms.

With the introduction of targeted drug therapies, a paradigm shift for the treatment of metastatic renal cell carcinoma has taken place. New compounds like sunitinib, sorafenib, bevacizumab and temsirolimus have become established as new therapeutic standards to replace the use of cytokines as standard therapy. Recently, these substances have been complemented by everolimus and pazopanib. An interdisciplinary consensus conference was held to discuss which criteria to consider when using these drugs (treatment sequence) and what questions remain unanswered based on the current study situation (open questions). Results from the 2009 conference provided the basis for the 2010 meeting. The results of the 2010 conference are presented as short theses.

[Interdisciplinary recommendations for the treatment of metastatic renal cell carcinoma]. / Interdisziplinäre Empfehlungen zur Behandlung des metastasierten Nierenzellkarzinoms.

With the introduction of targeted therapies, a -paradigm shift for the treatment of metastatic renal cell carcinoma has taken place. The use of cytokines as the long-standing standard therapy has declined. New compounds like sunitinib, -sorafenib, bevacizumab and temsirolimus have become established as new therapeutic standards. Since mid-2009, these substances have been complemented by everolimus. An interdisciplinary consensus conference was held to discuss what criteria to consider when using these drugs (treatment sequence) and what questions remain unanswered based on the current study situation (open questions). Results from the 2008 conference provided the basis for the 2009 meeting. The results of the 2009 conference are presented as short theses.

[What is most important is what comes across : Urological guidelines from the target group's point of view]. / Entscheidend ist, was ankommt : Urologische Leitlinien aus Sicht der Zielgruppe.

BACKGROUND: Guidelines are developed to improve the quality of patient care. The effect of German urologic guidelines has not been evaluated so far. Therefore, we aimed to systematically investigate the acceptance, use, and quality of the published guidelines from a user's perspective. METHODS: A link to an online questionnaire concerning use and barriers to the application of guidelines was distributed via e-mail by the German Society of Urology (DGU). German urologists' opinions on differences in national guideline quality were evaluated regarding prostate cancer (PCA), bladder cancer, germ cell tumors (GCT), renal cell carcinomas, and erectile dysfunction. RESULTS: Four hundred sixty-seven German urologists participated. More than 90% of the participants considered guidelines to be helpful. The Internet as the main tool for guideline distribution was favored by 28.4%, followed by publication in Urologe A. The main barrier to guideline usage was attributed to the lack of up-to date clinical data. Guidelines for GCT scored best in all quality categories and reached the highest level of use (65.8%), and 40.5% of participating urologists considered the additional establishment of comprehensive care centers for GCT as more effective for quality improvement than guideline development alone. For the other urologic tumors, especially PCA, guideline development was favored as a tool for quality improvement. CONCLUSION: More than 90% of participating urologists accept clinical guidelines as useful instruments in clinical practice and for therapeutic decisions. Our results should be integrated into guideline dissemination and implementation strategies in order to achieve a higher degree of treatment conformation to guidelines.

[Interdisciplinary recommendations for the treatment of metastatic renal cell carcinoma]. / Interdisziplinäre Empfehlungen zur Behandlung des metastasierten Nierenzellkarzinoms.

With the introduction of targeted therapies, a paradigm shift for the treatment of metastatic renal cell cancer has taken place. New compounds like sunitinib, sorafenib, bevacizumab and temsirolimus have become established as new therapeutic standards. An interdisciplinary consensus conference was held to discuss treatment sequences and open questions. Results from the 2007 conference provided the basis for the 2008 meeting. The results of the 2008 conference are presented as short theses.