Pre- and post-weaning nutrition status affects sheep mammary gland morphology and promotes differential gene expression.

Little is known about how varying the plane of nutrition before and after weaning can influence gene expression that drives mammary gland development (MGD). Therefore, the aim of this study was to investigate this paradigm in a seasonal sheep breed. Forty pre-weaning 30-day old Kurdish female lambs were fed either a low-nutrient and protein (L; 2.0 Mcal ME/kg DM; 8.70% crude protein [CP]) or high-nutrient and protein diet (H; 2.5 Mcal ME/kg DM; 14.80% CP). At d 120 (weaning), lambs were allocated into a 2 × 2 arrangement based on pre- and post-weaning diets, resulting in four groups (LL, LH, HL, HH). On d 210, mammary biopsy samples were taken for histomorphological and gene expression studies. Alveoli were larger in HH compared with all other groups (p < 0.05). Whilst estrogen receptor-alpha, progesterone receptor, growth hormone receptor and insulin-like growth factor binding protein-1 gene expression was modulated depending on pre- or post-weaning nutritional levels (p < 0.01). Overall, a consistent high plane of nutrition promoted MGD, with more a complex relationship evident between the expression of genes critical for mammary gland function and development. These findings provide scope for future tailored nutritional strategies to optimize both liveweight gain and MGD.

Short communication: effect of dietary supplementation with a mixture of fish and sunflower oils on the expression of key lipogenic and cholesterologenic genes in adipose tissues with different metabolic functions.

The present study investigated the effects of dietary fish and sunflower oils as sources of n-3, n-6 polyunsaturated fatty acids (PUFA) on the expression of key lipogenic and cholesterologenic genes in subcutaneous adipose tissue (SAT) and tail adipose tissue (TAT) of fat-tailed sheep. Twenty-six male Afshari lambs were divided into 4 groups. Three groups were fed a high concentrate basal diet plus 100 g/lamb/day oil supplement (OS; 60 g sunflower oil and 40 g fish oil) beyond a 21-day adaptation period for 10, 20, and 30 days (groups OS10, OS20, and OS30; n = 6, each) until slaughter. A control group was slaughtered at the last day of adaptation (OS0; n = 4). Expression of PPARγ, SREBP-1c, and SREBP-2 were determined in TAT and SAT. All transcription factors had lower expression in SAT than TAT. Feeding OS induced a similar pattern of SREBP-1c expression in both TAT and SAT with highest values in OS20. SREBP-2 mRNA decreased by > 50% in TAT of OS30 compared to OS0, whereas the expression of SREBP-2 mRNA did not change in SAT in the same period. PPARγ expression was not affected over time either in SAT or TAT. Plasma concentrations of cholesterol and blood urea nitrogen increased in OS20. The comparison of gene expression responses to OS in TAT vs. SAT suggest that PUFA-mediated effects on lipid metabolism differ between SAT and TAT, which may be linked to the specific role of TAT in energy and water balance under arid conditions.

Study of the intracellular nanoparticle-based radiosensitization mechanisms in F98 glioma cells treated with charged particle therapy through synchrotron-based infrared microspectroscopy.

The use of nanoparticles (NP) as dose enhancers in radiotherapy (RT) is a growing research field. Recently, the use of NP has been extended to charged particle therapy in order to improve the performance in radioresistant tumors. However, the biological mechanisms underlying the synergistic effects involved in NP-RT approaches are not clearly understood. Here, we used the capabilities of synchrotron-based Fourier Transform Infrared Microspectroscopy (SR-FTIRM) as a bio-analytical tool to elucidate the NP-induced cellular damage at the molecular level and at a single-cell scale. F98 glioma cells doped with AuNP and GdNP were irradiated using several types of medical ion beams (proton, helium, carbon and oxygen). Differences in cell composition were analyzed in the nucleic acids, protein and lipid spectral regions using multivariate methods (Principal Component Analysis, PCA). Several NP-induced cellular modifications were detected, such as conformational changes in secondary protein structures, intensity variations in the lipid CHx stretching bands, as well as complex DNA rearrangements following charged particle therapy irradiations. These spectral features seem to be correlated with the already shown enhancement both in the DNA damage response and in the reactive oxygen species (ROS) production by the NP, which causes cell damage in the form of protein, lipid, and/or DNA oxidations. Vibrational features were NP-dependent due to the NP heterogeneous radiosensitization capability. Our results provided new insights into the molecular changes in response to NP-based RT treatments using ion beams, and highlighted the relevance of SR-FTIRM as a useful and precise technique for assessing cell response to innovative radiotherapy approaches.

High frequency of BRAF V600E mutation in Iranian population ameloblastomas.

BACKGROUND: Ameloblastoma is a common locally invasive but slow-growing neoplasm of the jaws with an odontogenic origin. Association between BRAF V600E mutation and clinicopathologic features and behavior of ameloblastoma remains controversial. This study aimed to evaluate BRAF V600E gene mutation and expression of its related proteins with clinicopathologic parameters in conventional ameloblastoma. MATERIAL AND METHODS: 50 Formalin-fixed paraffin-embedded blocks were included in this study. Immunohistochemistry was done using rabbit monoclonal BRAF V600E mutation-specific antibody VE1. Quantitative real-time polymerase chain reaction assay was used for evaluating of BRAF V600E mutation. RESULTS: Expression of BRAF V600E antibody was Positive in 42 out of 50 cases (84%). 46 (92%) out of 50 specimens showed BRAF V600E mutation. There were 13 cases of recurrence (26%). 3 out of 4 cases with negative mutations did not show recurrence. CONCLUSIONS: We report the highest frequency (92%) of BRAF V600E mutation in ameloblastomas in the Iranian population. Although there was not a significant association between BRAF V600E­positive immunoexpression and recurrence and clinicopathologic parameters, its high frequency could emphasize its role as a therapeutic marker in the future.

Effect of metformin on germ cell-specific apoptosis, oxidative stress and epididymal sperm quality after testicular torsion/detorsion in rats.

The study was designed to evaluate the effects of metformin on apoptosis and epididymal sperm quality in a rat testicular ischaemia/reperfusion (I/R) injury model. A total of 72 male rats were divided into four groups (n = 18 for each group): group 1 (sham-operated group), group 2 (metformin group), group 3 (torsion/detorsion [T/D] + saline) and group 4 (T/D + 300 mg kg-1 metformin). Testicular torsion was achieved by rotating the right testis 720° in a clockwise direction for 1 hr. Tissue malondialdehyde (MDA) level and caspase-3 activity increased and the activities of catalase, superoxide dismutase and glutathione peroxidase decreased in comparison with sham-operated group 4 hr after detorsion (p < .001). In six rats of each group 24 hr after detorsion, histopathological changes and germ cell apoptosis were significantly deteriorated by measuring mean of seminiferous tubule diameters (MSTD) and TUNEL test. Moreover, 30 days after T/D, sperm concentration and motility were examined in six animals per group. Metformin pre-treatment reduced MDA and caspase-3 levels and normalised antioxidant enzyme activities 4 hr after detorsion, and germ cell apoptosis was significantly decreased, and the MSTD, as well as sperm functions, was significantly improved. Reduction in oxidative stress and apoptosis may have a major role in cytoprotective effects of metformin.

Numerical investigation of UF membrane to reduce energy consumption using double porosity approach.

Hollow fiber (HF) membranes with circular geometry, are used in many separation processes such as water and wastewater treatment. Since optimization of energy efficiency is important for wastewater treatment, the aim of this study was to investigate the effect of non-circular geometry of the inner surface of the HF on the separation performance. To this purpose, the HF bundle has been assumed as a double porous media having two porosities and permeabilities. Since these two parameters are defined by the geometry of the porous medium, any change in the geometry affects their values and the media performance. Therefore, in this study a mathematical modeling has been divided into five categories, including circular, oval, square, rectangular and triangular geometries, and their geometric properties have been calculated based on three different strategies. The results have been compared with the data obtained from literature and showed that the membrane inner surface to cross-section area ratio (a), axial permeability, and porosity in the inner region for the non-circular HF are larger than that of the circular HF and a increased 16%, 27%, 35% and 65% in ellipse, square, rectangle and triangle geometry, respectively, in comparison with the circle. Axial permeability increased 98%, 68%, 63%, and 26% for a triangle, rectangle, ellipse, and square respectively in the third strategy when compared to the circle. Due to 50% feed flow rate reduction, maximum transmembrane pressure (TMP) reduction was 85% related to the rectangular geometry in the first strategy and minimum was 55% corresponding to the triangle in the third strategy. As a increased up to 65%, TMP reduced by up to 200% and consequently energy consumption and operating costs of the system are decreased.

Evidence-based dentistry can effectively be taught to dental care professional students - A mixed methods study.

BACKGROUND: Little research exists in the teaching of evidence-based dentistry (EBD) to students in the fields of dental hygiene, dental nursing and orthodontic therapy. This study aims to analyse the effect of a 1-day EBD programme on knowledge and confidence whilst also gaining insight into students' experience of the intervention. METHOD: A mixed methods study was utilised with explanatory sequential design. The population consisted of dental hygiene (DH), dental nursing (DN) and orthodontic therapy (OT) students (N = 44). The intervention consisted of a 1-day active learning EBD programme, delivered via group projects and lectures. In the initial quantitative phase, a standardised questionnaire pre- and post -intervention measured changes in confidence for all participants, whilst change in knowledge was measured for DH and OT students only. Following this, focus groups were scheduled for all members of each discipline 3 months post-intervention for DN and 2 months post-intervention for DH and OT students. Semi-structured focus group schedules were drawn up, and groups organised according to the outcomes of quantitative data analysis. Qualitative results were analysed using a deductive adaptation of Burnard's thematic content analysis. RESULTS: Forty-two students took part (94.45%) in this study. Median knowledge scores increased from zero to two of five (P < .001), whilst median confidence score doubled from four to eight of eight (P < .001). Results of thematic content analysis were coincident with quantitative results; however, it also provided constructive feedback regarding design and content of the course. CONCLUSIONS: A 1-day bespoke programme in EBD increased students' confidence and knowledge in EBD skills. However, the findings further suggest that two successive half-day training sessions instead of one full-day training, tied in with coursework that requires the application of the acquired skills, may increase the learning experience further.

Intensity-modulated proton therapy, volumetric-modulated arc therapy, and 3D conformal radiotherapy in anaplastic astrocytoma and glioblastoma : A dosimetric comparison.

PURPOSE: The prognosis for high-grade glioma (HGG) patients is poor; thus, treatment-related side effects need to be minimized to conserve quality of life and functionality. Advanced techniques such as proton radiation therapy (PRT) and volumetric-modulated arc therapy (VMAT) may potentially further reduce the frequency and severity of radiogenic impairment. MATERIALS AND METHODS: We retrospectively assessed 12 HGG patients who had undergone postoperative intensity-modulated proton therapy (IMPT). VMAT and 3D conformal radiotherapy (3D-CRT) plans were generated and optimized for comparison after contouring crucial neuronal structures important for neurogenesis and neurocognitive function. Integral dose (ID), homogeneity index (HI), and inhomogeneity coefficient (IC) were calculated from dose statistics. Toxicity data were evaluated. RESULTS: Target volume coverage was comparable for all three modalities. Compared to 3D-CRT and VMAT, PRT showed statistically significant reductions (p < 0.05) in mean dose to whole brain (-20.2 %, -22.7 %); supratentorial (-14.2 %, -20,8 %) and infratentorial (-91.0 %, -77.0 %) regions; brainstem (-67.6 %, -28.1 %); pituitary gland (-52.9 %, -52.5 %); contralateral hippocampus (-98.9 %, -98.7 %); and contralateral subventricular zone (-62.7 %, -66.7 %, respectively). Fatigue (91.7 %), radiation dermatitis (75.0 %), focal alopecia (100.0 %), nausea (41.7 %), cephalgia (58.3 %), and transient cerebral edema (16.7 %) were the most common acute toxicities. CONCLUSION: Essential dose reduction while maintaining equal target volume coverage was observed using PRT, particularly in contralaterally located critical neuronal structures, areas of neurogenesis, and structures of neurocognitive functions. These findings were supported by preliminary clinical results confirming the safety and feasibility of PRT in HGG.

Comparative in vitro activity of carbapenems against clinical isolates of Acinetobacter baumannii.

AIMS: The aim of this multi-hospital study was to assess the in vitro activity of doripenem and its comparators, imipenem and meropenem, using the new CLSI breakpoints against a large population of a frequently isolated nosocomial pathogen, Acinetobacter baumannii. METHODS AND RESULTS: During a 2-year period, four referral or tertiary hospitals submitted 400 isolates of Ac. baumannii for susceptibility testing using imipenem, meropenem and doripenem via disc diffusion and E-test methods. A subset of 390 isolates was resistant to all three tested carbapenems. Doripenem and meropenem (MIC50 , 32 µg ml(-1) ) had comparable activity, albeit doripenem's activity was greater than imipenem (MIC50 , >32 µg ml(-1) ). A significantly higher proportion of the isolates were inhibited by doripenem than by imipenem at MIC values of 12, 16, 24 and 32 µg ml(-1) (P < 0·05). The cumulative percentage of imipenem MICs was lower compared to its comparators. The comparison of resistance rate to imipenem and meropenem based on old and new breakpoints showed <1% difference. The overall agreement between the two susceptibility testing methods was ≥95%. CONCLUSION: Doripenem has a slightly greater in vitro activity than imipenem in terms of zone breakpoints and MIC values, but its activity is comparable to meropenem. SIGNIFICANCE AND IMPACT OF THE STUDY: Doripenem should be considered as a therapeutic option for monotherapy or combination therapy, particularly when the therapeutic options are limited.

Effect of vitamin D on stress-induced hyperglycaemia and insulin resistance in critically ill patients.

AIM: Effects of vitamin D supplementation on the glycaemic indices and insulin resistance in diabetic and non-diabetic patients were studied. In this study, effects of vitamin D supplementation on stress-induced hyperglycaemia and insulin resistance were evaluated in non-diabetic surgical critically ill patients. METHODS: Adult surgical patients with stress-induced hyperglycaemia within the first 24 h of admission to the ICU were recruited. The patients randomly assigned to receive either vitamin D or placebo. Patients in the vitamin D group received a single dose of 600,000 IU vitamin D3 as intramuscular injection at time of recruitment. Besides demographic and clinical characteristics of the patients, plasma glucose, insulin, 25(OH) D and adiponectin levels were measured at the time of ICU admission and day 7. Homoeostasis model assessment for insulin resistance (HOMA-IR) and homestasis model assessment adiponectin (HOMA-AD) ratio were considered at the times of assessment. RESULTS: Comparing with the baseline, plasma 25(OH) D level significantly increased in the subjects who received vitamin D (p = 0.04). Improvement in fasting plasma glucose levels was detected in day 7 of the study compared with the baseline status in both groups. HOMA-IR showed a decrement pattern in vitamin D group (p = 0.09). Fasting plasma adiponectin levels increased significantly in the vitamin D group (p = 0.007), but not in the placebo group (p = 0.38). Finally, changes in HOMA-AD ratio were not significant in the both groups. CONCLUSION: Vitamin D supplementation showed positive effect on plasma adiponectin level, as a biomarker of insulin sensitivity in surgical critically ill patients with stress-induced hyperglycaemia. However, effects of vitamin D supplementation on HOMA-IR and HOMA-AD as indicators of insulin resistance were not significant.

Radiosensitization by histone deacetylase inhibition in an osteosarcoma mouse model.

BACKGROUND: Osteosarcomas (OS) are highly malignant and radioresistant tumors. Histone deacetylase inhibitors (HDACi) constitute a novel class of anticancer agents. We sought to investigate the effect of combined treatment with suberoylanilide hydroxamic acid (SAHA) and radiotherapy in OS in vivo. METHODS: Clonogenic survival of human OS cell lines as well as tumor growth delay of OS xenografts were tested after treatment with either vehicle, radiotherapy (XRT), SAHA, or XRT and SAHA. Tumor proliferation, necrosis, microvascular density, apoptosis, and p53/p21 were monitored by immunohistochemistry. The CD95 pathway was performed by flow cytometry, caspase (3/7/8) activity measurements, and functional inhibition of CD95 death signaling. RESULTS: Combined treatment with SAHA and XRT markedly reduced the surviving fraction of OS cells as compared to XRT alone. Likewise, dual therapy significantly inhibited OS tumor growth in vivo as compared to XRT alone, reflected by reduced tumor proliferation, impaired angiogenesis, and increased apoptosis. Addition of HDACi to XRT led to elevated p53, p21, CD95, and CD95L expression. Inhibition of CD95 signaling reduced HDACi- and XRT-induced apoptosis. CONCLUSION: Our data show that HDACi increases the radiosensitivity of osteosarcoma cells at least in part via ligand-induced apoptosis. HDACi thus emerge as potentially useful treatment components of OS.

Differentiation of irradiation and cetuximab induced skin reactions in patients with locally advanced head and neck cancer undergoing radioimmunotherapy: the HICARE protocol (head and neck cancer: immunochemo and radiotherapy with erbitux) - a multicenter phase IV trial.

BACKGROUND: In order to improve the clinical outcome of patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN) not being capable to receive platinum-based chemoradiation, radiotherapy can be intensified by addition of cetuximab, a monoclonal antibody that blocks the epidermal growth factor receptor (EGFR). The radioimmunotherapy with cetuximab is a feasible treatment option showing a favourable toxicity profile. The most frequent side effect of radiotherapy is radiation dermatitis, the most common side effect of treatment with cetuximab is acneiform rash. Incidence and severity of these frequent, often overlapping and sometimes limiting skin reactions, however, are not well explored. A clinical and molecular differentiation between radiogenic skin reactions and skin reactions caused by cetuximab which may correlate with outcome, have never been described before. METHODS/DESIGN: The HICARE study is a national, multicenter, prospective phase IV study exploring the different types of skin reactions that occur in patients with LASCCHN undergoing radioimmun(chemo)therapy with the EGFR inhibitor cetuximab. 500 patients with LASCCHN will be enrolled in 40 participating sites in Germany. Primary endpoint is the rate of radiation dermatitis NCI CTCAE grade 3 and 4 (v. 4.02). Radioimmunotherapy will be applied according to SmPC, i.e. cetuximab will be administered as loading dose and then weekly during the radiotherapy. Irradiation will be applied as intensity-modulated radiation therapy (IMRT) or 3D-dimensional radiation therapy. DISCUSSION: The HICARE trial is expected to be one of the largest trials ever conducted in head and neck cancer patients. The goal of the HICARE trial is to differentiate skin reactions caused by radiation from those caused by the monoclonal antibody cetuximab, to evaluate the incidence and severity of these skin reactions and to correlate them with outcome parameters. Besides, the translational research program will help to identify and confirm novel peripheral blood based molecular predictors and surrogates for treatment response and resistance. TRIAL REGISTRATION: Clinical Trial Identifier, NCT01553032 (clinicaltrials.gov)EudraCT number: 2010-019748-38.

The role of Helicobacter pylori infection in gastro-oesophageal reflux in Iranian children.

BACKGROUND: The relationship between Helicobacter pylori and gastro-oesophageal reflux disease (GORD) in children is controversial. AIM: To determine the role of H. pylori infection and GORD in children living in a region which is endemic for H. pylori infection. METHODS: A cross-sectional study was undertaken in 263 children aged 3-18 years, all of whom had symptoms of GORD and underwent upper gastro-intestinal endoscopy. H. pylori status was determined by conventional rapid urease test and Giemsa staining of antral and cardiac biopsies. Biopsies of the oesophagus and gastric mucosa were obtained from the lower oesophagus, the antrum and cardia according to standard protocol. RESULTS: Of the 263 patients, 81 (31·5%) had GORD and 162 (61·5%) had gastritis. There were 59 H. pylori-infected patients (22·4%) and 204 were uninfected. H. pylori infection was detected in 52 (88·1%) of the antral and 10 (1·9%) of the cardiac biopsies. Three (5·1%) of the biopsies revealed infection of both antrum and cardia and in seven (11·8%) only the cardia was infected. The prevalence of H. pylori infection among patients with GORD (13/83, 15%) was significantly lower than in those without GORD (46/180, 26%) (OR 0·54, CI 0·27-0·93, p<0·05). The prevalence of H. pylori infection among those with gastritis (48/162, 30%) was significantly higher than in those without gastritis (11/101, 10·8%) (OR 3·44, CI 1·69-7·015, p<0·001). CONCLUSION: H. pylori infection might protect against GORD.

Moderate over-feeding of different sources of metabolizable energy and protein improved gestational insulin resistance markers and maternal metabolic status of sheep around lambing.

The objective of this study was to determine the effect of moderate over-nutrition of energy (using flaxseed as a source of n-3 fatty acids) and protein (using rumen-protected lysine and methionine) around parturition on prepartal insulin resistance (IR) and periparturient metabolic status and performance of ewes. For this purpose, 32 apparently healthy ewes (2.5 ± 1 years old, 42.19 ± 1.65 kg body weight (BW)) were randomly selected out of 200 pregnant Zell ewes on d 50 before the expected lambing. After receiving a ten-day adaptation diet, eight ewes were randomly allocated to one of the following four dietary treatments: 1) the adaptation diet that meets the metabolizable energy (ME) and protein (MP) requirements of ewes during late pregnancy as recommended by National Research Council = NRC (2007) (Control = CON). 2) A diet with 10% higher levels of ME than NRC (2007) recommendations using corn grain as a source of extra ME (HEC). 3) A diet with 10% higher levels of ME compared to NRC (2007) recommendations using flaxseed for additional ME (HEF). 4) A diet with a 10% higher level of MP than NRC (2007) recommendations using rumen-protected lysine and methionine as a source of extra MP (PRO). While the dietary treatments did not affect animals' dry matter intake (DMI), the CON ewes lost more BW starting from d 10 to d 30 relative to parturition compared to others (P < 0.05). Milk protein and fat yield (g/d) were significantly higher for PRO and HEF compared to HEC and CON ewes (P < 0.05). Moderately over-fed ewes with MP and ME had an improved insulin sensitivity (IS) compared to CON ones. The source of additional ME also impacted IR indices because HEC showed an enhancement in IS than HEF animals (P < 0.05). A lower IS in CON ewes was parallel with higher concentrations of plasma urea at prepartum (P < 0.01), lower levels of plasma cholesterol, triglyceride (P < 0.01) and glucose post-partum (P < 0.05), and a tendency for higher levels of beta-hydroxybutyrate (BHB) and non-esterified fatty acids (NEFA) in CON ewes during both pre- and post-partum periods. There were negative correlations between plasma urea, BHB, and NEFA with IR markers on d 7 prepartum in line with these results. Comparing data, we could not find a significant change in metabolic status among ewes fed with either PRO or HEF/HEC. In conclusion, the inclusion of 10% extra MP and ME could improve late gestation maternal IS and the metabolic status of dams around lambing.

Reproductive performance, expression of TRAP6 and TGF-ß4 genes in utero-vaginal junction mucosa, and indicators of liver function in female Chukar partridge (Alectoris chukar) breeders fed with fish oil and calcitriol during the egg-laying period.

Reproductive attributes, expression of TRAP6 and TGF-ß mRNA in the mucosa of the utero-vaginal junction (UVJ) of oviduct, and liver function were evaluated in Chukar partridge (Alectoris chukar) breeders subjected to long-term oral administration of fish oil (FO) and/or calcitriol (CT). A total of forty-eight 1.5-year-old laying Chukar partridges and 16 age-matched males (female:male ratio of 3:1) were randomly allocated to four groups (4 replicates of 3 female birds and one male bird each). Breeder females in groups 1, 2, and 3 were orally administered daily with 0.2 mL (0.24 g)/500 g body weight FO, 0.2 mL solution containing 10 µg CT, or their combination (FO + CT) for 42 successive days, respectively. Pure crystalline calcitriol was dissolved in ethanol (30%) prior to administration. The control group (CON), received a similar volume of a 30% solution of ethanol only. Eggs were collected and incubated to evaluate the reproductive performance. Blood samples were taken on days 0, 21, and 42 of the trial for the quantification of serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). On day 43, one bird per replicate was killed by cervical dislocation to assess the expression of TRAP6 and TGF-ß genes in the UVJ mucosa. Administration of CT or FO + CT increased the egg production rate, fertility rate, and hatchability rate of the set eggs. Fertility duration and sperm penetration rate were higher in partridges receiving FO and (or) CT, but chick quality, and embryonic mortality were not affected by the treatment effect. Administration of CT or FO + CT decreased the serum ALT and AST levels. Administration of FO or CT was associated with a lower expression of TGF-ß mRNA in the UVJ mucosa. Oral administration of FO resulted in a reduction in the expression of TRAP6 in the UVJ mucosa. However, the birds fed with CT or FO + CT recorded a higher mRNA expression for TRAP6. Although the reproductive performance and TRAP6 expression were higher following the feeding of FO or FO + CT, expression of TGF-ß was decreased, suggesting plausibly that TGF-ß may not have a determinant effect on the reproductive attributes in female Chukar partridges. Further studies are required to understand the mechanisms underlying the effects of TRAP6 and TGF-ß on other reproductive criteria in partridges.

The effects of the fiber source and xylanase supplementation on production, egg quality, digestibility, and intestinal morphology in the aged laying hen.

This study was conducted to evaluate the effects of the fiber source (wheat bran [WB] or sugar beet pulp [SBP]) and xylanase supplementation on production, egg quality, ileal digestibility, intestinal morphology, and gastrointestinal pH in aged laying hens. A total of 540 laying hens (Lohman LSL Lite; 70 wk of lay) were randomized into 10 treatments (6 replicate cages of 9 birds) consisting of a corn soy control supplemented with 0, 3, or 6% WB or SBP with or without xylanase (100 mg of xylanase preparation per kg) for a period of 9 wk in a 5 × 2 factorial arrangement. Hens fed with the diets containing either of the levels of SBP or 6% WB had lower hen-day production, and addition of the enzyme improved hen-day production (P < 0.05), but it could not compensate for the lost production due to the higher levels of either of the fiber sources. Supplementation of 6% SBP to the control diet decreased egg mass (P < 0.05). All fiber-supplemented diets significantly decreased ADFI, which was restored on enzyme addition, with the exception of 3% WB diet. Treatments had no effects on egg weight, feed conversion ratio, egg quality, and serum and carcass traits, except for ileum weight, which was greater in hens fed with the 6% SBP diet (P < 0.05). Adding 3% SBP increased ileal DM digestibility (P < 0.05). Addition of 3% WB improved jejunal villus height, villus height-to-crypt depth ratio, and villus surface area (P < 0.05). Villus surface area, DM, organic matter, and protein digestibility increased as a result of enzyme supplementation (P < 0.05). Cecal pH was reduced on feeding diets containing 3% WB, containing 3% SBP, and with enzyme supplementation (P < 0.05). In conclusion, addition of 3% WB in a corn soy control diet has the potential to improve small intestine morphology in older hens without adverse effects on performance, especially if accompanied by the use of an enzyme, which simultaneously improved morphological traits and nutrient digestibility.

Rapid effective dose calculation for raster-scanning 4He ion therapy with the modified microdosimetric kinetic model (mMKM).

PURPOSE: To develop and verify effective dose (DRBE) calculation in 4He ion beam therapy based on the modified microdosimetric kinetic model (mMKM) and evaluate the bio-sensitivity of mMKM-based plans to clinical parameters using a fast analytical dose engine. METHODS: Mixed radiation field particle spectra (MRFS) databases have been generated with Monte-Carlo (MC) simulations for 4He-ion beams. Relative biological effectiveness (RBE) and DRBE calculation using MRFS were established within a fast analytical engine. Spread-out Bragg-Peaks (SOBPs) in water were optimized for two dose levels and two tissue types with photon linear-quadratic model parameters αph, ßph, and (α/ß)ph to verify MRFS-derived database implementation against computations with MC-generated mixed-field α and ß databases. Bio-sensitivity of the SOBPs was investigated by varying absolute values of ßph, while keeping (α/ß)ph constant. Additionally, dose, dose-averaged linear energy transfer, and bio-sensitivity were investigated for two patient cases. RESULTS: Using MRFS-derived databases, dose differences ≲2% in the plateau and SOBP are observed compared to computations with MC-generated databases. Bio-sensitivity studies show larger deviations when altering the absolute ßph value, with maximum D50% changes of ~5%, with similar results for patient cases. Bio-sensitivity analysis indicates a greater impact on DRBE varying (α/ß)ph than ßph in mMKM. CONCLUSIONS: The MRSF approach yielded negligible differences in the target and small differences in the plateau compared to MC-generated databases. The presented analyses provide guidance for proper implementation of RBE-weighted 4He ion dose prescription and planning with mMKM. The MRFS-DRBE calculation approach using mMKM will be implemented in a clinical treatment planning system.

Factors affecting sentinel lymph node detection failure in breast cancer patients using intradermal injection of the tracer.

OBJECTIVE: The standard method for axillary lymph node staging in early breast cancer is sentinel lymph node biopsy. In some patients the sentinel lymph node can not be localized during surgery and these patients have to undergo standard axillary lymph node dissection. In this study we have evaluated the predictors of sentinel lymph node localization failure using (99m)Tc-antimony sulfide colloid and intradermal injection combined with blue dye technique. MATERIAL AND METHODS: 202 consecutive patients with early stage breast cancer (clinically stage I or II) were retrospectively evaluated. Patients whose sentinel lymph node was localized during surgery were compared to those with localization failure considering several variables. RESULTS: Sentinel lymph node was successfully located on the pre-operative lymphoscintigraphy images in 180 patients (89%). Both univariate and multivariate analyses showed that only sentinel lymph node non-visualization by pre-operative lymphoscintigraphy, experience of the surgeon, and axillary lymph node involvement are associated with sentinel node localization failure during surgery. CONCLUSIONS: This study shows the importance of pre-operative lymphoscintigraphy in order to identify the group of patients with possible localization failure during surgery and warning the surgeon beforehand. We also recommend that all surgeons pass the learning curve of sentinel lymph node biopsy before routinely performing this procedure.

A combined panel of circulating microRNA as a diagnostic tool for detection of the non-small cell lung cancer.

BACKGROUND: Recently, much attention has been paid to use circulating microRNAs (miRs) as a non-invasive tumor marker. The present study for the first time was designed to evaluate concurrent use of miR-21, miR-638, miR148 and miR-152 as putative diagnostic tool for detection of non-small cell lung carcinoma (NSCLC). METHODS: Forty-three patients diagnosed as primary NSCLC was included in this study. The level of selected miRs was measured in whole blood specimens of patients and controls. The corresponding values were also obtained in stages I-IV. We also assessed possible correlation between selected miRs and the clinicopathological findings of studied individuals. RESULTS: miR-21 was increased in patients compared to controls (P = 0.004). In contrast, circulating miR-638, miR-148 and miR-152 was observed to be down-regulated in NSCLC patients than controls (P = 0.001, 0.003, 0.053, respectively). Rise in miR-21-5p expression and decreased blood level of miR-148a-3p was associated with higher stage of NSCLC. The highest sensitivity (90%) was observed for miR-21 while miR-148 had the highest specificity (71%). The corresponding sensitivity and specificity for combined-miRs-panel was 96.4% and 86.67%, respectively. CONCLUSION: In summary, our data suggested the diagnostic importance of combined-miR-panel including miR-21, miR-638, miR148 and miR-152 for effective discrimination of NSCLC from non-cancerous subjects.

Interference of tumour mutational burden with outcome of patients with head and neck cancer treated with definitive chemoradiation: a multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group.

BACKGROUND: Tumour mutational burden (TMB) estimated from whole exome sequencing or comprehensive gene panels has previously been established as predictive factor of response to immune checkpoint inhibitors (ICIs). Its predictive value for the efficacy of concurrent chemoradiation (cCRTX), a potential combination partner of ICI, remains unknown. METHODS: The accuracy of TMB estimation by an in-house 327-gene panel was established in the Cancer Genome Atlas (TCGA) head and neck squamous cell carcinoma (HNSCC) data set. Interference of TMB with outcome after cCRTX was determined in a multicentre cohort of patients with locally advanced HNSCC uniformly treated with cCRTX. Targeted next-generation sequencing was successfully applied in 101 formalin-fixed, paraffin-embedded pretreatment tumour samples. In a subset of cases (n = 40), tumour RNA was used for immune-related gene expression profiling by the nanoString platform. TMB was correlated with TP53 genotype, human papilloma virus (HPV) status, immune expression signatures and survival parameters. Results were validated in the TCGA HNSCC cohort. RESULTS: A high accuracy of TMB estimation by the 327-gene panel was established. High TMB was significantly associated with an increased prevalence of TP53 mutations and immune gene expression patterns unrelated to T cell-inflamed gene expression profiles. Kaplan-Meier analysis revealed significantly reduced overall survival in the patient group with high TMB (hazard ratio for death: 1.79, 95% confidence interval: 1.02-3.14; P = 0.042) which remained significant after correcting for confounding factors in the multivariate model. The prognostic value of TMB was confirmed in the TCGA HNSCC cohort. CONCLUSION: High TMB identifies HNSCC patients with poor outcome after cCRTX who might preferentially benefit from CRTX-ICI combinations.