A pleiotropy scan to discover new susceptibility loci for pancreatic ductal adenocarcinoma.

Pleiotropic variants (i.e., genetic polymorphisms influencing more than one phenotype) are often associated with cancer risk. A scan of pleiotropic variants was successfully conducted ten years ago in relation to pancreatic ductal adenocarcinoma susceptibility. However, in the last decade, genetic association studies performed on several human traits have greatly increased the number of known pleiotropic variants. Based on the hypothesis that variants already associated with a least one trait have a higher probability of association with other traits, 61,052 variants reported to be associated by at least one genome wide association study (GWAS) with at least one human trait were tested in the present study consisting of two phases (discovery and validation), comprising a total of 16,055 pancreatic ductal adenocarcinoma (PDAC) cases and 212,149 controls. The meta-analysis of the two phases showed two loci (10q21.1-rs4948550 (P=6.52×10-5) and 7q36.3-rs288762 (P=3.03×10-5) potentially associated with PDAC risk. 10q21.1-rs4948550 shows a high degree of pleiotropy and it is also associated with colorectal cancer risk while 7q36.3-rs288762 is situated 28,558 base pairs upstream of the Sonic Hedgehog (SHH) gene, which is involved in the cell differentiation process and PDAC etiopathogenesis. In conclusion, none of the single nucleotide polymorphisms (SNPs) showed a formally statistically significant association after correction for multiple testing. However, given their pleiotropic nature and association with various human traits including colorectal cancer, the two SNPs showing the best associations with PDAC risk merit further investigation through fine mapping and ad hoc functional studies.

Prevalence of nodal involvement in rectal cancer after chemoradiotherapy.

BACKGROUND: The purpose of this study was to investigate the prevalence of ypN+ status according to ypT category in patients with locally advanced rectal cancer treated with chemoradiotherapy and total mesorectal excision, and to assess the impact of ypN+ on disease recurrence and survival by pooled analysis of individual-patient data. METHODS: Individual-patient data from 10 studies of chemoradiotherapy for rectal cancer were included. Pooled rates of ypN+ disease were calculated with 95 per cent confidence interval for each ypT category. Kaplan-Meier and Cox regression analyses were undertaken to assess influence of ypN status on 5-year disease-free survival (DFS) and overall survival (OS). RESULTS: Data on 1898 patients were included in the study. Median follow-up was 50 (range 0-219) months. The pooled rate of ypN+ disease was 7 per cent for ypT0, 12 per cent for ypT1, 17 per cent for ypT2, 40 per cent for ypT3, and 46 per cent for ypT4 tumours. Patients with ypN+ disease had lower 5-year DFS and OS (46.2 and 63.4 per cent respectively) than patients with ypN0 tumours (74.5 and 83.2 per cent) (P < 0.001). Cox regression analyses showed ypN+ status to be an independent predictor of recurrence and death. CONCLUSION: Risk of nodal metastases (ypN+) after chemoradiotherapy increases with advancing ypT category and needs to be considered if an organ-preserving strategy is contemplated.

When patients are diagnosed with rectal cancer and the tumour grows beyond the rectal wall there is a high risk that the tumour has spread to nearby lymph nodes. This study showed that this relationship between tumour invasion depth and lymph node involvement is similar after treatment with (chemo)radiotherapy. Patients who have tumour cells remaining in the lymph nodes after (chemo) radiotherapy have a worse prognosis than patients who do not have cancer cells remaining in the lymph nodes. When an organ-preserving treatment is considered as an alternative therapy, this should be kept in mind during patient counselling.

Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma.

Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values <0.05 considered significant. K3326X and I157T were associated with increased risk of developing sporadic PDAC (odds ratio (ORdom ) = 1.78, 95% confidence interval (CI) = 1.26-2.52, p = 1.19 × 10-3 and ORdom = 1.74, 95% CI = 1.15-2.63, p = 8.57 × 10-3 , respectively). Neither mutation was significantly associated with risk of developing early-onset PDAC. This retrospective study demonstrates novel risk estimates of K3326X and I157T in sporadic PDAC which suggest that upon validation and in combination with other established genetic and non-genetic risk factors, these mutations may be used to improve pancreatic cancer risk assessment in European populations. Identification of carriers of these risk alleles as high-risk groups may also facilitate screening or prevention strategies for such individuals, regardless of family history.

Evaluation of yeast dietary supplementation in broilers challenged or not with Salmonella on growth performance, cecal microbiota composition and Salmonella in ceca, cloacae and carcass skin.

The dietary supplementation of Saccharomyces cerevisiae var. boulardii was evaluated in broilers challenged or not challenged with Salmonella Enteritidis (SE) using a 2 × 2 factorial arrangement. Depending on yeast inclusion at 0 (C) or 1 × 109 cfu/kg diet (Y) and SE challenge (0 or log 6.3 cfu/bird) on d 15, the experiment had four treatments C, Y, C-SE, and Y-SE, respectively. Each treatment had seven replicate floor pens with 15 broilers. Growth performance responses were determined weekly and overall for the 5 week experimental period. Salmonella levels and prevalence in ceca, cloacae, and carcass skin were determined by culture procedures, while cecal microbiota was determined by real time PCR. Yeast supplementation had no effect (PY > 0.05) on growth performance. For the overall post SE-challenge period (i.e., wk 3 to wk 5), Salmonella reduced body weight gain (BWG) (PSE < 0.001), feed intake (FI) (PSE = 0.032), and the European production efficiency (EPEF) factor (PSE = 0.005). Broilers Y-SE had higher (P < 0.001) overall BW gain compared to C-SE ones. Overall mortality was 2.14% and did not differ (P > 0.05) between treatments. Reduced Salmonella levels in the cloacae (P = 0.014) and on the breast skin (P = 0.006) and lower prevalence on the neck skin (P = 0.007) were noted for treatment Y-SE compared to C-SE. Yeast supplementation did not have an effect (P > 0.05) on cecal microbiota composition at d 1 and d 21 post SE-challenge. On the contrary, SE-challenge reduced cecal levels of total bacteria (PSE = 0.002), E. coli (PSE = 0.006), Bifidobacterium spp. (PSE = 0.006), Bacteroides spp. (PSE = 0.010), and Clostridial populations belonging to cluster I and cluster XIVa, (PSE = 0.047 and PSE = 0.001, respectively) on d 1 post SE-challenge. At 21 d post SE-challenge, only the levels of cecal Lactobacillus spp. (PSE = 0.001) and Bifidobacterium spp. (PSE = 0.049) were reduced compared to the non SE-challenged groups. In conclusion, yeast supplementation in SE challenged broilers (Y-SE) was beneficial for growth performance and reduced Salmonella presence compared to C-SE ones. The disturbance of cecal microbiota balance by SE merits further investigation for potential implications in gut and overall bird health.

Geographical distribution modelling for Neospora caninum and Coxiella burnetii infections in dairy cattle farms in northeastern Spain.

Maximum entropy ecological niche modelling and spatial scan statistic were utilized to predict the geographical range and to investigate clusters of infections for Neospora caninum and Coxiella burnetii in dairy cattle farms in Catalonia, northeastern Spain, using the Maxent and SaTScan programs, respectively. The geographical distribution of Neospora and Coxiella with the highest level of probability (P > 0·60) covers central Catalonia and spreads towards northeastern Catalonia which contains a high concentration of dairy cattle farms. The most important environmental factor that contributed to the ecological niche modelling was precipitation of driest month followed by elevation. Significant clusters (P < 0·001) were detected for Neospora and Coxiella infections in the western and eastern regions of Catalonia, respectively.

Prospective evaluation of health-related quality of life after laparoscopic colectomy for cancer.

BACKGROUND: The aim of the present study was to prospectively determine health-related quality of life (HRQoL) changes and affecting factors after elective laparoscopic colectomy for cancer. METHODS: The SF-36, EORTC QLQ-C30 and QLQ-CR29, and Gastrointestinal Quality of life Index (GIQLI) were used to assess 85 patients preoperatively and at 1, 3, 6, and 12 months. RESULTS: An initial drop form baseline values was observed in 3 of 8 SF-36 domains, 3 of 5 QLQ-C30 functional scales and 1 of 5 GIQLI subscales. Emotional functioning (EF) was better postoperatively even from the first month (p = 0.03). Most functional domains were improved compared to baseline. The statistically significant changes (p < 0.05) were in the SF-36: general health (GH) (3 months), physical function (PF) (12 months) and role limitations due to emotional problems (12 months); in the QLQ-C30: EF (12 months); in the GIQLI: the global score and PF at 12 months and EF (3, 6, 12 months). From the first month after surgery, most QLQ-C30 "symptom" items were better than baseline. QLQ-CR29 "anxiety" and the "defecation problems" scales were significantly better than baseline at 1, 12 and at 6, 12 months (p < 0.05). Advanced stage (III) and chemotherapy were linked to worse EF, social function (SF), GH and global quality of life (QOL) at 3 and 6 months (p < 0.01). Males appeared to have a worse HRQoL than females at 3 and 6 months, and in 5 of 8 SF-36 domains and 3 of 5 GIQLI subscales at 12 months (p < 0.05). According to the QLQ-CR29, rectal surgery was associated more often with "impotence," "stoma problems" and "incontinence" up to 6 months, and ostomies with "embarrassment" and "stoma problems" (p < 0.05). CONCLUSIONS: HRQoL generally improved over the first year after laparoscopic colectomy reaching even better levels than before surgery. There was an early postoperative improvement in patients' emotional status. The main factors affecting HRQoL seem to be tumor stage, chemotherapy and male sex.

Post-colectomy assessment of gastrointestinal function: a prospective study on colorectal cancer patients.

BACKGROUND: Anatomical changes after intestinal resection and the effects of adjuvant treatment for colorectal cancer may lead to gastrointestinal disturbances. The aim of our study was to assess gastrointestinal function using validated health-related quality of life (HRQoL) questionnaires that are able to reliably quantify patients' symptoms. METHODS: Two hundred and eighty-nine colorectal cancer patients underwent HRQoL assessment preoperatively and at 3,6 and 12 months postoperatively. They were evaluated with the Gastrointestinal Quality of Life Index (GIQLI) ["global" and "symptoms" scales and questions 3 ("bloating"), 4 ("excessive gas"), 6 ("gurgling noises"), 7 ("frequent bowel movements (BMs)"), 30 ("urgent BMs"), 31 ("diarrhea"), 32 ("constipation"), 36 ("uncontrolled stools")] and the European Organization for Research and Treatment of Cancer (EORTC) modules QLQ-C30 (symptom scales: "constipation" and "diarrhea") and QLQ-CR29 (symptom scales: "defecation problems," "incontinence," and "bloating"). RESULTS: GIQLI "global" and "symptom" indices and the majority of single-item scores and the EORTC QLQ-C30 "constipation" and "diarrhea" subscales showed significant postoperative improvement (p < 0.05). Females and younger age (<70 years) patients appeared to have worse postoperative gastrointestinal function. Rectal cancer patients had more "urgent BMs," "uncontrolled stools" and worse "global" and "symptom" scores at 3 months and more "diarrhea" at 3 and 6 months than colon cancer patients (p < 0.03). Right colectomy patients had less "excessive passage of gas," "constipation," and "uncontrolled stools" than left colectomy patients (3 months, p < 0.01). Anterior resection patients faced more gastrointestinal difficulties, especially in the first 6 months after surgery. Adverse effects related to stage and adjuvant treatment were predominant only at baseline (p < 0.05). GIQLI "diarrhea" and "constipation" scores were correlated with the respective EORTC QLQ-C30 domains (p = 0.0001). CONCLUSIONS: Overall, gastrointestinal function is improved after colorectal cancer surgery. However, women and younger patients are at higher risk of postoperative gastrointestinal dysfunction.

Occurrence of non-cerebral coenurosis in sheep.

This study reports seven rare cases of non-cerebral coenurosis in sheep. The sheep were slaughtered in abattoirs of Abu Dhabi (United Arab Emirates) but originated from India, Iran, Oman and Sudan. The prevalence of infection with non-cerebral coenurosis was 0.008%. The locations of the cysts were the triceps brachii muscle, the diaphragm, the infraspinatus muscle of the shoulder, the muscles of the thigh and the abdomen, and the ommentum. The Coenurus cysts were surrounded by a fibrous, semi-opaque membrane, cloudy white in colour. Altogether, 12 cysts were recovered and all contained a single bladderworm. Cysts had a volume of 7.3 ± 1.30 cm3 (ml), with 7.3 ± 4.0 clusters of scolices, and an average number of scolices 75.3 ± 24.4. These features in sheep were similar to those reported for non-cerebral Coenurus cysts in goats. No cysts were found in the brain or spinal cord of any of the infected sheep. No clinical evidence of non-cerebral coenurosis had been recorded during the antemortem veterinary inspection of the infected sheep.

A cost-utility analysis of laparoscopic vs open treatment of colorectal cancer in a public hospital of the Greek National Health System.

PURPOSE: Laparoscopic colectomy has been reported as a safe and oncologically similar operation to open colectomy. A number of expensive surgical instruments are necessary for the procedure which should be applied if it is cost-effective for the patient and the health system in general. The purpose of the current study was the economic evaluation of laparoscopic compared to open colectomy for the treatment of colon cancer in the Greek national health system. METHODS: Fifty patients undergoing open colectomy and 42 undergoing laparoscopic colectomy were enrolled in this case-control study. Length of hospital stay, duration of operation, complication rates, cost of equipment used, total costs and three questionnaires measuring quality of life /QoL (EQ-5D, SF-36 and QLQ-C30) at baseline, 1 and 3 months after the operation were recorded. RESULTS: No statistically significant difference in QoL measured by QALYs between laparoscopic and open colectomy was observed. On the other hand, cost utility analysis revealed that laparoscopic colectomy was more expensive considering the advantages it offers. CONCLUSIONS: Laparoscopic colectomy is not superior to open colectomy on a QoL basis in the Greek public hospital system and is less cost-effective compared to the open procedure. Since the expensive equipment used in laparoscopic colectomy seems to be the causative factor for the high cost of this type of operation, an effort should be made to reduce it either by using reusable instruments or by implementing policies aiming at suppliers cutting down equipment charges.

Rectoanal repair versus suture haemorrhoidopexy: a comparative study on suture mucopexy procedures for high-grade haemorrhoids.

BACKGROUND: The isolated application of Doppler-guided haemorrhoidal artery ligation (DGHAL) may fail due to the increased reprolapse rate for high-grade haemorrhoids. DGHAL has been combined with a proctoscopic-assisted transanal rectal mucopexy of the prolapsing tissue. The technique is called rectoanal repair (RAR) and is an evolution of various mucopexy and suture haemorrhoidopexy (SHP) techniques. A prominent external component may require minimal (muco-) cutaneous excision (MMCE) of protruding anoderm or minor cutaneous excision of skin tags. METHODS: Fifty-seven patients with symptomatic Goligher grade III and IV haemorrhoids underwent DGHAL followed by either RAR or SHP. In 26 cases, the addition of MMCE was necessary. RESULTS: No significant differences were observed between the two approaches with regards to pain scores measured with visual analogue scale (VAS). On postoperative day 1, mean pain score at rest was 5.81 (±2.23 SD) after SHP versus 5.08 (±2.35 SD) after RAR, while mean pain score at first defecation was 7.31 (±1.6 SD) versus 7.52 (±1.83 SD). There was no difference in the duration of analgesic requirements, postoperative complications and residual prolapse between the 2 procedures. The addition of MMCE did not affect postoperative pain nor analgesic requirements. With the exception of 8 patients who still had with skin tags or minimal protrusion, the remaining of patients (86 %) were asymptomatic and recurrence-free at an average follow-up of 20 months. Overall, 94.8 % of patients stated that they were satisfied with the results, and 91.2 % that they would repeat it if necessary. CONCLUSIONS: Performance of either SHP or RAR after DGHAL is a safe and effective surgical tactic for advanced grade haemorrhoids. Our initial results do not confirm any superiority of RAR over traditional SHP.

Risk factors and geospatial modelling for the presence of Fasciola hepatica infection in sheep and goat farms in the Greek temperate Mediterranean environment.

Risk factors related to herd and farmer status, farm and pasture management, and environmental factors derived by satellite data were examined for their association with the prevalence of F. hepatica in sheep and goat farms in Thessaly, Greece. Twelve farms (16.2%) and 58 farms (78.4%) of 74 had evidence of infection using coproantigen and serology respectively. The average normalized difference vegetation index (NDVI) of farm location for 12 months before sampling was the most significant environmental risk factor for F. hepatica infection based on high seropositivity. The risk of infection increased by 1% when the value of NDVI increased by 0.01 degree. A geospatial map was constructed to show the relative risk (RR) of Fasciola infection in sheep and goat farms in Thessaly. In addition, geospatial maps of the model-based predicted RR for the presence of Fasciola infection in farms in Thessaly and the entire area of Greece were constructed from the developed model based on NDVI. In conclusion, this study demonstrated that Thessaly should be regarded as an endemic region for Fasciola infection and it represents the first prediction model of Fasciola infection in small ruminants in the Mediterranean basin.

Doppler-guided haemorrhoidal artery ligation, rectoanal repair, sutured haemorrhoidopexy and minimal mucocutaneous excision for grades III-IV haemorrhoids: a multicenter prospective study of safety and efficacy.

OBJECTIVE: The isolated use of Doppler-guided haemorrhoidal artery ligation (DGHAL) may fail for advanced haemorrhoids (HR; grades III and IV). Suture haemorrhoidopexy (SHP) and mucopexy by rectoanal repair (RAR) result in haemorrhoidal lifting and fixation. A prospective evaluation was performed to evaluate the results of DGHAL combined with adjunctive procedures. METHOD: The study included 147 patients with HR (male patients: 102; grade III: 95, grade IV: 52) presenting with bleeding (73%) and prolapse (62%). RESULTS: More ligations were required for grade IV than grade III HR (10.7 + 2.8 vs 8.6 + 2.2, P < 0.001). SHP (28 patients) and RAR (18 patients) at 1-4 positions were deemed necessary in 46 (31%) patients. Minimal (muco-)cutaneous excision (MMCE) was added in 23 patients. SHP/RAR was applied more frequently in grade IV HR (60%vs 16%, P < 0.001). In patients not having MMCE, SHP/RAR was added in 57% of grade IV cases (P < 0.001). Complications included residual prolapse (10; two second surgery), bleeding (15; two second DGHAL), thrombosis (four), fissure (three) and fistula (one). Analgesia was required not at all, up to 1-3 days, 4-7 days and >7 days by 30%, 31%, 16% and 14% of the patients, respectively. SHP/RAR was associated with greater discomfort (17%vs 6%, P < 0.001). No differences were found between SHP and RAR. At an average follow-up of 15 months, 96% of patients were asymptomatic and 95% were satisfied. CONCLUSIONS: DGHAL with the selective application of SHP/RAR is a safe and effective technique for advanced grade HR.

Epidemiological survey of cestode-larva disease in Greek sheep flocks.

The epidemiological status of hydatidosis, cysticercosis, and gid in sheep and the production practices of sheep farmers that increase the risk of exposure of sheep to infecting agents of these diseases were investigated in Thessaly, central Greece during 2002-2006. A total of 700 hoggets (sheep up to the age of 1 year) and 1500 adult sheep were examined randomly at an abattoir survey and the prevalences of hydatidosis and cysticercosis were found 39.32% and 29.41%, respectively. Hoggets had significantly lower prevalences of hydatidosis and cysticercosis compared to adult sheep (p<0.001). The distribution of parasitic cysts showed an overdispersion pattern mostly in the hogget population. The proportion of fertile hydatid cysts was significantly higher in hoggets compared to adult sheep (p<0.001). A cohort of 74 sheep flocks was observed during the same period in a prospective survey to assess the incidence of gid. A total of 57 sheep belonging to 15 flocks (20.27% of investigated flocks) developed clinical signs of gid at an annual rate of 11.40+/-4.77 (95% C.I.). In the infected flocks there were 3.80+/-0.92 (95% C.I.) gid cases per flock. The mean age of onset of clinical signs for all sheep was 11.86+/-1.33 months (95% C.I.) (range 5-22 months) while for hoggets was 8.48+/-0.73 (95% C.I.) (range 5-12 months) and for adult sheep 17.23+/-1.42 (95% C.I.) (range 13-22 months). A significant difference was observed in the prevalence of unilateral blindness between hoggets (31.42%) and adult sheep (4.54%) (p<0.05). The most common production practices identified in a questionnaire survey of sheep farmers that may increase the risk of exposure of sheep to hydatidosis, cysticercosis, and gid were the improper disposal of dead animals, the access of farm dogs to offal of slaughtered sheep, the carelessness of farmers to treat farm dogs with anthelmintics, and the grazing of flocks in fields where stray dogs have free access.

Biological, seasonal and environmental factors associated with Pulex irritans infestation of dairy goats in Greece.

The objectives of the present study were to study the fauna of fleas infesting dairy goats in Greece, the spectrum of hosts each flea species infests, identify risk factors in the environment, and goat management practices that favour flea infestation of goats, and describe the seasonal variation of infestation in goats. For this purpose, a total of 64 herds, with a history of flea infestation in goats, were visited during June and July of 2002 for data collection on flea burdens, species of fleas on goats, and other farm or pet animal species in the farm. Also data were collected on herd characteristics and management along with the flea infestation status of the village where it was located through a questionnaire survey. Data on elevation and climatic characteristics of the villages where the herds were located were also used in the study. All fleas collected from goats, sheep, pigs, and cattle were identified as being Pulex irritans. All fleas collected from cats were identified as being Ctenocephalides felis. Dogs were infested either with P. irritans, C. canis, or C. felis, or with both C. canis and C. felis. Kids had a significantly higher flea burden than goats and the Skopelos breed had the highest flea burden of all breeds followed in diminishing order by the breeds Capra prisca, Saanen cross mix, and Alpine cross mix (p < 0.05). The gender of the animal had no significant effect on flea burden. Factors significantly affecting the flea burden of goats were duration of flea infestation in the herd, type of flea control, and manure imported prior to the appearance of fleas in the herd (p < 0.05). The flea burden of goats was highest during summer and lowest during winter (p < 0.01), with complete an absence of infestation in January and February. Finally, a significant difference (p < 0.05) was found between the average annual temperature of villages with flea infestation (15.59 degrees C) and villages without flea infestation (17.14 degrees C). It was concluded that P. irritans was a true infestation of goats in Greece.

Determination of prevalence and risk factors of infection with Babesia in small ruminants from Greece by polymerase chain reaction amplification.

A total of 124 blood samples were collected from 92 sheep and 32 goats from 21 randomly selected herds located in two regions of Greece. Data on the characteristics of the animals (species, gender, age, tick burden, presence of haemoglobinuria, prior treatment for babesiosis) and the herd (location, size, species of animals, dogs associated with the herds, tick burden of dogs associated with the herds) were collected through questionnaires. Nineteen animals (15%) produced the DNA fragment specific for Babesia of which 16 were sheep and three were goats. Nucleotide sequence of PCR products revealed 100% homology with Babesia ovis 18S rRNA gene. Nine farms (43%) were found positive for B. ovis. The percentage of positive animals in each farm varied between 10 and 61%. The relative risk of the presence of ticks in sheep and goats (p<0.01) and farm dogs (p<0.01) for PCR-positive results for B. ovis in sheep and goats was found 6.63 and 4.14, respectively.

Probiotic form effects on growth performance, digestive function, and immune related biomarkers in broilers.

The aim of this work was to assess the effect of dietary viable or heat inactivated probiotic forms (PF) combined or not with avilamycin (AV) used as a growth promoter, on broiler growth performance, nutrient digestibility, digestive enzyme activities, and expression of immune response related genes.Depending on the type of PF (i.e., no addition, viable, inactivated) and AV addition (no/yes), 450 one-day-old Cobb male broilers were allocated in the following 6 treatments according to a 3 × 2 factorial arrangement with 5 replicates of 15 broilers each for 6 wk: CoN: diet without any addition; CoN+A: combination of CoN with AV; ViP: viable PF - no AV; ViP+A: combination of ViP with AV; InP: inactivated PF - no AV; InP+A: combination of InP with AV.There were no interactions (P > 0.05) for overall performance parameters. In contrast, PF or AV addition improved BW gain (PPF= 0.015; PAV < 0.001), FCR (PPF < 0.001; PAV < 0.001) and production efficiency factor (PPF= 0.001; PAV= 0.001).Significant (PPF×AV ≤ 0.05) interaction effects regarding ileal digestibility (IAD) of DM and total tract apparent digestibility (TTAD) of DM and ether extracts (EE) were noted. In addition, PF affected IAD and TTAD of CP (PPF < 0.001, PPF= 0.004, respectively). Inactivated PF increased (PPR= 0.024) lipase activity in jejunal digesta.At spleen level InP and ViP+A down-regulated TGF-ß4 (PPF × AV = 0.035) compared to CoN and ViP, whereas ViP+A up-regulated iNOS (PPF × AV = 0.022). An anti-inflammatory effect of live and inactive PF and/or AV addition at cecal tonsils was shown by iNOS down-regulation (PPF × AV= 0.015) compared to CoN. Furthermore, AV down-regulated IFN-γ (PAV= 0.002).In conclusion, viable probiotic, as well as inactivated probiotic alone or in combination with avilamycin, improved nutrient digestibility. All dietary additives affected growth performance positively and induced an anti-inflammatory response at cecal level.

Therapeutic Potential of Secreted Molecules Derived from Human Amniotic Fluid Mesenchymal Stem/Stroma Cells in a Mice Model of Colitis.

Inflammatory bowel diseases (IBDs) are the result of pathological immune responses due to environmental factors or microbial antigens into a genetically predisposed individual. Mainly due to their trophic properties, a mounting interest is focused on the use of human mesenchymal stem/stromal cells (hMSCs) to treat IBD disease in animal models. The aim of the study is to test whether the secreted molecules, derived from a specific population of second trimester amniotic fluid mesenchymal stem/stromal cells, the spindle-shaped MSCs (SS-AF-MSCs), could be utilized as a novel therapeutic, cell free approach for IBD therapy. Induction of colitis was achieved by oral administration of dextran sulphate sodium (DSS) (3 % w/v in tap water), for 5 days, to 8-week-old NOD/SCID mice. The progression of colitis was assessed on a daily basis through recording the body weight, stool consistency and bleeding. Conditioned media (CM) derived from SS-AF-MSCs were collected, concentrated and then delivered intraperitoneally into DSS treated mice. To evaluate and determine the inflammatory cytokine levels, histopathological approach was applied. Administration of CM derived from SS-AF-MSCs cells reduced the severity of colitis in mice. More importantly, TGFb1 protein levels were increased in the mice received CM, while TNFa and MMP2 protein levels were decreased, respectively. Accordingly, IL-10 was significantly increased in mice received CM, whereas TNFa and IL-1b were decreased at mRNA level. Our results demonstrated that CM derived from SS-AF-MSCs cells is able to ameliorate DSS-induced colitis in immunodeficient colitis mouse model, and thus, it has a potential for use in IBD therapy.

Effects of raw biles and their non-protein fractions from fox, pig, sheep and chicken on the survival of Trichinella spp. in vitro.

The in vitro differential effect of fox, pig, sheep and chicken bile and corresponding non-protein fractions at various concentrations on the motility of released muscle larvae of Trichinella spiralis, Trichinella nativa and Trichinella nelsoni was examined. In many cases, the percentages of motile (live) larvae of the three Trichinella species cultured in the presence of the non-protein fractions of bile from the study animals were significantly higher (p<0.001) compared to their respective control cultures. In addition, the percentages of motile (live) larvae of all Trichinella species cultured in the presence of the non-protein fraction of bile at every concentration from all study animals were significantly higher (p<0.001) compared to their respective cultures in the presence of raw bile. Not only did results with non-protein fractions of bile differ from those with raw bile, but also the non-protein fraction, with increased dilution, showed a decrease in the percentages of motile larvae while the opposite was true with the raw bile (p<0.001). These observations indicate that the non-protein fraction of bile prolongs the in vitro survival of larvae.

Characteristics of non-cerebral coenurosis in tropical goats.

The epidemiological, clinical, and biochemical profile of non-cerebral coenurosis in goats and the morphological characteristics of the responsible metacestodes (cysts) were examined in a cross-sectional survey of slaughtered goats in abattoirs of the United Arab Emirates (U.A.E.) originating from Abu Dhabi and various tropical countries. The age, country of origin, and location of each cyst in the body of goats were recorded. Blood samples collected from infected and matching healthy goats were subjected to biochemical analysis. Data on the morphological characteristics of the cysts as well as the clusters, scoleces, and rostellar hooks in one cyst from each affected carcass were collected. The data collected were subjected to statistical analysis. A total of 2,284 slaughtered goats were examined and 40 goats were diagnosed as infected with non-cerebral coenurus cysts. The prevalence of non-cerebral coenurosis was 1.75% and the degree of parasite aggregation (k) was 0.003, which is indicative of overdispersion (k<1). The only abnormalities observed in the infected goats were palpation of large single cysts in thigh muscles and higher serum aspartate aminotransferase (AST) value. A total of 76 non-cerebral coenurus cysts from 14 different body locations were collected. No cysts were found in the brain or spinal cord. Cysts located in psoas muscles had on average significantly bigger volumes and higher numbers of scoleces and clusters compared to cysts located in other body parts (P-value=0.000). Significant differences in the morphometric measurements of the rostellar hooks were observed between cysts found in goats from different countries of origin (P-value<0.05) perhaps due to initial steps of allopatric speciation by geographic isolation. A significant positive correlation was found between number of scoleces and volume of cysts (b=6.37>5; R-Sq=89.4%; P-value=0.000) and between number of clusters and number of scoleces (b=25.13>1; R-Sq=79.8%; P-value=0.000) indicative of following a positive allometric growth as well as between number of clusters and volume of cysts (b=0.25<0.5; R-Sq=69.4%; P-value=0.000) indicative of following a negative allometric growth. The biological significance of the observed allometries is not known, but perhaps for evolutionary reasons the parasite is investing its resources more on the growth of scoleces, less on the growth of cyst volume, and even less on the number of clusters.

Association of CD133 polymorphisms and response to bevacizumab in patients with metastatic colorectal cancer.

BACKGROUND: Bevacizumab, an angiogenesis inhibitor is used in regimens for metastatic colorectal cancer (CRC). A minority of cancer cells with characteristics of cancer stem cells (CSC) may be responsible for progression and development of chemotherapy resistance in this disease. CD133 is a well-known CSC marker and is associated with angiogenesis, poor prognosis and resistance to chemotherapy. OBJECTIVE: The purpose of our study was to evaluate the association between the rs3130 and rs2286455 polymorphisms of the CD133 gene and the response, toxicity, and overall survival of patients with CRC on bevacizumab-based treatment. METHODS: Forty-three patients receiving bevacizumab, irinotecan and capecitabine and 15 patients receiving bevacizumab, irinotecan and 5-FU were included. Efficacy and toxicity were evaluated. KRAS mutation analysis and rs3130 and rs2286455 polymorphisms genotyping in the tumors and peripheral blood respectively were performed with PCR-RFLP. RESULTS: No association between KRAS mutated alleles and response was found. The rs3130 CC genotype was associated with reduced toxicity of treatments (p= 0.0017), and with lower overall survival on bevacizumab (p= 0.002). CONCLUSIONS: The CC genotype of rs3130 polymorphism in the CD133 gene can predict poorer overall survival in patients with metastatic CRC on bevacizumab which cannot be attributed to increased treatment toxicity.