Influence of different heat stress models on nutrient digestibility and markers of stress, inflammation, lipid, and protein metabolism in broilers.

This experiment determined the effects of different HS models and pair-feeding (PF) on nutrient digestibility and markers of stress, inflammation, and metabolism in broilers. Birds (720 total) were allocated into 12 environmentally controlled chambers and reared under thermoneutral conditions until 20 d. Until 41 d birds were exposed to 4 treatments, including: thermoneutral at 24°C (TN-al), daily cyclic HS (12 h at 24 and 12 h at 35°C; cyHS), constant HS at 35°C (coHS), and PF birds maintained at 24°C and fed to equalize FI with coHS birds (TN-coPF). At d 41, ileal digesta were collected to determine nutrient apparent ileal digestibility (AID). Blood, liver, and breast tissues were collected from 8 birds per treatment to determine the mRNA expression of stress, inflammation, and metabolism markers. An additional 8 TN-al birds were sampled after acute HS exposure at 35°C for 4 h (aHS), and 8 cyHS birds were sampled either right before or 4 h after HS initiation. Data were analyzed by 1-way ANOVA and means were separated using Tukey's HSD test. Compared with TN-al birds, AID of nitrogen and ether extract were reduced in coHS birds, and both cyHS and coHS reduced (P < 0.05) AID of total essential amino acids. TNFα and SOD2 expression were increased (P < 0.05) under aHS, coHS, and TN-coPF conditions. IL6 and HSP70 were increased (P < 0.05) under coHS and aHS, respectively. Expression of lipogenic enzymes ACCα and FASN were reduced by coHS and TN-coPF, while coHS increased the lipolytic enzyme ATGL (P < 0.05). IGF1 was lowered in coHS birds, and p70S6K and MyoG were reduced under coHS and TN-coPF (P < 0.05). Interestingly, MuRF1 and MAFbx were increased (P < 0.05) under coHS only. Overall, these results indicate that coHS has a greater impact on nutrient digestibility and metabolism than aHS and cyHS. Interestingly, increased protein degradation during HS appears to be mostly driven by HS per se and not the reduced FI.

Protective effects of the phytogenic feed additive "comfort" on growth performance via modulation of hypothalamic feeding- and drinking-related neuropeptides in cyclic heat-stressed broilers.

Identification of alternatives to antibiotics in livestock and poultry is necessary. Fueled by consumer preferences, phytogenic feed additives are increasingly used in the food system; however, their mode of action is not well defined. Here, we used broiler chickens, in which appetite and feeding behavior regulation are controlled by complex mechanisms, to determine the effect of the phytogenic feed additive "comfort" (PFA-C) as well as its underlying molecular mechanisms on growth performance in heat-stressed broiler chickens. Heat stress significantly increased birds' core body temperature, water intake, and the hypothalamic expression of heat shock protein (HSP) 70, whereas it decreased feed intake, BW, and woody breast incidence. Phytogenic feed additive "comfort" supplementation downregulated the hypothalamic expression of HSP70, reduced core body temperature, increased feed and water intake, and improved BW in HS broilers. At molecular levels, the effect of PFA-C on growth performance seemed to be mediated by modulation of hypothalamic expression of melanocortin receptor 2, arginine vasopressin, aquaporin 2, and sodium and potassium-transporting ATPase subunit beta 1 polypeptides. In summary, PFA-C supplementation ameliorates heat stress productivity losses via a potential cytoprotective effect, reduction of hypothalamic intracellular stress, and modulation of hypothalamic feeding- and drinking-related polypeptide expression.

Prognostic factors of overall survival for patients with FIGO stage IIIc or IVa ovarian cancer treated with neo-adjuvant chemotherapy followed by interval debulking surgery: A multicenter cohort analysis from the FRANCOGYN study group.

INTRODUCTION: The aim of this study was to identify prognostic factors of overall survival in patients with FIGO stage IIIc or IVa ovarian cancer (OC) treated by neo-adjuvant chemotherapy (NAC) followed by interval debulking surgery. MATERIALS AND METHODS: Data from 483 patients with ovarian cancer were retrospectively collected, from January 1, 2000 to December 31, 2016, from the FRANCOGYN database, regrouping data from 11 centers specialized in ovarian cancer treatment. Median overall survival was determined using the Kaplan-Meier method. Univariate and multivariate analysis were performed to define prognostic factors of overall survival. RESULTS: The median overall survival was 52 after a median follow up of 30 months. After univariate analysis, factors significantly associated with decreased overall survival were; no pelvic and/or para-aortic lymphadenectomy (p = 0.002), residual disease (CC1/CC2/CC3) after surgery (p < 0.001), positive cytology after NAC (p < 0.001), omental disease after NAC (p = 0.002), no pathologic complete response (pCR) (p = 0.002). In multivariate analysis, factors significantly associated with decreased overall survival were; residual disease after surgery (HR = 1.93; CI95% (1.16-3.21), p = 0.01) and positive cytology after NAC (HR = 1.59; CI95% (1.01-2.55), p = 0.05). Patients with no residual disease after surgery had a median overall survival of 64 months versus 35 months for patients with residual disease. Patients with negative cytology after NAC had a median overall survival of 71 months versus 43 months for patients with positive cytology after NAC. CONCLUSION: In this first and largest French based retrospective study, complete cytoreductive surgery in ovarian cancer remains the main prognostic factor of overall survival.

Surface wetting strategy prevents acute heat exposure-induced alterations of hypothalamic stress- and metabolic-related genes in broiler chickens.

Heat stress (HS) is devastating to poultry production worldwide, yet its biology and molecular responses are not well defined. Although advances in management strategy have partially alleviated the negative impact of HS, productivity still continues to decline when the ambient temperature rises. Therefore, identifying mechanism-based approaches to decrease HS susceptibility while improving production traits is critical. Recently, we made a breakthrough by applying a surface wetting strategy and showing that it improves growth performance compared with the current conventional cooling system. In the present study, we aimed to further define molecular mechanisms associated with surface wetting in ameliorating HS productivity loss in broilers. Five-week-old broiler chickens were exposed to acute HS (35°C for 2 h) alone or in combination with surface wetting. A control group was maintained at thermoneutral conditions (25°C). Core body temperature (BT) and feed intake were recorded. Blood was collected and hypothalamic tissues (main site involved in the regulation of energy homeostasis) were harvested to determine the expression profile of stress- and metabolic-related genes. Surface wetting prevents HS from increasing BT and plasma corticosterone levels ( < 0.05) and improves feeding and drinking behaviors. At molecular levels, surface wetting blocks the activation of hypothalamic heat shock protein and adenosine monophosphate-activated protein-induced by HS and significantly modulates the expression of feeding-related hypothalamic neuropeptides (agouti-related protein, proopiomelanocortin, orexin, orexin receptor, and leptin receptor). Taken together, our data represent the first evidence that surface wetting alleviates systemic and intracellular stress induced by HS and preserves the intracellular energy status, which, in turn, may result in improved broiler well-being and growth performance.

Expression profile of hypothalamic neuropeptides in chicken lines selected for high or low residual feed intake.

The R(+) and R(-) chicken lines have been divergently selected for high (R(+)) or low (R(-)) residual feed intake. For the same body weight and egg production, the R(+) chickens consume 40% more food than their counterparts R(-) lines. In the present study we sought to determine the hypothalamic expression profile of feeding-related neuropeptides in these lines maintained under fed or food-deprived conditions. In the fed condition, the suppressor of cytokine signaling 3 (SOCS3) was 17-fold lower (P<0.05) and the ghrelin receptor was 7-fold higher (P<0.05) in R(+) compared to R(-) chicken lines. The hypothalamic expression of the other studied genes remained unchanged between the two lines. In the fasted state, orexigenic neuropeptide Y and agouti-related peptide were more responsive, with higher significant levels in the R(+) compared to R(-) chickens, while no significant differences were seen for the anorexigenic neuropeptides pro-opiomelanocortin and corticotropin releasing hormone. Interestingly, C-reactive protein, adiponectin receptor 1 and ghrelin receptor gene expression were significantly higher (12-, 2- and 3-folds, respectively), however ghrelin and melanocortin 5 receptor mRNA levels were lower (4- and 2-folds, P=0.05 and P=0.03, respectively) in R(+) compared to R(-) animals. We identified several key feeding-related genes that are differently expressed in the hypothalamus of R(+) and R(-) chickens and that might explain the difference in feed intake observed between the two lines.

Evaluation and impact of residual disease in locally advanced cervical cancer after concurrent chemoradiation therapy: results of a multicenter study.

BACKGROUND: The aim of this study was to evaluate the diagnosis and impact of residual disease (RD) after concurrent chemoradiation therapy (CRT) in locally advanced cervical cancer (FIGO IB2-IVA). METHODS: This retrospective multicenter study included 159 patients who were treated with completion surgery after CRT between 2006 and 2012. Magnetic resonance imaging (MRI) was performed 4-6 weeks after CRT and compared to pathological evidence of residual disease. Kaplan-Meier survival curves were plotted and univariate/multivariate analyses were performed to assess the association between RD and the outcome. RESULTS: Residual disease was present in 45.3% of the patients and detected by MRI in 57.1%. The MRI had a 29.2% false positive rate and an 11.1% false negative rate. The overall survival (OS) rates at 3 and 5 years were 78.6% (CI 95% [71%-86.9%]) and 76.5% (CI 95% [68.2%-85.7%]), respectively. The disease free survival (DFS) rates at 3 and 5 years were 73.4% (CI 95% [65.6%-82%]) and 71.1% (CI 95% [62.7%-80.1%]), respectively. RD greater than 10 mm decreased DFS (HR = 4.84, p = 0.03), whereas RD between 1 and 10 mm (HR = 0.31, p = 0.58) and less than 1 mm (HR = 0.37, p = 0.54) had no impact on DFS. The OS was not changed by RD. DISCUSSION: The MRI accuracy value is not sufficient to select patients who might benefit from completion surgery. Residual disease over 10 mm decreased DFS but did not impact OS.

Visfatin gene expression in chickens is sex and tissue dependent.

The present study investigated the expression of visfatin mRNA in various tissues of male and female broiler chickens. We also studied the effect of leptin, cerulenin, and food deprivation, known effectors of energy balance and insulin action, on visfatin gene expression in chickens. Using reverse transcription polymerase chain reaction (RT-PCR) and Northern blot analysis, we detected chicken visfatin mRNA transcript in the kidney, hypothalamus, gizzard, liver, pancreas, proventriculus, breast and leg muscle, ovary, testis, lung, intestine, adipose tissue, and heart. Expression of the visfatin gene in various tissues of male and female chickens was determined by real-time quantitative PCR and found to be tissue and sex dependent. In both sexes, compared to other tissues, the visfatin gene is highly expressed in the muscle. Females exhibited greater (P<0.001) abundance of visfatin mRNA in adipose tissue compared to males, whereas compared to females, males showed greater (P<0.05) visfatin mRNA abundance in the kidney. Also, the regulation of visfatin gene expression by leptin, cerulenin, and food deprivation is tissue specific. Leptin decreased (P<0.05) visfatin mRNA abundance in the liver and hypothalamus, but not in muscle. In contrast, cerulenin increased (P<0.01) visfatin gene expression in the liver and in muscle, but not in the hypothalamus. Interestingly, visfatin mRNA levels increased (P<0.05) in the liver after 24-h food deprivation, but not in muscle or in the hypothalamus of genetically selected fat and lean line chickens. Our results showed that the visfatin gene is ubiquitously expressed in chickens with greater abundance in muscle, and that it is regulated in a tissue-specific manner by energy balance-related factors.

Effect of acid etching duration on tensile bond strength of composite resin bonded to erbium:yttrium-aluminium-garnet laser-prepared dentine. Preliminary study.

The purpose of this study was to compare the tensile bond strength of composite resin bonded to erbium:yttrium-aluminium-garnet (Er:YAG) laser-prepared dentine after different durations of acid etching. The occlusal third of 68 human third molars was removed in order to expose the dentine surface. The teeth were randomly divided into five groups: group B (control group), prepared with bur and total etch system with 15 s acid etching [37% orthophosphoric acid (H(3)PO(4))]; group L15, laser photo-ablated dentine (200 mJ) (laser irradiation conditions: pulse duration 100 micros, air-water spray, fluence 31.45 J/ cm(2), 10 Hz, non-contact hand pieces, beam spot size 0.9 mm, irradiation speed 3 mm/s, and total irradiation time 2 x 40 s); group L30, laser prepared, laser conditioned and 30 s acid etching; group L60, laser prepared, laser conditioned and 60 s acid etching; group L90, laser prepared, laser conditioned and 90 s acid etching. A plot of composite resin was bonded onto each exposed dentine and then tested for tensile bond strength. The values obtained were statistically analysed by analysis of variance (ANOVA) coupled with the Tukey-Kramer test at the 95% level. A 90 s acid etching before bonding showed the best bonding value (P < 0.05) when compared with all the other groups including the control group. There is no significance difference between other groups, nor within each group and the control group. There was a significant increase in tensile bond strength of the samples acid etched for 90 s.

Effects of a vegetable extract from Lupinus albus (LU105) on the production of matrix metalloproteinases (MMP1, MMP2, MMP9) and tissue inhibitor of metalloproteinases (TIMP1, TIMP2) by human gingival fibroblasts in culture.

This study examined the effects of a vegetable extract from Lupinus albus (LU105) on MMPs and TIMPs secreted by human gingival fibroblasts in culture. LU105 was extracted from seeds of L. albus and is freely soluble in water. Gelatin zymography showed that control human gingival fibroblasts maintained in culture for 48 h express pro-MMP2 (progelatinase A) in the culture medium while the active form of MMP2 (gelatinase A), the active form of MMP9 (gelatinase B), and pro-MMP9 (progelatinase B) are not detected. Fibroblasts derived from inflamed gingiva expressed in the culture medium increased amounts of pro-MMP2 (progelatinase A) compared with controls and significant amounts of pro-MMP9 (progelatinase B). LU105 diminished the expression by gingival fibroblasts derived from inflamed tissue of both pro-MMP2 and pro-MMP9. Furthermore LU105 did not modify the amount of TIMP2 expressed in culture by controls or by gingival fibroblasts derived from inflamed tissue. TIMP1 and MMP1 significantly decreased when LU105 was added in the culture media of gingival fibroblasts derived from inflamed tissue compared with control fibroblasts. Thus LU105 seems to offer an opportunity to restore a correct balance between MMP2, MMP9, MMP1, and their natural inhibitors, i.e., TIMP1 and TIMP2 in human inflamed gingiva.