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Abstract: The chemical modification of graphene greatly expands its potential applications in electronics, chemistry, and biology. Here, we report the rapid and extensive hydrogenation of single layer CVD graphene using the Birch reduction method. This method hydrogenates much more extensively than cold plasmas and electrochemical methods. Moreover, use of single layer graphene enables greater control of electronic conductivity than previously achieved with the Birch method using multilayer graphene or graphene oxide. Indeed, this method enables both the elimination of electronic conductivity through hydrogenation and the subsequent recovery of essentially pristine graphene with thermal annealing—a reversible >107 fold change in resistance. Raman and photoelectron spectroscopies show that the reaction is complete within 90s of immersion. Finally, we show that we can use the Birch reduction to functionalize graphene with tributyltin moieties. [Copyright &y& Elsevier]

Abstract: Introduction: Selective internal radiation therapy (SIRT) is emerging as a new therapeutic modality in recent years for management of non-resectable hepatic malignancies. Our experience in clinical application of this treatment is reported here. Material and methods: From June 2004, patients whose liver tumours were no longer amenable for any conventional treatment with either chemotherapy or surgery were considered for yttrium-90 microspheres treatment after discussion at our multidisciplinary meeting. A pre-treatment planning was carried out with visceral angiography and technetium-99m macroaggregated albumin (MAA) for assessment of both tumour volume and extrahepatic shunting in addition to a baseline PET and CT scans, respectively. Two weeks later, a second visceral angiogram was performed to deliver the calculated dosage of microspheres into the arterial system supplying the tumour. Patients were then followed up with tumour markers, repeat PET and CT scans of abdomen at 6 weeks and 3 monthly thereafter. Result: Twenty-one patients (F=11, M=10; age range 40–75 years, mean=58 years) received yttrium-90 microspheres consisting of liver metastases from colorectal primary (n =10) and non-colorectal primaries (n =8), and primary liver tumours (n =3). One patient received 2 treatments. The mean administered activity of microspheres delivered was 1.9GBq (range 1.2–2.5GBq). Injection of microspheres had no immediate effect on either clinical haematology or liver function tests. At follow-up, 86% of patients showed decreased activity on PET scan at 6 weeks (p =0.01). The mean pre-treatment SUV was 12.2±3.7 and the mean post-treatment SUV was 9.3±3.7, indicating a significant improvement measured with PET activity. Only 13% showed a reduction in the size of tumour on CT scan. For patients with colorectal liver metastases, there was no significant reduction in CEA level (127±115 vs 75±72μ/l, p =0.39). Complications were seen in 4 patients (19%) including radiation hepatitis (n =2), cholecystitis (n =1) and duodenal ulceration (n =1). All resolved without surgical intervention. Seven patients died at follow-up from progressive extrahepatic disease (33%). Conclusion: SIRT should be considered for patients with advanced liver cancer. It has a significant effect on liver disease in the absence of extrahepatic disease. PET imaging has an integral role in the assessment of patients treated with yttrium-90 SIR-Spheres. [Copyright &y& Elsevier]

Abstract: Quercetin has chemoprotective properties in experimental colon cancer models, and in vitro studies have demonstrated that quercetin inhibits HT-29 colon cancer cell growth. ErbB2 and ErbB3 receptor tyrosine kinases have been associated with the development of human colon cancer, and the expressions of both receptors are high in HT-29 cells. In this study, we assessed quercetin regulation of HT-29 and SW480 cell apoptosis and the influence of quercetin on the protein expression of ErbB2, ErbB3, Akt, Bax and Bcl-2. We cultured HT-29 cells in the presence of various concentrations (0, 25, 50, or 100 μmol/L) of quercetin or rutin. Quercetin inhibited HT-29 cell growth in a dose-dependent manner, whereas rutin had no effect on the cell growth. DNA that was isolated from cells treated with 50 μmol/L of quercetin exhibited an oliogonucleosomal laddering pattern characteristic of apoptotic cell death. Western blot analysis of cell lysates revealed that Bcl-2 levels decreased dose-dependently in cells treated with quercetin, but Bax remained unchanged. Quercetin increased levels of cleaved caspase-3 and the 89-kDa fragment of poly (ADP-ribose) polymerase. In addition, phosphorylated Akt levels were markedly lower in cells treated with 25 μmol/L quercetin, but total Akt levels decreased only at 100 μmol/L quercetin. Furthermore, a dose-dependent decrease in ErbB2 and ErbB3 levels was detected in quercetin-treated cells. The results obtained using SW480 cells were similar to those obtained with HT-29 cells. In conclusion, we have shown that quercetin inhibits cell growth and induces apoptosis in colon cancer cells, and that this may be mediated by its ability to down-regulate ErbB2/ErbB3 signaling and the Akt pathway. [Copyright &y& Elsevier]

To examine the effect of two types of resistant starch on blood glucose and insulin levels, colonic events, hypolipidemic actions and humoral immune responses, Sprague-Dawley streptozotocin-induced diabetic rats were fed diet containing resistant starch from corn or rice. The marked body weight loss by inducing diabetes was not recovered by feeding resistant starch, even though there are no differences in food intakes compared to the non-diabetic control rats. No significant effect of resistant starch feeding on blood glucose and insulin was found. Even though the length of small intestines, and cecum, colon and rectum together with the tissue weight of cecum were not affected by feeding resistant starch, the intestinal transit time was markedly shortened by both types of resistant starch and resistant starch from corn had a more pronounced effect. The short chain fatty acids in the intestinal contents did not appear to be different among the groups. Nonetheless, both of resistant starch from corn and rice significantly lowered plasma total lipid and cholesterol concentrations compared to the diabetic control. The total liver cholesterol lowering effect was observed with resistant starch from rice. Neither immunoglobulin G nor C3 were influenced by resistant starch. [Copyright &y& Elsevier]

Open pyeloplasty (OP) has traditionally been the standard for the operative management of ureteropelvic junction obstruction in children. With advances in minimally invasive pyeloplasty (MIP) techniques, it is quickly becoming a popular alternative in both adult and pediatric population. To evaluate the differences in outcomes between MIP and OP for the surgical correction of ureteropelvic junction obstruction in children. Data were obtained from the pediatric National Surgical Quality Improvement Program 2012–2017. We identified 1280 patients who underwent MIP and 1190 patients who underwent OP between 2012 and 2017. Propensity score matching was utilized to adjust for baseline differences. Univariate and multivariable regression were performed to assess odds of complications and procedure-related readmission. Patients who underwent OP had a significantly decreased operative time (192.42 vs 142.00 min, p < 0.001) compared to MIP. There was no significant difference in the rates of overall peri-operative complications (3.7% [MIP] vs 2.4% [OP] p = 0.397). On multivariable analysis, patients undergoing OP had a lower risk of procedure-related readmission (odds ratio [OR] 0.404, 95% confidence interval [CI] 0.157–0.951, p = 0.046) than MIP. In a multivariable linear regression model, the risk of having any postoperative complication, regardless of surgical approach, decreased with increasing patient age (OR 0.945, 95% CI 0.893–0.996, p = 0.037). Although recent small, retrospective institutional studies have found decreased hospitalization time of MIP as compared to OP, in our large prospective database, we found no such association. While some studies suggest a higher rate of wound complications in the OP group, this was not reproduced in our study as well. MIP was, in fact, associated with higher rate of readmissions as compared to the OP group, which may act as a surrogate of long-term complications in these patients. MIP offers an alternative to OP in the pediatric population with similar rates of peri-operative complications. However, our study shows decreased odds of procedure-related readmission in OP, which may serve as a surrogate for less postoperative complications in these patients. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "ACE-Inhibitor Use and the Long-Term Risk of Renal Failure in Diabetes," by S. Suissa and colleagues in the 2006 issue.

Keel bone fractures and osteoporosis are prevalent and damaging skeletal issues in the laying hen industry. There is a large interest in improving bone quality parameters to reduce or eliminate these conditions, thus improving bird welfare. Both essential fatty acids (EFA) and vitamin D can play a role in bone metabolism. The hypothesis of this study was that birds supplemented with lower n-6:n-3 EFA ratio or vitamin D would have improved bone properties compared to a control diet. A total of 3,520 Lohmann Brown-Lite pullets were used in this study. Pullets were housed on the floor from 0 to 17 wk of age and then moved to an aviary (17–52 wk of age). Starting at 12 wk of age, birds were split into diet treatments—control, flax, fish, or vitamin D diets with n-6:n-3 ratios of 6.750, 0.534, 0.534, and 6.750, respectively. Diets were formulated to be isonitrogenous and isocaloric. Basal vitamin D3 levels were formulated to be 2,760 IU/kg across all diets; for the vitamin D diet, the vitamin D3 level was increased to 5,520 IU/kg. Hens on fish and vitamin D diets had greater bone density, keel bone volume, digital bone mineral content, and keel condition compared to flax and control hens. Additionally, birds fed the vitamin D diet had the heaviest body weights compared to birds fed fish or control diets. Birds fed the flax and vitamin D diets had improved feather coverage across multiple body regions. Feeding an n-3 EFA- or vitamin D-enriched diet decreased mortality by 1.6 to 3.3% compared to the control. The fish and vitamin D diets generated mixed production performance. Compared to the other treatments, the vitamin D diet generated higher case weights but lower hen day percentage throughout the study. When compared to the other treatments, the fish diet had the lowest case weights but had a greater hen day percentage after 36 wk of age. Results indicate that a fish-based EFA and vitamin D supplementation show promise in improving skeletal health but require further investigation. [ABSTRACT FROM AUTHOR]

Mycotoxins, particularly deoxynivalenol (DON), are common contaminants in feed ingredients such as corn distiller's dried grains with solubles (DDGS) and pose significant risks to poultry health. This study investigated the effects of feeding naturally DON contaminated DDGS on growth performance, body composition, immunological response, and gastrointestinal health in young pullets. A total of 360, 4-week-old Hy-Line W36 pullets were randomly assigned to diets with increasing levels of naturally DON contaminated DDGS (0, 5, 10, 15, and 20%) over 28 days, resulting in dietary DON concentrations ranging from below the limit of quantification to 15.4 ppm. Diets with DON concentration exceeding 8.9 ppm, corresponding to 15% and 20% DDGS inclusion, resulted in significantly lower body weight gain (BWG) and feed intake (FI) from experimental day 14 to day 28 compared to DON concentration below 5.9 ppm (0, 5 and 10% DDGS groups; P = 0.024 and P = 0.007, respectively). Body composition analysis showed a higher tissue fat percentage in the 20% DDGS group (15.4 ppm DON) by day 28 compared to lower inclusion levels (P = 0.021). Immunologically, a significant increase in the CD4+:CD8+ ratio in spleen was observed in the 20% DDGS group compared to the 0% DDGS group (P = 0.013), whereas both 15 and 20% DDGS inclusion levels significantly increased the ratio in cecal tonsil (P < 0.001). Additionally, interleukin 1β ( IL-1β ) expression significantly increased in the cecal tonsil by day 28 with 15 and 20% DDGS inclusions (P = 0.002). Gut health was compromised as gut permeability increased linearly with increasing DDGS inclusion (linear, P = 0.043), aligning with significant alterations in the expression of the tight junction protein occludin ( OCLN ; P = 0.007). Antioxidant responses in the liver showed increased superoxide dismutase (SOD) activity in early exposure (day 13, P = 0.038), followed by decreased SOD activity (P = 0.001) and reduced glutathione (GSH) levels (P < 0.001) by day 28. In conclusion, feeding DON-contaminated DDGS at higher inclusion levels (15% and 20%) with final diet DON concentrations exceeding 8.9 ppm over 28 days adversely affects growth performance, immune function, and gut integrity in young pullets. [ABSTRACT FROM AUTHOR]

A 35-d study investigated the impact of dietary supplementation with Arginine (Arg) or branched-chain amino acids (BCAA) of broilers receiving low-protein diets whilst infected with mixed Eimeria species. All birds were given the same starter (d0–10) and finisher (d28–35) diets. The 4 grower diets used were a positive control (PC) with adequate protein (18.5%), a low protein diet (NC ; 16.5% CP), or the NC supplemented with Arg or BCAA. Supplemental AA was added at 50% above the recommended levels. The treatments were in a 4 × 2 factorial arrangement, with 4 diets, with or without Eimeria inoculation on d14. Birds and feed were weighed after inoculation in phases: prepatent (d14–17), acute (d18–21), recovery (d22–28), and compensatory (d29–35). Ileal digesta, jejunum, and breast tissue were collected on d21, 28, and 35. There was no diet × Eimeria inoculation on growth performance at any phase. Infected birds weighed less and consumed less feed (P < 0.05) in all phases. In the prepatent and acute phases, birds on the Arg diets had higher weight gain (P < 0.05) and lower FCR, similar to PC, when compared to NC and BCAA-fed ones. Infection reduced AA digestibility on d21 and 28 (Met and Cys). However, birds that received supplemental AA had higher digestibility (P < 0.05) of their respective supplemented AA on d 21 only. Infected birds had lower (P < 0.05) BO + AT and higher PEPT1 expression on d21. There was a diet × Eimeria interaction (P = 0.004) on gene expression at d28; 4EBP1 genes were significantly downwardly expressed (P < 0.05) in birds fed Arg diet, irrespective of infection. Infected birds exhibited an upward expression (P < 0.05) of Eef2 on d21 and d28 but experienced a downward expression on d35. Supplemental Arg and BCAA had variable effects on growth performance, apparent ileal AA digestibility, and genes of protein synthesis and degradation, but the effect of Arg on promoting weight gain, irrespective of the Eimeria challenge, was more consistent. [ABSTRACT FROM AUTHOR]

The global egg industry is rapidly transitioning to cage-free egg production from conventional cages. Hens housed in cage-free systems have an increased prevalence of keel damage that could lead to reduced egg production and compromised well-being. The objective of this study was to determine the effects of dietary supplementation of n-3 fatty acids and vitamin D 3 on keel damage in hens housed in multi-tier aviary systems (AV). Brown hens were placed in 4 AV system rooms after rearing at 17 wk of age (woa) with each room containing 576 birds. At 12 woa, rooms were randomly assigned to a dietary treatment of flaxseed oil, fish oil, vitamin D 3 , or control. Focal birds (36 per treatment) were longitudinally examined for keel damage using quantitative computed tomography (QCT) at nine timepoints from 16 to 52 woa. Three-dimensional digital twins of the keels were created from the QCT scans and visually assessed for damage. An overall keel severity score was recorded as well as the location, direction, and severity of each deviation or fracture. Severity was ranked on a 0 to 5 scale with 0 being no damage and 5 being severe. Damage scores were analyzed utilizing odds ratios with main effects of age and treatment. At 16 woa, 80% of hens had overall keel scores of 0 and 20% had scores of 1. At 52 woa, all hens had damage, with 31% having a score of 1, 61% scored 2 to 3, and 8% scored 4 to 5. Most fractures were not observed until peak lay. Dietary treatments did not affect likelihood of fracture incidences, but younger birds had lower odds of incurring keel fractures than older birds (P < 0.0001). The initial incidences of keel deviations occurred earlier than fractures, with most birds obtaining a keel deviation by 28 woa. Keel damage was not able to be prevented, but the age at which keel fractures and deviations initiate appear to be different, with deviations occurring during growth and fractures during lay. [ABSTRACT FROM AUTHOR]

Fluorescein isothiocyanate-dextran (FITC-d) is being used as an indicator of intestinal paracellular permeability in poultry research. Especially with the industry moving toward antibiotic-free production, intestinal function and integrity issues have been a research focus. An increasing number of scientific conference abstracts and peer-reviewed journal publications have shown that 4-kDa FITC-d is an efficient marker candidate for measurement of intestinal permeability and can be applied in broiler research. However, experimental protocols vary by personnel, instruments used, and research institution, and potential concerns related to this assay have yet to receive the same amount of attention. Understanding protocol consistency within and across laboratories is vital for obtaining accurate, consistent, and comparable experimental results. This review is aimed to 1) summarize different FITC-d assays in broiler research from peer-reviewed publications during the past 6 yr and 2) discuss factors that can potentially affect intestinal permeability results when conducting the FITC-d assay. In summary, it is essential to pay attention to details, including gavage dose, fasting period, sample handling and lab analysis details when conducting the assay in broiler research. Differences in birds (breed/strain, age, and gender) and experimental design (diet, health status/challenge model, and sampling age) need to be considered when comparing serum FITC-d concentration results between different in vivo animal trials. [ABSTRACT FROM AUTHOR]

Recently, several studies have reported that sarcopenia and sarcopenic obesity (SO) could worsen postoperative complications after PD. This study aims to evaluate the effects of preoperative sarcopenia and SO following PD in pancreatic head cancer (PHD). Preoperative sarcopenia and SO were assessed in 548 patients undergoing PD for PHC at Samsung Medical Centre between 2007 and 2016. The visceral adipose tissue-to-skeletal muscle ratio was calculated from cross-sectional visceral fat and muscle areas on preoperative CT images. The overall survival (OS) and rate of clinically relevant postoperative pancreatic fistula (CR-POPF) among postoperative complications were extracted from prospectively maintained databases. Preoperative sarcopenia was present in 252 patients (45.9%). The 5-year survival rates of patients with non-sarcopenia and sarcopenia were 28.4% and 23.4% (p = 0.046). Preoperative SO was present in 202 patients (36.9%). After multivariable analysis, the presence of SO was the only independent risk factor for CR-POPF (p = 0.018). Sarcopenia can be a risk factor affecting decreased OS after PD in patients with PHC. SO is the only predictive factor for CR-POPF after PD in patients with PHC. More observational studies are needed to evaluate the effects of sarcopenia and SO on survival after PD. [ABSTRACT FROM AUTHOR]

We investigated the effects of supplementing low protein diets with methionine (Met) or threonine (Thr) during a mixed Eimeria (consisting of E. acervulina, E. maxima and E. tenella) challenge in broilers. All birds were fed the same starter diet (d1–9) and finisher diet (d28–35) which met Cobb 500 nutrient specifications. Birds were allocated to 1 of 4 dietary treatments from d9 to 28: a standard protein diet (19% CP); a low protein diet (16% CP); or the low protein diet supplemented with Met or Thr at 50% above recommendations. On d14, half of the birds were challenged, and half of the birds were unchallenged. From d14 to 28, feed intake was recorded daily and BW every 3 or 4 d. Oocyst excretion was measured daily from d18 to 27. On d21 and 28, 3 birds per pen were euthanized to assess nutrient digestibility, cytokine expression and intestinal histology. During the acute stage of the challenge, challenged birds reduced ADFI and ADG (P < 0.05). In the pre-patent and recovery stages, birds given the 16% CP diets increased ADFI (P < 0.05), meanwhile there were no differences in ADG in these stages (P > 0.05). Nutrient digestibility was reduced in challenged birds in the acute stage (P < 0.05) but tended to be greater than in unchallenged birds during the recovery stage. There was no significant effect of diet on oocyst excretion or intestinal histology (P > 0.05). Interactions were observed between diet and challenge on IL-10 and IL-21 expression in the cecal tonsils during the acute stage of the challenge (P < 0.05), due to reduced IL-10 expression in challenged Thr birds and greater IL-21 expression in challenged Met birds. Supplementation with Thr or Met had limited effects on the outcomes of a mixed Eimeria challenge but provides benefits to the host by enhancing their immune response. [ABSTRACT FROM AUTHOR]

Despite the acknowledged significance of nutrition in bone development, effects of methionine (Met) and cysteine (Cys) on bone quality remain under-researched, particularly during Eimeria challenge. We investigated the effects of different supplemental Met to Cys ratios (MCR) on bone quality of broilers under Eimeria challenge. A total of 720 fourteen-day old Cobb500 broilers were allocated into a 5 × 2 factorial arrangement. Five diets with Met and Cys supplemented at MCR of 100:0, 75:25, 50:50, 25:75, and 0:100 were fed to the birds with or without Eimeria challenge. Body composition was measured by dual energy x-ray absorptiometry, and the femur bone characteristics were assessed by microtomography. Data were analyzed by two-way ANOVA and orthogonal polynomial contrast. The results reaffirmed the detrimental effects of Eimeria challenge on bone quality. On 9 d post inoculation (DPI), significant interaction effects were found for whole body bone mineral content (BMC), lean tissue weight, and body weight (P < 0.05); in the nonchallenged group (NCG), these parameters linearly decreased as MCR decreased (P < 0.05). In the challenged group (CG), body weight and lean tissue weight were unaffected by MCR, and BMC linearly increased as MCR decreased (P < 0.05). For the cortical bone of femoral metaphysis on 6 DPI, bone mineral density (BMD) linearly increased as MCR decreased (P < 0.05). Bone volume to tissue volume ratio (BV/TV) in the CG linearly increased as MCR decreased (P < 0.05). On 9 DPI, BMC and TV linearly increased as MCR decreased (P < 0.05) in the NCG. BMD and BV/TV changed quadratically as MCR decreased (P < 0.05). For the trabecular bone of femoral metaphysis on 9 DPI, BV/TV, and trabecular number linearly increased as MCR decreased (P < 0.05) in the NCG. For the femoral diaphysis, BV, TV, BMC on 6 DPI, and BMD on 9 DPI linearly increased as MCR decreased (P < 0.05). In conclusion, this study showed that both Eimeria challenge and varying supplemental MCR could influence bone quality of broilers. [ABSTRACT FROM AUTHOR]

A study was conducted to investigate effects of different methionine (Met) to cysteine (Cys) supplementation ratios (MCR) on growth performance, oxidative status, intestinal health, immune responses, and methionine metabolism in broilers under Eimeria challenge. A total of 720 male Cobb500 broilers (14-day-old) were allocated in a 2 × 5 factorial arrangement (5 diets, with or without challenge) with 6 replicates per treatment. The total sulfur amino acid concentrations were consistent across treatments meeting the breeder's recommendation, only MCR varied. The diets were labeled as MET100; MET75; MET50; MET25; and MET0, representing MCR of 100:0; 75:25; 50:50; 25:75; and 0:100, respectively. Data were analyzed by 2-way ANOVA and orthogonal polynomial contrast. Growth performance declined linearly or quadratically as MCR decreased (P < 0.01). On 6-day postinoculation (DPI), interaction effects (P < 0.01) were found; BW and body weight gain were lower in MET0 compared to the other treatments in the nonchallenged groups, whereas not in the challenged groups. On 6 and 9 DPI, serum total antioxidant capacity linearly decreased as MCR decreased (P < 0.05). Hepatic activities of glutathione peroxidase on 6 DPI and superoxide dismutase on 9 DPI changed quadratically as MCR decreased (P < 0.05). The digestibility of Met linearly decreased whereas the digestibility of Cys linearly increased as MCR decreased. The ileal crypt depth linearly decreased as MCR decreased (P < 0.01) on 6 DPI. The expression of transforming growth factor beta on 6 and 9 DPI, tumor necrotic factor alpha and interleukin 10 on 9 DPI changed quadratically as MCR decreased (P < 0.05). Eimeria challenge increased expression of Met adenosyltransferase and cystathionine gamma-lyase, whereas decreasing the expression of other Met metabolism genes (P < 0.01) on 6 DPI. Expression of Met metabolism genes linearly increased as MCR decreased (P < 0.05). In conclusion, different Met to Cys supplementation ratios exerted linearly or quadratically effects on the growth performance, oxidative status, intestinal health, and metabolism of Met in broiler chickens under Eimeria infection. [ABSTRACT FROM AUTHOR]

The aim of this experiment was to investigate how different levels of Eimeria infection affect the performance, intestinal health, oxidative status, and egg production of Hy-Line W-36 pullets and laying hens. Three hundred and sixty Hy-Line W-36 pullets, aged 15 wk, were randomly distributed into 5 treatment groups, each comprising 6 replicates and a nonchallenged control. At 15 wk, pullets were inoculated with different levels of mixed Eimeria species as high-dose, medium-high, medium-low, and low-dose treatments. The growth performance and average daily feed intake (ADFI) were measured from 0- to 18-days postinoculation (DPI), whereas hen day egg production (HDEP) was recorded from wk 19. The markers of gastrointestinal health and oxidative status were measured at 6 DPI, 14 DPI, and 23 wk of age. The findings revealed a significant linear reduction in growth performance in response to increased Eimeria challenge dosage on 6 and 14 DPI (P < 0.0001, P -L < 0.0001). An interaction between the graded level of Eimeria infection and DPI was observed for ADFI. The challenged pullets showed a reduction in ADFI starting at 4 DPI, which persisted until 14 DPI, when ADFI recovered back to normal. The most significant drop in feed intake was observed in 6 DPI in all the Eimeria -infected groups. The markers of gastrointestinal health (gastrointestinal permeability and tight junction proteins) were upregulated in challenged pullets because of infection, whereas the relative mRNA expression of key nutrient transporters was downregulated following infection on 6 and 14 DPI (P < 0.05). As a result of an infection on 6 DPI, the oxidative equilibrium was shifted toward the oxidative stress, and at the same time, upregulation of proinflammatory and inflammatory cytokines was observed (P < 0.05). An interaction between the Eimeria challenge dosage and bird age was observed for HDEP (P = 0.0427). The pullets infected with Eimeria started to lay eggs later than the Control birds. However, the HDEP of the challenged groups became similar to Control only at wk 22, 3 wk after laying eggs. In conclusion, coccidiosis reduced growth performance, altered gastrointestinal health, induced oxidative stress, and delayed egg production when infected at the prelay stage of pullets and negatively impacted the laying hens' overall performance. [ABSTRACT FROM AUTHOR]

A study was conducted to evaluate the efficacy of fructooligosaccharides (FOS) in controlling the infection of Salmonella Enteritidis (SE) in White Leghorns. A total of 30 laying hens (white leghorns W-36) were challenged both orally and cloacally with approximately 108 colony-forming units of nalidxic acid resistant SE (SENAR) and divided into 3 treatments: 1) SENAR challenged + 0.0% FOS, 2) SENAR challenged + 0.5% FOS (Nutraflora), and 3) SENAR challenged + 1.0% FOS. SENAR recovery via fecal shedding was measured at 3- and 6-d post-infection (dpi), whereas in the ceca and internal organs, SENAR recovery was measured at 7-d post-infection. In the first experiment, there was a 1.0 log10 and a 1.3 log10 reduction in cecal SENAR by supplementation of FOS at 0.5 and 1.0%, respectively. In the second experiment, there was a 0.6 log10 and a 0.8 log10 reduction in cecal SENAR by supplementation of FOS at 0.5 and 1.0%, respectively. Fecal shedding was significantly lower in 1.0% FOS supplemented groups compared to SENAR challenge 0.0% FOS. There was no significant difference among the 3 treatments on SENAR recovery in liver with gall bladder and ovaries. However, the frequency of positive SENAR in the ovaries (10 to 40%) in SENAR challenge 0.0% FOS was significantly lower than liver with gall bladder (60 to 80%) in both experiments. There was a significant upregulation of toll-like receptor-4 in 1.0% FOS and interferon gamma in both 0.5 and 1.0% FOS. Histologic measurements of ileal villi height and crypt depth were similar across all treatments. Immunohistochemistry analyses of ileal samples showed that immunoglobulin A positive cells increased as FOS concentration increased reaching significance at 1.0% as well as altered cytokine gene expression in the ileum. Further, FOS supplementation also reduced cecal SENAR and feces SENAR levels. Collectively, the results suggest that dietary supplementation with FOS may impair SE pathogenesis while modulating humoral immunity within the gut-associated lymphoid tissue. [ABSTRACT FROM AUTHOR]

An experiment was carried out to evaluate the impact of mixed Eimeria challenge on skeletal health of Hy-Line W-36 pullets. A total of 540, 16-day-old pullets were randomly allocated into 5 treatment groups, including a nonchallenged control. A mixed Eimeria species solution containing 50,000 E. maxima , 50,000 E. tenella , and 250,000 E. acervulina oocysts per mL was prepared and challenged to 1 group as a high-dose treatment. The 2-fold serial dilution was done to prepare the medium-high (25,000 E. maxima ; 25,000 E. tenella ; 125,000 E. acervulina), the medium-low (12,500 E. maxima ; 12,500 E. tenella ; 62,500 E. acervulina), and the low (6,250 E. maxima ; 6,250 E. tenella ; 31,250 E. acervulina) dose treatments which were challenged to 3 corresponding groups, respectively. The mineral apposition rate (MAR) was measured from 0 to 14 d post inoculation (DPI) and 14 to 28 DPI using calcein injection. The microstructural architecture of the femur was analyzed using the Skyscan X-ray microtomography (microCT) on 6, 14, and 28 DPI. The results showed that the MAR decreased linearly with an increase in the challenged dose (P < 0.05) during 0 to 14 DPI. The results of microCT revealed that cortical and total BMD, BMC, bone volume (BV), and bone volume as a fraction of tissue volume (BV/TV) of femur decreased both linearly (P < 0.05). Conversely, the total number of pores increased linearly with an increase in challenge dosages on 6 and 14 DPI. Trabecular BMD, BV, BV/TV, trabecular number, and trabecular thickness decreased linearly with an increase in the challenge dosages (P < 0.05) on 6 DPI. Furthermore, Eimeria infection significantly increased the number of osteoclasts and osteoclastic activity (P = 0.001). The result of this study suggests that the mixed Eimeria challenge negatively impacts the quality of skeletal health in a linear or quadratic manner with an increase in the concentration of Eimeria oocysts. The negative impact on long bone development might be due to malabsorption, nutrient deficiency during the infection, along with oxidative stress/inflammation disrupting the balance of osteoblastic and osteoclastic cells and their functions. [ABSTRACT FROM AUTHOR]

We investigated the effects of supplementing arginine (Arg) and branched-chain amino acids (BCAA) in broilers fed reduced-protein diets and challenged with Eimeria spp. All birds were fed the same starter diet meeting Cobb 500 nutrient specifications from d 1 to 9. Four grower diets: positive control (PC) with 20.0% crude protein (CP); reduced-protein negative control (NC) with 17.5% CP; or NC supplemented with Arg or BCAA at 50% above recommendations (ARG or BCAA) were fed to the birds from d 9 to 28. Birds were allocated in a 2 × 4 factorial arrangement (4 diets, each with or without challenge), with 8 replicates per treatment. On d 14, the challenge groups were orally gavaged with mixed Eimeria spp. Intestinal permeability was higher (P < 0.05) in NC than PC, whereas the permeability of ARG and BCAA groups did not differ significantly from PC. On d 28, a significant interaction (P < 0.01) was observed in CD8+: CD4+ ratios in cecal tonsils (CT), Eimeria challenge increased the ratios in all groups except for the ARG group. On d 21, a significant interaction was found for CD4+CD25+ percentages in CT (P < 0.01) that Eimeria challenge increased the percentages only in PC and NC groups. On d 21 and 28, significant interactions (P < 0.01) were found for macrophage nitric oxide (NO) production. In nonchallenged birds, NO was higher in the ARG group than other groups, but in challenged birds, NO was higher in both ARG and BCAA groups. On d 21, a significant interaction was found for bile anticoccidial IgA concentrations (P < 0.05) that Eimeria challenge increased IgA only in NC and ARG groups. The results suggest that a reduced-protein diet exacerbates the impact of the Eimeria challenge on intestinal integrity, but this could be mitigated by Arg and BCAA supplementations. Arginine and BCAA supplementations in reduced-protein diets could be beneficial for broilers against Eimeria infection by enhancing the immune responses. The beneficial effects of Arg supplementation tended to be more pronounced compared to BCAA supplementation. [ABSTRACT FROM AUTHOR]

The study was conducted to investigate the effects of 2 isoforms of methionine on growth performance and intestinal health induced by methionine (Met) deficiency and Eimeria infection in broilers. A total of 720 one-day old male chicks (Cobb500) were randomly allocated to 10 groups in a 2 × 5 factorial arrangement (6 reps/group, 12 birds/cage) with diets and Eimeria challenge as the main factors. Hundred percent DL-Met, 100% L-Met, 80% DL-Met, and 80% L-Met diets were formulated to meet approximately 100 or 80% of the total sulfur amino acid (TSAA) requirement with DL-Met or L-Met as Met supplementation sources. The 60% TSAA basal diet (60% Met) was formulated without Met supplementation. At d14, the challenge groups were gavaged with mixed Eimeria spp. Growth performance was recorded on d7, 14, 20 (6-day postinfection [ DPI ]), and 26 (12 DPI). The gut permeability was measured on 5 and 11 DPI. Antioxidant status and gene expression of immune cytokines and tight junction proteins were measured on 6 and 12 DPI. Data were analyzed by 1-way and 2-way ANOVA before and after the challenge, respectively. Orthogonal polynomial contrasts were used for post hoc comparison. Overall, the Eimeria challenge and 60% Met diet significantly reduced growth performance, antioxidant status, and mRNA expression of tight junction genes and immune cytokines. For other Met treatments, the L-Met groups had significantly higher BWG and lower FCR than the DL-Met group from d 1 to 20. The L-Met groups had less gut permeability than the DL-Met groups on 5 DPI. Compared to the 80% Met groups, the 100% Met groups reduced gut permeability. At 6 DPI, the 80% Met groups showed higher ZO1 expression than the 100% Met groups. The challenge groups had higher Muc2 expression and GSH/GSSG compared to the nonchallenge groups, and SOD activity was lower in the L-Met groups compared to the DL-Met groups at 6 DPI. The 100% Met groups had higher GPx activity than the 80% Met groups at 12 DPI. In conclusion, during coccidiosis, the 100% Met groups had better gut integrity and antioxidant status. Met supplementation in the form of L-Met improved growth performance in the starter phase and gut permeability in the challenge phase. [ABSTRACT FROM AUTHOR]

Background: RET rearrangements are targetable, oncogenic lung cancer drivers. While previous series have shown durable clinical benefit with pemetrexed-based therapies in ALK- and ROS1-rearranged lung cancers, the benefits of pemetrexed-based treatments in patients with RET-rearranged lung cancers relative to other genomic subsets have not previously been explored. Patients and methods: A retrospective review of patients with pathologically confirmed stage IIIB/IV lung adenocarcinomas and evidence of a RET, ROS1, or ALK rearrangement, or a KRAS mutation was conducted. Patients were eligible if they received treatment with pemetrexed alone or in combination. The primary outcome of progression-free survival (PFS), and secondary outcomes of overall response rate (ORR, RECIST v1.1), time to progression (TTP), and time to treatment discontinuation were compared between RET-rearranged and groups of ROS1-rearranged, ALK-rearranged, and KRAS-mutant lung cancers. Results: We evaluated 104 patients. Patients with RET-rearranged lung cancers (n = 18) had a median PFS of 19 months [95% confidence interval (CI) 12-not reached (NR)] that was comparable with patients with ROS1-(23 months, 95% CI 14-NR, n = 10) and ALK-rearranged (19 months, 95% CI 15-36, n = 36) lung cancers, and significantly improved compared with patients with KRAS-mutant lung cancers (6 months, 95% CI 5-9, P < 0.001, n = 40). ORR (45%), median TTP (20 months, 95% CI 17-NR), and median time to treatment discontinuation (21 months, 95% CI 6-NR) in patients with RET-rearranged lung cancers were not significantly different compared with patients with ALK- and ROS1-rearranged lung cancers, and improved compared with patients with KRAS-mutant lung cancers. Conclusion: Durable benefits with pemetrexed-based therapies in RET-rearranged lung cancers are comparable with ALK- and ROS1-rearranged lung cancers. When selecting therapies for patients with RET-rearranged lung cancers, pemetrexed-containing regimens should be considered. [ABSTRACT FROM AUTHOR]

The combination of increased genetic potential and changes in management strategies (i.e., antibiotic-free, no antibiotics ever, and every day feeding of replacement pullets) influences the nutritional needs of poultry. Traditionally, nutritionists have focused on meeting the amino acid needs for production performance and yield however, increasing specific amino acid concentrations can benefit gastrointestinal development and integrity, enhance immune response potential, influence behavior, and benefit sustainability. Commercialization of additional feed grade amino acids beyond methionine, lysine, and threonine, enables targeted increases to achieve these benefits. As such, this paper addresses the functional roles of amino acids in meeting poultry production, health, and sustainability goals. [ABSTRACT FROM AUTHOR]

A study was aimed to investigate the effects of mixed Eimeria challenge on performance, gastrointestinal health, oxidative stress, inflammation, and expression of nutrient transporter genes of Hy-Line W-36 pullets. A total of 540, 16-d old pullets were randomly allocated into 5 treatment groups with 6 replicate cages, including a nonchallenged control group. A mixed Eimeria species solution containing 50,000 E. maxima , 50,000 E. tenella , and 250,000 E. acervulina oocysts per mL was prepared and challenged to one group as a high-dose treatment (High). The 2-fold serial dilution was done to prepare the medium-high (Med-High : 25,000 E. maxima ; 25,000 E. tenella ; and 125,000 E. acervulina), the medium-low (Med-Low : 12,500 E. maxima ; 12,500 E. tenella ; and 62,500 E. acervulina), and the low (Low : 6,250 E. maxima ; 6,250 E. tenella ; and 31,250 E. acervulina) dose treatments, and these dosages were challenged to 3 remaining groups, respectively. Growth performance, daily feed intake (FI), and mortality were calculated from 0-14 d postinfection (DPI). Gastrointestinal permeability (GP) was measured on 3, 5, 6, 7, and 9 DPI. The result indicated significant linear responses to the Eimeria challenge dosage in average body weight and body weight gain (P < 0.0001). An interaction between treatment and DPI was observed for FI (P < 0.0001). Feed intake significantly dropped from 4 DPI and did not recover until 12 DPI in the challenged groups. The lowest FI for each of the challenged groups was observed on 5 DPI. Gastrointestinal permeability increased linearly, peaking at 5 DPI, and was recovered back to normal by 9 DPI in the challenged groups. Furthermore, gene expression of tight junction proteins was linearly upregulated by increased Eimeria dosages. The oxidative status of the pullets was lowered in the challenged groups than the nonchallenged control group, whereas the expression of inflammatory and proinflammatory cytokines was upregulated by Eimeria challenge on 6 DPI (P < 0.05). The highest mortality was observed in pullets challenged with the High, followed by the Med-High (P < 0.0001) on 5 DPI. In summary, the mixed Eimeria challenge linearly reduced the growth performance of pullets with an increase in oxidative stress and inflammation. A severe effect of Eimeria on gastrointestinal health was observed on 5 or 6 DPI as suggested by GP, tight junction genes, and mortality results. This study indicates that Eimeria infection can be a threat to gastrointestinal health related issues in pullets. [ABSTRACT FROM AUTHOR]

It is unclear whether health provider accreditation ensures or promotes quality of care. Using baseline data from the Quality Improvement Demonstration Study (QIDS) in the Philippines we measured the quality of pediatric care provided by private and public doctors working at the district hospital level in the country's central region. We found that national level accreditation by a national insurance program influences quality of care. However, our data also show that insurance payments have a similar, strong impact on quality of care. These results suggest that accreditation alone may not be sufficient to promote high quality of care. Further improvements may be achieved with properly monitored and well-designed payment or incentive schemes. [ABSTRACT FROM AUTHOR]

There is a wide variation (13% to 74%) in the reported prevalence of heart failure associated with normal left ventricular (LV) systolic function (diastolic heart failure). There is no published information on this condition in China. To ascertain the prevalence of diastolic heart failure in this community, 200 consecutive patients with the typical features of congestive heart failure were studied with standard 2-dimensional Doppler echocardiography. A LV ejection fraction (LVEF) >45% was considered normal. The results showed that 12.5% had significant valvular heart disease. Of the remaining 175 patients, 132 had a LVEF >45% (75%). Therefore, 66% of patients with a clinical diagnosis of heart failure had a normal LVEF. Heart failure with normal LV systolic function was more common than systolic heart failure in those >70 years old (65% vs 47%; p = 0.015). Most (57%) had an abnormal relaxation pattern in diastole and 14% had a restrictive filling pattern. In the systolic heart failure group, a restrictive filling pattern was more common (46%). There were no significant differences in the sex distribution, etiology, or prevalence of LV hypertrophy between these 2 heart failure groups. In conclusion, heart failure with a normal LVEF or diastolic heart failure is more common than systolic heart failure in Chinese patients with the symptoms of heart failure. This may be related to older age at presentation and the high prevalence of hypertension in this community. [ABSTRACT FROM AUTHOR]

This study aimed to determine the effect of the housing environment and laying hen strain on tibia and femur properties. A 3 × 2 factorial arrangement of 3 housing environments (conventional cages [ CC ], enriched colony cages [ EC ], and free range [ FR ]) and 2 laying hen strains (Hy-Line W-36 [ W-36 ] and Hy-Line Brown [ HB ]) in a completely randomized design was conducted from 32 to 85 wk of age. Six left tibias were collected at 8 different time points (38, 45, 52, 59, 65, 72, 79, and 85 wk of age), whereas 6 left femurs were collected at 3 time points (38, 65, and 85 wk of age). Tibias were evaluated for tibia breaking strength (TBS) and ash percentage, whereas femurs were evaluated for bone mineral density (BMD), bone mineral content, bone volume as a fraction tissue volume, and porosity percentage from total, cortical, medullary, and trabecular bones. The higher TBS (P = 0.0005) and ash percentage (P = 0.045) was observed in hens raised in FR systems compared with those raised in the CC. Overall, TBS of W-36 hens was significantly greater than that of HB hens (P < 0.0001); however, there was no difference in the ash percentage between the strains (P > 0.05). An interaction between the housing environment and hen strain was observed for BMD (P = 0.04), wherein W-36 hens raised in the FR system had higher BMD than HB hens. Similarly, hens raised in FR systems had higher trabecular bone volume than those raised in CC (P = 0.022). Hen strain influenced total and cortical bone properties: BMD, bone volume as a fraction tissue volume, and porosity percentage, wherein W-36 hens had better properties than HB hens (P < 0.05). Trabecular BMD was higher in W-36 hens than in HB hens (P = 0.04), whereas bone volume was higher in HB hens (P < 0.0001). The results suggest that raising laying hens in alternative housing systems that have provision for exercise such as FR reduces structural bone loss, stimulate structural bone formation, and improve breaking strength of bones; however, it varies with the strain. [ABSTRACT FROM AUTHOR]

Transcranial Doppler monitoring showed no evidence of microemboli for 10 minutes after direct-current cardioversion for atrial fibrillation. [ABSTRACT FROM AUTHOR]