Gastric submucosal haematoma caused by an amyloidoma in the setting of multiple myeloma

Publication date: Available online 15 December 2017
Source:Arab Journal of Gastroenterology
Author(s): Stella C. Pak, John-Phillip T. Markovic
This is a case of a 67-year-old woman with a history of multiple myeloma with amyloidosis who presented with massive hematemesis. Emergent upper endoscopy revealed a mass on the greater curvature of the stomach, which measured approximately 3 cm in width and 7 cm in length. The patient underwent a wedge resection of the gastric mass without complication. Microscopic examination of the gastric mass revealed amorphous deposits that were congophilic in nature and stained positive with Alcian blue. These findings are consistent with amyloidosis. The patient had a favourable postoperative recovery and was discharged from the hospital. This case highlights the need for clinicians to be aware of the possibility of spontaneous gastric haemorrhage secondary to light chain (AL) amyloidosis, especially in patients with a known bone marrow disorder.



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Protective effects of curcumin against doxorubicin-induced toxicity and resistance: a review

Publication date: Available online 14 December 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Mohammad Mohajeri, Amirhossein Sahebkar
Doxorubicin (DOX)-induced toxicity and resistance are major obstacles in chemotherapeutic approaches. Despite effective in the treatment of numerous malignancies, some clinicians have voiced concern that DOX has the potential to cause debilitating consequences in organ tissues, especially the heart. The mechanisms of toxicity and resistance are respectively related to induction of reactive oxygen species (ROS) and up-regulation of ATP-binding cassette (ABC) transporter. Curcumin (CUR) with several biological and pharmacological properties is expected to restore DOX-mediated impairments to tissues. This review is intended to address the current knowledge on DOX adverse effects and CUR protective actions in the heart, kidneys, liver, brain, and reproductive organs. Coadministration of CUR and DOX is capable of ameliorating DOX toxicity pertained to antioxidant, apoptosis, autophagy, and mitochondrial permeability.



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Molecular characterization, RNA interference and recombinant protein approach to study the function of the putative Molt Inhibiting Hormone (FmMIH1) gene from the shrimp Fenneropenaeus merguiensis

Publication date: Available online 14 December 2017
Source:Peptides
Author(s): Huafang Liang, Yin Lau, Ting Ting Zhou, Xiaoyuan Li, Bin Li, Siuming F. Chan
The Molt Inhibiting Hormone gene and cDNA of the banana shrimp Fenneropenaeus merguiensis (FmMIH1) has been cloned and characterized. FmMIH1 possesses most of the characteristics of the eyestalk CHH/MIH/GIH family subtype-II neuropeptides. FmMIH1 open reading frame consists of 315 bp encoding for 105 amino acid residues. The mature peptide of FmMIH1 consists of 76 amino acid residues, a glycine residue at position 11 of the mature peptide and 6 cysteine residues located in the conserved position. In addition to eyestalk, high levels of FmMIH1 transcript could also be detected in the intestine. FmMIH1 transcript level is low throughout the post-molt, early to mid-intermolt and premolt. However, a sharp increase could be observed in late intermolt (C3 stage). Both alignment and phylogenetic analysis reveal that FmMIH1 is most similar to the MIH1 of other shrimps. For functional assay, RNA interference results show that a significant 2.3 days (P < 0.05) reduction in molt cycle duration could be observed in shrimp receiving dsFmMIH1 injection. Surprisingly, injection of recombinant FmMIH1 could also cause a significant reduction of the molt cycle (average 1.9 days, P < 0.05). We hypothesize that the recombinant protein is biological inactive but it competes with the endogenous MIH for carrier protein binding and consequently reduces the amount of biological MIH that could reach the targets. In conclusion, the result of this study will provide us new insight to manipulate molting/growth in crustaceans.



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Vasodilator and hypotensive effects of the spider peptide Lycosin-I in vitro and in vivo

Publication date: Available online 14 December 2017
Source:Peptides
Author(s): Binbin Ma, Zhouhuan Xi, Jiahui Li, Tianqi Gao, Runzhi Liao, Shuhang Wang, Xianyao Li, Yaqin Tang, Zheng Wang, Shengjie Hou, Jinying Jiang, Meichun Deng, Zhigui Duan, Xing Tang, Liping Jiang
Lycosin-I, a spider peptide isolated from the venom of the spider Lycosa singoriensis, has anti-bacteria and anti-cancer properties in organisms. However, cardiovascular effects of Lycosin-I have not been studied. In this study, we investigated for the first time the vasodilator and hypotensive effects of Lycosin-I and the possible mechanisms, in order to develop a promising treatment for hypertension-related diseases. For in vitro experiments, thoracic aortas were isolated, and divided into two groups, endothelium-intact and endothelium-denuded aortic rings. Lycosin-I induced a remarkable dose-dependent relaxation in endothelium-intact aortic rings pre-treated with phenylephrine (p < 0.05), while it showed no obvious vasodilator effects in endothelium-denuded aortic rings (p > 0.05). The vasodilator effects of Lycosin-I were significantly weakened by a nitric oxide synthase (NOS) inhibitor, L-NAME (p < 0.001) and a selective inhibitor of nitric oxide (NO)-sensitive soluble guanylate cyclase (sGC), ODQ (p < 0.05), respectively. The levels of endothelial nitric oxide synthase (eNOS) phosphorylation and the NO production were significantly higher in human umbilical vascular endothelial cells pre-cultured with Lycosin-I than the control (p < 0.001), determined via western blot analysis and ozone-chemiluminescence technology. For in vivo experiments, arterial and venous catheters were inserted for mean arterial pressure (MAP) recording and drug administration in anaesthetized spontaneously hypertensive rats. Lycosin-I caused a transient drop of MAP 2 minutes after the administration compared with the saline control (p < 0.001). In conclusion, Lycosin-I has the potential to be an anti-hypertensive drug by endothelium-dependent vasodilatation, in which eNOS and NO-sensitive sGC are two main involved factors.



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outside front cover

Publication date: June 2017
Source:Seminars in Oncology, Volume 44, Issue 3





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Masthead

Publication date: June 2017
Source:Seminars in Oncology, Volume 44, Issue 3





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Editorial Board

Publication date: June 2017
Source:Seminars in Oncology, Volume 44, Issue 3





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Table of Contents

Publication date: June 2017
Source:Seminars in Oncology, Volume 44, Issue 3





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Genetic analysis of predicted fatty acid profiles of milk from Danish Holstein and Danish Jersey cattle populations

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): L. Hein, L.P. Sørensen, M. Kargo, A.J. Buitenhuis
The objective of this paper was to assess the genetic variability of the detailed fatty acid (FA) profiles of Danish Holstein (DH) and Danish Jersey (DJ) cattle populations. We estimated genetic parameters for 11 FA or groups of FA in milk samples from the Danish milk control system between May 2015 and October 2016. Concentrations of different FA and FA groups in milk samples were measured by mid-infrared spectroscopy. Data used for parameter estimation were from 132,732 first-parity DH cows and 21,966 first-parity DJ cows. We found the highest heritabilities for test day measurements in both populations for short-chain FA (DH = 0.16; DJ = 0.16) and C16:0 (DH = 0.14; DJ = 0.16). In DH, the highest heritabilities were also found for saturated FA and monounsaturated FA (both populations: 0.15). Genetic correlations between the fatty acid traits showed large differences between DH and DJ for especially short-chain FA with the other FA traits measured. Furthermore, genetic correlations of total fat with monounsaturated FA, polyunsaturated FA, short-chain FA, and C16:0 differed markedly between DH and DJ populations. In conclusion, we found genetic variation in the mid-infrared spectroscopy-predicted FA and FA groups of the DH and DJ cattle populations. This finding opens the possibility of using genetic selection to change the FA profiles of dairy cattle.



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Calf management risk factors on dairy farms associated with male calf mortality on veal farms

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): D.L. Renaud, D.F. Kelton, S.J. LeBlanc, D.B. Haley, T.F. Duffield
The objective of this cross-sectional herd-level study was to assess the association of calf management practices on source dairy farms with mortality risk on veal farms. From April to October 2016, 52 source dairy farms supplying male calves to 2 veal operations were visited once. A questionnaire was administered that covered all areas of calf management, calves between 1 and 10 d of age were examined using a standardized health scoring system, and blood was taken to evaluate passive transfer of immunoglobulins. The mortality risk for calves from each dairy farm was calculated based on the number of male calves sold from the dairy farm and that died during 2016 at the veal operations. The mean mortality risk was calculated for both veal farms and, based on the veal facility-adjusted mortality risk, dairy farms were classified as high- or low-mortality source farms. Using the information gathered at the 52 source dairy farms, a logistic regression model was used to assess factors associated with being a high-mortality source farm. Suppliers to veal farm 1 had a mean mortality risk of 9.6% and suppliers to veal farm 2 had a mean mortality risk of 4.2%. The lower mortality risk at veal farm 2 was partially influenced by a shorter period of observation. Of the 182 calves examined during the single visit to the source dairy farms, 41% of male calves and 29% of female calves had at least one identifiable health abnormality. The risk of failure of passive transfer on source dairy farms was low, with only 13% of calves tested having <10 mg of IgG/mL of serum. The subset of calves examined at the source dairy farm was not followed prospectively to the veal farms. Using a tube feeder or pail to feed colostrum, bedding male calves on wood shavings or chopped straw at the source dairy farm, and the herd veterinarian not routinely and actively inquiring about the health and performance of calves during regular herd visits were significantly associated with the farm being classified as a high-mortality source dairy farm. Checking the calving pen at an interval of every 3 h or more during the day was associated with a lower probability of being classified as a high-mortality source dairy farm. The results of this study suggest that there are management practices on the source farm that contribute to the risk of mortality on veal farms.



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Heritabilities and genetic correlations in the same traits across different strata of herds created according to continuous genomic, genetic, and phenotypic descriptors

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): Tong Yin, Sven König
The most common approach in dairy cattle to prove genotype by environment interactions is a multiple-trait model application, and considering the same traits in different environments as different traits. We enhanced such concepts by defining continuous phenotypic, genetic, and genomic herd descriptors, and applying random regression sire models. Traits of interest were test-day traits for milk yield, fat percentage, protein percentage, and somatic cell score, considering 267,393 records from 32,707 first-lactation Holstein cows. Cows were born in the years 2010 to 2013, and kept in 52 large-scale herds from 2 federal states of north-east Germany. The average number of genotyped cows per herd (45,613 single nucleotide polymorphism markers per cow) was 133.5 (range: 45 to 415 genotyped cows). Genomic herd descriptors were (1) the level of linkage disequilibrium (r²) within specific chromosome segments, and (2) the average allele frequency for single nucleotide polymorphisms in close distance to a functional mutation. Genetic herd descriptors were the (1) intra-herd inbreeding coefficient, and (2) the percentage of daughters from foreign sires. Phenotypic herd descriptors were (1) herd size, and (2) the herd mean for nonreturn rate. Most correlations among herd descriptors were close to 0, indicating independence of genomic, genetic, and phenotypic characteristics. Heritabilities for milk yield increased with increasing intra-herd linkage disequilibrium, inbreeding, and herd size. Genetic correlations in same traits between adjacent levels of herd descriptors were close to 1, but declined for descriptor levels in greater distance. Genetic correlation declines were more obvious for somatic cell score, compared with test-day traits with larger heritabilities (fat percentage and protein percentage). Also, for milk yield, alterations of herd descriptor levels had an obvious effect on heritabilities and genetic correlations. By trend, multiple trait model results (based on created discrete herd classes) confirmed the random regression estimates. Identified alterations of breeding values in dependency of herd descriptors suggest utilization of specific sires for specific herd structures, offering new possibilities to improve sire selection strategies. Regarding genomic selection designs and genetic gain transfer into commercial herds, cow herds for the utilization in cow training sets should reflect the genomic, genetic, and phenotypic pattern of the broad population.



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Inclusion of calcium hydroxide-treated corn stover as a partial forage replacement in diets for lactating dairy cows

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): Brittany A. Casperson, Aimee E. Wertz-Lutz, Jim L. Dunn, Shawn S. Donkin
Chemical treatment may improve the nutritional value of corn crop residues, commonly referred to as corn stover, and the potential use of this feed resource for ruminants, including lactating dairy cows. The objective of this study was to determine the effect of prestorage chopping, hydration, and treatment of corn stover with Ca(OH)2 on the feeding value for milk production, milk composition, and dry matter intake (DMI). Multiparous mid-lactation Holstein cows (n = 30) were stratified by parity and milk production and randomly assigned to 1 of 3 diets. Corn stover was chopped, hydrated, and treated with 6% Ca(OH)2 (as-fed basis) and stored in horizontal silo bags. Cows received a control (CON) total mixed ration (TMR) or a TMR in which a mixture of treated corn stover and distillers grains replaced either alfalfa haylage (AHsub) or alfalfa haylage and an additional portion of corn silage (AH+CSsub). Treated corn stover was fed in a TMR at 0, 15, and 30% of the diet DM for the CON, AHsub, and AH+CSsub diets, respectively. Cows were individually fed in tiestalls for 10 wk. Milk production was not altered by treatment. Compared with the CON diet, DMI was reduced when the AHsub diet was fed and tended to be reduced when cows were fed the AH+CSsub diet (25.9, 22.7, and 23.1 ± 0.88 kg/d for CON, AHsub, and AH+CSsub diets, respectively). Energy-corrected milk production per unit of DMI (kg/kg) tended to increase with treated corn stover feeding. Milk composition, energy-corrected milk production, and energy-corrected milk per unit of DMI (kg/kg) were not different among treatments for the 10-wk feeding period. Cows fed the AHsub and AH+CSsub diets had consistent DMI over the 10-wk treatment period, whereas DMI for cows fed the CON diet increased slightly over time. Milk production was not affected by the duration of feeding. These data indicate that corn stover processing, prestorage hydration, and treatment with calcium hydroxide can serve as an alternative to traditional haycrop and corn silage in diets fed to mid-lactation dairy cows.



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Effect of leaving milk trucks empty and idle for 6 h between raw milk loads

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): Eva Kuhn, Lisbeth Meunier-Goddik, Joy G. Waite-Cusic
The US Pasteurized Milk Ordinance (PMO) allows milk tanker trucks to be used repeatedly for 24 h before mandatory clean-in-place cleaning, but no specifications are given for the length of time a tanker can be empty between loads. We defined a worst-case hauling scenario as a hauling vessel left empty and dirty (idle) for extended periods between loads, especially in warm weather. Initial studies were conducted using 5-gallon milk cans (pilot-scale) as a proof-of-concept and to demonstrate that extended idle time intervals could contribute to compromised raw milk quality. Based on pilot-scale results, a commercial hauling study was conducted through partnership with a Pacific Northwest dairy co-op to verify that extended idle times of 6 h between loads have minimal influence on the microbiological populations and enzyme activity in subsequent loads of milk. Milk cans were used to haul raw milk (load 1), emptied, incubated at 30°C for 3, 6, 10, and 20 h, and refilled with commercially pasteurized whole milk (load 2) to measure cross-contamination. For the commercial-scale study, a single tanker was filled with milk from a farm known to have poorer quality milk (farm A, load 1), emptied, and refilled immediately (0 h) or after a delay (6 h) with milk from a farm known to have superior quality milk (farm B, load 2). In both experiments, milk samples were obtained from each farm's bulk tank and from the milk can or tanker before unloading. Each sample was microbiologically assessed for standard plate count (SPC), lactic acid bacteria (LAB), and coliform counts. Selected isolates were assessed for lipolytic and proteolytic activity using spirit blue agar and skim milk agar, respectively. The pilot-scale experiment effectively demonstrated that extended periods of idle (>3 h) of soiled hauling vessels can significantly affect the microbiological quality of raw milk in subsequent loads; however, extended idle times of 6 h or less would not measurably compromise milk quality in subsequent loads in commercial tankers. Current tanker sanitation practices appear to be sufficient for maintaining raw milk SPC, LAB, and coliform levels, which are important measures of milk quality.



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Breastfeeding-associated microbiota in human milk following supplementation with Lactobacillus rhamnosus GG, Lactobacillus acidophilus La-5, and Bifidobacterium animalis subspecies lactis Bb-12

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): Melanie Rae Simpson, Ekaterina Avershina, Ola Storrø, Roar Johnsen, Knut Rudi, Torbjørn Øien
Breastfeeding is one of the major factors affecting the early development of the infant gut microbiota, and weaning is associated with a shift in the gut microbiota toward a more adult composition. Through breastfeeding, infants receive bioactive components that shape their microbiota while also being exposed to the breast milk and breast surface microbial communities. Recent studies have suggested the possibility of an entero-mammary route of microbial transfer, opening the possibility of infant gut microbiota modulation through maternal probiotic supplementation. In this study, we have analyzed breast milk samples collected at 10 d and 3 mo postpartum from women participating in the Probiotics in the Prevention of Allergy among Children in Trondheim placebo controlled trial. Women who were randomized to the probiotic arm of the Probiotics in the Prevention of Allergy among Children in Trondheim trial received a fermented milk supplemented with Lactobacillus rhamnosus GG, Lactobacillus acidophilus La-5, and Bifidobacterium animalis ssp. lactis Bb-12, consuming this daily from 4 wk before their expected due date until 3 mo after birth. In total, 472 breast milk samples were assessed for the administered bacteria using quantitative real-time PCR and the microbiota transferred during breastfeeding was analyzed using 16S ribosomal RNA gene sequencing of 142 samples. We found that breastfeeding is unlikely to be a significant source of L. rhamnosus GG, L. acidophilus La-5, and B. animalis ssp. lactis Bb-12 for infants in the probiotic arm of the trial. Furthermore, maternal supplementation did not significantly affect the overall composition of the breast milk microbiota transferred during breastfeeding. We also present a descriptive analysis of this microbiota, which was largely dominated by Streptococcus and Staphylococcus genera at both 10 d and 3 mo postpartum. Samples collected at 3 mo postpartum had a statistically significant lower presence and relative abundance of the Staphylococcus genus. These samples also had a greater number of observed species and diversity, including more operational taxonomic units from the Rothia, Veillonella, Granulicatella, and Methylbacterium genera.



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Computed tomography study of the fetal development of the dairy cow stomach complex

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): S. Al Masri, R. Reincke, H. Huenigen, O. Gemeinhardt, K.C. Richardson, J. Plendl
In the fetal development of animals, critical physiological and anatomical events influence the long-term health and performance of the offspring. To identify the critical growth phases of the fetal bovine stomach, we used computed tomography imaging on 30 German Holstein fetuses to examine the fetal bovine stomach in situ. Computed tomography allows the study of diverse parameters such as the volume of the stomach chambers in situ without the need for sophisticated filling preparation techniques. The absolute volume, relative volume, and monthly volume increase of each stomach chamber were determined. Computed tomography was a reliable method for in situ examination of the fetal bovine stomach complex from the third month of gestation onward. It was able to detect an abnormal position of the abomasum in 2 fetuses. The crown-rump length of the fetuses studied ranged from 9.5 to 89 cm (from 2.2 to 8.3 mo of gestation). Over this timeline, the changes in the relative volumes of the ruminoreticulum and abomasum were inversely related. Until mo 5 of gestation, the relative volume of the ruminoreticulum increased steadily, whereas that of the abomasum decreased. Thereafter, the relative volume of the ruminoreticulum became gradually smaller, and that of the abomasum became larger; by mo 8, the abomasum was larger than the ruminoreticulum. All stomach chambers had large increases in volume over the gestation period and we observed differences in development patterns and volume changes of the individual stomach chambers over this period. The largest monthly volume increase of the stomach complex was between mo 4 and 5 of gestation. In this period, the volume of the ruminoreticulum increased 43.8 times, that of the omasum 38.9 times, and that of the abomasum 30.03 times. Between mo 5 and 6 of gestation, the abomasum had another growth spurt, with a monthly volume increase of 10.4 times. These 2 time points in the gestation period may be critical phases of fetal development that should be considered in the management of pregnant cattle.



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Temperature modulates the production and activity of a metalloprotease from Pseudomonas fluorescens 07A in milk

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): Maura P. Alves, Rafael L. Salgado, Monique R. Eller, Roberto Sousa Dias, Sérgio Oliveira de Paula, Antonio Fernandes de Carvalho
This work evaluated the expression and activity of a metalloprotease released by Pseudomonas fluorescens 07A in milk. Low relative expression of the protease by the strain was observed after incubation for 12 h at 25°C while the strain was in the logarithmic growth phase. After 24 h, protease production significantly increased (P < 0.05) and remained constant for up to 48 h, a time range during which the strain remained in the stationary phase. Conversely, at refrigeration temperatures, at 12 h the strain was still in the lag phase and expressed the protease at higher levels than when the logarithmic phase was reached. Casein fractions were highly degraded by P. fluorescens 07A, the purified protease, and the bacterial pellet on d 7 of incubation at 25°C and to a lesser extent at 10°C for the sample incubated with the bacterium. Heat treatment at 90°C for 5 min completely inactivated the proteolytic activity of the purified protease and the bacterial pellet. This work contributes to the knowledge about the conditions of milk storage that influence the production and activity of this extracellular metalloprotease. The results demonstrate the need to find alternative strategies to control the synthesis and activity of proteolytic enzymes in the dairy industry to ensure the quality of processed products.



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Reliability of sampling strategies for measuring dairy cattle welfare on commercial farms

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): Jennifer M.C. Van Os, Christoph Winckler, Julia Trieb, Soraia V. Matarazzo, Terry W. Lehenbauer, John D. Champagne, Cassandra B. Tucker
Our objective was to evaluate how the proportion of high-producing lactating cows sampled on each farm and the selection method affect prevalence estimates for animal-based measures. We assessed the entire high-producing pen (days in milk <100; range = 81–241 cows) on 10 California farms using measures from the Welfare Quality Protocol for Cattle. Cows were restrained in head locks and visually evaluated for body condition, dirtiness, skin alterations (hair loss, lesions, or swelling), discharge (ocular, nasal, vulvar), diarrhea, and impaired respiration. Lameness was scored upon release. Prevalence was calculated as a percentage of assessed cows. The most common conditions were dirty hindquarters (33.5 ± 10.7%, mean ± standard deviation) and lesions or swelling on the carpal joint (34.4 ± 7.0%) and hock (26.4 ± 16.7%). Diarrhea (8.0 ± 5.8%), lameness (moderate = 7.3 ± 4.7%, severe = 2.2 ± 2.2%), and neck (5.8 ± 12.6%), flank (4.5 ± 5.0%), or hindquarter alterations (5.5 ± 3.9%) were less common. Very fat cows, vulvar discharge, and impaired respiration were rare (≤1%) and were excluded from further analysis. Four sampling strategies were used to generate 20 estimates for each animal-based measure. The strategies were (1) selecting every 10th, 5th, 4th, 3rd, 2nd, 2 of 3, or 3 of 4 cows at the feed bunk (7 estimates/measure); (2) randomly selecting 7 matching proportions of the pen; (3) randomly selecting cows using 3 sample size calculations from the Welfare Quality Protocol; and (4) selecting the first, middle, or final third of cows exiting the milking parlor. Estimates were compared with true values using regression analysis and were considered accurate if they met 3 criteria: the coefficient of determination was ≥0.9 and the slope and intercept did not differ significantly from 1 and 0, respectively. All estimates met the slope and intercept criteria, whereas the coefficient of determination increased when more cows were sampled. All estimates were accurate for neck alterations, ocular discharge (22.2 ± 27.4%), and carpal joint hair loss (14.1 ± 17.4%). Selecting a third of the milking order or using the Welfare Quality sample size calculations failed to accurately estimate all measures simultaneously. However, all estimates were accurate when selecting at least 2 of every 3 cows locked at the feed bunk. Using restraint position at the feed bunk did not differ systematically from computer-selecting the same proportion of cows randomly, and the former may be a simpler approach for welfare assessments.



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Dynamics of methanogenesis, ruminal fermentation, and alfalfa degradation during adaptation to monensin supplementation in goats

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): Z.J. Li, H. Ren, S.M. Liu, C.J. Cai, J.T. Han, F. Li, J.H. Yao
This study aimed to examine the temporal (hourly within a day and daily over the long term) effects of monensin on CH4 emissions, ruminal fermentation, and in situ alfalfa degradation in dairy goats during dietary monensin supplementation by controlling the confounding effects of feed intake and ambient temperature. Six ruminally cannulated dairy goats were used, and they were housed in environmental chambers and fed a restricted amount of ration throughout the experiment. The experiment included a baseline period of 20 d followed by a treatment period of 55 d with 32 mg of monensin/d. During the whole experiment, CH4 production was measured every 5 d, whereas fermentation characteristics and in situ alfalfa degradation were analyzed every 10 d. The CH4-depressing effect of monensin was time dependent on the duration of treatment, highly effective at d 5 but thereafter decreased gradually until d 55 even though CH4-suppressing effect still remained significant. The decreasing effects of monensin on ruminal acetate proportion and acetate to propionate ratio also faded over days of treatment, and the acetate proportion returned up to the pre-supplementation level on d 50. Monensin supplementation elevated ruminal propionate proportion and decreased the effective ruminal degradability of alfalfa NDF, but both measurements tended to recover over time. The postprandial increase rate of hourly CH4 emissions was reduced, whereas that of propionate proportion was enhanced by monensin supplementation. However, the postprandial responses to monensin in CH4 emission rates, ruminal VFA profiles, and in situ degradation kinetics declined with both hours after feeding and days of treatment. Our results suggest that the CH4-suppressing effect of monensin supplementation in goats was attributed to reductions in both ruminal feed degradation and acetate to propionate ratio, but those reductions faded with time, hours after feeding, and days of treatment.



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Influence of conjugated linoleic acids and vitamin E on biochemical, hematological, and immunological variables of dairy cows during the transition period

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): S. Schäfers, D. von Soosten, U. Meyer, C. Drong, J. Frahm, A. Tröscher, W. Pelletier, H. Sauerwein, S. Dänicke
The objective of this experiment was to determine the effects of conjugated linoleic acid (CLA) and vitamin E as well as their interaction on biochemical and hematological variables and on leukocyte populations and their functionality. We assigned 59 German Holstein cows between the 2nd and 9th lactation to 4 dietary groups in a 2 × 2 factorial design with the factors CLA and vitamin E. Six weeks before calving the cows had a BCS of 3.7 to provoke a higher risk of developing ketosis, which might impair their immune function. Blood samples for analyses were taken on d −42, −14, −7, −3, 1, 3, 7, 10, 14, 21, 28, 35, 42, 56, and 70 relative to parturition. Furthermore, peripheral blood mononuclear cells were cultured on d −42, −7, 1, 7, 14, 28, and 70 relative to calving. Most variables were characterized by a high variation between d 7 antepartum and d 7 postpartum. Treatments did not elicit any effect, with the exception of vitamin E, which increased serum urea concentrations and decreased monocyte percentages. Haptoglobin, aspartate-aminotransferase, red blood cell count, leukocyte percentage and populations, as well as peripheral blood mononuclear cells were influenced by parity. In conclusion, the impairment of immune function caused by calving was more severe in cows in ≥3rd parity than in younger cows. However, neither vitamin E nor CLA supplementation was successful to stabilize parity or parturition related variance in hematological and immunological traits.



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Varying the ratio of Lys:Met while maintaining the ratios of Thr:Phe, Lys:Thr, Lys:His, and Lys:Val alters mammary cellular metabolites, mammalian target of rapamycin signaling, and gene transcription

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): X. Dong, Z. Zhou, B. Saremi, A. Helmbrecht, Z. Wang, J.J. Loor
Amino acids are not only precursors for but also signaling molecules regulating protein synthesis. Regulation of protein synthesis via AA occurs at least in part by alterations in the phosphorylation status of mammalian target of rapamycin (mTOR) pathway proteins. Although the ideal profile of Lys:Met to promote milk protein synthesis during established lactation in dairy cows has been proposed to be 3:1, aside from being the most-limiting AA for milk protein synthesis, the role of Met in other key biologic pathways such as methylation is not well characterized in the bovine. The objective of this study was to determine the influence of increasing supplemental Met, based on the ideal 3:1 ratio of Lys to Met, on intracellular metabolism related to protein synthesis and mTOR pathway phosphorylation status. MAC-T cells, an immortalized bovine mammary epithelial cell line, were incubated (n = 5 replicates/treatment) for 12 h with 3 incremental doses of Met while holding Lys concentration constant to achieve the following: Lys:Met 2.9:1 (ideal AA ratio; IPAA), Lys:Met 2.5:1 (LM2.5), and Lys:Met 2.0:1 (LM2.0). The ratios of Thr:Phe (1.05:1), Lys:Thr (1.8:1), Lys:His (2.38:1), and Lys:Val (1.23:1) were the same across the 3 treatments. Applying gas chromatography–mass spectrometry metabolomics revealed distinct clusters of differentially concentrated metabolites in response to Lys:Met. Lower Phe, branched-chain AA, and putrescine concentrations were observed with LM2.5 compared with IPAA. Apart from greater intracellular Met concentrations, further elevations in Met level (LM2.0) led to greater intracellular concentrations of nonessential AA (Pro, Glu, Gln, and Gly) compared with IPAA and greater essential AA (EAA; Met, Ile, and Leu) and nonessential AA (Pro, Gly, Ala, Gln, and Glu) compared with LM2.5. However, compared with IPAA, mRNA expression of β-casein and AA transporters (SLC7A5, SLC36A1, SLC38A2, SLC38A9, and SLC43A1) and mTOR phosphorylation were lower in response to LM2.5 and LM2.0. Overall, the results of this study provide evidence that increasing Met while Lys and the ratios of Phe, Thr, His, and Val relative to Lys were held constant could increase the concentration and utilization of intracellular EAA, in particular branched-chain AA, potentially through improving the activity of AA transporters partly controlled by mTOR signaling. Because EAA likely are metabolized by other tissues upon absorption, a question for future in vivo studies is whether formulating diets for optimal ratios of EAA in the metabolizable protein is sufficient to provide the desired levels of these AA to the mammary cells.



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Lactobacillus casei asp23 gene contributes to gentamycin resistance via regulating specific membrane-associated proteins

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): Wenyi Zhang, Chenxia Cao, Jie Zhang, Lai-Yu Kwok, Heping Zhang, Yongfu Chen
Lactobacillus casei Zhang is a probiotic strain originally isolated from koumiss. Previously, we showed that an alkaline shock protein (encoded by asp23) was involved in the adaptation of L. casei Zhang to gentamycin. In the present study, we compared the proteomes of the asp23 mutant and its parent strain grown in the presence of gentamycin. The results showed that 22 and 21 proteins were significantly up- and downregulated, respectively (>1.5-fold difference). By parallel reaction monitoring analysis, we further validated that specific membrane-associated proteins were important in regulating the antibiotics-induced cell wall stress. The findings provide insight into the physiological role of the asp23 gene in the growth response of L. casei when exposed to antibiotic stress.



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Reproductive performance and herd exit dynamics of lactating dairy cows managed for first service with the Presynch-Ovsynch or Double-Ovsynch protocol and different duration of the voluntary waiting period

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): M.L. Stangaferro, R. Wijma, M. Masello, J.O. Giordano
The objective of this experiment was to evaluate the reproductive performance and herd exit dynamics of dairy cows managed for first service with programs varying in method of submission for insemination and voluntary waiting period (VWP) duration. Holstein cows from a commercial farm in New York were randomly allocated to receive timed artificial insemination (TAI) after the Double-Ovsynch protocol (GnRH, 7 d later PGF2α, 3 d later GnRH, 7 d later GnRH, 7 d later PGF2α, 56 h later GnRH, and 16 to 18 h later TAI) at 60 ± 3 d in milk (DIM) (DO60 = 458), TAI after Double-Ovsynch at 88 ± 3 DIM (DO88 = 462), or a combination of AI at detected estrus (starting at 50 ± 3 d in milk) and TAI with the Presynch-Ovsynch protocol (PGF2α, 14 d later PGF2α, 12 d later GnRH, 7 d later PGF2α, 56 h later GnRH, and 16 to 18 h later TAI; PSOv = 450). Subsequent artificial insemination (AI) services were conducted at detected estrus or the Ovsynch protocol (32 ± 3 d after AI GnRH, 7 d later PGF2α, 56 h later GnRH, and 16 to 18 h later TAI) for cows not reinseminated at detected estrus. In a subgroup of cows, cyclicity (based on progesterone concentration), uterine health (vaginal discharge and uterine cytology), and BCS were evaluated at baseline (DO60 and DO88 = 33 ± 3 DIM; PSOv = 34 ± 3 DIM), beginning of the synchronization protocol (DO60 = 33 ± 3 DIM; DO88 = 61 ± 3 DIM; PSOv = 34 ± 3 DIM), and within −5 (PSOv) or −10 d (DO) of the VWP end (DO60 = 50 ± 3 DIM; DO88 = 78 ± 3 DIM; PSOv = 45 ± 3 DIM). Effects of treatments were assessed with multivariable statistical methods relevant for each outcome variable. Cows in the DO88 treatment had delayed time to pregnancy during lactation (DO60 vs. DO88 hazard ratio = 1.53, 95% confidence interval = 1.32 to 1.78; PSOv vs. DO88 hazard ratio = 1.37, 95% confidence interval = 1.19 to 1.61) and, within multiparous cows, the DO88 and PSOv treatments had greater risk of leaving the herd than cows in the DO60 treatment (DO88 vs. DO60 hazard ratio = 1.49, 95% confidence interval = 1.11 to 2.00; PSOv vs. DO60 hazard ratio = 1.39, 95% confidence interval = 1.03 to 1.85). Cows in the DO88 treatment had improved uterine health, greater BCS, and reduced incidence of anovulation than cows in DO60 and PSOv; however, overall pregnancy per AI 39 ± 3 d after AI was similar for the 3 treatment groups. In summary, reproductive management strategies that led to similar average DIM to the first service (∼60 d) through a combination of AI at estrus with TAI (PSOv) or all TAI (DO60) resulted in reduced time to pregnancy after calving when compared with an all TAI program (DO88) with a VWP of 88 d. Within the multiparous cow group, those that received all TAI with a VWP duration of 60 d were less likely to leave the herd than cows in the other treatments.



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Method comparison and validation of a prototype device for measurement of ionized calcium concentrations cow-side against a point-of-care instrument and a benchtop blood-gas analyzer reference method

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): R.C. Neves, T. Stokol, K.D. Bach, J.A.A. McArt
The objective of this study was to assess an optimized ion-selective electrode Ca-module prototype as a potential cow-side device for ionized Ca (iCa) measurements in bovine blood. A linearity experiment showed no deviation from linearity over a range of iCa concentrations compared with a commercial point-of-care (POC) device commonly used in the field (POCVS; VetScan i-STAT, Abaxis North America, Union City, CA) and a laboratory gold standard benchtop blood-gas analyzer [reference analyzer (RA); ABL-800 FLEX, Radiometer Medical, Copenhagen, Denmark]. Coefficient of variation on 3 samples with high, within-range, and low iCa concentrations ranged from 1.0 to 3.9% for the prototype. A follow-up validation experiment was performed, in which our objectives were to (1) assess the performance of the prototype cow-side against the POCVS (farm gold-standard) using fresh non-anticoagulated whole-blood samples; (2) assess the performance of the prototype and the POCVS against the RA in a diagnostic laboratory using blood collected in a heparin-balanced syringe; and (3) assess the agreement of the prototype and POCVS on-farm (fresh non-anticoagulated whole blood) against the RA on heparin-balanced blood. Finally, sensitivity and specificity of the results obtained by the prototype and the POCVS cow-side compared with the results obtained by the laboratory RA using 3 different iCa cut points for classification of subclinical hypocalcemia were calculated. A total of 101 periparturient Holstein cows from 3 dairy farms in New York State were used for the second experiment. Ionized Ca results from the prototype cow-side were, on average, 0.06 mmol/L higher than the POCVS. With heparin-balanced samples under laboratory conditions, the prototype and POCVS measured an average 0.04 mmol/L higher and lower, respectively, compared with the RA. Results from the prototype and POCVS cow-side were 0.01 mmol/L higher and 0.05 mmol/L lower, respectively, compared with results from the laboratory RA on heparinized blood. Sensitivity and specificity for the prototype and the POCVS under farm conditions at 3 potential subclinical hypocalcemia cut points were 100 and ≥93.5%, respectively. This novel ion-selective electrode Ca-module could become a rapid low-cost tool for assessing iCa cow-side, while qualitatively allowing classification of subclinical hypocalcemia on-farm.



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Replacing maize silage plus soybean meal with red clover silage plus wheat in diets for lactating dairy cows

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): Franziska Schulz, Edwin Westreicher-Kristen, Karin Knappstein, Joachim Molkentin, Andreas Susenbeth
The objectives of this study were to evaluate the effects of replacing maize silage plus soybean meal with red clover silage (RCS) plus wheat on feed intake, diet digestibility, N partitioning, urinary excretion of purine derivatives, and milk production in dairy cows. Forty-four lactating German Holstein cows were used in a 4 × 4 Latin square design with 21-d periods composed of a 13-d adaptation phase followed by an 8-d sampling phase. Experimental diets offered as total mixed ration consisted of a constant forage-to-concentrate ratio (75:25) with targeted proportions of RCS-to-maize silage of 15:60 (RCS15), 30:45 (RCS30), 45:30 (RCS45), and 60:15 (RCS60) on a dry matter (DM) basis. Increasing the proportion of RCS plus wheat in the diet decreased linearly the intake of DM from 22.4 to 19.8 kg/d, and of organic matter from 21.1 to 18.1 kg/d. The apparent total tract digestibility (ATTD) of DM and organic matter did not differ across diets and averaged 68.4 and 70.5%, respectively. However, ATTD of N decreased linearly from 68.5 to 63.2%, whereas ATTD of neutral detergent fiber and acid detergent fiber increased linearly from 50.4 to 59.6% and from 48.4 to 57.7%, respectively, when increasing the proportion of RCS plus wheat. Fecal N excretion increased from 31.6 (RCS15) to 37.2% (RCS60) of N intake, whereas urinary N excretion was the lowest (32.8% of N intake) with RCS45. Hence, N efficiency (milk N/N intake) decreased linearly with incremental levels of RCS plus wheat, being the lowest when feeding RCS60 (25.4%), probably due to increased nonprotein N proportion in total dietary N. Urinary excretion of purine derivatives decreased linearly from 378 to 339 mmol/d, which suggests that increasing levels of RCS plus wheat reduced the microbial crude protein flow at the duodenum. Milk yield and milk protein concentration declined linearly from 35.9 to 30.2 kg/d and from 3.20 to 3.01%, respectively, when increasing the proportion of RCS plus wheat. In conclusion, caution should be taken before introducing high levels of RCS plus wheat in diets of high-yielding dairy cows. However, RCS plus wheat can be included up to 30% of the dairy cow diet (DM basis) without a reduction in lactation performance.



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Economic costs of recorded reasons for cow mortality and culling in a pasture-based dairy industry

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): J.I. Kerslake, P.R. Amer, P.L. O'Neill, S.L. Wong, J.R. Roche, C.V.C. Phyn
The objective of this study was to determine the economic costs associated with different reasons for cow culling or on-farm mortality in a pasture-based seasonal system. A bioeconomic model was developed to quantify costs associated with the different farmer-recorded reasons and timing of cow wastage. The model accounted for the parity and stage of lactation at which the cows were removed as well as the consequent effect on the replacement rate and average age structure of the herd. The costs and benefits associated with the change were quantified, including animal replacement cost, cull salvage value, milk production loss, and the profitability of altered genetic merit based on industry genetic trends for each parity. The total cost of cow wastage was estimated to be NZ$23,628/100 cows per year (NZ$1 = US$0.69) in a pasture-based system. Of this total cost, NZ$14,300/100 cows worth of removals were for nonpregnancy and unknown reasons, and another NZ$3,631/100 cows was attributed to low milk production, mastitis, and udder problems. The total cost for cow removals due to farmer-recorded biological reasons (excluding unknown, production, and management-related causes) was estimated to be NZ$13,632/100 cows per year. Of this cost, an estimated NZ$10,286/100 cows was attributed to nonpregnancy, mastitis, udder problems, calving trouble, and injury or accident. There is a strong economic case for the pasture-based dairy industries to invest in genetic, herd health, and production management research focused on reducing animal wastage due to reproductive failure, mastitis, udder problems, injuries or accidents, and calving difficulties.



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Multi-year evaluation of stocking rate and animal genotype on milk production per hectare within intensive pasture-based production systems

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): E.L. Coffey, L. Delaby, C. Fleming, K.M. Pierce, B. Horan
The objective of this experiment was to evaluate the effect of stocking rate (SR) and animal genotype (BR) on milk production, body weight (BW), and body condition score (BCS) within intensive pasture-based systems. A total of 533 lactation records, from 246 elite genetic merit dairy cows were available for analysis; 68 Holstein-Friesian (HF) and 71 Jersey × Holstein-Friesian (JxHF) crossbred cows in each of 4 consecutive years (2013–2016, inclusive). Cows from each BR were randomly allocated to 1 of 3 whole-farm comparative SR treatments, low (LSR; 1,200 kg of BW/ha), medium (MSR; 1,400 kg of BW/ha), and high (HSR; 1,600 kg of BW/ha), and remained in the same SR treatments for the duration of the experiment. The effects of SR, BR, and their interaction on milk production/cow and per hectare, BW, BCS, and grazing characteristics were analyzed. Total pasture utilization per hectare consumed in the form of grazed pasture increased linearly as SR increased: least in LSR (10,237 kg of dry matter/ha), intermediate in MSR (11,016 kg of dry matter/ha), and greatest in HSR (11,809 kg of dry matter/ha). Milk and milk solids (MS) yield per hectare was greatest for HSR (15,942 and 1,354 kg, respectively), intermediate for MSR (14,191 and 1,220 kg, respectively), and least for LSR (13,186 and 1,139 kg, respectively) with similar trends evident for fat, protein, and lactose yield/ha. At higher SR (MSR and HSR), MS yield per kg of BW per ha was reduced (0.85 and 0.82 kg of MS/kg of BW, respectively) compared with LSR (0.93 kg of MS/kg of BW/ha). Holstein-Friesian cows achieved fewer grazing days per hectare (−37 d), and produced more milk (+561 kg/ha) but less fat plus protein (−57 kg/ha) compared with JxHF cows; the JxHF cows were lighter. At similar BW per hectare, JxHF cows produced more fat plus protein/ha during the grazing season at low (1,164 vs. 1,113 kg), medium (1,254 vs. 1,185 kg), and high (1,327 vs. 1,380 kg) SR. In addition, JxHF cows produced more fat plus protein per kg of BW/ha (0.90 kg) compared with HF cows (0.84 kg). The results highlight the superior productive efficiency of high genetic potential crossbred dairy cows within intensive pasture-based production systems.



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Evaluation of Large-Aperture Imaging Through the ex Vivo Human Abdominal Wall

Publication date: Available online 14 December 2017
Source:Ultrasound in Medicine & Biology
Author(s): Nick Bottenus, Will Long, Matthew Morgan, Gregg Trahey
Current clinical abdominal imaging arrays are designed to maximize angular field of view rather than the extent of the coherent aperture. We illustrate, in ex vivo experiments, the use of a large effective aperture to perform high-resolution imaging, even in the presence of abdominal wall-induced acoustic clutter and aberration. Point and lesion phantom targets were imaged through a water path and through three excised cadaver abdominal walls to create different clinically relevant clutter effects with matched imaging targets. A 7.36-cm effective aperture was used to image the targets at a depth of 6.4 cm, and image quality metrics were measured over a range of aperture sizes using synthetic aperture techniques. In all three cases, although degradation compared with the control was observed, lateral resolution improved with increasing aperture size without loss of contrast. Spatial compounding of the large-aperture data drastically improved lesion detectability and produced contrast-to-noise ratio improvements of 83%–106% compared with the large coherent aperture. These studies indicate the need for the development of large arrays for high-resolution abdominal diagnostic imaging.



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FDA Benefit‐Risk Assessment of Osimertinib for the Treatment of Metastatic Non‐Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor T790M Mutation

AbstractOn March 30, 2017, the U.S. Food and Drug Administration (FDA) approved osimertinib for the treatment of patients with metastatic, epidermal growth factor receptor (EGFR) T790M mutation‐positive, non‐small cell lung cancer (NSCLC), as detected by an FDA‐approved test, whose disease has progressed following EGFR tyrosine kinase inhibitor (TKI) therapy. Approval was based on demonstration of a statistically significant difference in the primary endpoint of progression‐free survival (PFS) when comparing osimertinib with chemotherapy in an international, multicenter, open‐label, randomized trial (AURA3). In this confirmatory trial, which enrolled 419 patients, the PFS hazard ratio for osimertinib compared with chemotherapy per investigator assessment was 0.30 (95% confidence interval 0.23–0.41), p < .001, with median PFS of 10.1 months in the osimertinib arm and 4.4 months in the chemotherapy arm. Supportive efficacy data included PFS per blinded independent review committee demonstrating similar PFS results and an improved confirmed objective response rate per investigator assessment of 65% and 29%, with estimated median durations of response of 11.0 months and 4.2 months, in the osimertinib and chemotherapy arms, respectively. Patients received osimertinib 80 mg once daily and had a median duration of exposure of 8 months. The toxicity profile of osimertinib compared favorably with the profile of other approved EGFR TKIs and chemotherapy. The most common adverse drug reactions (>20%) in patients treated with osimertinib were diarrhea, rash, dry skin, nail toxicity, and fatigue. Herein, we review the benefit‐risk assessment of osimertinib that led to regular approval, for patients with metastatic NSCLC harboring EGFR TKI whose disease has progressed on or after EGFR TKI therapy.Implications for Practice.Osimertinib administered to metastatic non‐small cell lung cancer (NSCLC) patients harboring an EGFR T790M mutation, who have progressed on or following EGFR TKI therapy, demonstrated a substantial improvement over platinum‐based doublet chemotherapy as well as durable intracranial responses. The ability to test for the T790M mutation in plasma using the FDA‐approved cobas EGFR Mutation Test v2 (Roche, Basel, Switzerland) identifies patients with NSCLC tumors not amenable to biopsy. Since a 40% false‐negative rate has been observed with the circulating tumor DNA test, re‐evaluation of the feasibility of tissue biopsy is recommended to identify patients with a false‐negative plasma test result who may benefit from osimertinib.

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Phase II Study of BEZ235 versus Everolimus in Patients with Mammalian Target of Rapamycin Inhibitor‐Naïve Advanced Pancreatic Neuroendocrine Tumors

AbstractLessons Learned. Treatment with BEZ235 has not been shown to demonstrate increased efficacy compared with everolimus and may be associated with a poorer tolerability profile.The hypothesis of dual targeting of the phosphatidylinositol 3‐kinase and mammalian target of rapamycin pathways in patients with advanced pancreatic neuroendocrine tumors may warrant further study using other agents.Background.This phase II study investigated whether targeting the phosphatidylinositol 3‐kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway via PI3K, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) inhibition using BEZ235 may be more effective than mTORC1 inhibition with everolimus in patients with advanced pancreatic neuroendocrine tumors (pNET) who are naïve to mTOR inhibitor therapy.Methods.Patients with advanced pNET were randomized (1:1) to oral BEZ235 400 mg twice daily or oral everolimus 10 mg once daily on a continuous dosing schedule. The primary endpoint was progression‐free survival (PFS). Secondary endpoints included safety, overall response rate (ORR), overall survival (OS), and time to treatment failure.Results.Enrollment in this study was terminated early (62 enrolled of the 140 planned). The median PFS was 8.2 months (95% confidence interval [CI]: 5.3 to not evaluable [NE]) with BEZ235 versus 10.8 months (95% CI: 8.1–NE) with everolimus (hazard ratio 1.53; 95% CI: 0.72–3.25). The most commonly reported all‐grade adverse events (>50% of patients regardless of study treatment relationship) with BEZ235 were diarrhea (90.3%), stomatitis (74.2%), and nausea (54.8%).Conclusion.BEZ235 treatment in mTOR inhibitor‐naïve patients with advanced pNET did not demonstrate increased efficacy compared with everolimus and may be associated with a poorer tolerability profile.

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Patient‐Reported Comorbidity and Survival in Older Adults with Cancer

AbstractBackground.Our ability to optimize the care of older adults with cancer and comorbid illnesses is insufficient because most clinical trials lack systematic measurement. The primary purpose of this study was to evaluate the association between patient‐reported comorbidity and all‐cause mortality using various comorbidity scoring algorithms.Materials and Methods.The Carolina Senior Registry was linked with the North Carolina Central Cancer Registry to obtain mortality data. Comorbidity was assessed using the patient‐reported Older Americans Resources and Services Questionnaire subscale that assesses 13 specific conditions and the degree to which each impairs activities. Multivariable Cox proportional hazard regression models were used to evaluate the association between comorbidities and all‐cause mortality.Results.The study sample included 539 patients; the median age was 72 years, 72% were female, and 47% had breast cancer. Overall, 92% reported ≥1 comorbid condition, with a mean of 2.7 conditions (range 0–10), with arthritis and hypertension the most common (52% and 50%, respectively). Approximately 60% reported a functional limitation related to comorbidity. After adjusting for time from diagnosis to geriatric assessment, age, cancer type, and stage, the risk of death increased by 5% for each unit increase in comorbidity burden score (adjusted hazard ratio [HR] = 1.05, 95% confidence interval [CI]: 1.01–1.10) and 12% for each comorbid condition impacting function (HR = 1.12, 95% CI: 1.02–1.23).Conclusion.Comorbid conditions in older adults with cancer are highly prevalent and associated with all‐cause mortality, particularly those conditions that impair function. Routine comorbidity assessment should be included in clinical trials and can be measured via a simple one‐page patient‐reported questionnaire.Implications for Practice.In order to optimize and personalize the care of older adults with cancer, systematic measurement of comorbidities is necessary in both clinical trials and routine practice. Patient‐reported comorbid conditions in older adults with cancer are highly prevalent and are associated with increased risk of all‐cause mortality, particularly for those conditions that impair function. Comorbidity can be systematically measured via a one‐page patient‐reported questionnaire and should be incorporated into future clinical trials and considered for use in oncology clinics to aid in assessing older adults with cancer.

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Results of Fertility‐Sparing Surgery for Expansile and Infiltrative Mucinous Ovarian Cancers

AbstractBackground.No series had been reported focusing on the results of fertility‐sparing surgery in stage I mucinous ovarian cancers according to histotype (infiltrative vs. expansile). Investigating such outcomes was the aim of the present study.Materials and Methods.The present study was a retrospective analysis of patients treated conservatively with preservation of the uterus and contralateral ovary from 1976 to 2016. The pathology of the tumors was reviewed by two expert pathologists according to the 2014 World Health Organization (WHO) classification criteria. Oncologic and fertility results were analyzed.Results.Twenty‐one patients fulfilled the inclusion criteria, twelve with expansile and nine with infiltrative cancer. All patients had a unilateral tumor and underwent unilateral salpingo‐oophorectomy in one‐step (n = 6) or two‐step (n = 15) surgeries. All but one had complete peritoneal staging surgery based on cytology, omentectomy, and random peritoneal biopsies. Ten had nodal staging surgery. The International Federation of Gynecology and Obstetrics stages were IA (n = 9), IC1 (n = 6), and IC2 (n = 6); the nuclear grades were grade 1 (n = 9), grade 2 (n = 5), and grade 3 (n = 1). Two patients recurred (one expansile and one infiltrative type) 19 and 160 months after surgery, respectively. One stage IA, nuclear grade 2 expansile tumor recurred on the spared ovary; the patient remains alive. The other stage IA infiltrative tumor recurred as peritoneal spread; the patient is alive with disease. Six patients became pregnant; four with expansile tumors and two with infiltrative tumors.Conclusion.The type of mucinous cancer has no impact on the oncologic outcome in this series of patients treated conservatively. Fertility‐sparing surgery should be considered for early‐stage infiltrative‐type tumors.Implications for Practice.According to the most recently updated World Health Organization classification guidelines, mucinous cancers should be classified as either expansile or infiltrative. The infiltrative type has a poorer prognosis, but there are no data about the safety of fertility‐sparing surgery (FSS) in this context. A collection of 21 cases reviewed by two expert pathologists this study is the first devoted to the conservative treatment of mucinous tumors according to both subtypes. The key result was that the type of mucinous cancer has no impact on the oncologic outcome; thus, FSS may be considered in both subtypes.

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Molecular Biomarkers of Primary and Acquired Resistance to T‐Cell‐Mediated Immunotherapy in Cancer: Landscape, Clinical Implications, and Future Directions

AbstractThe emergence of immunotherapy has revolutionized cancer treatment in recent years. Inhibitors of immune checkpoints, including antibodies against cytotoxic T‐lymphocyte‐associated protein 4, programmed cell death protein 1, and programmed death ligand 1, have demonstrated notable efficacy in certain advanced cancers. Unfortunately, many patients do not benefit from these therapies and either exhibit primary resistance to treatment or develop acquired mechanisms of resistance after initially responding to therapy. Here, we review the genomic and immune traits that may promote resistance to T‐cell‐mediated immunotherapy, with a focus on identifying potential biomarkers that could eventually be used in the clinical setting to guide treatment selection. We summarize the clinical evidence for these markers and discuss how current understanding of resistance mechanisms can inform future studies and aid clinical decision‐making in order to derive maximum benefit from immunotherapy.Implications for Practice.Immunotherapy has rapidly progressed as a treatment modality for multiple cancers, but it is still unclear which patients are likely to benefit from these therapies. Studies of resistance mechanisms have only recently started to identify biomarkers that can help predict patient outcomes. This review summarizes the available clinical data in regard to immunotherapy resistance, with a focus on molecular biomarkers that may be useful in guiding clinical decision‐making. It discusses possible applications of these biomarkers and highlights opportunities for further clinical discovery.

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Disentangling the effects of parental food restriction on child's risk of overweight

Publication date: 1 April 2018
Source:Appetite, Volume 123
Author(s): Valérie Godefroy, Camille Champel, Laura Trinchera, Natalie Rigal
The links between parental restriction of food intake, child's eating behaviour and child's adiposity are still unclear. Our aim was to validate a model suggesting an underlying mechanism for the impact of parental restriction on child's adiposity through a broad dimension of child's eating temperament entitled the appetite reactivity (including both appetite arousal and appetite persistence). Using an online questionnaire administered at home to children aged between 8 and 11 years (N = 414) with one or both of their parents, we measured: based on child's reports, the perceived maternal restriction of child's food intake, the appetite reactivity and both the desired and the eaten mean food portion sizes; based on parental reports, the mean food portion size given to the child and the child's BMI. Structural equation modelling was used to test a model linking measured variables. A well-fitting structural model (AGFI = 0.91; RMSEA = 0.07; SRMR = 0.08) was identified, showing that: (i) perceived maternal restriction of child's food intake negatively impacts child's appetite arousal and food portion size but positively influences child's appetite persistence; (ii) the two components of appetite reactivity have a positive effect on child's adiposity which is partly mediated by child's actual food portion size. Results suggest an explanation for the controversy surrounding the links between parental food restriction and child's adiposity: through its negative impact on child's appetite arousal and food portion size, parental control may protect against overweight, but because of its positive effect on appetite persistence, it can also be detrimental.



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Systemic treatment in adult uterine sarcomas

Publication date: Available online 14 December 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): I.M.E. Desar, P.B. Ottevanger, C. Benson, W.T.A. van der Graaf
Uterine sarcomas (US) are rare mesenchymal tumours of the uterus and are divided mainly into uterine leiomyosarcoma (uLMS), low grade endometrial stromal sarcoma (LG-ESS), high grade endometrial stromal sarcoma (HG-ESS), adenosarcomas and high grade undifferentiated sarcoma (HGUS). US are often high-grade tumours with a high local recurrence rate and metastatic risk. We here discuss the current standard of care and knowledge of systemic therapy for adult uterine sarcomas, in particular uLMS, LG-ESS, HG-ESS and HGUS, in both the adjuvant as well as the metastatic setting.



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Corrigendum to the plant heat stress transcription factor (Hsf) family: Structure, function and evolution. [BBAGRM 1819 (2) 104–119]

Publication date: Available online 14 December 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Klaus-Dieter Scharf, Thomas Berberich, Ingo Ebersberger, Lutz Nover




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Immediate effects of kinesio taping on pain and postural stability in patients with chronic low back pain

Publication date: Available online 14 December 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Seyda Toprak Celenay, Derya Ozer Kaya
ObjectivePostural control of patients with chronic low back pain (CLBP) is usually impaired. Effects of treatment applications on postural stability have not been well investigated. The aim of this study was to investigate the immediate effects of kinesio taping on pain and postural stability in patients with CLBP.MethodsOne hundred and one patients with CLBP (age: 53.00 (10.69) years, body mass index (BMI): 31.52 (5.57) kg/m²) were included in this study. Kinesio taping was applied on paravertebral muscles and sacrum with muscle and ligament techniques. Postural stability was assessed with Biodex Balance System^® (USA) both at static and dynamic mode in bilateral standing position. The base was set "static" for static mode, and set between"12-1" for dynamic mode. Pain intensity was evaluated with the pain section (0–5 points) of Oswestry Disability Index, including ten items (pain, personal care, lifting, walking, sitting, standing, sleeping, sex life, social life, travelling), pre- and post-application.ResultsThe static overall (pre: 1.49 (1.15), post: 1.25 (1.11)) and antero-posterior (pre: 0.96 (0.86), post: 0.74 (0.59)), dynamic overall (pre: 3.12 (2.26), post: 2.73 (2.44)) and medio-lateral postural sway scores (pre: 1.62 (1.12), post: 1.24 (0.75)), and pain (pre: 2.00 (0.00–5.00), post: 1.00 (0.00–4.00)) decreased after the application (p < .05). However, no differences were observed in static medio-lateral (pre: 0.84 (0.78), post: 0.82 (1.01)) and dynamic antero-posterior postural sway scores (pre: 2.33 (1.99), post: 2.12 (2.33)), (p > .05).ConclusionsKinesio taping may immediately improve postural stability and decrease pain of patients with CLBP.



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A critical overview of the current myofascial pain literature – January 2018

Publication date: Available online 14 December 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Jan Dommerholt, Todd Hooks, Li-Wei Chou, Michelle Finnegan
The majority of papers included in the quarterly review discuss various aspects of dry needling (DN), which continues to be of interest to researchers and clinicians. A study by Liu et al. is the first paper to examine the effects of DN of acetylcholine, esterase and receptors. The study provides support for the integrated trigger point hypothesis and for DN. A paper by Hightower and colleagues found an intriguing link between low magnesium levels in the drink water supply, vitamin D, and myofascial pain, cancer, tendon ruptures, and colon polyps. Contributions originated in the Brazil, China, Gemany, Iran, India, Poland, South Korea, Spain, Taiwan, Turkey, and the US.



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Excitotoxicity in encephalopathy associated with STEC O-157 infection

Publication date: Available online 14 December 2017
Source:Brain and Development
Author(s): Shigenobu Ishida, Kumi Yasukawa, Mai Koizumi, Katsuhiro Abe, Nozomi Hirai, Takafumi Honda, Hiroshi Sakuma, Hiroko Tada, Jun-ichi Takanashi
Cytokines play an important role in the pathogenesis of the severe complications of Shiga toxin-producing Escherichia coli (STEC) infection, such as hemolytic uremic syndrome (HUS) and acute encephalopathy. A 3-year-old boy with acute encephalopathy associated with STEC O-157 HUS showed increased levels of IL-6 and IL-10, which normalized after methylprednisolone pulse therapy, and additionally exhibited a transient increase of glutamine on MR spectroscopy. This finding suggests that excitotoxicity, in addition to hypercytokinemia, may play an important role in the pathogenesis of HUS encephalopathy.



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Nitrate trends in groundwater of the Campania region (southern Italy)

Abstract

The Environmental Protection Agency of the Campania region in Italy (ARPAC) manages a groundwater quality monitoring network. For almost all the polluted waters, the key parameter driving the classification is the concentration of nitrate; hence, the Campania region, in coherence with the EU regulations, outlined the vulnerable areas and undertook remediation policies. The best groundwater quality is recorded for carbonate aquifers of the Apennine chain; on the contrary, the Tyrrhenian coastal plains are affected by severe contamination, with a locally very contaminated groundwater of the shallow and also the deeper aquifers. The study is especially focused on a large coastal plain of Campania region, where nitrate concentration sometimes exceeds 200 mg/L. The study, based on almost 200 sampling points for the whole region during the period 2003–2015 (approx two samples per year), verified the effectiveness of the groundwater monitoring network, the present distribution of nitrate in groundwater, and the evolution of nitrate trends at different scales: regional, groundwater body, and single well, using spatial and time series statistical approaches. Significant variations in contamination evolution within the study area have been observed and the correlation with land use has been highlighted.

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Editorial Board

Publication date: February 2018
Source:Biomaterials, Volume 154





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A review on exudates detection methods for diabetic retinopathy

Publication date: January 2018
Source:Biomedicine & Pharmacotherapy, Volume 97
Author(s): Shilpa Joshi, P.T. Karule
The presence of exudates on the retina is the most characteristic symptom of diabetic retinopathy. As exudates are among early clinical signs of DR, their detection would be an essential asset to the mass screening task and serve as an important step towards automatic grading and monitoring of the disease. Reliable identification and classification of exudates are of inherent interest in an automated diabetic retinopathy screening system. Here we review the numerous early studies that used for automatic exudates detection with the aim of providing decision support in addition to reducing the workload of an ophthalmologist.



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Long non-coding RNA OIP5-AS1 functions as an oncogene in lung adenocarcinoma through targeting miR-448/Bcl-2

Publication date: February 2018
Source:Biomedicine & Pharmacotherapy, Volume 98
Author(s): Jun Deng, Huan Deng, Chunfeng Liu, Yujia Liang, Songping Wang
LncRNAs are increasingly verified to be aberrantly expressed in cancers. The abnormal expression of lncRNAs has turned out to be closely related to tumorigenesis or tumor progression. It has been reported that lncRNA OPI5-AS1 serves as a crucial regulator in tumors. However, the specific function of OIP5-AS1 on the progression of lung adenocarcinoma is still uncertain. In this paper, we mainly elucidated that OIP5-AS1 exerts oncogenic functions in human lung adenocarcinoma through targeting miR-448. We inspected that the expression of OIP5-AS1 was definitely high in lung adenocarcinoma tissues and cells, while miR-448 was sluggishly expressed in lung adenocarcinoma. OIP5-AS1 and miR-448 was negatively related to each other, the result was obtained from Pearson correlation analysis. We discovered a fact that OIP5-AS1 could directly sponge miR-448 through using dual luciferase reporter assay, RIP assay and RNA pull-down assay. Cell proliferation, migration and invasion were restrained after we disrupted the expression of OIP5-AS1 in lung adenocarcinoma. We also certified that OIP5-AS1 could sponge and regulate miR-448 to affect cell function in lung adenocarcinoma. MiR-448 could target Bcl-2 and affect the expression of Bcl-2. Then, we discovered that the expression of OIP5-AS1 and Bcl-2 was positively related. So we affirmed that lncRNA OIP5-AS1 modulated the expression of Bcl-2 by targeting miR-448 in lung adenocarcinoma cells.



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Baicalin attenuates diet induced nonalcoholic steatohepatitis by inhibiting inflammation and oxidative stress via suppressing JNK signaling pathways

Publication date: February 2018
Source:Biomedicine & Pharmacotherapy, Volume 98
Author(s): Xueqing Zhong, Hailin Liu
Nonalcoholic steatohepatitis may develop into hepatic cirrhosis. The therapeutic drugs for NASH are absent. Baicalin (BC) has hepatoprotective effect, while whether BC could prevent the development of NASH is unknown. This study aimed to investigate the effect of BC on the development of diet induced NASH and the possible mechanisms involved. Mice were fed with high fat and high cholesterol (HFC) diet to establish a NASH model, BC (0.5% w/w) was added into the diet to evaluate its effect on NASH. Mice fed an HFC diet developed NASH in 12 weeks. BC administration attenuated hepatic steatosis, inflammation and fibrosis induced by HFC diet. The NALFD activity score (NAS) was sharply decreased by BC. Mice serum ALT and AST were decreased in the BC group. BC decreased hepatic inflammatory cell infiltration, inflammatory genes (MCP-1, TNFα) and fibrosis genes (COL1, α-SMA, TGFβ) mRNA expression. BC has antioxidant function evidenced by upregulated hepatic GSH and SOD levels and downregulated MDA levels. BC restored some oxidative stress markers including 4-HNE, 8-OHdG in liver. Western blot analysis stated that BC suppressed pro-inflammatory COX-2 levels, pro-oxidative CYP2E1 levels and phosphorylation of JNK in mice liver. Collectively, BC can attenuate diet induced NASH and the mechanism in which possibly due to its anti-inflammatory and anti-oxidant effects via blockade of the activation of JNK.



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HDACis (class I), cancer stem cell, and phytochemicals: Cancer therapy and prevention implications

Publication date: January 2018
Source:Biomedicine & Pharmacotherapy, Volume 97
Author(s): Sahar Bayat, Mahmoud Shekari Khaniani, Jalal Choupani, Mohammad Reza Alivand, Sima Mansoori Derakhshan
Epigenetics is independent of the sequence events that physically affect the condensing of chromatin and genes expression. The unique epigenetic memories of various cells trigger exclusive gene expression profiling. According to different studies, the aberrant epigenetic signatures and impaired gene expression profiles are master occurrences in cancer cells in which oncogene and tumor suppressor genes are affected. Owing to the facts that epigenetic modifications are performed earlier than expression and are reversible, the epigenetic reprogramming of cancer cells could be applied potentially for their prevention, control, and therapy. The disruption of the acetylation signature, as a master epigenetic change in cancers, is related to the expression and the activity of HDACs. In this context, class I HDACs play a significant role in the regulation of cell proliferation and cancer. More recently, cancer stem cell (CSC) has been introduced as a minority population of tumor that is responsible for invasiveness, drug resistance, and relapse of cancers. It is now believed that controlling CSC via epigenetic reprogramming such as targeting HDACs could be helpful in regulating the acetylation pattern of chromatin. Recently, a number of reports have introduced some phytochemicals as HDAC inhibitors. The use of phytochemicals with the HDAC inhibition property could be potentially efficient in overcoming the mentioned problems of CSCs. This review presents a perspective concerning HDAC-targeted phytochemicals to control CSC in tumors. Hopefully, this new route would have more advantages in therapeutic applications and prevention against cancer.



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Amine-functionalized diatom frustules: a platform for specific and sensitive detection of nitroaromatic explosive derivative

Abstract

In the present study, an attempt was made to develop a proof of concept for the detection of nitroaromatic explosive derivatives through the photoluminescence (PL) quenching process using functionalized diatom frustules as a sensing platform. The diatom frustules are composed of nanostructured, highly porous biogenic silica material and emit strong, visible blue PL upon UV excitation. PL-active biosilica was isolated from the marine diatom Nitzschia sp. and was amine-functionalized to develop a sensing platform. Functionalized diatom frustules were further characterized using field emission scanning electron microscope and a series of spectroscopic methods. When nitroaromatic compounds were bound to the functionalized diatom frustules biosilica, the PL intensity from the functionalized biosilica was partially quenched due to the electrophilic nature of the nitro (–NO) groups. The quenching process confirmed the Meisenheimer complex formation and was investigated by using Fourier transform infrared spectroscopy and time-resolved photoluminescence studies. The developed platform was further evaluated for its sensitivity and specificity, and the limit of detection (LOD) of the assay was determined as 1 μM for a series of nitroaromatic explosive compounds. In conclusion, the developed sensing platform will have great utility in the development of on-site detection platforms for sensitive detection of warfare explosive nitroaromatic compounds from the environment.

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Rectus abdominis detrusor myoplasty (RADM) for acontractile/hypocontractile bladder in spinal cord injury patients: preliminary report

-Urinary bladder dysfunction in the form of acontractile/hypocontractile bladder is very common after spinal cord injury and it may lead to recurrent urinary tract infection (UTI), stones formation, and deteriorating renal function. Conventionally, these patients evacuate their bladders by life-long clean intermittent catheterization (CIC) or an indwelling catheter (IC). For these patients, another option is to use innervated skeletal muscle wrap around the bladder to augment detrusor function and voluntary evacuation of bladder.

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Surviving fourniers gangrene: multivariable analysis and a novel scoring system to predict length of stay.

There is no contemporary scoring system to predict hospital length of stay and morbidity in Fournier's gangrene. A retrospective study was conducted to formulate a scoring system to predict duration of hospitalization, resource utilization, need for reconstruction, morbidity and mortality.

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Active Surveillance of Low-Risk Papillary Microcarcinoma of the Thyroid Proposed as First-Line Management

New Rochelle, NY, December 14, 2017—A 10-year study of more than 1,200 patients with low-risk papillary microcarcinoma (PMC) of the thyroid led researchers to conclude that close and continuous monitoring is an acceptable first-line approach to patient management instead of immediate surgery to remove the tumor. The article entitled "Insights into the Management of Papillary Microcarcinoma of the Thyroid" is part of a special section on Japanese Research led by Guest Editor Yoshiharu Murata, Nagoya University, Japan, in the January 2018 issue of Thyroid, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers and the official journal of the American Thyroid Association (ATA). The article is available free on the Thyroid website.

Coauthors Akira Miyauchi, Yasuhiro Ito, and Hitomi Oda, Kuma Hospital, Kobe, Japan, report that in only 8% of patients with PMC evaluated during the study period did the tumor increase in size by 3 mm or more, and only 3.8% of patients had a new metastasis. PMCs were least likely to grow in older patients (60 years of age or older). Furthermore, compared to a management approach of "active surveillance," patients who underwent immediate surgery had significantly higher risks of unfavorable events and more than 4 times the total cost of PMC treatment.

"The seminal observations by the groups from Kuma Hospital and the Cancer Institute Hospital in Tokyo from Japan indicate that the vast majority of papillary thyroid microcarcinomas have an indolent behavior and that active surveillance may be an alternative approach in many patients," says Peter A. Kopp, MD, Editor-in-Chief of Thyroid and Professor of Medicine, Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL. "Similar prospective studies are now underway in other parts of the world. Ultimately, the goal is to avoid unnecessary treatment. The challenge that lies ahead of us is to identify the small group of patients with papillary thyroid microcarcinomas that require active intervention."

About the Journal
Thyroid, the official journal of the American Thyroid Association, is an authoritative peer-reviewed journal published monthly online with open access options and in print. The Journal publishes original articles and timely reviews that reflect the rapidly advancing changes in our understanding of thyroid physiology and pathology, from the molecular biology of the cell to clinical management of thyroid disorders. Complete tables of content and a sample issue may be viewed on the Thyroid website The complete Thyroid Journal Program includes the highly valued abstract and commentary publication Clinical Thyroidology, led by Editor-in-Chief Jerome M. Hershman, MD and published monthly, and the groundbreaking videojournal companion VideoEndocrinology, led by Editor Gerard Doherty, MD and published quarterly. Complete tables of content and sample issues may be viewed on the Thyroid website.

About the Society
The American Thyroid Association (ATA) is the leading worldwide organization dedicated to the advancement, understanding, prevention, diagnosis, and treatment of thyroid disorders and thyroid cancer. ATA is an international membership medical society with over 1,700 members from 43 countries around the world. Celebrating its 94th anniversary, the ATA delivers its mission — of being devoted to thyroid biology and to the prevention and treatment of thyroid disease through excellence in research, clinical care, education, and public health — through several key endeavors: the publication of highly regarded professional journals, Thyroid, Clinical Thyroidology, and VideoEndocrinology; annual scientific meetings; research grant programs for young investigators, biennial clinical and research symposia; support of online professional, public and patient educational programs; and the development of guidelines for clinical management of thyroid disease and thyroid cancer. The ATA promotes thyroid awareness and information through its online Clinical Thyroidology for the Public (distributed free of charge to over 11,000 patients and public subscribers) and extensive, authoritative explanations of thyroid disease and thyroid cancer in both English and Spanish. The ATA website serves as the clinical resource for patients and the public who look for reliable information on the Internet.

About the Publisher
Mary Ann Liebert, Inc., publishers is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Diabetes Technology & Therapeutics, Journal of Women's Health, and Metabolic Syndrome and Related Disorders. Its biotechnology trade magazine, GEN (Genetic Engineering & Biotechnology News), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's more than 80 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc., publishers website.

The post Active Surveillance of Low-Risk Papillary Microcarcinoma of the Thyroid Proposed as First-Line Management appeared first on American Thyroid Association.

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Oral health-related quality of life depending on dental and periodontal health in different patients before and after liver transplantation

Abstract

Background

The aim of this study was to evaluate the oral health-related quality of life (OHRQoL) depending on dental and periodontal health of different patients before and after liver transplantation (pre- and postLTx) compared to a healthy control group (HC).

Methods

OHRQoL was rated using the German short form of Oral Health Impact Profile (OHIP G14). To estimate dental health, the decayed (D-T), missing (M-T), and filled (F-T) teeth index (DMF-T) was used. Periodontal health was classified as healthy/mild, moderate, or severe periodontitis. The following statistics are used: Mann-Whitney U test, Kruskal-Wallis test, chi-square test, and Fisher test (α = 5%).

Results

A total of 24 preLTx, 47 postLTx, and 75 HC patients were included. Significant differences in DMF-T, D-T, M-T, and F-T scores were detected between groups (p < 0.001). Prevalence of periodontitis was comparable between groups (p = 0.340). OHRQoL was reduced in pre- and postLTx (OHIP G14 preLTx 4.2 [1.5; 0–4.0], postLTx 4.1 [1; 0–5.0], HC 1.4 [0; 0–2.0]; p = 0.003), without associations to their oral status (p > 0.05).

Conclusions

These preliminary findings show a reduced OHRQoL without associations to their oral status, which might indicate an influence of potential disease-related factors on OHRQoL. Further studies with larger groups are necessary to verify this observation.

Clinical relevance

A special dental care of patients before and after LTx is needed, including a comprehensive assessment of the individual patient's OHRQoL.

http://ift.tt/2B2hVyk

Transgene escape and persistence in an agroecosystem: the case of glyphosate-resistant Brassica rapa L. in central Argentina

Abstract

Brassica rapa L. is an annual Brassicaceae species cultivated for oil and food production, whose wild form is a weed of crops worldwide. In temperate regions of South America and especially in the Argentine Pampas region, this species is widely distributed. During 2014, wild B. rapa populations that escaped control with glyphosate applications by farmers were found in this area. These plants were characterized by morphology and seed acidic profile, and all the characters agreed with B. rapa description. The dose-response assays showed that the biotypes were highly resistant to glyphosate. It was also shown that they had multiple resistance to AHAS-inhibiting herbicides. The transgenic origin of the glyphosate resistance in B. rapa biotypes was verified by an immunological test which confirmed the presence of the CP4 EPSPS protein and by an event-specific GT73 molecular marker. The persistence of the transgene in nature was confirmed for at least 4 years, in ruderal and agrestal habitats. This finding suggests that glyphosate resistance might come from GM oilseed rape crops illegally cultivated in the country or as a seed contaminant, and it implies gene flow and introgression between feral populations of GM B. napus and wild B. rapa. The persistence and spread of the resistance in agricultural environments was promoted by the high selection pressure imposed by intensive herbicide usage in the prevalent no-till farming systems.

http://ift.tt/2kubL1Q

Sternoclavicular Joint Infection Presenting as Nonspecific Chest Pain

Publication date: Available online 14 December 2017
Source:The Journal of Emergency Medicine
Author(s): Scott A. McAninch, Clinton Smithson, Andrew L. Juergens, Jason N. Collins, Amrita Nanda
BackgroundSternoclavicular joint infection (SJI), to include septic arthritis (SA), is a rare cause of chest pain and is often found in patients with significant risk factors and sources for SA. Most acute care laboratory results lack significant sensitivity to rule out SA. Radiographic findings in common acute care imaging often does not reveal findings of SA and osteomyelitis in the acute phase of the infection.Case ReportWe present a patient without significant risk factors for SA, who initially presented with 3 days of pain to the left chest, left neck and shoulder. He had fever and was treated with a short course of antibiotics for possible pneumonia. His symptoms recurred along with fever 36 days after the initial onset of symptoms and was then diagnosed radiographically with left-sided SJI.Why Should an Emergency Physician Be Aware of This?This case reinforces the need to maintain a broad differential diagnosis in the evaluation for chest pain and pursue advanced imaging, such as magnetic resonance imaging, when the pretest probability of SJI is high, especially in the acute phase of the infection.



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Textbook of Critical Care, 7th edition. Vincent JL, Abraham E, Moore FA, Kochanek PM, Fink MP. Philadelphia, Elsevier Inc., Expert Consult eBook, 2017, 1362 pages, $274.99.

Publication date: Available online 14 December 2017
Source:The Journal of Emergency Medicine
Author(s): Edward J. Otten




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Inhibition of Abeta Proteotoxicity by Paeoniflorin in Caenorhabditis elegans Through Regulation of Oxidative and Heat Shock Stress Responses

Rejuvenation Research , Vol. 0, No. 0.


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Graphical abstract TOC

Publication date: 1 January 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 1





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Evaluation of alkylating pyrrole-imidazole polyamide conjugates by a novel method for high-throughput sequencer

Publication date: 1 January 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 1
Author(s): Gengo Kashiwazaki, Rina Maeda, Takashi Kawase, Kaori Hashiya, Toshikazu Bando, Hiroshi Sugiyama
N-Methylpyrrole-N-methylimidazole (PI) polyamides are a class of DNA minor groove binders with DNA sequence-specificity. DNA-alkylating PI polyamide conjugates are attractive candidates as anticancer drugs acting through DNA damage and its subsequent inhibition of cell proliferation. One example is a chlorambucil-PI polyamide conjugate targeting the runt-related transcription factor (RUNX) family. RUNX1 has pro-oncogenic properties in acute myeloid leukemia, and recently the chlorambucil-PI polyamide conjugate was demonstrated to have anticancer effects. Herein, we apply another DNA-alkylating agent, seco-CBI, to target the consensus sequence of the RUNX family. Two types of CBI conjugates were prepared and their binding properties were characterized by Bind-n-Seq analysis using a high-throughput sequencer. The sequencing data were analyzed by two methods, MERMADE and our new MR (motif identification with a reference sequence), and the resultant binding motif logos were as predicted from the pairing rules proposed by Dervan et al. This is the first report to employ the MR method on alkylating PI polyamide conjugates. Moreover, cytotoxicity of conjugates 3 and 4 against a human non-small cell lung cancer, A549, were examined to show promising IC50s of 120 nm and 63 nm, respectively. These findings suggest seco-CBI-PI polyamide conjugates are candidates for oncological therapy.

Graphical abstract

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Design, synthesis and biological evaluation of novel indole-xanthendione hybrids as selective estrogen receptor modulators

Publication date: 1 January 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 1
Author(s): Ramit Singla, Kunj Bihari Gupta, Shishir Upadhyay, Monisha Dhiman, Vikas Jaitak
Ground breaking clinical therapeutic advances in the treatment of breast cancer (BC) is the introduction of selective estrogen receptor modulators (SERMs). We have expeditiously designed and synthesized indole-xanthendione hybrids by coalescing the indole nucleus with xanthendione. All the compounds were first screened for anti-proliferative activity, cytotoxicity and ER-α binding affinity by utilizing ER-α dominant T47D BC cell lines, PBMCs and ER-α competitor assay kit. From this study, two representative compounds 6e and 6f showing most promising activity were advanced for gene expression studies for targeting ER-α. Cell imaging experiment undoubtedly indicate that both the compounds were able to cross cellular bio membrane and accumulate thus instigating cytotoxicity. RT-PCR and Western blotting experiments further strengthened that both compounds altered the expression of mRNA and receptor protein of ER-α, thereby forestalling downstream transactivation and signalling pathway in T47D cells line. Structural investigation from induced fit simulation study suggest that indole moiety of the compounds 6e and 6f helps in the anchoring of the xanthendione moiety in the hydrophobic region of the cavity thus enabling the compound to bind in antagonistic conformation similar to bazedoxifene by extensive hydrogen bonding and Van der Waals forces. All these finding collectively imply that compound 6e and 6f represents a novel potent ER-α antagonist and in the development of SERMs for the management of BC.

Graphical abstract

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Identification of potent lysophosphatidic acid receptor 5 (LPA5) antagonists as potential analgesic agents

Publication date: 1 January 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 1
Author(s): Yuichiro Kawamoto, Ryushi Seo, Nobuhito Murai, Hideki Hiyama, Hiromasa Oka
Lysophosphatidic acid (LPA) plays an important role in a variety of cellular functions. In particular, LPA5 receptor is highly expressed in spinal cord and dorsal root ganglion, which are associated with pain. This fact prompted us to hypothesize that LPA5 antagonists show analgesic effects. To search for potent LPA5 antagonists with blood brain barrier (BBB) permeability, we conducted high throughput screening (HTS). In HTS campaign, we found a 2H-isoquinoline-1-one scaffold showing antagonistic activity against LPA5 and synthesized a series of 2H-isoquinoline-1-one derivatives and evaluated their LPA5 activities. Among these compounds, compound 7e showed potent LPA5 activity with an IC50 value of 0.12 μM, and acceptable BBB permeability. Furthermore, it showed effective analgesic effect in a chronic constriction injury rat model. Therefore, 7e may have a potential as novel pain therapeutic approach.

Graphical abstract

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Antitussive and expectorant activities of licorice and its major compounds

Publication date: 1 January 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 1
Author(s): Yi Kuang, Bin Li, Jingran Fan, Xue Qiao, Min Ye
Licorice has been used as an antitussive and expectorant herbal medicine for a long history. This work evaluated the activities of 14 major compounds and crude extracts of licorice, using the classical ammonia-induced cough model and phenol red secretion model in mice. Liquiritin apioside (1), liquiritin (2), and liquiritigenin (3) at 50 mg/kg (i.g.) could significantly decrease cough frequency by 30–78% (p < .01). The antitussive effects could be partially antagonized by the pretreatment of methysergide or glibenclamide, but not naloxone. Moreover, compounds 1–3 showed potent expectorant activities after 3 days treatment (p < .05). The water and ethanol extracts of licorice, which contain abundant 1 and 2, could decrease cough frequency at 200 mg/kg by 25–59% (p < .05), and enhance the phenol red secretion (p < .05), while the ethyl acetate extract showed little effect. These results indicate liquiritin apioside and liquiritin are the major antitussive and expectorant compounds of licorice. Their antitussive effects depend on both peripheral and central mechanisms.

Graphical abstract

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Novel sulfenamides and sulfonamides based on pyridazinone and pyridazine scaffolds as CB1 receptor ligand antagonists

Publication date: 1 January 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 1
Author(s): Gabriele Murineddu, Francesco Deligia, Giulio Ragusa, Laura García-Toscano, María Gómez-Cañas, Battistina Asproni, Valentina Satta, Elena Cichero, Ruth Pazos, Paola Fossa, Giovanni Loriga, Javier Fernández-Ruiz, Gerard A. Pinna
A series of sulfenamide and sulfonamide derivatives was synthesized and evaluated for the affinity at CB1 and CB2 receptors. The N-bornyl-S-(5,6-di-p-tolylpyridazin-3-yl)-sulfenamide, compound 11, displayed good affinity and high selectivity for CB1 receptors (Ki values of 44.6 nM for CB1 receptors and >40 μM for CB2 receptors, respectively). The N-isopinocampheyl-sulfenamide 12 and its sulfonamide analogue 22 showed similar selectivity for CB1 receptors with Ki values of 75.5 and 73.2 nM, respectively. These novel compounds behave as antagonists/inverse agonists at CB1 receptor in the [³⁵S]-GTPγS binding assays, and none showed adequate predictive blood–brain barrier permeation, exhibiting low estimated LD50. However, testing compound 12 in a supraspinal analgesic test (hot-plate) revealed that it was as effective as the classic CB1 receptor antagonist rimonabant, in reversing the analgesic effect of a cannabinoid agonist.

Graphical abstract

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Graphical abstract TOC

Publication date: 1 January 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 1





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Synthesis and evaluation of a potent, well-balanced EP2/EP3 dual agonist

Publication date: 1 January 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 1
Author(s): Akihiro Kinoshita, Masato Higashino, Koji Yoshida, Yoshiyuki Aratani, Akito Kakuuchi, Keisuke Hanada, Hiroyuki Takeda, Atsushi Naganawa, Hidekazu Matsuya, Kazuyuki Ohmoto
A highly potent and well-balanced dual agonist for the EP2 and EP3 receptors is described. Optimization of the lead compound was accomplished in consideration of the relative agonist activity against each EP subtype receptor and the pharmacokinetic profile. As the result, 2-[(2-{(1R,2R)-2-[(1E,4S)-5-cyclopentyl-4-hydroxy-4-methyl-1-penten-1-yl]-5-oxocyclopentyl}eth-yl)thio]-1,3-thiazole-4-carboxylic acid (10) showed excellent potency (human EC50 EP2 = 1.1 nM, EP3 = 1.0 nM) with acceptable selectivity over the EP1 and EP4 subtypes (>2000-fold). Further fine-tuning of compound 10 led to identification of ONO-8055 as a clinical candidate. ONO-8055 was effective at an extremely low dose (0.01 mg/kg, po, bid) in rats, and dose-dependently improved voiding dysfunction in a monkey model of underactive bladder (UAB). ONO-8055 is expected to be a novel and highly promising drug for UAB.

Graphical abstract

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