Prepartum application of internal teat sealant or intramammary amoxicillin on dairy heifers: Effect on udder health, survival, and performance

Publication date: Available online 8 December 2017
Source:Journal of Dairy Science
Author(s): V.S. Machado, R.C. Bicalho
Intramammary infusion of antimicrobials (IA) and application of an internal teat sealant (ITS) at the end of the lactation is a common strategy to prevent and treat intramammary infections during the dry period. In heifers, precalving IA has been reported to improve udder health and milk quality; however, the effect of ITS in heifers housed in freestall barns is still unknown. The objective of this study was to investigate the effect of prepartum application of ITS or IA on udder health of dairy heifers. A total of 886 heifers were randomly allocated into 1 of 4 treatment groups when they were 245 ± 3 d pregnant. Control heifers (CON) did not receive any treatment. Heifers in the ITS group received the application of ITS containing 2.6 g of bismuth subnitrate. Animals in the IA group received intramammary administration of 62.5 mg of amoxicillin. Heifers in IA+ITS group received intramammary administration of amoxicillin followed by ITS application. The follow-up period was 270 d in milk (DIM). Clinical mastitis was diagnosed and treated by trained farm personnel throughout the study period. Composite milk somatic cell counts (SCC) were determined monthly for the first 9 mo of lactation by Dairy Herd Improvement Association. Subclinical mastitis was defined as a cow having a SCC >200,000 cells/mL for at least 1 test day and not diagnosed with clinical mastitis during the study period. At 7 ± 3 DIM, composite milk samples were collected for bacteriological analysis for a subset of the study animals. The presence of pathogens in milk at 7 ± 3 DIM was more frequently detected in the CON heifers compared with animals enrolled in the treatment groups. Heifers in IA+ITS group had a decreased incidence of clinical mastitis compared with CON heifers (12.9 vs. 21.4%). Additionally, the incidence of subclinical mastitis was decreased for IA+ITS heifers compared with CON counterparts (20.1 vs. 43.8%). During the first 9 mo of lactation, IA and IA+ITS heifers had lower SCC linear scores compared with ITS and CON counterparts. Although IA+ITS treatment successfully improved udder health, it did not result in better milk yield, fertility, and survivability. In conclusion, ITS alone was not effective in improving udder health; however, the combination of ITS and IA decreased the incidence of clinical and subclinical mastitis during the first 9 mo of lactation. Additionally, IA+ITS had a long-term effect on the SCC linear score throughout the study period.



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A resynchronization of ovulation program based on ovarian structures present at nonpregnancy diagnosis reduced time to pregnancy in lactating dairy cows

Publication date: Available online 8 December 2017
Source:Journal of Dairy Science
Author(s): R. Wijma, M.M. Pérez, M. Masello, M.L. Stangaferro, J.O. Giordano
Our objective was to evaluate time to pregnancy after the first service postpartum and pregnancy per artificial insemination (P/AI) in dairy cows managed with 2 resynchronization of ovulation programs. After first service, lactating Holstein cows were blocked by parity (primiparous vs. multiparous) and randomly assigned to the d 32 Resynch (R32; n = 1,010) or short Resynch (SR; n = 1,000) treatments. Nonpregnancy diagnosis (NPD) was conducted 32 ± 3 d after AI by transrectal ultrasonography. Nonpregnant cows in R32 received the Ovsynch protocol: GnRH, PGF2α 7 d later, GnRH 56 h later, and timed AI (TAI) 16 to 18 h later. Cows in SR with a corpus luteum (CL) ≥15 mm and a follicle ≥10 mm at NPD received PGF2α, PGF2α 24 h later, GnRH 32 h later, and TAI 16 to 18 h later. Cows in SR without a CL ≥15 mm or a follicle ≥10 mm at NPD received a modified Ovsynch protocol with 2 PGF2α treatments and progesterone (P4) supplementation (GnRH plus CIDR, PGF2α and CIDR removal 7 d later, PGF2α 24 h later, GnRH 32 h later, and TAI 16 to 18 h later). Blood samples were collected from a subgroup of cows at the GnRH before TAI (R32 = 114; SR = 121) to measure P4 concentration. Binomial outcomes were analyzed with logistic regression and hazard of pregnancy (R32 = 485; SR = 462) with Cox's proportional regression in SAS (SAS Institute, Cary, NC). For P/AI analysis, the TAI service was the experimental unit (R32 = 720; SR = 819). Models included treatment and parity as fixed effects and farm as random effect. The hazard of pregnancy was greater for the SR treatment (hazard ratio = 1.18; 95% confidence interval: 1.01–1.37). Median time to pregnancy was 95 and 79 d for the R32 and SR treatments, respectively. At NPD, 71.3 and 71.2% of cows had a CL for the R32 and SR treatments, respectively. Treatment did not affect overall P/AI 32 ± 3 d after AI (R32 = 31.0% vs. SR = 33.9%) or for cows with a CL at NPD (R32 = 32.7% vs. SR = 32.8%). For cows with no CL at NPD, P/AI was greater for the SR treatment (36.9%) than for the R32 treatment (28.6%). Pregnancy loss from 32 to 63 d after AI was similar for all services combined (R32 = 8.3% vs. SR = 10.4%) and for cows with no CL at NPD (R32 = 13.2% vs. SR = 7.2%) but tended to be affected by treatment for cows with a CL at NPD (R32 = 6.8% vs. SR = 11.9%). Treatment affected the proportion of cows with P4 ≤0.5 ng/mL at the GnRH before TAI for all cows (R32 = 68.4% vs. SR = 81.8%), tended to have an effect among cows with a CL (R32 = 70.0% vs. SR = 81.8%), and had no effect for cows with no CL (R32 = 64.7% vs. SR = 81.8%). We concluded that the SR program reduced time to pregnancy because of a reduction of the interbreeding interval for cows with a CL at NPD and greater P/AI in cows with no CL at NPD.



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A clinical and histopathological comparison of the effectiveness of salicylic acid to a compound of inorganic acids for the treatment of digital dermatitis in cattle

Publication date: Available online 8 December 2017
Source:Journal of Dairy Science
Author(s): N. Capion, E.K. Larsson, O.L. Nielsen
Bovine digital dermatitis (DD) is a painful infectious disease, causing lameness, reduced animal welfare, and production losses in dairy herds. The main factors contributing to DD are an infection with Treponema spp. and poor hygiene. Topical treatment has primarily consisted of antibiotics; however, the demand for effective nonantibiotic alternatives is increasing. The objective was to evaluate the performance of 3 nonantibiotic topical treatments (salicylic acid and a compound of inorganic acids in a 20% solution and in a dry form) on DD in a commercial dairy herd. Within the 30-d test period, 42 DD lesions on 33 Holstein cows were assigned to receive 1 of the 3 treatments. Lesions were biopsied before and after treatment and were clinically evaluated 5 times. Improved lesions were clinically defined as either healed (regeneration of the skin) or healing (dry lesions covered by a scab). Unhealed lesions were defined as either active [with a raw, moist, strawberry-like (granulating) surface] or mature (with a raised papillomatous appearance). The effectiveness of treatment was evaluated histopathologically using the following scores: 0 (no spirochetes present), 1 (small number of spirochetes present in the epidermis), 2 (moderate number of spirochetes present and reaching an intermediary level in the epidermis), and 3 (large number of spirochetes present and reaching the deepest part of the epidermis or the superficial dermis). The improvement rate was 10/14 (71%) for salicylic acid, 11/15 (73%) for the inorganic acid solution, and 8/13 (62%) for the inorganic acid powder. The analysis showed no difference among treatments. The association between clinical score and histopathological score was determined by an odds ratio. The odds ratio of a healed lesion having spirochetes in the epidermis was 0.58 and that of an active DD lesion having spirochetes in the epidermis was 26.5.



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Technical note: Validation of the BHBCheck blood β-hydroxybutyrate meter as a diagnostic tool for hyperketonemia in dairy cows

Publication date: Available online 8 December 2017
Source:Journal of Dairy Science
Author(s): K.J. Sailer, R.S. Pralle, R.C. Oliveira, S.J. Erb, G.R. Oetzel, H.M. White
Accurate cow-side blood β-hydroxybutyrate (BHB) detection meters are valuable tools for rapid diagnosis of hyperketonemia. The main objective of this study was to compare the blood BHB measured in whole blood by the BHBCheck meter (PortaCheck, Moorestown, NJ) to a previously validated meter, Precision Xtra meter (Abbott Laboratories, Abbott Park, IL) and a colorimetric laboratory assay. Samples (n = 426) were collected from postpartum primiparous and multiparous Holstein cows (n = 79 cows) enrolled in 1 of 2 experiments (Exp) with different sampling schedules (Exp 1: n = 39 cows, 58 samples; Exp 2: n = 40 cows, 368 samples). In both Exp, whole-blood samples were collected from the coccygeal vessels after morning milking, before morning feeding. Blood samples were used immediately for BHB quantification via the BHBCheck meter and the Precision Xtra meter. Blood was also collected into evacuated tubes containing no additive (Exp 1) or potassium oxalate/sodium fluoride (Exp 2), which were centrifuged for serum or plasma separation and stored at −20°C for subsequent analysis. Laboratory quantification of BHB concentration was done by the BHB LiquiColor Assay (EKF Diagnostics-Stanbio, Boerne, TX; certified for serum and plasma). Data were analyzed by UNIVARIATE, CORR, FREQ, REG, and LOGISTIC procedures of SAS 9.4 (SAS Institute Inc., Cary, NC). Within this sample set, average parity was 3.3 lactations and DIM was 14 d. The proportion of samples classified as hyperketonemia (BHB ≥1.2 mmol/L) was 25, 28, and 31% as determined by the colorimetric assay, BHBCheck meter, and Precision Xtra meter, respectively. The correlation for BHBCheck meter BHB concentration compared with the colorimetric assay concentrations was r = 0.96, with a sensitivity of 91% and specificity of 93%. Correlation, sensitivity, and specificity of the Precision Xtra meter concentrations were 0.97, 98%, and 92%, respectively. Bland-Altman plots demonstrated minimal bias for both meters. Area under the receiver operator characteristic curve suggests adequate diagnostic accuracy of both meters. Overall, accuracy, sensitivity, and specificity of the BHBCheck meter was similar to the Precision Xtra meter and laboratory assay, indicating the BHBCheck meter is appropriate for use as a cow-side diagnostic test for hyperketonemia in dairy cows.



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Dairy system, parity, and lactation stage affect enteric methane production, yield, and intensity per kilogram of milk and cheese predicted from gas chromatography fatty acids

Publication date: Available online 8 December 2017
Source:Journal of Dairy Science
Author(s): Giovanni Bittante, Alessio Cecchinato, Stefano Schiavon
Ruminants (and milk production) contribute to global climate change through enteric methane emissions (EME), and any attempt to reduce them is complicated by the fact that they are difficult and expensive to measure directly. In the case of dairy cows, a promising indirect method of estimating EME is to use the milk fatty acid profile as a proxy, as a relationship exists between microbial activity in the rumen and the molecules available for milk synthesis in the mammary gland. In the present study, we analyzed the detailed fatty acid profiles (through gas chromatography) of a large number of milk samples from 1,158 Brown Swiss cows reared on 85 farms with the aim of testing in the field 2 equations for estimating EME taken from a published meta-analysis. The average estimated methane yield (CH4 emission per kg of dry matter intake, 21.34 ± 1.60 g/kg) and methane intensity (per kg of corrected milk, 14.17 ± 1.78 g/kg), and the derived methane production (CH4 emissions per day per cow, 357 ± 109 g/d) were similar to those previously published. Using data from model cheese makings from individual cows, we also calculated estimated methane intensity per kilogram of fresh cheese (99.7 ± 16.4 g/kg) and cheese solids (207.5 ± 30.9 g/kg). Dairy system affected all EME estimates. Traditional dairy farms, and modern farms including corn silage in the TMR exhibited greater estimated methane intensities. We found very wide variability in estimated EME traits among different farms within dairy system (0.33 to 0.61 of total variance), suggesting the need to modify the farms' feeding regimens and management practices to mitigate emissions. Among the individual factors, parity order affected all estimated EME traits excepted methane yield, with an increase from first lactation to the following ones. Lactation stage exhibited more favorable estimated EME traits during early lactation, concomitant with the availability of nutrients from body tissue mobilization for mammary synthesis of milk. Our results showed a coherence between the EME traits estimated from the analysis of milk fatty acids and the expectations according to current knowledge. Further research is needed to validate the results obtained in this study in other breeds and populations, to assess the magnitude of the genetic variation and the potential of these phenotypes to be exploited in breeding programs with the aim to mitigate emissions.



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A genome-wide association study for left-sided displacement of the abomasum using a high-density single nucleotide polymorphism array

Publication date: Available online 8 December 2017
Source:Journal of Dairy Science
Author(s): S. Lehner, I. Zerbin, K. Doll, J. Rehage, O. Distl
Left-sided displacement of the abomasum (LDA) is a frequent disease in dairy cattle causing significant financial losses for dairy farmers. Heritability (h²) of this complex disease was estimated at up to 0.5 in German Holstein (GH) cattle. Using the Bovine High Density BeadChip (Illumina Inc., San Diego, CA) comprising 588,753 single nucleotide polymorphisms (SNP) after quality control for 126 LDA cases and 280 population-based controls, we used a mixed linear model analysis in a genome-wide association study (GWAS). We identified 6 genomic regions for LDA on bovine chromosomes 2, 8, 13, 20, 24, and X that were significantly associated with LDA. Each of these regions was covered by 4 to 12 LDA-associated SNP. Single SNP within these regions explained up to 7.3% of the phenotypic variance. An independent sample of 1,554 GH cows, including 539 controls and 1,015 cases, were genotyped for 8 SNP highly associated with LDA on Bos taurus autosomes (BTA) 2, 8, 13, and 24, as well as 6 SNP located in previously identified LDA regions on BTA1, 5, 11, and 27 using competitive allele-specific PCR genotyping technology (KASP). The analysis using the KASP genotypes confirmed LDA-associated loci on BTA2, 8, 13, and 27. These genomic regions may contribute to the susceptibility to LDA in Holstein cows and may harbor functional variants for LDA.



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Genetic parameters for αS1-casein and αS2-casein phosphorylation isoforms in Dutch Holstein Friesian

Publication date: Available online 8 December 2017
Source:Journal of Dairy Science
Author(s): Z.H. Fang, H. Bovenhuis, H.J.F. van Valenberg, P. Martin, T. Huppertz, M.H.P.W. Visker
Relative concentrations of αS1-casein and αS2-casein (αS1-CN and αS2-CN) phosphorylation isoforms vary considerably among milk of individual cows. We estimated heritabilities for αS2-CN phosphorylation isoforms, determined by capillary zone electrophoresis from 1,857 morning milk samples, and genetic correlations among αS2-CN phosphorylation isoforms in Dutch Holstein Friesian. To investigate if phosphorylation of αS1-CN and αS2-CN are due to the same genetic mechanism, we also estimated genetic correlations between αS1-CN and αS2-CN phosphorylation isoforms as well as the genetic correlations between the phosphorylation degrees (PD) of αS1-CN and αS2-CN defined as the proportion of isoforms with higher degrees of phosphorylation in total αS1-CN and αS2-CN, respectively. The intra-herd heritabilities for the relative concentrations of αS2-CN phosphorylation isoforms were high and ranged from 0.54 for αS2-CN-10P to 0.89 for αS2-CN-12P. Furthermore, the high intra-herd heritabilities of αS1-CN PD and αS2-CN PD imply a strong genetic control of the phosphorylation process, which is independent of casein production. The genetic correlations between αS2-CN phosphorylation isoforms are positive and moderate to high (0.33–0.90). Furthermore, the strong positive genetic correlation (0.94) between αS1-CN PD and αS2-CN PD suggests that the phosphorylation processes of αS1-CN and αS2-CN are related. This study shows the possibility of breeding for specific αS1-CN and αS2-CN phosphorylation isoforms, and relations between the phosphorylation degrees of αS1-CN and αS2-CN and technological properties of milk need to be further investigated to identify potential benefits for the dairy industry.



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The effect of different treatments for early-lactation hyperketonemia on liver triglycerides, glycogen, and expression of key metabolic enzymes in dairy cattle

Publication date: Available online 8 December 2017
Source:Journal of Dairy Science
Author(s): S. Mann, F.A. Leal Yepes, J.J. Wakshlag, E. Behling-Kelly, J.A.A. McArt
Despite the widespread use of treatments for postpartum hyperketonemia in dairy cows, there is currently a lack of evidence comparing their effects on both the resolution of hyperketonemia and the potential effects on the liver of affected animals. The objective of our work was to investigate the effect of commonly used hyperketonemia treatments on hepatic triglyceride and glycogen content as well as on the mRNA and protein abundance of key enzymes involved in gluconeogenesis, ketogenesis, and lipid metabolism. Multiparous Holstein cows between 3 and 9 d in milk were screened 3 times per week and enrolled in the study when whole-blood β-hydroxybutyrate concentrations measured ≥1.2 mmol/L. Cows were randomly allocated to 1 of 4 groups: (1) 500 mL of a 50% d-glucose solution intravenously once a day for 3 d (n = 8), (2) 300 mL of propylene glycol orally once a day for 3 d (n = 8), (3) 500 mL of a 50% d-glucose solution intravenously and 300 mL of propylene glycol orally once a day for 3 d (n = 8), or (4) an untreated control group (n = 8). Liver biopsies were taken on the day of enrollment as well as on the day following completion of treatments. Liver triglyceride and glycogen content were determined by colorimetric and fluorometric methods, respectively. Gene and protein expression of pyruvate carboxylase, phosphoenolpyruvate carboxykinase 1, glucose-6-phosphatase, 3-hydroxy-3-methylglutaryl-CoA synthase 2, acetyl-CoA carboxylase, and carnitine palmitoyltransferase 1A were compared between groups and time points using quantitative reverse transcriptase PCR and Western blotting techniques, respectively. In addition, the ratio of light chain 3B II:I was determined by Western blotting. Plasma samples from both time points for each enrolled cow were submitted for chemistry analysis. Data were analyzed using a repeated measures ANOVA taking into account the paired nature of the data, and differences between all groups and time points were controlled for multiple comparisons using the Tukey procedure. No difference was found in triglyceride or glycogen concentration between treatment groups. The gene expression of pyruvate carboxylase decreased in the group receiving both treatments, whereas protein expression of this enzyme increased in all groups over time. The autophagy marker light chain 3B II:I decreased in the group receiving both glucose and propylene glycol. No other changes in gene or protein expression of key hepatic enzymes were associated with treatments. We conclude that intravenous glucose and oral propylene glycol, commonly used treatments for ketosis in postpartum dairy cows, administered alone or in combination for a duration of 3 d did not have important beneficial or detrimental effects on selected indicators of liver composition and function in cows with hyperketonemia.



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The effects of L-type amino acid transporter 1 on milk protein synthesis in mammary glands of dairy cows

Publication date: Available online 8 December 2017
Source:Journal of Dairy Science
Author(s): Ye Lin, Xiaoyu Duan, He Lv, Yang Yang, Ying Liu, Xuejun Gao, Xiaoming Hou
The mammary gland requires the uptake of AA for milk protein synthesis during lactation. The L-type amino acid transporter 1 (LAT1, encoded by SLC7A5), found in many different types of mammalian cells, is indispensable as a transporter of essential AA to maintain cell growth and protein synthesis. However, the function of LAT1 in regulating milk protein synthesis in the mammary gland of the dairy cow remains largely unknown. For the current study, we characterized the relationship between LAT1 expression and milk protein synthesis in lactating dairy cows and investigated whether the mammalian target of rapamycin complex1 (mTORC1) signaling controls the expression of LAT1 in their mammary glands. We found that LAT1 and the heavy chain of its chaperone, 4F2, were expressed in mammary tissues of lactating cows, with the expression levels of LAT1 and the 4F2 heavy chain being significantly greater in lactating mammary tissues with high-milk protein content (milk yield, 33.8 ± 2.1 kg/d; milk protein concentration >3%, wt/vol,; n = 3) than in tissues from cows with low-milk protein content (milk yield, 33.7 ± 0.5 kg/d; milk protein concentration <3%, wt/vol; n = 3). Immunofluorescence staining of sectioned mammary tissues from cows with high and low milk protein content showed that LAT1 was located on the whole plasma membrane of alveolar epithelial cells, suggesting that LAT1 provides essential AA to the mammary gland. In cultured mammary epithelial cells from the dairy cows with high-milk protein content, knockdown of LAT1 expression decreased cell viability and β-casein expression; in contrast, overexpression of LAT1 had the opposite effect. Inhibition of mTORC1 by rapamycin attenuated the phosphorylation of molecules related to mTORC1 signaling and caused a marked decrease in LAT1 expression in the cultured cells; expression of β-casein also decreased significantly. These results suggest that LAT1 is involved in milk protein synthesis in the mammary glands of lactating dairy cows and that the mTORC1 signaling pathway might be a control point for regulation of LAT1 expression, which could ultimately be used to alter milk protein synthesis.



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Estrous detection intensity and accuracy and optimal timing of insemination with automated activity monitors for dairy cows

Publication date: Available online 8 December 2017
Source:Journal of Dairy Science
Author(s): C.N.S. LeRoy, J.S. Walton, S.J. LeBlanc
The objectives of this observational study were to assess the ability of automated activity monitoring (AAM) to detect estrus for first insemination, the accuracy of detection, and the optimum interval from the estrus alert from the AAM system to insemination. Four commercial farms using 1 of 2 commercial AAM systems were studied over 1 yr. Cows were inseminated between 55 and 80 d in milk (DIM) based on AAM only, then by a combination of AAM and timed artificial insemination (AI). Blood progesterone was measured in 1,014 cows at wk 5, 7, and 9 postpartum; purulent vaginal discharge (PVD) was assessed at wk 5; and lameness and BCS at wk 7. Overall, AAM detected 83% of cows in estrus by 80 DIM. Cows that had 3 serum progesterone <1 ng/mL, had PVD, or were both lame and had BCS ≤2.5 has lesser odds of being detected in estrus by 80 DIM (62, 68, and 53%, respectively). Blood samples were collected on the day of 445 AI based on AAM and 323 timed AI. The proportion of cows not in estrus (progesterone >1 ng/mL) on the day of AI was similar between AAM (4 ± 1.8%) and timed AI (3 ± 1.2%). Managers elected, based on subjective criteria, not to inseminate 17% of cows for which an AAM estrus alert was issued, of which 43% were not in estrus. Activity data were extracted from AAM software for 1,399 AI. Onset of estrus was calculated using the same or similar data processing criteria as the AAM system. Producers recorded the time of AI. The interval from onset of estrus to AI was categorized as 0 to 8, 8 to 16, or 16 to 24 h. We found no effect of AAM system on the probability of pregnancy per AI, but noted an interaction of interval with parity. For multiparous cows, the probability of pregnancy per AI was 31%, which did not differ with the interval to AI. For primiparous cows, the odds of pregnancy were greater if AI occurred 0 to 8 h (49%) than 8 to 16 (36%) or 16 to 24 h (31%) after the estrus alert from the AAM. Automated activity monitoring can detect estrus for first AI in just over the length of 1 estrous cycle for over 80% of cows, but the remainder would likely require intervention for timely insemination. For multiparous cows, performing AI based on AAM once per day would not affect pregnancy per AI, but for primiparous cows AI within 8 h of the onset of estrus may be advantageous.



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Editorial Board

Publication date: November–December 2017
Source:Médecine & Droit, Volume 2017, Issues 146–147





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Contents

Publication date: November–December 2017
Source:Médecine & Droit, Volume 2017, Issues 146–147





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Risques de la régulation médicale en médecine d’urgence. Analyse des dossiers de plaintes de la permanence des soins ambulatoire au SAMU du Var

Publication date: Available online 20 November 2017
Source:Médecine & Droit
Author(s): Pierre-Luc Hamelin, Jean-Jacques Arzalier
IntroductionLes demandes de soins non programmés sans caractère urgent et relevant de la permanence des soins ambulatoire (PDSA) sont régulées par un médecin régulateur chargé d'identifier la demande et d'orienter le patient. Nous nous sommes attachés à rechercher les facteurs de risques de contentieux en régulation médicale de la PDSA par l'analyse des plaintes et des lettres de réclamation.Matériels et méthodeNous avons inclus les affaires relevant de la PDSA au SAMU du Var qui ont été suivies d'une plainte ou d'une réclamation entre le 1^er janvier 2004 et le 31 décembre 2010. Nous avons analysé les dossiers de régulation médicale, les enregistrements téléphoniques, les lettres de réclamation, les rapports d'expertise et les jugements.RésultatsSur les 342 400 affaires traitées par les régulateurs de la PDSA, dix-huit ont fait l'objet d'une demande d'explication et dix d'une plainte ou d'une demande indemnitaire. En proportion, les réclamations et les plaintes touchent principalement les affaires gérées en nuit profonde. L'activité en régulation par elle-même ne constitue donc pas un facteur important de contentieux. Par contre, les trois affaires marquées par un désaccord de l'appelant vis-à-vis de la décision médicale se sont soldées par le décès du patient. La non-adhésion du requérant à la décision doit amener le régulateur à réévaluer la gravité de la situation. Les propos tenus par le médecin doivent rester empathiques à défaut de quoi il risque de se les voir reprocher par l'expert ou le juge.ConclusionLa prise en compte du facteur humain et de la fatigue en régulation est essentielle. Le signalement interne des dysfonctionnements liés à la régulation permettrait l'anticipation et la prévention des contentieux et servirait de base aux revues de morbi-mortalité et aux actions de formation continue. L'implication personnelle du responsable de service lors des phases d'instruction ou de jugement est utile afin de faire comprendre les difficultés spécifiques de la régulation.IntroductionThe non-urgent care requests depending on the continuity of care system have to be regulated by a regulating doctor of a medical emergency service call center. We aim to determine the risk factor of litigations about the regulation of the continuity of care system. So, the cases with friendly complaint and those with litigation have been compared.MethodsThe all calls to the medical emergency service of the Var depending on the continuity care system between the January 1st, 2014 and December 31st, 2010 and with friendly complaint or litigation have been included. All the medical regulation files, call records, complaint letters, expert reports and summons have analyzed.ResultsOn the 342,400 calls within the field of the continuity of care system, eighteen friendly complaints et ten litigations with or without claims for compensation have been included. Proportionally, complaints and litigations mainly affect the cases treated during dark night hours (00:00 to 08:00). The workload in the call center does not represent a risk factor of litigation. However, in the three cases in which the caller did not agree with the regulating doctor's decision the patient died. Moreover, pressured by the disagreement with his decision, the regulating doctor has to reevaluate the severity of the situation and has to remain empathetic in these words. In fact, in case of conflict during the call, the doctor may be punished because of his words.ConclusionThe prevention of fatigue is important. The malfunctions of the medical regulation center must be declared by staff to prevent and anticipate litigations. Moreover, that should help to improve procedures and individual practices. Finally, we enhanced the involvement of the managers during legal procedures in order to explain to the judge the specific difficulties of medical regulation.



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Paclitaxel, Cisplatin,5-FU vs. Radiotherapy Plus Paclitaxel, Cisplatin as Preoperative Therapy for Locally Advanced ESC

Conditions:   Esophageal Cancer Stage IIB;   Esophageal Cancer Stage III
Interventions:   Combination Product: Paclitaxel, Cisplatin Plus 5-FU (TCF);   Radiation: radiochemotherapy
Sponsors:   Tianjin Medical University Cancer Institute and Hospital;   Shanghai Chest Hospital;   Henan Cancer Hospital;   The First Affiliated Hospital with Nanjing Medical University;   First Affiliated Hospital of Chongqing Medical University;   The First Affiliated Hospital of Anhui Medical University
Not yet recruiting

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Rapid Assessment of Esophageal Adenocarcinoma Risk Test

Conditions:   Barrett Esophagus;   Esophageal Adenocarcinoma
Intervention:   Device: Cytosponge
Sponsor:   Columbia University
Not yet recruiting

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Sequential or Concurrent Chemoradiotherapy in Patients With Locoregionally Advanced NPC

Condition:   Nasopharyngeal Carcinoma
Interventions:   Drug: gemcitabine and cisplatin (Induction and adjuvant chemotherapy);   Radiation: IMRT;   Drug: gemcitabine and cisplatin (Induction chemotherapy);   Radiation: IMRT and concurrent cisplatin
Sponsors:   Chaosu Hu;   Zhejiang Cancer Hospital;   Jiangxi Provincial Cancer Hospital;   First Affiliated Hospital of Wenzhou Medical Univeristy;   Affiliated Hospital of Jiangnan University;   Fujian Cancer Hospital
Not yet recruiting

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Testing the role of fiscal policy in the environmental degradation: the case of Turkey

Abstract

This study introduces a new research topic that investigates the relationship between fiscal development and carbon emissions in Turkey through testing Environmental Kuznets Curve (EKC) hypothesis. Annual data covering the period, 1960–2013, has been used and in addition to gross domestic product and energy consumption, fiscal policy variables have been regressed on the level of carbon emissions in Turkey. Results reveal that fiscal policies and carbon emissions are in long-term equilibrium relationship in Turkey; carbon dioxide emission level converges towards long-term paths as contributed by fiscal policy. The effects of fiscal aggregates on the level of carbon dioxide emissions are negatively significant revealing that growth in fiscal aggregates leads to declines on the levels of carbon emissions. This proves that as far as environmental effects are concerned, fiscal policies regarding energy sector is successful in Turkey. Thus, the major finding of this study confirmed the validity of the fiscal policy-induced EKC hypothesis in the case of Turkey.

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Plasticity in Olfactory Epithelium: Is It a Sniffer or Shape Shifter?

Publication date: 7 December 2017
Source:Cell Stem Cell, Volume 21, Issue 6
Author(s): Arvind Konkimalla, Purushothama Rao Tata
Precise lineage trajectories and the cellular sources that contribute to regeneration after injury are largely unknown in many tissues. In this issue of Cell Stem Cell, Gadye et al. (2017) and Lin et al. (2017) show that olfactory epithelial cells transit through unique and unfamiliar paths of differentiation and undergo lineage reversion, respectively, during regeneration.

Teaser

Precise lineage trajectories and the cellular sources that contribute to regeneration after injury are largely unknown in many tissues. In this issue of Cell Stem Cell, Gadye et al. (2017) and Lin et al. (2017) show that olfactory epithelial cells transit through unique and unfamiliar paths of differentiation and undergo lineage reversion, respectively, during regeneration.


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Saving Stem Cells after Stress

Publication date: 7 December 2017
Source:Cell Stem Cell, Volume 21, Issue 6
Author(s): Katherine Y. King
Inflammatory signals can activate hematopoietic stem cells (HSCs), but how HSCs regain quiescence after stress is unclear. In this issue of Cell Stem Cell, Chen et al. (2017) delineate an elegant histamine-dependent feedback mechanism through which myeloid bone marrow cells restore quiescence of myeloid-biased HSCs, with implications for blood disorders, aging, and immunity.

Teaser

Inflammatory signals can activate hematopoietic stem cells (HSCs), but how HSCs regain quiescence after stress is unclear. In this issue of Cell Stem Cell, Chen et al. (2017) delineate an elegant histamine-dependent feedback mechanism through which myeloid bone marrow cells restore quiescence of myeloid-biased HSCs, with implications for blood disorders, aging, and immunity.


http://ift.tt/2BUblKh

iPSC Reprogramming Is Not Just an Open and Shut Case

Publication date: 7 December 2017
Source:Cell Stem Cell, Volume 21, Issue 6
Author(s): Peter C. Scacheri, Paul J. Tesar
What exactly happens to chromatin as cells undergo an identity change? In this issue of Cell Stem Cell, Li et al. (2017) and Knaupp et al. (2017) offer new insights by mapping in exquisite detail chromatin accessibility dynamics as mouse embryonic fibroblasts are reprogrammed into induced pluripotent stem cells.

Teaser

What exactly happens to chromatin as cells undergo an identity change? In this issue of Cell Stem Cell, Li et al. (2017) and Knaupp et al. (2017) offer new insights by mapping in exquisite detail chromatin accessibility dynamics as mouse embryonic fibroblasts are reprogrammed into induced pluripotent stem cells.


http://ift.tt/2kaI8T4

Intermittent Reprogramming: A Breath of Fresh Air for Lung Regeneration

Publication date: 7 December 2017
Source:Cell Stem Cell, Volume 21, Issue 6
Author(s): Amy L. Firth
Recently in Stem Cell Reports, Guo et al. (2017) adopted an intermittent reprogramming strategy to generate "induced Progenitor-Like (iPL)" cells, which can maintain lineage commitment while undergoing controlled expansion. The iPLCs were successfully engrafted into a damaged airway, highlighting this significant advancement for regenerative medicine strategies in the lung.

Teaser

Recently in Stem Cell Reports, Guo et al. (2017) adopted an intermittent reprogramming strategy to generate "induced Progenitor-Like (iPL)" cells, which can maintain lineage commitment while undergoing controlled expansion. The iPLCs were successfully engrafted into a damaged airway, highlighting this significant advancement for regenerative medicine strategies in the lung.


http://ift.tt/2BXBZBJ

Locked and Loaded: Inflammation Training Prepares Skin Epithelial Stem Cells for Trauma

Publication date: 7 December 2017
Source:Cell Stem Cell, Volume 21, Issue 6
Author(s): Valentina Proserpio, Salvatore Oliviero, Giacomo Donati
Memory of a trauma and how to cope with it is useful for acting rapidly in the event of a second traumatic incident. Recently, Naik et al. (2017) reported in Nature that skin epithelial stem cells have this ability by maintaining long-term chromatin features acquired during the first assault.

Teaser

Memory of a trauma and how to cope with it is useful for acting rapidly in the event of a second traumatic incident. Recently, Naik et al. (2017) reported in Nature that skin epithelial stem cells have this ability by maintaining long-term chromatin features acquired during the first assault.


http://ift.tt/2k9Bdd2

Organizing Organoids: Stem Cells Branch Out

Publication date: 7 December 2017
Source:Cell Stem Cell, Volume 21, Issue 6
Author(s): Jamie A. Davies
In this issue of Cell Stem Cell, Taguchi and Nishinakamura (2017) describe a carefully optimized method for making a branch-competent ureteric bud, a tissue fundamental to kidney development, from mouse embryonic stem cells and human induced pluripotent stem cells. The work illuminates embryology and has important implications for making more realistic kidney organoids.

Teaser

In this issue of Cell Stem Cell, Taguchi and Nishinakamura (2017) describe a carefully optimized method for making a branch-competent ureteric bud, a tissue fundamental to kidney development, from mouse embryonic stem cells and human induced pluripotent stem cells. The work illuminates embryology and has important implications for making more realistic kidney organoids.


http://ift.tt/2BZkOQA

Dr. Maria Millan: Transplant Surgeon Leads CIRM Operations

Publication date: 7 December 2017
Source:Cell Stem Cell, Volume 21, Issue 6
Author(s): Kathleen Wong




http://ift.tt/2k9Tbfj

mTORC1 Activation during Repeated Regeneration Impairs Somatic Stem Cell Maintenance

Publication date: 7 December 2017
Source:Cell Stem Cell, Volume 21, Issue 6
Author(s): Samantha Haller, Subir Kapuria, Rebeccah R. Riley, Monique N. O'Leary, Katherine H. Schreiber, Julie K. Andersen, Simon Melov, Jianwen Que, Thomas A. Rando, Jason Rock, Brian K. Kennedy, Joseph T. Rodgers, Heinrich Jasper
The balance between self-renewal and differentiation ensures long-term maintenance of stem cell (SC) pools in regenerating epithelial tissues. This balance is challenged during periods of high regenerative pressure and is often compromised in aged animals. Here, we show that target of rapamycin (TOR) signaling is a key regulator of SC loss during repeated regenerative episodes. In response to regenerative stimuli, SCs in the intestinal epithelium of the fly and in the tracheal epithelium of mice exhibit transient activation of TOR signaling. Although this activation is required for SCs to rapidly proliferate in response to damage, repeated rounds of damage lead to SC loss. Consistently, age-related SC loss in the mouse trachea and in muscle can be prevented by pharmacologic or genetic inhibition, respectively, of mammalian target of rapamycin complex 1 (mTORC1) signaling. These findings highlight an evolutionarily conserved role of TOR signaling in SC function and identify repeated rounds of mTORC1 activation as a driver of age-related SC decline.

Graphical abstract

Teaser

Studying flies and mice, Jasper and colleagues demonstrate that repeated regenerative episodes result in the loss of tissue stem cells (SCs) due to the transient activation of the growth regulator mTORC1 during SC activation. Pharmacological inhibition of mTORC1 can prevent this loss and limit the age-related decline in SC numbers.


http://ift.tt/2BWr23q

Chromatin Accessibility Dynamics during iPSC Reprogramming

Publication date: 7 December 2017
Source:Cell Stem Cell, Volume 21, Issue 6
Author(s): Dongwei Li, Jing Liu, Xuejie Yang, Chunhua Zhou, Jing Guo, Chuman Wu, Yue Qin, Lin Guo, Jiangping He, Shenyong Yu, He Liu, Xiaoshan Wang, Fang Wu, Junqi Kuang, Andrew P. Hutchins, Jiekai Chen, Duanqing Pei
Cell-fate decisions remain poorly understood at the chromatin level. Here, we map chromatin remodeling dynamics during induction of pluripotent stem cells. ATAC-seq profiling of MEFs expressing Oct4-Sox2-Klf4 (OSK) reveals dynamic changes in chromatin states shifting from open to closed (OC) and closed to open (CO), with an initial burst of OC and an ending surge of CO. The OC loci are largely composed of genes associated with a somatic fate, while the CO loci are associated with pluripotency. Factors/conditions known to impede reprogramming prevent OSK-driven OC and skew OC-CO dynamics. While the CO loci are enriched for OSK motifs, the OC loci are not, suggesting alternative mechanisms for chromatin closing. Sap30, a Sin3A corepressor complex component, is required for the OC shift and facilitates reduced H3K27ac deposition at OC loci. These results reveal a chromatin accessibility logic during reprogramming that may apply to other cell-fate decisions.

Graphical abstract

Teaser

Li et al. show that Yamanaka factors remodel the nuclear architecture of MEFs following a binary logic that may guide further improvement in reprograming technology and be applicable for other cell-fate decisions.


http://ift.tt/2BZEdRk

Transient and Permanent Reconfiguration of Chromatin and Transcription Factor Occupancy Drive Reprogramming

Publication date: 7 December 2017
Source:Cell Stem Cell, Volume 21, Issue 6
Author(s): Anja S. Knaupp, Sam Buckberry, Jahnvi Pflueger, Sue Mei Lim, Ethan Ford, Michael R. Larcombe, Fernando J. Rossello, Alex de Mendoza, Sara Alaei, Jaber Firas, Melissa L. Holmes, Shalima S. Nair, Susan J. Clark, Christian M. Nefzger, Ryan Lister, Jose M. Polo
Somatic cell reprogramming into induced pluripotent stem cells (iPSCs) induces changes in genome architecture reflective of the embryonic stem cell (ESC) state. However, only a small minority of cells typically transition to pluripotency, which has limited our understanding of the process. Here, we characterize the DNA regulatory landscape during reprogramming by time-course profiling of isolated sub-populations of intermediates poised to become iPSCs. Widespread reconfiguration of chromatin states and transcription factor (TF) occupancy occurs early during reprogramming, and cells that fail to reprogram partially retain their original chromatin states. A second wave of reconfiguration occurs just prior to pluripotency acquisition, where a majority of early changes revert to the somatic cell state and many of the changes that define the pluripotent state become established. Our comprehensive characterization of reprogramming-associated molecular changes broadens our understanding of this process and sheds light on how TFs access and change the chromatin during cell-fate transitions.

Graphical abstract

Teaser

Knaupp and Buckberry et al. show that during reprogramming cells undergo major chromatin remodeling in three phases. Further, they find that Oct4 and Sox2 extensively target sites where the DNA is only accessible during the intermediate stages of reprogramming, which coincides with somatic transcription factor displacement and recruitment to those sites.


http://ift.tt/2BXb752

Stimulation of B-Raf increases c-Jun and c-Fos expression and upregulates AP-1-regulated gene transcription in insulinoma cells

Publication date: Available online 8 December 2017
Source:Molecular and Cellular Endocrinology
Author(s): Daniel S. Langfermann, Oliver G. Rössler, Gerald Thiel
Stimulation of pancreatic β-cells with glucose activates the protein kinases B-Raf and extracellular signal-regulated protein kinase that participate in glucose sensing. Inhibition of both kinases results in impairment of glucose-regulated gene transcription. To analyze the signaling pathway controlled by B-Raf, we expressed a conditionally active form of B-Raf in INS-1 insulinoma cells. Here, we show that stimulation of B-Raf strongly activated the transcription factor AP-1 which is accompanied by increased c-Jun and c-Fos promoter activities, an upregulation of c-Jun and c-Fos biosynthesis, and elevated transcriptional activation potentials of c-Jun and c-Fos. Mutational analysis identified the AP-1 sites within the c-Jun promoter and the serum response element (SRE) within the c-Fos promoter as the essential genetic elements connecting B-Raf stimulation with AP-1 activation. In line with this, the transcriptional activation potential of the SRE-binding protein Elk-1 was increased following B-Raf activation. The signal pathway from B-Raf to AP-1 required the activation of c-Jun. We identified the cyclin D1 gene as a delayed response gene for AP-1 following stimulation of B-Raf in insulinoma cells. Moreover, MAP kinase phosphatase-1 and the Ca²⁺/calmodulin-dependent protein phosphatase calcineurin were identified to function as shut-off-devices for the signaling cascade connecting B-Raf stimulation with the activation of AP-1. The fact that stimulation with glucose, activation of L-type voltage-gated Ca²⁺ channels, and stimulation of B-Raf all trigger an activation of AP-1 indicates that AP-1 is a point of convergence of signaling pathways in β-cell.

Graphical abstract

http://ift.tt/2kDVcV1

Lysophosphatidylcholine and its phosphorothioate analogues potentiate insulin secretion via GPR40 (FFAR1), GPR55 and GPR119 receptors in a different manner

Publication date: Available online 8 December 2017
Source:Molecular and Cellular Endocrinology
Author(s): Anna Drzazga, Hjalti Kristinsson, Maciej Sałaga, Hubert Zatorski, Maria Koziołkiewicz, Edyta Gendaszewska-Darmach, Peter Bergsten
Lysophosphatidylcholine (LPC) is an endogenous ligand for GPR119 receptor, mediating glucose-stimulated insulin secretion (GSIS). We demonstrate that LPC facilitates GSIS in MIN6 pancreatic β-cell line and murine islets of Langerhans by recognizing not only GPR119 but also GPR40 (free fatty acid receptor 1) and GPR55 activated by lysophosphatidylinositol. Natural LPCs are unstable when administered in vivo limiting their therapeutic value and therefore, we present phosphorothioate LPC analogues with increased stability. All the modified LPCs under study (12:0, 14:0, 16:0, 18:0, and 18:1) significantly enhanced GSIS. The 16:0 sulfur analogue was the most potent, evoking 2-fold accentuated GSIS compared to the native counterpart. Interestingly, LPC analogues evoked GPR40-, GPR55-and GPR119-dependent [Ca²⁺]i signaling, but did not stimulate cAMP accumulation as in the case of unmodified molecules. Thus, introduction of a phosphorothioate function not only increases LPC stability but also modulates affinity towards receptor targets and evokes different signaling pathways.

Graphical abstract

http://ift.tt/2kDPiTH

Scholar : These new articles for South African Theatre Journal are available online

The online platform for Taylor & Francis Online content New for South African Theatre Journal and online now on Taylor & Francis Online: Book Review The contemporary political play: rethinking dramaturgical structure Greg Homann Pages: 1-4 | DOI: 10.1080/10137548.2017.1410382 Reader in comedy: an anthology of theory and criticism Anton Krueger Pages: 1-4 | DOI: 10.1080/10137548.2017.1409523 Routledge Performance Archive - http://ift.tt/1txaJgs "Take a Tour" to find out more and recommend the Archive to your librarian to arrange a free trial for your institution. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : These new articles for Environmental Forensics are available online

The online platform for Taylor & Francis Online content New for Environmental Forensics and online now on Taylor & Francis Online: Original Articles Pyrolysis-GC-MS analysis of crude and heavy fuel oil asphaltenes for application in oil fingerprinting Brenden J. Riley, Chris Lennard, Stephen Fuller & Val Spikmans Pages: 1-13 | DOI: 10.1080/15275922.2017.1408163 Polycyclic aromatic hydrocarbons in indoor and outdoor air in Turkey: Estimations of sources and exposure Fatma Esen & Gizem Kayikci Pages: 1-11 | DOI: 10.1080/15275922.2017.1408162 Comparisons of particulate-bound mercury (PBM) compositions in soil and vegetation at a traffic site Guor-Cheng Fang, Chaur-Tsuen Lo, Meng-Hsien Cho, Yuan-Jie Zhuang, Chao-Yang Huang, You-Fu Xiao & Kai-Hsiang Tsai Pages: 1-7 | DOI: 10.1080/15275922.2017.1408156 Odor dispersion modeling with CALPUFF: Case study of a waste and residue treatment incineration and utilization plant in Kocaeli, Turkey Şenay Çetin Doğruparmak, Hakan Pekey & Demet Arslanbaş Pages: 1-8 | DOI: 10.1080/15275922.2017.1408160 Research Paper Seasonal variation of water-soluble inorganic ions in PM10 in a city of northwestern turkey Zehra Bozkurt Pages: 1-13 | DOI: 10.1080/15275922.2017.1408159 Reviews Studies on polycyclic aromatic hydrocarbons in two sediment cores from the huaxi reservoir, china: Assessment of levels, sources, and ecological risk Long Wang, Mengshu Han, Qiuhua Li & Fan Jiang Pages: 1-9 | DOI: 10.1080/15275922.2017.1408158 Hoping to have your article read by anyone, anywhere and at any time? Find out more about publishing open access with Ecosystem Health and Sustainability. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : Philosophical Magazine, Volume 98, Issue 2, January 2018 is now available online on Taylor & Francis Online

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The online platform for Taylor & Francis Online content Philosophical Magazine, Volume 98, Issue 2, January 2018 is now available online on Taylor & Francis Online. This new issue contains the following articles: Part A: Materials Science Helium irradiation-induced defects in deformed 316L stainless steel Yihao Gong, Shuoxue Jin, Eryang Lu, Peng Kuang, Te Zhu, Xingzhong Cao, Liping Guo & Baoyi Wang Pages: 95-106 | DOI: 10.1080/14786435.2017.1396377 Evaluation of structural vacancies for 1/1-Al–Re–Si approximant crystals by positron annihilation spectroscopy K. Yamada, H. Suzuki, H. Kitahata, Y. Matsushita, K. Nozawa, F. Komori, R. S. Yu, Y. Kobayashi, T. Ohdaira, N. Oshima, R. Suzuki, Y. Takagiwa, K. Kimura & I. Kanazawa Pages: 107-117 | DOI: 10.1080/14786435.2017.1392631 Atomic scale study of the anti-vortex domain structure in polycrystalline ferroelectric Xiaobao Tian, Xiaoqiao He & Jian Lu Pages: 118-138 | DOI: 10.1080/14786435.2017.1396374 Suppression of charge ordering and thermal hysteresis of electronic transport and magnetisation in La0.5Ca0.5Mn1−xNixO3 Ankam Bhaskar, M.-S. Huang & Chia-Jyi Liu Pages: 139-154 | DOI: 10.1080/14786435.2017.1396376 Part B: Condensed Matter Physics Electronic and optical properties of black phosphorus doped with Au, Sn and I atoms E. Kutlu, P. Narin, S. B. Lisesivdin & E. Ozbay Pages: 155-164 | DOI: 10.1080/14786435.2017.1396375 Free access to articles in this Editor's Choice collection from the Journal of Control and Decision. Don't miss it! To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Molecular Anatomy of the Developing Human Retina

Publication date: Available online 7 December 2017
Source:Developmental Cell
Author(s): Akina Hoshino, Rinki Ratnapriya, Matthew J. Brooks, Vijender Chaitankar, Matthew S. Wilken, Chi Zhang, Margaret R. Starostik, Linn Gieser, Anna La Torre, Mario Nishio, Olivia Bates, Ashley Walton, Olivia Bermingham-McDonogh, Ian A. Glass, Rachel O.L. Wong, Anand Swaroop, Thomas A. Reh
Clinical and genetic heterogeneity associated with retinal diseases makes stem-cell-based therapies an attractive strategy for personalized medicine. However, we have limited understanding of the timing of key events in the developing human retina, and in particular the factors critical for generating the unique architecture of the fovea and surrounding macula. Here we define three key epochs in the transcriptome dynamics of human retina from fetal day (D) 52 to 136. Coincident histological analyses confirmed the cellular basis of transcriptional changes and highlighted the dramatic acceleration of development in the fovea compared with peripheral retina. Human and mouse retinal transcriptomes show remarkable similarity in developmental stages, although morphogenesis was greatly expanded in humans. Integration of DNA accessibility data allowed us to reconstruct transcriptional networks controlling photoreceptor differentiation. Our studies provide insights into human retinal development and serve as a resource for molecular staging of human stem-cell-derived retinal organoids.

Teaser

Hoshino et al. describe transcriptome dynamics and spatiotemporal analyses of developing human retina, demonstrating distinct periods of neurogenesis in the fovea versus nasal retina. Comparison with mouse retinal transcriptomes and integration with open chromatin datasets reveal evolutionary conservation of developmental regulatory networks and unique characteristics of human retinal differentiation.


http://ift.tt/2j93xjm

E2F/DP Prevents Cell-Cycle Progression in Endocycling Fat Body Cells by Suppressing dATM Expression

Publication date: Available online 7 December 2017
Source:Developmental Cell
Author(s): Ana Guarner, Robert Morris, Michael Korenjak, Myriam Boukhali, Maria Paula Zappia, Capucine Van Rechem, Johnathan R. Whetstine, Sridhar Ramaswamy, Lee Zou, Maxim V. Frolov, Wilhelm Haas, Nicholas J. Dyson
To understand the consequences of the complete elimination of E2F regulation, we profiled the proteome of Drosophila dDP mutants that lack functional E2F/DP complexes. The results uncovered changes in the larval fat body, a differentiated tissue that grows via endocycles. We report an unexpected mechanism of E2F/DP action that promotes quiescence in this tissue. In the fat body, dE2F/dDP limits cell-cycle progression by suppressing DNA damage responses. Loss of dDP upregulates dATM, allowing cells to sense and repair DNA damage and increasing replication of loci that are normally under-replicated in wild-type tissues. Genetic experiments show that ectopic dATM is sufficient to promote DNA synthesis in wild-type fat body cells. Strikingly, reducing dATM levels in dDP-deficient fat bodies restores cell-cycle control, improves tissue morphology, and extends animal development. These results show that, in some cellular contexts, dE2F/dDP-dependent suppression of DNA damage signaling is key for cell-cycle control and needed for normal development.

Graphical abstract

Teaser

Guarner et al. examine the consequences of eliminating E2F function in vivo in Drosophila and uncover a mechanism by which E2F maintains cell quiescence in the fat body, where highly differentiated cells grow via endocycles. E2F is required in the fat body to repress dATM and suppress DNA damage responses to limit cell-cycle progression.


http://ift.tt/2kDhnL0

Postinflammatory Hyperpigmentation: Epidemiology, Clinical Presentation, Pathogenesis and Treatment

Abstract

Postinflammatory hyperpigmentation (PIH) is a reactive hypermelanosis that develops following cutaneous inflammation. Common causes of PIH include intrinsic skin conditions (e.g., acne and eczema) as well as external insults to the skin, such as burn injuries and dermatologic procedures. PIH more commonly occurs in individuals with darker skin, for whom it is often a source of significant psychological distress. Several therapeutic modalities are available for the treatment of PIH, including topical agents, chemical peels, and energy-based devices. We review the epidemiology, clinical presentation, pathogenesis, and treatment of PIH.

http://ift.tt/2nK0ZJW

Characteristics of computed tomography perfusion parameters in non-small-cell-lung-cancer and its relationship to histology, size, stage an treatment response

Publication date: July–August 2018
Source:Clinical Imaging, Volume 50
Author(s): Carmen Trinidad López, Miguel Souto Bayarri, Roque Oca Pernas, Carlos Delgado Sánchez-Gracián, Maria González Vázquez, Antonio Vaamonde Liste, Gonzalo Tardáguila De La Fuente, Javier De La Fuente Aguado
ObjectivesTo analyze computed tomography perfusion (CTP) parameters in NSCLC.Materials and methodsProspective study, 152 patients with NSCLC. CTP parameters were correlated with histology, stage, size and response to conventional chemotherapy/radiotherapy.ResultsNeuroendocrine tumours presented higher BV (p 0.002). Negative correlation of PMB (p 0.003) and positive of MTT (p 0.046) with T stage was found. BF showed negative correlation with size. No differences were found with the RECIST levels of response to chemotherapy/radiotherapy.ConclusionsCTP parameters were highly variable. Neuroendocrine tumours presented higher BV and PMB values. Perfusion parameters do not differ depending on the stage and do not predict response to treatment.



http://ift.tt/2ka2L1P

Pyoderma gangrenosum récidivant du post-partum et cardiomyopathie fatale

Publication date: Available online 7 December 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): I. Naciri, M. Meziane, L. Benzekri, M. Ghaouti, K. Senouci, B. Hassam
IntroductionNous rapportons l'observation d'un pyoderma gangrenosum (PG) récidivant du post-partum, associé à une cardiomyopathie du post-partum (CMPP).ObservationUne femme de 23 ans signalait avoir eu un abcès du sein gauche lors de sa quatrième grossesse. Cette lésion avait évolué, après drainage chirurgical, vers une ulcération inflammatoire traitée par des soins locaux atraumatiques. Lors de sa cinquième grossesse, la patiente développait une ulcération large et douloureuse en regard d'une cicatrice de césarienne, malgré l'introduction d'une antibiothérapie à large spectre. Les prélèvements bactériologiques étaient négatifs. L'examen histologique était en faveur d'un PG. Une semaine après l'introduction d'une corticothérapie générale, elle présentait brutalement des signes d'insuffisance cardiaque. L'échocardiographie trans-thoracique permettait de retenir le diagnostic de CMPP, dont l'évolution était fatale.DiscussionCette observation soulève la question de la relation entre PG et grossesse, et décrit l'association d'un PG et d'une CMPP. La survenue du PG lors de la grossesse est rare ; elle pourrait être induite par l'élévation des taux de G-CSF constatée chez les femmes enceintes. L'association à une CMPP chez notre patiente pourrait être expliquée par le développement d'un climat anti-angiogénique en fin de grossesse, auquel s'ajouterait une agression myocardique inflammatoire neutrophilique en lien avec le PG.BackgroundWe report a case of recurrent post-partum pyoderma gangrenosum (PG) complicated by post-partum cardiomyopathy (PPCM).Patients and methodsA 23-year-old woman presented with a previous medical history of aseptic abscess of the left breast in her fourth pregnancy, which developed after surgical drainage of an inflammatory ulceration treated by atraumatic topical care. During her fifth pregnancy, the patient presented a large and painful ulceration in relation to the scar of the Caesarean section, despite the introduction of broad-spectrum antibiotic therapy. Bacteriological samples were negative. Histological examination militated in favor of PG. One week after initiation of corticosteroid therapy, the patient suddenly showed signs of heart failure. Based on trans-thoracic echocardiography PPCM was diagnosed, and the outcome was fatal.DiscussionThis observation raises the question of the relationship between PG and pregnancy and describes the association of PG and PPCM. PG occurs rarely during pregnancy and it may be induced by the rise in G-CSF levels found in pregnant women. The association with PPCM seen in our patient could have been due to the development of an anti-angiogenic climate at the end of pregnancy, together with inflammatory myocardial aggression linked to the PG.



http://ift.tt/2BVZJ9s

Dorsal hippocampal cannabinergic and GABAergic systems modulate memory consolidation in passive avoidance task

Publication date: Available online 7 December 2017
Source:Brain Research Bulletin
Author(s): Mohammad Nasehi, Parisa Gerami, Fatemeh Khakpai, Mohammad-Reza Zarrindast
In the present research, we examined the possible interaction between the hippocampal CB2 and GABAA receptors on modulation of memory consolidation. In this research, step-down passive avoidance task was used to evaluate memory consolidation in adult male NMRI mice. The results showed that post-training intra-CA1 administration of muscimol (0.05 and 0.1μg/mouse) impaired memory consolidation as evidenced by a decrease in step-down latency on the test day, which was suggestive of drug-produced amnesia. However co-administration of different doses of muscimol (0.01, 0.05 and 0.1μg/mouse) along with a not-effect dose of AM630 (1μg/mouse) or GP1a (1μg/mouse) had no significant effect on impairment of memory consolidation induced by muscimol. Although post-training intra-CA1 administration of the cannabinoid CB2 receptor antagonist, AM630 (1, 10 and 100μg/mouse) alone had no effect, its co-administration with an effective dose of muscimol (0.05μg/mouse) impaired memory consolidation. Furthermore, post-training intra-CA1 microinjection of cannabinoid CB2 receptor agonist, GP1a (100μg/mouse) impaired memory consolidation. Interestingly, post-training intra-CA1 co-injection of different doses of GP1a (1, 10 and 100μg/mouse) along with an effect dose of muscimol (0.05μg/mouse) significantly intensified impairment of memory consolidation induced by GP1a (10μg/mouse). Moreover, all above doses of drugs did not significantly change locomotor activity. These findings suggest possible interaction between the CA1 cannabinoid CB2 and GABAA mechanisms on modulation of memory consolidation in mice.



http://ift.tt/2iI7Tdr

Limited access to special education services for school-aged children with developmental delay

Publication date: January 2018
Source:Research in Developmental Disabilities, Volume 72
Author(s): Erica Twardzik, Ellen Smit, Bridget Hatfield, Michelle C. Odden, Alicia Dixon-Ibarra, Megan MacDonald
BackgroundCurrent policy in Oregon limits eligibility of children diagnosed with developmental delay for school-based services. Due to eligibility definitions, children with developmental delay may face additional barriers transitioning from early intervention/early childhood special education into school-based special education services.AimsExamine the relationship between enrollment in school-based special education programs given a change in primary disability diagnosis.MethodsLogistic regression models were fit for children who enrolled in early intervention/early childhood special education services with a primary disability diagnosis of developmental delay and changed primary disability diagnosis before third grade (n=5076).ResultsOdds of enrollment in future special education were greater in children with a change in primary disability diagnosis after the age of five in comparison to children that had a change in primary disability diagnosis before the age of five, while adjusting for demographic characteristics (adjusted odds ratio: 2.37, 95% CI 1.92, 2.92).ConclusionResults suggest that children who are diagnosed with a developmental delay and exit early childhood special education due to maximum age of eligibility are more likely to enroll in special education compared to children without a gap in service access.ImplicationsGaps in service access during early development are associated with the need for supportive services later on in life.



http://ift.tt/2j8Hs4q

Levels, dietary intake, and health risk of potentially toxic metals in vegetables, fruits, and cereal crops in Pakistan

Abstract

Food safety is a major concern worldwide and human beings are frequently exposed to potentially toxic metals (PTMs) through consumption of vegetables, fruits, and cereal crops grown in contaminated areas. The present study investigates the concentrations of PTMs such as chromium (Cr), nickel (Ni), zinc (Zn), arsenic (As), cadmium (Cd), and lead (Pb) in the foodstuffs (fruits, vegetables, and cereals) collected from different markets of Khyber Pakhtunkhwa, Pakistan. Samples of fruits (banana, tangerine, apple, and guava), vegetables (tomato, onion, potato, pea, and lady finger), and cereals (rice, kidney beans, and chick peas) were acid-extracted and analyzed using ICP-MS. The concentrations of Cr, Zn, Pb, As, and Cd in fruits (54, 50, 50, 45, and 4% samples, respectively), vegetables (53, 43, 63, 80, and 46%), and cereals (37, 62, 25, 70, and 25%) exceeded their respective permissible limits set by FAO/WHO (2001). The results showed that the highest mean concentration was observed for Ni (14.95 mg/kg), Pb (0.57 mg/kg), and Cd (0.27 mg/kg) in vegetables followed by fruits and cereals. However, the highest mean concentration of As (0.44 mg/kg) was observed in cereal crops followed by vegetables and fruits. The individual health risk of PTMs via consumption of fruits, vegetables, and cereals were found within safe limits for adults and children. Nevertheless, the total HRI values (fruits + vegetables + cereals) for Ni, As, and Cd for both adults and children were observed > 1 and may posed potential risk for the community consuming these foodstuffs on a daily basis.

Graphical abstract

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Municipal solid waste compost as a novel sorbent for antimony(V): adsorption and release trials at acidic pH

Abstract

The ability of two municipal solid waste composts (MSW-Cs) to sorb antimony(V) in acidic conditions (pH 4.5) was investigated. Sorption isotherms and kinetics showed that both MSW-Cs could sorb antimony(V), even if in different amounts (~ 0.18 and 0.24 mmol g⁻¹ of Sb(V) by MSW-C1 and MSW-C2, respectively). These differences were ascribed to the chemical composition of composts, as well as to the total acidity of their humic substances. The Sb(V) sorption by both MSW-Cs followed a pseudo-second-order kinetic model, while the sorption isotherms data fitted the Freundlich model better than the Langmuir one. The humic acids extracted from composts contributed to 4.26 and 8.24% of Sb(V) sorption by MSW-C1 and MSW-C2 respectively. SEM-EDX spectra of the MSW-C+Sb(V) systems showed a certain association of Ca(II) with Sb(V), while sequential extraction procedures indicated that more than 80% of the Sb(V) sorbed was strongly retained by MSW-Cs. On the other hand, treatment with oxalic acid at pH 4.5 favored the release of more than 98 and 65% of the Sb(V) sorbed by MSW-C1 and MSW-C2 respectively, supporting a possible role of calcium in Sb(V) retention. The results from this study suggest that MSW-Cs could be used as amendments for the in-situ immobilization of Sb(V) in acidic-polluted soils.

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Protective effects of fucoxanthin and fucoxanthinol against tributyltin-induced oxidative stress in HepG2 cells

Abstract

Tributyltin (TBT) is a biocide extremely toxic to a wide range of organisms, which has been used for decades for industrial purposes. Fucoxanthin is a natural carotenoid that is isolated from seaweed, and fucoxanthinol is a major primary metabolite of fucoxanthin. Although fucoxanthin and fucoxanthinol have been reported to possess anti-oxidant activities in vitro, little is known as to whether they protect against TBT-induced oxidative stress in cultured cells. In the present study, the protective effect of fucoxanthin and fucoxanthinol against oxidative stress induced by TBT was investigated. The data showed that incubation of HepG2 cells with 0.2 μM TBT significantly increased cell apoptosis, whereas treatment with fucoxanthin or fucoxanthinol (3 μM) significantly recovered cell viability. In addition, fucoxanthinol treatment significantly decreased the intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) in HepG2 cells incubated with TBT. Moreover, fucoxanthin and fucoxanthinol markedly increased the expression level of Bcl-2/Bax. These results demonstrated that both fucoxanthin and fucoxanthinol effectively prevented cytotoxicity in HepG2 cells treated with TBT, and the protective effect was likely associated with decreased intracellular ROS and MDA and increased Bcl-2/Bax levels.

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Phytotoxic effects of silver nanoparticles in tobacco plants

Abstract

The small size of nanoparticles (NPs), with dimensions between 1 and 100 nm, results in unique chemical and physical characteristics, which is why they are implemented in various consumer products. Therefore, an important concern is the potential detrimental impact of NPs on the environment. As plants are a vital part of ecosystem, investigation of the phytotoxic effects of NPs is particularly interesting. This study investigated the potential phytotoxicity of silver nanoparticles (AgNPs) on tobacco (Nicotiana tabacum) plants and compared it with the effects of the same AgNO₃ concentrations. Accumulation of silver in roots and leaves was equally efficient after both AgNP and AgNO₃ treatment, with predominant Ag levels found in the roots. Exposure to AgNPs did not result in elevated values of oxidative stress parameters either in roots or in leaves, while AgNO₃ induced oxidative stress in both plant tissues. In the presence of both AgNPs and AgNO₃, root meristem cells became highly vacuolated, which indicates that vacuoles might be the primary storage target for accumulated Ag. Direct AgNP uptake by root cells was confirmed. Leaf ultrastructural studies revealed changes mainly in the size of chloroplasts of AgNP-treated and AgNO₃-treated plants. All of these findings indicate that nano form of silver is less toxic to tobacco plants than silver ions.

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Changes to tetracyclines and tetracycline resistance genes in arable soils after single and multiple applications of manure containing tetracyclines

Abstract

The influence of manure containing tetracyclines (TCs) on the prevalence of antibiotic resistance genes in soils remains poorly understood. Here, three different TCs (oxytetracycline (OTC), tetracycline (TC), and chlortetracycline (CTC)) were mixed respectively with unpolluted manure to fertilize arable soil. The soil received either a single application of 0 μg kg⁻¹, 300 μg kg⁻¹ (TC and CTC), or 700 μg kg⁻¹ (OTC) or multiple applications every 14 days for 140 days. Four tetracycline resistance genes (TRGs), including tet(A), tet(L), tet(M), and tet(Q), were monitored. Although the abundances of the four TRGs in the single application treatment initially increased rapidly, they decreased over time and were significantly lower than those of the repeated treatments after day 112. All additions of TCs stopped on day 140, but we continued to assess the long-term accumulation of TRGs. Most of the TRGs were detected even after the TC-containing manures had not been applied for more than 15 months. The abundance of the TRGs after ceasing fertilization with the TC-containing manures was higher in the repeated application treatments than in the single application treatments. Therefore, more attention should be paid to repeated applications of antibiotic-containing manure to arable soils.

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Characterization of tyrosinase inhibitory constituents from the aerial parts of Humulus japonicus using LC-MS/MS coupled online assay

Publication date: Available online 7 December 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Hyo Hee Yang, Kyung-Eon Oh, Yang Hee Jo, Jong Hoon Ahn, Qing Liu, Ayman Turk, Jae Young Jang, Bang Yeon Hwang, Ki Yong Lee, Mi Kyeong Lee
In the screening of natural products for the development as cosmetic ingredients, the EtOAc-soluble fraction of Humulus japonicus showed tyrosinase inhibitory activity. HPLC-MS/MS coupled online tyrosinase assay of EtOAc-soluble fraction of H. japonicus characterized the twenty-eight constituents including two unknown ones and their tyrosinase inhibitory activity. Fractionation of H. japonicus using various chromatographic techniques yielded thirty-eight compounds. The chemical structures of isolated compounds were identified by spectroscopic analysis. As characterized by HPLC-MS/MS analysis, we isolated twenty-four predicted compounds and further identified two unknown ones, named humulusides A (1) and B (2). Additional ten compounds were also identified by purification. Tyrosinase inhibitory activity of isolated compounds were evaluated, which was closely correlated with the results from HPLC-MS/MS coupled online tyrosinase assay. Consistent with predicted data, two major compounds, trans-N-coumaroyltyramine (14) and cis-N-coumaroyltyramine (15) showed tyrosinase inhibition with IC50 values of 40.6 and 36.4 μM. Taken together, H. japonicus is suggested as whitening ingredient in cosmetic products. In addition, HPLC-MS/MS coupled tyrosinase assay is powerful tool for predicting active compounds with short time and limited amounts, although identification of new compounds and verification of predicted data are also needs to be demonstrated by further experiment.

Graphical abstract

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2-Mezhyltetrahydro-3-benzazepin-1-ols – the missing link in SAR of GluN2B selective NMDA receptor antagonists

Publication date: Available online 7 December 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Sougata Dey, Dirk Schepmann, Bernhard Wünsch
The NMDA receptor containing GluN2B subunits represents a promising target for the development of drugs for the treatment of various neurological disorders including neurodegenerative diseases. In order to study the role of CH3 and OH moieties trisubstituted tetrahydro-3-benzazepines 4 were designed as missing link between tetra- and disubstituted 3-benzazepines 2 and 5. The synthesis of 4 comprises eight reaction steps starting from alanine. The intramolecular Friedel-Crafts acylation to obtain the ketone 12 and the base-catalyzed elimination of trifluoromethanesulfinate (CF3SO2^-) followed by NaBH4 reduction represent the key steps. The GluN2B affinity of the cis-configured 3-benzazepin-1-ol cis-4a with a 4-phenylbutyl side chain (Ki = 252 nM) is considerably lower than the GluN2B affinity of (R,R)-2 (Ki = 17 nM) indicating the importance of the phenolic OH moiety for the interaction with the receptor protein. Introduction of an additional CH3 moiety in 2-position led to a slight decrease of GluN2B affinity as can be seen by comparing the affinity data of cis-4a and 5. The homologous phenylpentyl derivative cis-4b shows the highest GluN2B affinity (Ki = 56 nM) of this series of compounds. According to docking studies cis-4a adopts the same binding mode as the cocrystallized ligand ifenprodil-keto 1A and 5 at the interface of the GluN2B and GluN1a subunits. The same crucial H-bonds are formed between the C(=O)NH2 moiety of Gln110 within the GluN2B subunit and the protonated amino moiety and the OH moiety of (R,R)-cis-4a.

Graphical abstract

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First evidence of bacterial translocation from the intestinal tract as a route of Helicobacter cinaedi bacteremia

Abstract

Background

The route of Helicobacter cinaedi bacteremia has not yet been clarified. Although bacterial translocation from the intestinal tract into the circulation has been suggested, it has not been demonstrated thus far. The objective of this study was to investigate the port of entry of this bacterium.

Material and Methods

We conducted a retrospective study on patients with H. cinaedi bacteremia between March 2009 and May 2013. Records of patients in whom H. cinaedi was detected in both blood and stool cultures were extracted. H. cinaedi was identified using gyrB-targeted PCR. Pulse-field gel electrophoresis was used to investigate the consistency of the genotypes.

Results

Seventy-one patients were diagnosed with H. cinaedi bacteremia during the study period. H. cinaedi was detected in both blood and stool samples of 21 patients. Pulse-field gel electrophoresis was used to investigate the consistency of the genotypes in 18 evaluable strains (from 9 patients). The pulse-field gel electrophoresis patterns of the stool- and blood-derived strains of H. cinaedi were consistent among all 9 patients. Most of the 9 patients analyzed were immunocompromised and being treated with anticancer drugs or steroids, which suggests reduced intestinal immunity.

Conclusions

This is the first study to demonstrate that bacterial translocation from the intestinal tract could represent one route of H. cinaedi bacteremia.

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Population pharmacokinetics of articaine with 1:200,000 epinephrine during third molar surgery and simulation of high-dose regimens

Publication date: 1 March 2018
Source:European Journal of Pharmaceutical Sciences, Volume 114
Author(s): Yoann Cazaubon, Cédric Mauprivez, Catherine Feliu, Laurent Binet, Olivier Oget, Claire Gozalo, Zoubir Djerada
Background and objectivesArticaine is more and more used in third molar surgery under local anesthesia (LA). The objectives of this analysis were to characterize the pharmacokinetics of articaine for this type of surgery and to simulate dosing regimens.MethodsNon-linear mixed-effects modeling conducted in Monolix 4.4.0 was used to describe articaine plasma concentration-time data from 20 patients. Monte Carlo simulations were then performed to evaluate the probability of cardiotoxic target attainment (PCTA) of various dosage regimens.ResultsArticaine concentration data were best described by a linear one-compartment model, with an additional depot compartment for submucosal route with a zero-order transfer to central compartment. Age and gender were found to influence duration transfer (Tk0) and elimination rate constant (Ke), respectively. Simulated maximum recommended dose regimen (7mg/kg) had a PCTA of 0%. Simulated higher doses of 10mg/kg and 15mg/kg had a PCTA of 0% and about 1–4%, respectively.ConclusionsThe model adequately described the articaine pharmacokinetics. This is the first PK model qualified for articaine administered by submucosal route. The simulations suggest that maximum recommended dose regimen is safe concerning the cardiotoxicity in healthy patients.

Graphical abstract

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Editorial board

Publication date: December 2017
Source:Revue des Maladies Respiratoires, Volume 34, Issue 10





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The dynamics of native Atoh7 protein expression during mouse retinal histogenesis, revealed with a new antibody

Publication date: Available online 7 December 2017
Source:Gene Expression Patterns
Author(s): Joel B. Miesfeld, Tom Glaser, Nadean L. Brown
The Atoh7 transcription factor catalyzes the rate-limiting step in the specification of retinal ganglion cells (RGCs). As a tool to study vertebrate retinal development, we validate an antibody that recognizes human and mouse Atoh7 polypeptide, using informative knockout and transgenic mouse tissues and overexpression experiments. The transient features of Atoh7 protein expression during retinal neurogenesis match the expected pattern at the tissue and cellular level. Further, we compare endogenous Atoh7 to established RGC markers, reporter mouse lines and cell cycle markers, demonstrating the utility of the antibody to investigate molecular mechanisms of retinal histogenesis.



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Does radiotherapy prior to surgery improve long term prognosis in pediatric colorectal cancer in lower- and upper-middle income countries with limited resources? Our experience and literature review

Publication date: Available online 7 December 2017
Source:Journal of the Egyptian National Cancer Institute
Author(s): Yacoob Omar Carrim, Luvo Gaxa, Francisca van der Schyff, Nndweleni Meshack Bida, Fareed Omar, Zarina Lockhat
Colorectal carcinoma in children and adolescents is extremely rare, with an annual incidence <0.3 cases per million, most frequently reported in the second decade of life. It accounts for severe morbidity and poor prognosis owing to the low index of suspicion, delayed diagnosis, advanced stage at presentation and the aggressive tumor nature. Patients present with abdominal pain, vomiting, constipation, abdominal distension, rectal tenesmus, iron-deficiency anemia, change in bowel habit and weight loss. Rectal bleeding is an uncommon presentation in children. Bowel obstruction presents frequently in children compared to adults. In 90% of pediatric cases, colorectal carcinoma occurs sporadically. In 10%, predisposing conditions and syndromes are identified. We present a case study of a 12-year-old female with advanced colorectal cancer without a predisposing disease or syndrome, who received radio-chemotherapy ten weeks prior to radical abdominopelvic surgery, followed by radio-chemotherapy postoperatively, with a positive outcome.



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Downregulation of Caspase 8 in a group of Iranian breast cancer patients – A pilot study

Publication date: Available online 7 December 2017
Source:Journal of the Egyptian National Cancer Institute
Author(s): Masoumeh Aghababazadeh, Najmeh Dorraki, Fahimeh Afzal Javan, Asieh Sadat Fattahi, Masoumeh Gharib, Alireza Pasdar
PurposeIt is now well known that evading apoptosis, as a cancer hallmark, can lead to tumour initiation, progression and metastasis. As a result of genome wide association studies, an initiator protease in this pathway, caspase 8 (CASP8), has been found to be an important gene regarding breast cancer susceptibility. The alterations of the expression of this gene have been reported in breast cancer cell lines. Given that in previous studies expression analysis of this gene had only been done in breast cancer cell lines, in this study we aimed to evaluate the expression of this gene in breast cancer tissues versus adjacent normal tissues, using real-time quantitative method.MethodsCaspase 8 mRNA expression was quantified using comparative RT-qPCR in 27 fresh frozen breast tumours and 27 adjacent normal tissues. Moreover, relationship between the expression changes of CASP8 in tumour tissue and various clinical and pathological features were evaluated in an Iranian population.ResultsThe present study showed that expression of CASP8 was significantly reduced in tumour tissues compared to neighbouring normal tissues (p = .004). CASP8 expression was significantly correlated with the status of hormone receptors (ER and PR).ConclusionTo the best of our knowledge, this study is the first report on reduced expression of CASP8 in breast cancer versus adjacent normal tissues. Our data support previous results obtained from cell lines and therefore highlights the seminal role of the induction of CASP8 expression, as a novel therapeutic approach, in order to sensitize tumour cells to apoptotic stimuli.



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Cytological diagnosis of a rare case of cutaneous metastasis from transitional cell carcinoma, renal pelvis

Publication date: Available online 7 December 2017
Source:Journal of the Egyptian National Cancer Institute
Author(s): Pragya Singh, Sachin Kolte, Gunjesh Kumar Singh
Transitional cell carcinoma (TCC) arising from renal pelvis rarely gives rise to cutaneous metastasis. Due to the insufficient literature, the exact incidence is not known till date. Moreover, the diagnosis is confirmed on histopathological examination with the aid of immunohistochemistry wherever needed. We are presenting a case of a 70-year-old female with metastatic TCC from the renal pelvis to the abdominal skin, which was diagnosed on cytology alone along with the cell block preparation. We also highlight the important cytomorphological and immunohistochemical features noted, which need to be known to avoid any diagnostic delay.



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Comments on “Solid pseudopapillary neoplasm of the pancreas: Management and long-term outcome”

Publication date: Available online 7 December 2017
Source:European Journal of Surgical Oncology
Author(s): Xing Wang, Xubao Liu




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