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Πέμπτη 10 Αυγούστου 2017

Effect of Cholecalciferol therapy on serum FGF 23 in vitamin D deficient patients: a randomized clinical trial

Abstract

Introduction

Fibroblast growth factor-23 plays an important role in regulating systemic phosphate homeostasis, and vitamin D metabolism. However, the effect of Cholecalciferol therapy on FGF23 serum level in patients with vitamin D deficiency has not been studied, yet.

Materials and methods

This is a double-blind, randomized clinical trial on 119 vitamin D deficient patients in 2016. Biochemical variables of treatment and placebo groups were analyzed after 12 weeks of 50,000 IU of Cholecalciferol vs. placebo therapy once a week, by SPSS18.

Results

After Cholecalciferol therapy, delta of serum PTH in treatment group was less than the controls (P < 0.001). However, delta values of serum 25(OH)D3, 1,25(OH)2D3 and FGF23 in vitamin D treated group were more than the placebo-treated ones (P < 0.001, P = 0.002, and P = 0.04, respectively). Moreover, FGF23 serum level in treatment group was associated with serum calcium (P = 0.005, r = −0.256), and serum 1,25(OH)2D3 (P < 0.001, r = 0.529).

Conclusions

We propose that in these patients 1,25(OH)2D3 has a positive association with serum FGF23, and hypostasized that serum calcium might be a down regulator of serum FGF23.



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Scholar : These new articles for Behaviour & Information Technology are available online

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Assessing the determinants of flow experience in the adoption of learning management systems: the moderating role of perceived institutional support
Ikram Ullah Khan , Zahid Hameed, Yugang Yu & Safeer Ullah Khan
Pages: 1-15 | DOI: 10.1080/0144929X.2017.1362475


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Cosmetics, Vol. 4, Pages 28: Safety and Efficacy of Dextran-Rosmarinic Acid Conjugates as Innovative Polymeric Antioxidants in Skin Whitening: What Is the Evidence?

Cosmetics, Vol. 4, Pages 28: Safety and Efficacy of Dextran-Rosmarinic Acid Conjugates as Innovative Polymeric Antioxidants in Skin Whitening: What Is the Evidence?

Cosmetics doi: 10.3390/cosmetics4030028

Authors: Ortensia Parisi Rocco Malivindi Fabio Amone Mariarosa Ruffo Rosella Malanchin Federica Carlomagno Cristiana Piangiolino Vincenzo Nobile Vincenzo Pezzi Luca Scrivano Francesco Puoci

Background: Melanins are high molecular weight pigments responsible for the mammalian skin and hair colour and play a key role in skin protection from UV radiation; however, their overproduction and excessive accumulation lead to pigmentation problems including melasma, freckles, uneven colouring, and age spots. Therefore, the modulation of melanin synthesis represents a critical issue in medicine and cosmetology. In the present study, an innovative polymeric antioxidant to be used as skin whitening agent is developed by the conjugation of dextran with rosmarinic acid. Methods: Dextran-rosmarinic acid conjugates (DEX-RA) were synthesized in a one-pot method starting from Origanum vulgare aqueous leaf extract and dextran. The total polyphenol content and the antioxidant activity were assessed by Folin-Ciocalteau assay and 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and bleaching tests, respectively. The efficacy of DEX-RA was evaluated by inhibition of tyrosinase activity, in vitro diffusion and stability studies and in vivo studies. The biocompatibility of the conjugates was investigated by 3-[4,5-Dimethylthiaoly]-2,5-diphenyltetrazoliumbromide (MTT) and EPISKIN™ model. Results: Efficacy and safety studies confirmed the antioxidant and tyrosinase inhibitory activities and the biocompatibility of the synthesized conjugates. Conclusion: The polymeric conjugates, comparing to the free antioxidant, show a long-lasting efficacy combined to an enhanced stability resulting in an improved performance of the cosmetic formulations prepared using this innovative whitening agent as a bioactive ingredient.



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Scholar : Isotopes in Environmental and Health Studies, Volume 53, Issue 5, October 2017 is now available online on Taylor & Francis Online

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Isotopes in Environmental and Health Studies, Volume 53, Issue 5, October 2017 is now available online on Taylor & Francis Online.



This new issue contains the following articles:

Special section dedicated to Professor Peter Fritz on the occasion of his 80th birthday

Tribute to Professor Peter Fritz on the occasion of his 80th birthday
Gerhard Strauch & Peter Krumbiegel
Pages: 441-443 | DOI: 10.1080/10256016.2017.1299720


Peter Fritz – an old friend and colleague
Roberto Gonfiantini
Pages: 444-445 | DOI: 10.1080/10256016.2017.1350659


Comparison of δ81Br and δ37Cl composition of volatiles, salt precipitates, and associated water in terrestrial evaporative saline lake systems
Corinne Hanlon, Randy Stotler, Shaun Frape & Rhys Gwynne
Pages: 446-465 | DOI: 10.1080/10256016.2017.1324856


Interpretation of environmental tracer data for conceptual understanding of groundwater flow: an application for fractured aquifer systems in the Kłodzko Basin, Sudetes, Poland
Mariusz Mądrala, Mirosław Wąsik & Piotr Małoszewski
Pages: 466-483 | DOI: 10.1080/10256016.2017.1330268


Estimating the spatial distribution of artificial groundwater recharge using multiple tracers
Christian Moeck, Dirk Radny, Adrian Auckenthaler, Michael Berg, Juliane Hollender & Mario Schirmer
Pages: 484-499 | DOI: 10.1080/10256016.2017.1334651


Hydrology of the North Klondike River: carbon export, water balance and inter-annual climate influences within a sub-alpine permafrost catchment
Anthony Lapp, Ian Clark, Andrew Macumber & Tim Patterson
Pages: 500-517 | DOI: 10.1080/10256016.2017.1355795


Articles

Controls over spatial and seasonal variations on isotopic composition of the precipitation along the central and eastern portion of Brazil
Didier Gastmans , Vinícius Santos, Juliana Aparecida Galhardi, João Felipe Gromboni, Ludmila Vianna Batista, Konrad Miotlinski, Hung Kiang Chang & José Silvio Govone
Pages: 518-538 | DOI: 10.1080/10256016.2017.1305376


Tracing sources of nitrate using water chemistry, land use and nitrogen isotopes in the Ganjiang River, China
Peng Wang, Junzheng Liu, Shuhua Qi, Shiqin Wang & Xiaoling Chen
Pages: 539-551 | DOI: 10.1080/10256016.2017.1328417


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How Asian countries understand policy experiment as policy pilots?
Kilkon Ko & Kayoung Shin
Pages: 1-13 | DOI: 10.1080/02185377.2017.1360784


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Manipulating laterality and polarity of transcranial direct current stimulation to optimise outcomes for anomia therapy in an individual with chronic Broca's aphasia | Open Access
Margaret Sandars, Lauren Cloutman & Anna M. Woollams
Pages: 1-25 | DOI: 10.1080/02687038.2017.1350631


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Copeptin as a marker of an altered CRH axis in pituitary disease

Abstract

Background

Copeptin (pre-proAVP) secreted in equimolar amounts with vasopressin closely reflects vasopressin release. Copeptin has been shown to subtly mirror stress potentially mediated via corticotrophin-releasing hormone. To further test a potential direct interaction of corticotrophin-releasing hormone with copeptin release, which could augment vasopressin effects on pituitary function, we investigated copeptin response to corticotrophin-releasing hormone.

Patients and methods

Cortisol, adrenocorticotropin and copeptin were measured in 18 healthy controls and 29 subjects with a history of pituitary disease during standard corticotrophin-releasing hormone test.

Results

Patients with previous pituitary disease were subdivided in a group passing the test (P1, n = 20) and failing (P2, n = 9). The overall copeptin response was higher in controls than in subjects with pituitary disease (area under the curve, p = 0.04 for P1 + P2) with a maximum increase in controls from 3.84 ± 2.86 to 12.65 ± 24.87 pmol/L at 30 min, p < 0.05. In contrast, both groups of pituitary patients lacked a significant copeptin response to corticotrophin-releasing hormone, and even in P1, where adrenocorticotropin concentrations increased fourfold (mean, 21.48 vs. 91.53 pg/mL, p < 0.01), copeptin did not respond (e.g., 4.35 ± 5.81 vs. 5.36 ± 6.79 pmol/L, at 30 min, p = ns).

Conclusions

Corticotrophin-releasing hormone is able to stimulate copeptin release in healthy controls suggesting a direct interaction of corticotrophin-releasing hormone and vasopressin/vasopressin. Interestingly, this relation is altered already in the group of pituitary patients who pass the standard corticotrophin-releasing hormone test indicating (1) the corticotrophin-releasing hormone–adrenocorticotropin–cortisol response is largely independent from the vasopressin system, but (2) the corticotrophin-releasing hormone–vasopressin interaction reflected by copeptin may be much more sensitive to reveal subtle alterations in the regulation of pituitary function.



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Scholar : These new articles for Applied Measurement in Education are available online

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Original Articles

Evaluating Score and Decision Consistency across Claims in a Validation Argument
Jonathan Schmidgall
This is the author accepted version which has not been proofed or edited


Journal of Social Work Education
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Pollution level and inhalation exposure of ambient aerosol fluoride as affected by polymetallic rare earth mining and smelting in Baotou, north China

Publication date: October 2017
Source:Atmospheric Environment, Volume 167
Author(s): Buqing Zhong, Lingqing Wang, Tao Liang, Baoshan Xing
Airborne fluoride associated with total suspended particles (TSP) and respirable particulate (PM10) in the rare earth mining and smelting areas were analyzed during August 2012 and March 2013. In March, average concentrations of fluoride bound to TSP in the mining and smelting areas were 0.598 ± 0.626 μg/m3 and 3.615 ± 4.267 μg/m3, respectively, whereas that in August were 0.699 ± 0.801 μg/m3 and 1.917 ± 2.233 μg/m3, respectively. TSP samples were classified into four categories by different sampling periods and locations using Kohonen's self-organizing map, which demonstrates that high airborne fluoride concentrations in March in the smelting area were probably attributed to industrial emissions from smelting activities and wind-blown dust from tailings pond, influenced by meteorologic parameters such as temperature, relative humidity, precipitation and wind speed. The mean daily amount of fluoride inhaled in the mining and smelting areas were estimated to be in the range of 2.77–57.61 μg/day and 3.39–64.32 μg/day, respectively. These results indicate the high potential exposure level of fluoride inhaled for local residents in the polymetallic mining and smelting areas.

Graphical abstract

image

Teaser

A Kohonen's Self-organizing map was applied to interpret correlation patterns among fluoride concentrations in aerosols and meteorological conditions.


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Strong signatures of high-latitude blocks and subtropical ridges in winter PM10 over Europe

Publication date: October 2017
Source:Atmospheric Environment, Volume 167
Author(s): Jose M. Garrido-Perez, Carlos Ordóñez, Ricardo García-Herrera
This paper analyses the impact of high-latitude blocks and subtropical ridges on daily PM10 (particulate matter ≤ 10 μm) observations obtained from the European Environment Agency's air quality database (AirBase) for the winter period of 2000–2010. The response of the pollutant concentrations to the location of blocks and ridges with centres in two main longitudinal sectors (Atlantic, ATL, 30°–0° W; European, EUR, 0°–30° E) is examined. In particular, EUR blocking is associated with a collapse of the boundary layer as well as reduced wind speeds and precipitation occurrence, yielding large positive anomalies which average 12 μg m−3 over the whole continent. Conversely, the enhanced zonal flow around 50°–60° N and the increased occurrence of precipitation over northern-central Europe on days with ATL ridges favour the ventilation of the boundary layer and the impact of washout processes, reducing PM10 concentrations on average by around 8 μg m−3. The presence of EUR blocks is also concurrent with an increased probability of exceeding the air quality target (50 μg m−3 for 24-h averaged PM10) and the local 90th percentiles for this pollutant at many sites in central Europe, while the opposite effect is found for ridges. In addition, the effect of synoptic persistence on the PM10 concentrations is stronger for EUR blocks than for ATL ridges. This could benefit the predictability of PM10 extremes over wide areas of the region. Finally, we have found that the combined or isolated effect of both synoptic patterns can partly control the interannual variability of winter mean PM10 at many sites of north-western and central Europe, with coefficients of determination (R2) exceeding 0.80 for southern Germany. These results indicate that the response of the particulate matter (PM) concentrations to large-scale circulation patterns is stronger than previously reported for Europe and other mid-latitude regions.



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A Phase II Multicentre, Open-Label, Proof-of-Concept Study of Tasquinimod in Hepatocellular, Ovarian, Renal Cell, and Gastric Cancers

Abstract

Background

Tasquinimod is a small molecule with immunomodulatory, anti-angiogenic, and anti-metastatic properties that targets the tumor microenvironment. This study aimed to obtain a clinical proof of concept that tasquinimod was active and tolerable in patients with advanced solid tumors.

Patients and Methods

This early stopping design, open-label, proof-of-concept clinical trial evaluated the clinical activity of tasquinimod in four independent cohorts of patients with advanced hepatocellular (n = 53), ovarian (n = 55), renal cell (n = 38), and gastric (n = 21) cancers. Tasquinimod was given orally every day (0.5 mg/day for at least 2 weeks, with dose increase to 1 mg/day) until radiological progression according to Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 criteria, intolerable toxicity, or patient withdrawal. The primary efficacy endpoint was progression-free survival (PFS) rate according to RECIST 1.1 by central assessment.

Results

Interim futility analyses at 8 weeks (6 weeks for the gastric cancer cohort) found adequate clinical activity of tasquinimod only in the hepatocellular cohort and recruitment to the other three cohorts was stopped. PFS rates were 26.9% at 16 weeks, 7.3% at 24 weeks, 13.2% at 16 weeks, and 9.5% at 12 weeks, respectively, in hepatocellular, ovarian, renal cell, and gastric cancer cohorts. The pre-defined PFS threshold was not reached in the hepatocellular cancer cohort at the second stage of the trial. The most common treatment-related adverse events were fatigue (48.5%), nausea (34.1%), decreased appetite (31.7%), and vomiting (24.6%).

Conclusions

This study failed to demonstrate clinical activity of tasquinimod in heavily pre-treated patients with advanced hepatocellular, ovarian, renal cell, and gastric cancer.

Trial registration

NCT01743469.



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Diagnostic dilemma: ALPS versus Evans syndrome

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Publication date: Available online 9 August 2017
Source:Clinical Immunology
Author(s): Evan Li, Amanda B. Grimes, Nicholas L. Rider, Donald H. Mahoney, Thomas A. Fleisher, William T. Shearer




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Scholar : These new articles for Asian Security are available online

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Erratum

Erratum
Pages: 1-1 | DOI: 10.1080/14799855.2017.1364075


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Scholar : These new articles for Australian Journal of Linguistics are available online

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Original Articles

Towards a Panchronic Perspective on a Diachronic Issue: The Rhyme <-uiw> in Old Burmese
Frederic Pain
Pages: 1-41 | DOI: 10.1080/07268602.2017.1350129


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Infantile hypophosphatasia combined with vitamin B6-responsive seizures and reticular formation lesions on magnetic resonance imaging: A case report

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Publication date: Available online 9 August 2017
Source:Brain and Development
Author(s): Mitsuharu Fukazawa, Junichiro Tezuka, Momoko Sasazuki, Natsuko Masumoto, Haruhisa Baba, Takehiko Doi, Yasushi Tsutsumi, Yuji Mizuno, Futoshi Mihara, Hideki Nakayama
BackgroundHypophosphatasia (HPP) is a rare genetic disorder characterized by rachitic bone manifestations and a low serum alkaline phosphatase (ALP) level. It is caused by mutations in the tissue non-specific alkaline phosphatase (TNSALP) gene, which encodes the tissue non-specific isozyme of ALP. HPP patients exhibit various presentations depending on their age at onset, such as infantile HPP combined with vitamin B6-responsive seizures.Case presentationA newborn with infantile HPP presented with tonic convulsions from day 5 after birth and received intravenous vitamin B6 (10mg/kg/day pyridoxal phosphate). Eleven days later, frequent apneic episodes occurred, and head magnetic resonance imaging (MRI) showed bilateral reticular formation lesions in the brain stem, including the medulla oblongata. After the pyridoxal phosphate dose was increased (to 40mg/kg/day), the patient's seizures and apnea resolved, and her MRI findings also improved. Genetic testing revealed that she was homozygous for the 1559delT mutation of TNSALP.ConclusionsHigh-dose pyridoxal phosphate is a useful treatment for HPP-induced seizures and might improve reticular formation lesions.



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Copeptin as a marker of an altered CRH axis in pituitary disease

Abstract

Background

Copeptin (pre-proAVP) secreted in equimolar amounts with vasopressin closely reflects vasopressin release. Copeptin has been shown to subtly mirror stress potentially mediated via corticotrophin-releasing hormone. To further test a potential direct interaction of corticotrophin-releasing hormone with copeptin release, which could augment vasopressin effects on pituitary function, we investigated copeptin response to corticotrophin-releasing hormone.

Patients and methods

Cortisol, adrenocorticotropin and copeptin were measured in 18 healthy controls and 29 subjects with a history of pituitary disease during standard corticotrophin-releasing hormone test.

Results

Patients with previous pituitary disease were subdivided in a group passing the test (P1, n = 20) and failing (P2, n = 9). The overall copeptin response was higher in controls than in subjects with pituitary disease (area under the curve, p = 0.04 for P1 + P2) with a maximum increase in controls from 3.84 ± 2.86 to 12.65 ± 24.87 pmol/L at 30 min, p < 0.05. In contrast, both groups of pituitary patients lacked a significant copeptin response to corticotrophin-releasing hormone, and even in P1, where adrenocorticotropin concentrations increased fourfold (mean, 21.48 vs. 91.53 pg/mL, p < 0.01), copeptin did not respond (e.g., 4.35 ± 5.81 vs. 5.36 ± 6.79 pmol/L, at 30 min, p = ns).

Conclusions

Corticotrophin-releasing hormone is able to stimulate copeptin release in healthy controls suggesting a direct interaction of corticotrophin-releasing hormone and vasopressin/vasopressin. Interestingly, this relation is altered already in the group of pituitary patients who pass the standard corticotrophin-releasing hormone test indicating (1) the corticotrophin-releasing hormone–adrenocorticotropin–cortisol response is largely independent from the vasopressin system, but (2) the corticotrophin-releasing hormone–vasopressin interaction reflected by copeptin may be much more sensitive to reveal subtle alterations in the regulation of pituitary function.



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Title page

Publication date: August 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1868, Issue 1





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Daily lying behavior of lactating Holstein cows during an estrus synchronization protocol and its associations with fertility

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Publication date: Available online 10 August 2017
Source:Journal of Dairy Science
Author(s): B.F. Silper, A.M.L. Madureira, L.B. Polsky, S. Soriano, A.F. Sica, J.L.M. Vasconcelos, R.L.A. Cerri
Objectives were to quantify lying behavior (LB) during an estradiol and progesterone-based synchronization protocol, to assess risk factors for ovulation, pregnancy per AI (P/AI), and degree of behavioral change at estrus, and to investigate the associations between estrus LB and walking activity. Holstein cows (43.6 ± 11.0 kg of milk/d) were fitted with leg-mounted accelerometers. Total lying time/d (L_time), bout frequency (bout_N), average lying bout duration, and relative increase in walking activity (ACT%) were evaluated for 1,411 timed artificial insemination events. The day with lowest L_time or bout_N among d −2, −1, and 0 (day of timed artificial insemination) determined the day of behavioral estrus. The variables L_time% and bout_N% represent relative ratios between lowest L_time and baseline (d −7), L_time, and lowest bout_N, and baseline (d −7) bout_N, respectively {e.g., (lowest L_time/baseline L_time) × 100]. Correlation coefficients between L_time% and bout_N% and ACT% were −0.38 and −0.31, respectively. Estrus LB change was considered large if <75% of baseline and small if ≥75% of baseline for both L_time% and bout_N%; average lying bout duration did not change with estrus. Lowest L_time% and bout_N% corresponded to, respectively, 65 ± 21% (mean ± standard deviation; 447 ± 157 min/d) and 65 ± 24% (8.5 ± 4.0 bouts/d) of baseline. The change in L_time% at estrus was smaller when cows had milk yield above average; the change in bout_N% was smaller among multiparous cows and for estrus occurring in the colder season. Likelihood of ovulation was greater when there was larger change in L_time% [odds ratio = 4.9; ovulation rate = 93 (large change) and 76% (small change)], as well as when a corpus luteum was present at start of protocol (odds ratio = 3.6; in the model with L_time%). Likelihood of pregnancy at d 32 was 1.6 times greater for estrus with large change in LB [L_time% or bout_N%; P/AI = 34% (large change in L_time%) and 26% (small change in L_time%)]. Among estrus events with ACT% ≥300% (high intensity), classification by small or large L_time% did not influence P/AI at 32 d. The magnitude of LB change at estrus and its association with fertility suggest potential application toward improved use of activity monitors (e.g., increased estrus detection, fertility prediction). The contribution of LB to accuracy of estrus detection when physical activity is known remains to be addressed. The relationship between intensity of estrus expression and fertility requires further investigations of its physiological rationale and on-farm applications.



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Genetic analysis of new progesterone-based fertility traits in dairy cows measured on-farm

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Publication date: Available online 10 August 2017
Source:Journal of Dairy Science
Author(s): Diana Sorg, Monika Wensch-Dorendorf, Kati Schöpke, Gunter Martin, Renate Schafberg, Nicole Reinhold, Steffen Pache, Hermann Swalve
The objectives of this study were (1) to analyze the agreement of a standard laboratory ELISA for progesterone (P4) with an automated on-farm ELISA kit operated under commercial conditions in 1,297 milk samples from 50 dairy cows; (2) to study the influence of the method of detection of luteal activity on genetic parameters of fertility traits based on P4 measured with an automated on-farm ELISA once weekly from wk 3 to 9 postpartum in the milk of 1,304 cows; and (3) to study the influence of sampling frequency (once or twice weekly from wk 3 to 9) on the same traits from 296 cows. Luteal activity can be detected when there is an active corpus luteum in the ovary producing P4 and indicating the onset of reproductive cyclicity after calving. The on-farm ELISA overestimated P4 contents by a mean square error of prediction of 2.76 ng/mL and had an intermediate Spearman correlation with the laboratory kit (0.54). For the second objective, the postpartum interval to the commencement of luteal activity (C-LA), proportion of luteal activity between d 15 and 63 postpartum (P-LA), calculated as the number of samples above the threshold for high P4 values divided by the number of all samples, and delay of first ovulation (DOV1), defined as C-LA occurring later than d 45 postpartum, were derived from the P4 profiles. Both C-LA and DOV1 were determined by (a) thorough qualitative visual inspection of the profile, (b) the profile's mean as threshold for the first increase in P4 postpartum, indicating commencement of luteal activity, and (c) 3 ng/mL as threshold for the first increase in P4, a value that has been used by many other studies. Similarly, P-LA was determined by using methods (b) and (c). Estimates of heritability were 0.04 to 0.13 for C-LA, 0.12 to 0.23 for P-LA, and 0.03 to 0.07 for DOV1. Genetic correlation of P-LA with C-LA and with the profile's mean P4 was −1.00. The profile's mean had a higher estimate of heritability (0.11–0.12) than C-LA or DOV1. It can be calculated as the arithmetic mean of all P4 values of a profile, whereas C-LA, P-LA, and DOV1 need a definition of a threshold for high P4 values. We therefore suggest the profile's mean as a promising candidate for further research. For the third objective, once-weekly sampling was mimicked by neglecting every second sample, and C-LA and DOV1 shifted toward a later onset of cyclicity. Thus, a common standard for sampling regimen and detection algorithm is essential to avoid incompatibility between studies.



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Technical note: Use of an automated grooming brush by heifers and potential for radiofrequency identification-based measurements of this behavior

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Publication date: Available online 10 August 2017
Source:Journal of Dairy Science
Author(s): Rachel L. Toaff-Rosenstein, Martin Velez, Cassandra B. Tucker
Healthy cattle readily use grooming brushes but this behavior subsides when animals become ill. Tracking use of a brush may provide an opportunity for health monitoring, especially if the process could be automated. We assessed how healthy heifers groom themselves on a brush and hypothesized that radiofrequency identification (RFID) could be used to accurately and automatically record this behavior. Angus and Hereford heifers (n = 16) were fitted with 2 ultra-high-frequency RFID ear tags and monitored in groups of 8 while housed in a pen with an electronic brush, video cameras, and 4 RFID antennas. Each heifer was observed for a 6-h period using continuous video recordings, and brush contact was characterized in terms of anatomic region involved (head/neck, trunk, or posterior) and when not touching the brush but within 1 body length of it. The RFID data were collected for the same period and then processed such that intervals of up to 16 s with no detections but contained between 2 recordings were also considered positive (animal in brush proximity). Brush proximity (RFID) was regressed against brush contact duration (video) and the sensitivity and specificity for each individual heifer calculated. Across heifers, the majority of brush use involved the head/neck, although a few heifers demonstrated relatively large amounts of posterior contact, which contributed to false-negative readings when antennas failed to read the ear tags. Furthermore, for the majority of time that animals were near the brush, they were not in contact with it but rather standing or lying nearby, resulting in false-positive readings. It follows that the ability of the RFID system to accurately detect brush contact varied widely across individual heifers (sensitivity 0.54–1.0; specificity 0.59–0.98), with RFID generally overestimating the duration of brush proximity relative to actual time spent in brush contact. The implication is that RFID-based ear tag recording of brush proximity relative to continuous video observations of contact does not yield accurate results in certain heifers and therefore, as currently configured, is not a reliable representation of this type of grooming behavior.



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Fertility of lactating Holstein cows submitted to a Double-Ovsynch protocol and timed artificial insemination versus artificial insemination after synchronization of estrus at a similar day in milk range

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Publication date: Available online 10 August 2017
Source:Journal of Dairy Science
Author(s): V.G. Santos, P.D. Carvalho, C. Maia, B. Carneiro, A. Valenza, P.M. Fricke
Our objective was to compare the AI submission rate and pregnancies per artificial insemination (P/AI) at first service of lactating Holstein cows submitted to a Double-Ovsynch protocol and timed artificial insemination (TAI) versus artificial insemination (AI) to a detected estrus after synchronization of estrus at a similar day in milk range. Lactating Holstein cows were randomly assigned to receive their first TAI after a Double-Ovsynch protocol (DO; n = 294) or to receive their first AI after a synchronized estrus (EST; n = 284). Pregnancy status was determined 33 ± 3 d after insemination and was reconfirmed 63 ± 3 d after insemination. Data were analyzed by ANOVA and logistic regression using the MIXED and GLIMMIX procedures of SAS (SAS Institute Inc., Cary, NC). By design, days in milk at first insemination did not differ between treatments (76.9 ± 0.2 vs. 76.7 ± 0.3 for DO vs. EST cows, respectively), but more DO cows were inseminated within 7 d after the end of the voluntary waiting period than EST cows (100.0 vs. 77.5%). Overall, DO cows had more P/AI than EST cows at both 33 d (49.0 vs. 38.6%) and 63 d (44.6 vs. 36.4%) after insemination, but pregnancy loss from 33 to 63 d after insemination did not differ between treatments. Primiparous cows had more P/AI than multiparous cows 33 and 63 d after insemination, but the treatment by parity interaction was not significant. Synchronization rate to the hormonal protocols was 85.3%, which did not differ between treatments; however, synchronized DO cows had more P/AI 33 d after insemination than synchronized EST cows (54.7 vs. 44.5%). In summary, submission of lactating Holstein cows to a Double-Ovsynch protocol and TAI for first insemination increased the percentage of cows inseminated within 7 d after the end of the voluntary waiting period and increased P/AI at 33 and 63 d after first insemination resulting in 64 and 58% more pregnant cows, respectively, than submission of cows for first AI after detection of estrus at a similar day in milk range. We conclude that, because the proportion of synchronized cows did not differ between treatments, DO cows had more P/AI than EST cows because of an intrinsic increase in fertility after submission to a fertility program.



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Effect of dietary supplementation with heat-treated canola meal on ruminal nutrient metabolism in lactating dairy cows

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Publication date: Available online 10 August 2017
Source:Journal of Dairy Science
Author(s): S.J. Krizsan, H. Gidlund, F. Fatehi, P. Huhtanen
An experiment was conducted to quantify the effects of incremental levels of heat-moisture-treated canola meal (TCM) fed to dairy cows on the relationship between ruminal nutrient digestion and milk production. Experimental diets were fed to 4 multiparous rumen-cannulated Nordic Red cows, averaging (mean ± standard deviation) 681 ± 54.8 kg of body weight, 111 ± 16 d in milk, and 29.1 ± 9.1 kg of milk/d at the start of the study, in a Latin square design with four 21-d periods. The 4 experimental dietary treatments consisted of a basal diet of grass silage and crimped barley, and 3 diets in which the crimped barley was replaced with TCM, giving 3 incremental levels of protein supplementation. Nutrient flow was quantified by the omasal sampling technique using 3 markers (Cr, Yb, and indigestible neutral detergent fiber). Continuous infusion of 15N was used to label bacterial crude protein. Additionally, ruminal sampling and evacuations and measurements of total-tract digestibility were conducted. The experimental diets provided 132, 148, 164, and 180 g of crude protein/kg of dry matter. The increased level of TCM linearly increased dry matter intake from 15.1 to 16.6 kg/d and energy-corrected milk yield from 21.0 to 25.6 kg/d. The increased proportion of TCM when substituting barley with TCM was associated with greater total-tract digestibility of neutral detergent fiber and potentially digestible neutral detergent fiber, which could be explained by increased digestion rate of potentially digestible neutral detergent fiber. Omasal flow of nonammonia N naturally increased with greater dietary TCM inclusion, but the increased intestinal supply of rumen-undegradable protein was partly offset by diminished microbial protein synthesis when feeding more TCM. This was also reflected in a decreased proportion of milk protein from ruminal bacterial protein when TCM supplementation increased.



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Short communication: Detection of stx2 and elt genes in bovine milk by using a multiplex PCR system

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Publication date: Available online 10 August 2017
Source:Journal of Dairy Science
Author(s): R.D.S. Nandi, A.C. Campos, J.J. Puño-Sarmiento, R.P. Maluta, S.P.D. Rocha, R.K.T. Kobayashi, G. Nakazato
The aim of this study was to detect 2 important toxin genes from diarrheagenic Escherichia coli (DEC) in bovine milk using a new multiplex PCR. To standardize the multiplex PCR, the stx2 and elt genes were investigated for the detection of Shiga toxin-producing Escherichia coli (STEC) and enterotoxigenic E. coli (ETEC), respectively. The DNA template was prepared with a thermal procedure (boiling) and a commercial kit. Samples consisted of UHT and pasteurized milk, both skimmed, and STEC and ETEC were tested in concentrations between 101 and 109 cfu/mL. With the thermal procedure, the multiplex PCR system detected both pathotypes of E. coli at 109 cfu/mL in UHT and pasteurized milk. When the commercial kit was used for template preparation, STEC and ETEC could be detected at concentrations as low as 104 cfu/mL in UHT and pasteurized milk. Negative controls (Listeria monocytogenes, Salmonella Typhimurium, Salmonella Enteritidis, and Escherichia coli strain APEC 13) were not amplified with the multiplex PCR. These results indicate that the multiplex PCR was a rapid (less than 6 h) and efficient method to detect STEC and ETEC in milk using different methods for DNA preparation; however, the commercial kit was more sensitive than the thermal procedure.



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New insights on the metabolism of ricinoleic acid in ruminants

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Publication date: Available online 10 August 2017
Source:Journal of Dairy Science
Author(s): Susana P. Alves, Cintia M. Araujo, Rita C. Queiroga, Marta S. Madruga, Michelle O.M. Parente, Ariosvaldo N. Medeiros, Rui J.B. Bessa
Dairy goats were fed a total mixed ration with or without the inclusion of castor oil (40 g/kg of DM) to study the metabolism of ricinoleic acid (12-OH,cis-9–18:1). Ten goats, at 39.7 ± 4.0 d in milk, were individually penned and allocated at random to the 2 experimental diets. Goats were manually milked twice a day. Milk fatty acids (FA) were analyzed as methyl esters and hydroxyl groups were derivatized in trimethylsilyl ethers. Apart from ricinoleic acid, 6 FA were only detected in the milk of the castor oil group. Ricinoleic acid composed 0.3% of total FA in milk of the castor oil group, whereas the hydroxy-FA (8-OH-14:0, 10-OH-16:0, and 12-OH-18:0) and oxo-FA (8-oxo-14:0, 10-oxo-16:0, and 12-oxo-18:0) reached 7.5% of total FA in milk. We anticipate that these FA were derived from the metabolism of ricinoleic acid, although it was not clear if they were produced in the rumen or in the tissues. To confirm that, we conducted in vitro batch incubations repeated for 3 consecutive weeks with castor oil (40 g/kg of DM) and strained rumen fluid from 2 fistulated sheep. To examine the products formed over time, incubation tubes were stopped at 0, 6, 12, 24, 48, and 72 h. The results of the in vitro experiment showed that ricinoleic acid was metabolized in the rumen at a slow rate and the main products formed were 12-OH-18:0 and 12-oxo-18:0, by hydrogenation of the cis-9 double bond, followed by oxidation of the hydroxyl group, respectively. Our results suggest that the 12-OH-18:0 and 12-oxo-18:0 escape rumen and are further metabolized through partial β-oxidation in ruminant tissues. We propose that the 10-OH-16:0 and 8-OH-14:0 found in goat milk of the castor oil group are successive products of the β-oxidation of 12-OH-18:0, and the 10-oxo-16:0 and 8-oxo-14:0 are successive products of the 12-oxo-18:0 in tissues. Overall, our results indicate that ricinoleic acid is extensively metabolized in the rumen and tissues, producing mainly oxo- and hydroxy-FA that are further excreted in milk.



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Involvement of plasma adipokines in metabolic and reproductive parameters in Holstein dairy cows fed with diets with differing energy levels

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Publication date: Available online 10 August 2017
Source:Journal of Dairy Science
Author(s): N. Mellouk, C. Rame, J.L. Touzé, E. Briant, L. Ma, D. Guillaume, D. Lomet, A. Caraty, T. Ntallaris, P. Humblot, J. Dupont
This study aimed to investigate the association between plasma adipokine concentrations and metabolic and reproductive parameters in Holstein dairy cows fed diets with different energy levels during the peripartum period. The experiment started 1 mo before first calving and was maintained for 2 lactations. Dry matter intake and energy balance in animals fed a low-energy (LE) diet were significantly lower than that of animals fed a high-energy (HE) diet in the first lactation. Body weight, milk production, back fat thickness, and plasma concentrations of fatty acids, glucose, and insulin were not affected by diet, whereas plasma leptin and adiponectin concentrations were lower and plasma resistin concentrations higher in animals fed the LE diet. Unlike concentrations of adiponectin, plasma resistin concentrations were positively correlated with back fat thickness and plasma fatty acids concentrations and negatively correlated with dry matter intake and plasma leptin concentrations. No effect of diet was found on reproductive variables; that is, pregnancy rates at 35 or 90 d after artificial insemination (AI); numbers of small (3–5 mm), medium (>5 and ≤7 mm), and large (>7 mm) follicles; calving-to-AI and calving-to-calving intervals; and magnitude and duration of the LH surge. However, the commencement of luteal activity after first calving occurred sooner and the frequency of LH pulses was higher in the HE group than in the LE group. A significant positive correlation was found between the number of follicles (of any size) and the area under the curve of plasma resistin concentrations. The number of small follicles was also positively correlated with the nadir of plasma resistin concentrations. Taken together, these results suggest that dietary energy content in the range applied here can alter the resumption of ovarian activity and LH pulsatility without affecting fat mobilization. Plasma adipokine profiles (leptin, resistin, and adiponectin) were significantly altered by diet and negative energy balance but relationships with reproductive variables were limited to follicular growth characteristics and plasma resistin concentrations.



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Short communication: Apparent ruminal synthesis of B vitamins in lactating dairy cows fed Saccharomyces cerevisiae fermentation product

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Publication date: Available online 10 August 2017
Source:Journal of Dairy Science
Author(s): D.S. Castagnino, Y. Ying, M.S. Allen, R. Gervais, P.Y. Chouinard, C.L. Girard
Apparent ruminal synthesis and duodenal flow of thiamin, riboflavin, niacin, vitamin B6, folates, and vitamin B12 were evaluated in an experiment using 15 ruminally and duodenally cannulated lactating Holstein cows fed a basal diet, according to a crossover design, supplemented or not with 56 g/d of Saccharomyces cerevisiae fermentation product. Duration of the treatment period was 28 d. The basal ration had 28% neutral detergent fber, 30% starch and 16.5% crude protein; forages were corn silage (67% of forage dry matter) and alfalfa silage (33% of forage dry matter). Concentrations of B vitamins were analyzed in feed and duodenal digesta. Apparent ruminal synthesis of each B vitamin was calculated as the duodenal flow minus the intake. Under the present experimental conditions, a dietary supplement of Saccharomyces cerevisiae fermentation product had no effect apparent synthesis of B vitamins in the rumen or on the amounts of these vitamins reaching the duodenum and available for absorption by the dairy cow.



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Short communication: Molecular characteristics, antimicrobial susceptibility, and pathogenicity of clinical Nocardia cyriacigeorgica isolates from an outbreak of bovine mastitis

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Publication date: Available online 10 August 2017
Source:Journal of Dairy Science
Author(s): Wei Chen, Yongxia Liu, Herman W. Barkema, Jian Gao, Jeroen De Buck, John P. Kastelic, Gang Liu, Tariq Ali, Muhammad Shahid, Bo Han
The occurrence of nocardial mastitis, mostly in the context of outbreaks, has been reported in many countries. However, there is a paucity of reports regarding detailed characterization of Nocardia cyriacigeorgica from bovine mastitis. Thus, herein we report characteristics, antimicrobial susceptibility patterns, molecular identification, and pathogenicity of N. cyriacigeorgica isolated from an outbreak of clinical mastitis in a dairy herd in northern China. A total of 182 (80.2%) lactating cows had clinical mastitis with severe inflammation and firmness of the udder, reduced milk production, and anorexia, with no apparent clinical response to common antibiotics. Out of 22 mastitic milk samples submitted to our laboratory, 12 N. cyriacigeorgica were isolated and characterized using standard microbiological analysis, 16S rRNA gene sequencing, random amplified polymorphic DNA PCR analysis, biochemical assays, and antibiotic susceptibility testing. Additionally, in vivo experiments were done to determine pathogenicity of these clinical mastitis isolates. All isolates were resistant to ampicillin, amoxicillin-clavulanic acid, ciprofloxacin, minocycline, rifampicin, and aminoglycosides (type VI pattern). Additionally, intramammary inoculation of mice with N. cyriacigeorgica caused chronic inflammatory changes, including hyperemia, edema, and infiltration of lymphocytes and neutrophils, as well as hyperplasia of lymph nodules in mammary glands. Therefore, we concluded that N. cyriacigeorgica was involved in the current outbreak of mastitis. To our best knowledge, this is the first report to characterize N. cyriacigeorgica isolated from cases of bovine mastitis in China.



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Consumer acceptance of dairy products with a saturated fatty acid–reduced, monounsaturated fatty acid–enriched content

Publication date: Available online 10 August 2017
Source:Journal of Dairy Science
Author(s): Oonagh Markey, Kallis Souroullas, Colette C. Fagan, Kirsty E. Kliem, Dafni Vasilopoulou, Kim G. Jackson, David J. Humphries, Alistair S. Grandison, David I. Givens, Julie A. Lovegrove, Lisa Methven
Agriculture-based reformulation initiatives, including oleic acid–rich lipid supplementation of the dairy cow diet, provide a novel means for reducing intake of saturated fatty acids (SFA) at a population level. In a blinded manner, this study evaluated the consumer acceptance of SFA-reduced, monounsaturated fatty acid–enriched (modified) milk, Cheddar cheese, and butter when compared with control and commercially available comparative samples. The effect of providing nutritional information about the modified cheese was also evaluated. Consumers (n = 115) rated samples for overall liking (appearance, flavor, and texture) using 9-point hedonic scales. Although no significant differences were found between the milk samples, the modified cheese was liked significantly less than a regular-fat commercial alternative for overall liking and liking of specific modalities and had a lower liking of texture score compared with the control cheese. The provision of health information significantly increased the overall liking of the modified cheese compared with tasting the same sample in a blinded manner. Significant differences were evident between the butter samples for overall liking and modalities of liking; all of the samples were significantly more liked than the commercial butter and sunflower oil spread. In conclusion, this study illustrated that consumer acceptance of SFA-reduced, monounsaturated fatty acid–enriched dairy products was dependent on product type. Future research should consider how optimization of the textural properties of fatty acid–modified (and fat-reduced) cheese might enhance consumer acceptance of this product.



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Associations between biosecurity practices and bovine digital dermatitis in Danish dairy herds

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Publication date: Available online 10 August 2017
Source:Journal of Dairy Science
Author(s): Victor H.S. Oliveira, Jan T. Sørensen, Peter T. Thomsen
The relationship between biosecurity and digital dermatitis (DD) was evaluated in 8,269 cows from a convenience sample of 39 freestall dairy herds. The hypothesis was that poor implementation of biosecurity was associated with higher within-herd prevalence of DD. All lactating cows were scored as negative or positive for DD at the hind legs during milking in the milking parlor. Information about biosecurity was obtained through questionnaires addressed to farmers, on-farm observations, and information from the Danish Cattle Database (www.seges.dk). These assessment tools covered potential infection sources of DD pathogens to susceptible cows (e.g., via animals, humans, manure, vehicles, equipment, and facilities). External and internal biosecurity measures were explanatory variables in 2 separate logistic regression models, whereas within-herd DD prevalence was the outcome. Overall DD prevalence among cows and herds were 24 and 97%, respectively; the within-herd DD prevalence ranged from 0 to 56%. Poor external biosecurity measures associated with higher prevalence of DD were recent animal purchase, access to pasture, lack of boots available for visitors, farm staff working at other dairy farms as well, hoof trimming without a professional attending, and animal transporters having access to cattle area. For internal biosecurity, higher DD prevalence were associated with infrequent hoof bathing, manure scraping less than 8 times a day, manure removal direction from cows to heifers, animal pens' exit without water hoses, manure-handling vehicle used in other activities, and water troughs contaminated with manure. These findings showed that improvements on biosecurity may be beneficial for controlling DD in dairy herds. The study is relevant for farmers facing problems with DD, as well as hoof trimmers, advisors, and veterinarians, who can use the results for optimized recommendations regarding biosecurity in relation to DD. Furthermore, our results might be considered by future studies investigating DD pathogen reservoirs and transmission routes.



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Two-step large-volume magnetic separation combined with PCR assay for sensitive detection of Listeria monocytogenes in pasteurized milk

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Publication date: Available online 10 August 2017
Source:Journal of Dairy Science
Author(s): Dan Luo, Xiaolin Huang, Yan Mao, Chaochao Chen, Fulai Li, Hengyi Xu, Yonghua Xiong
Immunomagnetic separation (IMS) is an effective tool for the preconcentration and purification of food-borne pathogens from complex food samples because of its high capture efficiency (CE). In conventional IMS, antibodies are usually conjugated on the surface of magnetic beads (MB); the random orientation and conformation changes of antibodies on the MB surface can decrease their bioactivity. Moreover, the Brownian motion of immobilized antibodies is weakened, thereby rendering their binding efficiency with bacteria lower than that of free antibodies. Thus, abundant antibodies are commonly required to ensure high CE for IMS, particularly for large volumes. In this study, a 2-step large-volume magnetic separation (10 mL) was proposed to preconcentrate Listeria monocytogenes from pasteurized milk. First, the biotinylated anti-L. monocytogenes monoclonal antibodies (mAb) were bound with L. monocytogenes in 10 mL of diluted milk through an antigen-antibody interaction, and then streptavidin-labeled MB were used to capture biotin-mAb coated with L. monocytogenes by biotin and streptavidin interaction. Under optimal conditions, the CE of 2-step magnetic separation was >90% with L. monocytogenes concentrations ranging from 8 × 100 to 8 × 104 cfu/mL, whereas the amount of biotin-mAb was 14 fold lower than that of the conventional IMS method. Coupled with a PCR assay, the detection limit of the proposed method was 8 × 100 cfu/mL in pure culture and 8 × 101 cfu/mL in pasteurized milk without any pre-enrichment process. Moreover, the overall detection time, including sample preparation, large-volume magnetic separation, and PCR, took less than 7 h. In summary, the developed 2-step large-volume IMS combined with PCR was highly sensitive and low cost and, thus, has considerable potential for the rapid screening of food-borne pathogenic bacteria.



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Effect of fermented milk containing Lactobacillus rhamnosus SD11 on oral microbiota of healthy volunteers: A randomized clinical trial

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Publication date: Available online 10 August 2017
Source:Journal of Dairy Science
Author(s): P. Rungsri, N. Akkarachaneeyakorn, M. Wongsuwanlert, S. Piwat, P. Nantarakchaikul, R. Teanpaisan
The aims of this study were to evaluate whether short-term consumption of fermented milk containing Lactobacillus rhamnosus SD11 affected levels of oral microbiota in vivo and whether L. rhamnosus SD11 could colonize in the human mouth. We also monitored for potential side effects of the probiotic. The applicability of using L. rhamnosus SD11 compared with Lactobacillus bulgaricus as a starter culture for fermented milk was evaluated. After informed consent, 43 healthy young adults were recruited and randomly assigned to either the probiotic or control group and received fermented milk containing L. rhamnosus SD11 or L. bulgaricus, respectively, once daily for 4 wk. The numbers of mutans streptococci, lactobacilli, and total bacteria in saliva were counted at baseline and then after 4 and 8 wk. An oral examination was performed at baseline and after 8 wk. The persistence of L. rhamnosus SD11 was investigated by DNA fingerprinting using arbitrary primer-PCR. Results demonstrated that statistically significant reductions in mutans streptococci and total bacteria were observed in the probiotic group compared with the control group, and the number of lactobacilli was significantly increased in both groups after receiving fermented milks. Lactobacillus rhamnosus SD11 could be detected (in >80% of subjects) up to 4 wk following cessation of dosing among subjects in the probiotic group. No side effects were reported. Thus, L. rhamnosus SD11 could be used as a starter culture for fermented milk. Daily consumption of L. rhamnosus SD11-containing fermented milk for 4 wk may have beneficial effects on oral health by reducing salivary levels of mutans streptococci. The probiotic was apparently able to colonize the oral cavity for a longer time than previously reported. However, the potential benefits of probiotic L. rhamnosus SD11 on oral health require further evaluation with a larger group of volunteers in a longer-term study.



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Association between ambient temperature and humidity, vaginal temperature, and automatic activity monitoring on induced estrus in lactating cows

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Publication date: Available online 9 August 2017
Source:Journal of Dairy Science
Author(s): Liam B. Polsky, Augusto M.L. Madureira, Eraldo L. Drago Filho, Sergio Soriano, Alex. F. Sica, José L.M. Vasconcelos, Ronaldo L.A. Cerri
The objective of this study was to determine the association between ambient temperature and humidity, vaginal temperature, and automated activity monitoring in synchronized cows. Lactating Holstein cows (n = 641; 41.5 ± 9.4 kg of milk/d) were fitted with leg-mounted pedometers, resulting in 843 evaluated activity episodes of estrus. Vaginal temperature was monitored using thermometers attached to an intravaginal device as part of a timed artificial insemination (TAI) protocol; vaginal temperature was recorded every 10 min for 3 d. Ambient temperature and relative humidity were monitored using an external thermometer placed in the center of each pen. Milk production and body condition score (BCS) data were collected at the time of thermometer insertion. All statistical analysis was performed in R (http://ift.tt/1TYoqFc) using Pearson correlation, analysis of variance, and logistic regression. Heat stress was calculated based on the percentage of time the cow spent with a vaginal temperature ≥39.1°C (PCT39) 9 to 11 d before TAI, and was classified as high (≥22.9%) or low (<22.9%). The mean vaginal temperature was 38.9 ± 0.2°C, and the mean maximum and minimum vaginal temperatures were 39.7 ± 0.5°C and 38.0 ± 0.8°C, respectively, with an average amplitude of 1.71 ± 0.9°C. Mean relative increase (RI) of estrus walking activity was 237.0 ± 160%. Animals with low BCS had a lower RI compared with cows with medium BCS (260.31 ± 17.45% vs. 296.42 ± 6.62%). Cows in early lactation showed lower RI compared with mid- and late-lactation animals (265.40 ± 9.90% vs. 288.36 ± 11.58% vs. 295.75 ± 11.29% for early, mid, and late lactation, respectively). Temperature-humidity index (THI) conditions categorized as low (THI ≤65) were associated with greater RI compared with medium (>65 to <70) and high THI (≥70). We detected no significant effect of PCT39 or milk production on RI, whereas parity exhibited a tendency. Cows that displayed greater RI at estrus had greater pregnancies per artificial insemination (P/AI) than cows with low RI (27 vs. 20%) or no RI (27 vs. 12%). Primiparous cows had greater P/AI than multiparous cows (27 vs. 20%), and cows in early and mid lactation had improved P/AI than those in late lactation (26 vs. 22 vs. 16% for early, mid, and late lactation, respectively). An interaction was observed between PCT39 and THI on P/AI, where a subpopulation of cows with high PCT39 had decreased P/AI under high THI conditions, but no differences in P/AI were observed for high PCT39 cows under medium or low THI conditions (13 vs. 24 vs. 26%). Future research should aim to refine variables related to hyperthermia and to understand the effects of body temperature on estrus expression and pregnancy rates.



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Τετάρτη 9 Αυγούστου 2017

Beyond Genomics - Targeting the Epigenome in Diffuse Large B-Cell Lymphoma

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Publication date: Available online 9 August 2017
Source:Cancer Treatment Reviews
Author(s): Andrea Kühnl, David Cunningham, Ian Chau
After decades of intense research on genetic alterations in cancer and successful implementation of genetically-based targeted therapies, the field of cancer epigenetics is only beginning to be fully recognized. The discovery of frequent mutations in genes modifying the epigenome in diffuse large B-cell lymphoma (DLBCL) has highlighted the outstanding role of epigenetic deregulation in this disease. Identification of epigenetically-driven DLBCL subgroups and development of novel epigenetic drugs have rapidly advanced. However, further insights are needed into the biological consequences of epigenetic alterations and the possibility of restoring the aberrant epigenome with specific therapies to bring this treatment concept further into clinical practice. This review will summarize the main epigenetic changes found in DLBCL and their potential for precision medicine approaches.



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Novel method of extracting motion from natural movies

Publication date: Available online 9 August 2017
Source:Journal of Neuroscience Methods
Author(s): Wataru Suzuki, Noritaka Ichinohe, Toshiki Tani, Taku Hayami, Naohisa Miyakawa, Satoshi Watanabe, Hiroshige Takeichi
BackgroundThe visual system in primates can be segregated into motion and shape pathways. Interaction occurs at multiple stages along these pathways. Processing of shape-from-motion and biological motion is considered to be a higher-order integration process involving motion and shape information. However, relatively limited types of stimuli have been used in previous studies on these integration processes.New methodWe propose a new algorithm to extract object motion information from natural movies and to move random dots in accordance with the information. The object motion information is extracted by estimating the dynamics of local normal vectors of the image intensity projected onto the x-y plane of the movie.ResultsAn electrophysiological experiment on two adult common marmoset monkeys (Callithrix jacchus) showed that the natural and random dot movies generated with this new algorithm yielded comparable neural responses in the middle temporal visual area.Comparison with existing methodsIn principle, this algorithm provided random dot motion stimuli containing shape information for arbitrary natural movies. This new method is expected to expand the neurophysiological and psychophysical experimental protocols to elucidate the integration processing of motion and shape information in biological systems.ConclusionsThe novel algorithm proposed here was effective in extracting object motion information from natural movies and provided new motion stimuli to investigate higher-order motion information processing.



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Dissipation kinetics, pre-harvest residue limits, and hazard quotient assessments of pesticides flubendiamide and fluopicolide in Korean melon ( Cucumis melo L. var. makuwa ) grown under regulated conditions in plastic greenhouses

Abstract

The dissipation kinetics, pre-harvest residue limits, and hazard quotient (HQ) assessments of the pesticides flubendiamide and fluopicolide were conducted for Korean melon (Cucumis melo L. var. makuwa) cultivated at two different sites. A single extraction and cleanup procedure was carried out using acetone (partitioned with dichloromethane) and amino solid-phase extraction cartridges, respectively. Residue analysis was performed by HPLC with ultraviolet detection. Both pesticides showed excellent linearity with correlation coefficients of 0.9999 and 0.9996 for flubendiamide and fluopicolide, respectively. The accuracy (expressed as recovery %) at three spiking levels was 92.0–103.6 and 82.8–105.3%, and the precision (expressed as relative standard deviation) was 1.7–3.4 and 2.7–5.3% for flubendiamide and fluopicolide, respectively. The initial residues of flubendiamide/fluopicolide were 0.326/0.376 and 0.206/0.298 mg/kg at sites 1 and 2, respectively. These amounts were substantially lower than the maximum residue limits (MRLs = 1 and 0.5 mg/kg for flubendiamide and fluopicolide, respectively) established by the Korean Ministry of Food and Drug Safety. The half-lives of flubendiamide were 5.8 and 6.5 days, and those of fluopicolide were 6.7 and 9.1 days at sites 1 and 2, respectively. The shorter half-lives were attributed to seasonal variations (higher temperatures) and enzymatic and metabolic profiling. The risk assessment HQs of flubendiamide were 0.217/0.249 on day 0, which decreased to 0.102/0.168 on day 5, and to 0.065/0.88 on day 10; the HQ values for fluopicolide were 0.029/0.042, 0.022/0.025, and 0.010/0.019 on day 0, day 5, and day 10, for sites 1/2, respectively. From this data, we concluded that the fruits could be consumed safely.



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Flexible biodegradable citrate-based polymeric step-index optical fiber

Publication date: October 2017
Source:Biomaterials, Volume 143
Author(s): Dingying Shan, Chenji Zhang, Surge Kalaba, Nikhil Mehta, Gloria B. Kim, Zhiwen Liu, Jian Yang
Implanting fiber optical waveguides into tissue or organs for light delivery and collection is among the most effective ways to overcome the issue of tissue turbidity, a long-standing obstacle for biomedical optical technologies. Here, we report a citrate-based material platform with engineerable opto-mechano-biological properties and demonstrate a new type of biodegradable, biocompatible, and low-loss step-index optical fiber for organ-scale light delivery and collection. By leveraging the rich designability and processibility of citrate-based biodegradable polymers, two exemplary biodegradable elastomers with a fine refractive index difference and yet matched mechanical properties and biodegradation profiles were developed. Furthermore, we developed a two-step fabrication method to fabricate flexible and low-loss (0.4 db/cm) optical fibers, and performed systematic characterizations to study optical, spectroscopic, mechanical, and biodegradable properties. In addition, we demonstrated the proof of concept of image transmission through the citrate-based polymeric optical fibers and conducted in vivo deep tissue light delivery and fluorescence sensing in a Sprague-Dawley (SD) rat, laying the groundwork for realizing future implantable devices for long-term implantation where deep-tissue light delivery, sensing and imaging are desired, such as cell, tissue, and scaffold imaging in regenerative medicine and in vivo optogenetic stimulation.



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PNIPAAm-co-Jeffamine® (PNJ) scaffolds as in vitro models for niche enrichment of glioblastoma stem-like cells

Publication date: October 2017
Source:Biomaterials, Volume 143
Author(s): John M. Heffernan, James B. McNamara, Sabine Borwege, Brent L. Vernon, Nader Sanai, Shwetal Mehta, Rachael W. Sirianni
Glioblastoma (GBM) is the most common adult primary brain tumor, and the 5-year survival rate is less than 5%. GBM malignancy is driven in part by a population of GBM stem-like cells (GSCs) that exhibit indefinite self-renewal capacity, multipotent differentiation, expression of neural stem cell markers, and resistance to conventional treatments. GSCs are enriched in specialized niche microenvironments that regulate stem phenotypes and support GSC radioresistance. Therefore, identifying GSC-niche interactions that regulate stem phenotypes may present a unique target for disrupting the maintenance and persistence of this treatment resistant population. In this work, we engineered 3D scaffolds from temperature responsive poly(N-isopropylacrylamide-co-Jeffamine M-1000® acrylamide), or PNJ copolymers, as a platform for enriching stem-specific phenotypes in two molecularly distinct human patient-derived GSC cell lines. Notably, we observed that, compared to conventional neurosphere cultures, PNJ cultured GSCs maintained multipotency and exhibited enhanced self-renewal capacity. Concurrent increases in expression of proteins known to regulate self-renewal, invasion, and stem maintenance in GSCs (NESTIN, EGFR, CD44) suggest that PNJ scaffolds effectively enrich the GSC population. We further observed that PNJ cultured GSCs exhibited increased resistance to radiation treatment compared to GSCs cultured in standard neurosphere conditions. GSC radioresistance is supported in vivo by niche microenvironments, and this remains a significant barrier to effectively treating these highly tumorigenic cells. Taken in sum, these data indicate that the microenvironment created by synthetic PNJ scaffolds models niche enrichment of GSCs in patient-derived GBM cell lines, and presents tissue engineering opportunities for studying clinically important behaviors such as radioresistance in vitro.



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Astrocytes and endoplasmic reticulum stress: A bridge between obesity and neurodegenerative diseases

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Publication date: Available online 10 August 2017
Source:Progress in Neurobiology
Author(s): Cynthia A. Martin-Jiménez, Ángela García-Vega, Ricardo Cabezas, Gjumrakch Aliev, Valentina Echeverria, Janneth González, George E. Barreto
Endoplasmic reticulum (ER) is a subcellular organelle involved in protein folding and processing. ER stress constitutes a cellular process characterized by accumulation of misfolded proteins, impaired lipid metabolism and induction of inflammatory responses. ER stress has been suggested to be involved in several human pathologies, including neurodegenerative diseases and obesity. Different studies have shown that both neurodegenerative diseases and obesity trigger similar cellular responses to ER stress. Moreover, both diseases are assessed in astrocytes as evidences suggest these cells as key regulators of brain homeostasis. However, the exact contributions to the effects of ER stress in astrocytes in the various neurodegenerative diseases and its relation with obesity are not well known. Here, we discuss recent advances in the understanding of molecular mechanisms that regulate ER stress-related disorders in astrocytes such as obesity and neurodegeneration. Moreover, we outline the correlation between the activated proteins of the unfolded protein response (UPR) in these pathological conditions in order to identify possible therapeutic targets for ER stress in astrocytes. We show that ER stress in astrocytes shares UPR activation pathways during both obesity and neurodegenerative diseases, demonstrating that UPR related proteins like ER chaperone GRP 78/Bip, PERK pathway and other exogenous molecules ameliorate UPR response and promote neuroprotection.



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Valproic Acid Sensitizes Breast Cancer Cells to Hydroxyurea through Inhibiting RPA2 Hyperphosphorylation-Mediated DNA Repair Pathway

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Publication date: Available online 9 August 2017
Source:DNA Repair
Author(s): Youjia Tian, Guochao Liu, Hui Wang, Zhujun Tian, Zuchao Cai, Fengmei Zhang, Yue Luo, Shue Wang, Gongshe Guo, Xiaowei Wang, Simon Powell, Zhihui Feng
It was reported that valproic acid (VPA, a histone deacetylase inhibitor) can sensitize cancer cells to hydroxyurea (HU, a ribonucleotide reductase inhibitor) for chemotherapy, although the mechanism of VPA-induced HU sensitization is unclear. In this study, we systematically characterized VPA-induced HU sensitization of breast cancer cells. Multiple breast cancer cell models were employed to investigate whether the safe concentration of 0.5mM VPA and 2mM HU can result in DNA double-strand breaks (DSBs) and impact cell survival. Furthermore, the underlying mechanism was explored through cell biology assays, including clonogenic survival, homologous recombination (HR) activity, immunoblot and immunofluorescence. We found that VPA and HU cooperatively suppressed cancer cell survival. VPA resulted in the accumulation of more DNA double-strand breaks (DSBs) in response to HU-induced replication arrest and was able to block HU-stimulated homologous recombination (HR) through inhibiting the activity of two key HR repair proteins by hyperphosphorylation of replication protein A2 (RPA2-p) and recombinase Rad51. However, apoptosis was not detected under this condition. In addition, the results from the survival fraction in the cells expressing defective RPA2-p showed that VPA disrupted the HU-induced RPA2-p-Rad51-mediated HR pathway. Importantly, these findings were further supported by analyzing primary-culture cells from the tissue of chemical carcinogen (DMBA)-induced breast cancer in rats. Thus, our data demonstrated that VPA and HU synergistically suppressed tumor cells via disturbing RPA2-p-mediated DNA repair pathway, which provides a new way for combining chemotherapeutic drugs to sensitize breast cancer cells.



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