Age-Related Remodeling of the JAK/STAT/SOCS Signaling Pathway and Associated Myocardial Changes: From Histological to Molecular Level

Publication date: Available online 4 August 2017
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): Basma Emad aboulhoda
BackgroundThe cellular and molecular mechanisms implicated in age-associated changes in myocardial structure are of paramount importance since they cause profound alterations in the functional response and represent targets for alleviating age-related pathologies. One of these mechanisms is the JAK/STAT/SOCS signaling pathway.Aim of the studyThe present study is designed to elucidate age-dependent changes of the myocardium to provide morphological basis displaying the pathogenesis of myocardial hypertrophy, fibrosis and inflammation with aging.Material and MethodsThirty male Sprague Dawley rats aged; 6, 30 and 36 months were used in this study. The animals were divided into three age groups, young adult, senile and very senile rats, respectively. The heart weight/body weight ratio was determined. The heart was subjected to gross morphologic examination, microscopic examination using H&E and Masson's trichrome stains and immunohistochemical examination for detection of JAK, pSTAT3, α-SMA, β-MHC and CD45. Western blotting was also carried out to detect SOCS genes. Real-time PCR was used to detect the inflammatory markers TNFα and IL1β and the hypertrophy marker α −SKA. Biochemical analysis of cardiac troponin I and creatine kinase-MB was done. Quantitative histomorphometric estimations included estimation of cardiac myocyte cross sectional area, estimation of the area percent of collagen fibers in Masson's trichrome stained sections and determination of optical density in immunostained sections. Electron microscopic examination was done to determine capillary density.ResultsJak and pSTAT3 were predominantly localized to the nuclei and exhibited progressive decline with aging, while SOCS3 activity displayed an age-related increase. The aged myocardium displayed profound age associated structural changes as well as myocardial hypertrophy, fibrosis and inflammation in senile and very senile rats.ConclusionThe age-related modifications in the JAK/STAT/SOCS signaling as well as the age-associated pathological changes in myocardial structure are of particular interest as they provide further insight in age-associated heart pathologies and represent potential targets for cardioprotective and therapeutic approaches.



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Application of phosphate solubilizing bacteria in immobilization of Pb and Cd in soil

Abstract

In the present study, heavy metal (HM)-tolerant phosphate solubilizing bacteria (PSB) were isolated and their performance during the remediation of Pb and Cd in contaminated soil was studied. A total of 16 bacterial strains and one consortium were isolated, and the consortium had the highest phosphate solubilizing ability and HM tolerance. Great variations between the Fourier transform infrared (FTIR) spectra of consortium cells before and after adsorption of Pb²⁺ and Cd²⁺ revealed that amide I/amide II bonds and carboxyl on the cell surface were involved in binding of metal ions. High-throughput sequencing technique revealed that the consortium was composed of Enterobacter spp., Bacillus spp., and Lactococcus spp. The consortium was added into contaminated soil, and its potential ability in dissolution of phosphate from Ca₃(PO₄)₂ and subsequent immobilization of HMs was tested. Results showed that when Ca₃(PO₄)₂ was applied at 10.60 mg/g soil, PSB addition significantly increased soil available phosphate content from 12.28 to 17.30 mg/kg, thereby enhancing the immobilization rate of Pb and Cd from 69.95 to 80.76% and from 28.38 to 30.81%, respectively. Microcalorimetric analysis revealed that PSB addition significantly improved soil microbial activity, which was possibly related with the decreased HMs availability and the nutrient effect of the solubilized phosphate. The present study can provide a cost-effective and environmental-friendly strategy to remediate multiple HM-contaminated soils.

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aPKC Cycles between Functionally Distinct PAR Protein Assemblies to Drive Cell Polarity

Publication date: Available online 3 August 2017
Source:Developmental Cell
Author(s): Josana Rodriguez, Florent Peglion, Jack Martin, Lars Hubatsch, Jacob Reich, Nisha Hirani, Alicia G. Gubieda, Jon Roffey, Artur Ribeiro Fernandes, Daniel St Johnston, Julie Ahringer, Nathan W. Goehring
The conserved polarity effector proteins PAR-3, PAR-6, CDC-42, and atypical protein kinase C (aPKC) form a core unit of the PAR protein network, which plays a central role in polarizing a broad range of animal cell types. To functionally polarize cells, these proteins must activate aPKC within a spatially defined membrane domain on one side of the cell in response to symmetry-breaking cues. Using the Caenorhabditis elegans zygote as a model, we find that the localization and activation of aPKC involve distinct, specialized aPKC-containing assemblies: a PAR-3-dependent assembly that responds to polarity cues and promotes efficient segregation of aPKC toward the anterior but holds aPKC in an inactive state, and a CDC-42-dependent assembly in which aPKC is active but poorly segregated. Cycling of aPKC between these distinct functional assemblies, which appears to depend on aPKC activity, effectively links cue-sensing and effector roles within the PAR network to ensure robust establishment of polarity.

Graphical abstract

Teaser

PAR polarity pathway-mediated cell polarization relies on a conserved network of proteins including PAR-3, CDC-42, PAR-6, and aPKC. Rodriguez, Peglion et al. uncover a division of labor whereby PAR-6 and aPKC cycle between distinct cue-sensing and effector assemblies that act cooperatively to polarize the one-cell C. elegans zygote.


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Patient interest in and familiarity with anti-aging therapies: A survey of the general dermatology clinic population

Summary

Background

The appearance of aging skin is a common complaint among dermatology patients. There is an expanding market for anti-aging therapies, but little information is available regarding which patients utilize these treatments and patient preferences regarding treatment.

Aims

To describe the patient population utilizing anti-aging therapies, assess patient familiarity with treatment options, and learn where treatment information is most often obtained.

Patients/Methods

Three hundred patients were surveyed in the University of Michigan General Dermatology Clinic.

Results

Fifty-three percent of the general dermatology patient population has used an anti-aging treatment in the past; 66% reported interest in the future use. Interest is high among all genders, ages, and incomes. Most subjects obtained treatment information from magazines, but subjects were more likely to pursue treatment if information was obtained from a dermatologist.

Conclusion

Demographics of anti-aging therapy are changing, and a wide variety of patients pursue treatment. Patients are largely unfamiliar with most treatment options and are more likely to pursue treatment after receiving treatment information from a dermatologist. The information presented in this study is helpful to both dermatologists and marketers of anti-aging products.

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Polygonatum Sibiricum Polysaccharide Promotes Osteoblastic Differentiation Through the ERK/GSK-3β/β-Catenin Signaling Pathway In Vitro

Rejuvenation Research , Vol. 0, No. 0.


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Laser treatments of active acne

Abstract

The utility of laser therapy is increasingly being recognized in the treatment of active acne vulgaris. We aimed to perform a narrative review of the medical literature on the use of laser therapy for the treatment of active acne vulgaris. We performed a PubMed literature search on September 1, 2016 using the search terms "active acne," "acne," "laser therapy," and "laser surgery." Case reports, case series, cohort, and controlled trials were included. Studies of lasers in the treatment of acne, including erbium glass, Nd:YAG, pulse dye laser (PDL), potassium titanyl phosphate (KTP) laser, and laser-based photodynamic therapy, have been published. While treatment of active acne with lasers has been successful, many studies are limited by small patient number and lack of control populations and comparison to standard therapies for active acne. Laser therapies are increasingly becoming part of or an adjunct to the medical treatment of active acne and are a useful treatment modality.

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Influence of radiotherapy on the dentin properties and bond strength

Abstract

Objectives

The objective of this study was to evaluate the biomechanical properties of dentin and the microtensile bond strength (μTBS) performed before or after radiotherapy (RT).

Material and methods

Dentin chemical composition (infrared spectroscopy—FTIR), SEM images, and mechanical properties (Vickers microhardness—VHN and elastic modulus—E) were evaluated comparing no irradiated and irradiate dentin (n = 5). RT was defined by application of 72 Gy (1.8 Gy daily, 5 days per week, during 8 weeks) with sample immersed in distilled water. μTBS evaluated three groups (n = 10): NI—no irradiated; IB—irradiation before restoration; and IA—irradiation after restoration. Resin-dentin sticks (1.0 mm²) were obtained and submitted to μTBS. Analysis of the bonding interface was made by confocal microscopy.

Results

After RT, percentage ratio of FTIR analysis showed increased absorption for all bands. SEM image showed a disorganized dentin structure. Two-way ANOVA showed increased VHN (p = 0.005) and decreased E (p < 0.001). For μTBS, one-way ANOVA and Duncan test showed significant differences among groups (p = 0.018). IB group presented the lowest bond strength values.

Conclusions

RT alters the absorption bands and SEM images showed a disorganization of the dentin structure. Mechanical properties were changed with increased VHN and decreased E. μTBS was affected by the radiotherapy and restoration period (before or after).

Clinical relevance

RT causes changes that contribute to increased risk of tooth decay. Restorative treatments can be performed using adhesive procedures, but it is preferable to be performed before of the irradiation protocol, to guarantee better adhesive properties to restoration.

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Repression of Stress-Induced LINE-1 Expression Protects Cancer Cell Subpopulations from Lethal Drug Exposure

Publication date: Available online 3 August 2017
Source:Cancer Cell
Author(s): Gulfem Dilek Guler, Charles Albert Tindell, Robert Pitti, Catherine Wilson, Katrina Nichols, Tommy KaiWai Cheung, Hyo-Jin Kim, Matthew Wongchenko, Yibing Yan, Benjamin Haley, Trinna Cuellar, Joshua Webster, Navneet Alag, Ganapati Hegde, Erica Jackson, Tracy Leah Nance, Paul Garrett Giresi, Kuan-Bei Chen, Jinfeng Liu, Suchit Jhunjhunwala, Jeff Settleman, Jean-Philippe Stephan, David Arnott, Marie Classon
Maintenance of phenotypic heterogeneity within cell populations is an evolutionarily conserved mechanism that underlies population survival upon stressful exposures. We show that the genomes of a cancer cell subpopulation that survives treatment with otherwise lethal drugs, the drug-tolerant persisters (DTPs), exhibit a repressed chromatin state characterized by increased methylation of histone H3 lysines 9 and 27 (H3K9 and H3K27). We also show that survival of DTPs is, in part, maintained by regulators of H3K9me3-mediated heterochromatin formation and that the observed increase in H3K9me3 in DTPs is most prominent over long interspersed repeat element 1 (LINE-1). Disruption of the repressive chromatin over LINE-1 elements in DTPs results in DTP ablation, which is partially rescued by reducing LINE-1 expression or function.

Graphical abstract

Teaser

Guler et al. show that drug-tolerant persisters (DTPs), a cancer cell subpopulation surviving lethal drugs, are partly maintained by a repressed chromatin state, prominently at LINE-1 elements. Disrupting the repressive chromatin results in death of DTPs, which is partially rescued by reducing LINE-1 expression.


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Methylene blue mediated photobiomodulation on human osteoblast cells

Abstract

Photobiomodulation (PBM) and photodynamic therapy (PDT) are two major methods, which use light in medicine and dentistry. PBM uses low-level laser light to induce cell proliferation and activity. In contrast, PDT use laser light combined with a photosensitizer (PS) to cause cell death. Due to similar, not fully understood mechanisms and biphasic response of light, unexpected and complex outcomes may be observed. In the present study, the effect of 635 nm laser light, with power density 50 mW/cm², at three different energy densities (0.5, 1, and 2 J/cm² which last 10, 20, and 40 s, respectively) mediated by methylene blue (MB) on the human osteoblast cell line (ATCC-CRL-11372, Rockville, MD, USA) was investigated. Cell viability (MTT assay and acridine orange/propidium iodide staining) and proliferation (Alamar Blue assay) were assessed at 24, 48, and 72 h post irradiation. Alkaline phosphatase (ALP) activity, mineralization (Alizarin Red staining) and gene expressions (RT-PCR analysis) were analyzed at 7th and 14th days after treatment. Five groups were formed as the control group (no MB, no irradiation), MB (only 0.05 μM MB), MB + 0.5 J/cm², MB + 1 J/cm², and MB + 2 J/cm². Cell viability was decreased at 72 h (ANOVA; p < 0.05) for MB + 0.5 J/cm², MB + 1 J/cm², and MB + 2 J/cm² groups. Although proliferation does not seem to be effected by MB-mediated laser application, osteo-anabolic activity is altered. ALP activity was significantly increased at day 7 (ANOVA; p < 0.05) for MB-combined laser groups; on the other hand, mineralization was significantly decreased (ANOVA; p < 0.05) in all treatment groups. Alkaline phosphatase and collagen-I expressions were upregulated in MB + 2 J/cm² group at 7th and 14th days, respectively. These results may contribute to the low-dose PDT researches and understanding PBM effects on osteoblast behavior but further studies are needed since inappropriate conditions may lead to undesirable results for both therapies.

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Acute generalized exanthematous pustulosis and polyarthritis associated with a novel CARD14 mutation

Abstract

Acute generalised exanthematous pustulosis (AGEP) is a rare toxicoderma characterised by an acute onset rash, with many sterile pustules on the surface, high fever and increased acute phase reactants. We report the case of a patient who presented to the dermatology department with an AGEP and polyarthritis, in which a novel CARD14 mutation was identified. The pathophysiological mechanism of AGEP remains unclear, although mutations in the IL36RN gene have been identified in a small subset of AGEP patients. Similarly, mutations in the CARD14 gene have been linked to pustular types of psoriasis and familiar cases of pityriasis rubra pilaris; however, there are no reports associating mutations in the CARD14 gene with AGEP.

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Prevalence and risk factors of hand eczema in hospital-based nurses in northern China

Abstract

Background/Objectives

This study aimed to evaluate the prevalence of hand eczema among nurses in northern China and to analyse associated risk factors.

Methods

A retrospective self-reported questionnaire was designed and distributed to 1322 nurses who were selected from three regional hospitals. Risk factors related to hand eczema in nurses were analysed using multivariable logistic regression.

Results

Hand eczema was present in 183/934 respondents (20%) and was not significantly associated with gender or workplace (P > 0.05). Factors such as the use of moisturiser (odds ratio [OR] 0.6; 95% confidence interval [CI] 0.3–1.0) and not wearing impervious gloves (OR 0.5; 95% CI 0.3–0.7) were associated with lower odds of developing hand eczema. A personal (OR 5.7; 95% CI 3.9–8.2) and family history (OR 2.3; 95% CI 1.5–3.5) of atopy, washing hands more than 20 times per day (OR 1.6; 95% CI 1.1–2.4), and more years working as a nurse (OR 1.1; 95% CI 1.0–1.1) were associated with higher odds of developing hand eczema.

Conclusions

A personal and familial history of atopy, the prolonged use of impervious gloves, washing hands more than 20 times per day and more years in work as a nurse are all risk factors for increased hand eczema in nurses.

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Drug eruption caused by enzalutamide: A case and literature review of androgen receptor inhibitor-related drug eruptions

Abstract

Enzalutamide is an androgen receptor inhibitor. We report a new cutaneous eruption to this drug and review cases of drug eruptions caused by androgen receptor inhibitors.

http://ift.tt/2wqqYFE

Synthesis and activity of opioid peptidomimetics with β2- and β3-amino acids

Publication date: Available online 3 August 2017
Source:Peptides
Author(s): Katarzyna Gach-Janczak, Justyna Piekielna-Ciesielska, Anna Adamska-Bartłomiejczyk, Renata Perlikowska, Rafał Kruszyński, Alicja Kluczyk, Julia Krzywik, Jarosław Sukiennik, Maria Camilla Cerlesi, Girolamo Calo, Andrzej Wasilewski, Marta Zielińska, Anna Janecka
Morphiceptin (Tyr-Pro-Phe-Pro-NH2) is a selective ligand of the mu opioid receptor, an important target in pain regulation. In this study, morphiceptin was modified at positions 2 or 3 by introduction of β²- or β³-amino acids and additionally in position 1 by replacing Tyr by Dmt (2',6'-dimethyltyrosine), which resulted in obtaining enzymatically stable analogs with mixed opioid receptor affinity profiles. An analog of the sequence Dmt-D-Ala-(R)-β²-1-Nal-Pro-NH2 [Nal=3-(1-naphthyl)-alanine] showed very high activity at the mu and delta receptors in the calcium mobilization functional test but did not cross the artificial membrane imitating the blood-brain barrier. In the in vivo test this analog induced strong antinociceptive effect in the writhing test in mice after intraperitioneal but also oral administration and inhibited diarrhea similarly to loperamide. Therefore, it may become an interesting lead compound in the development of peripherally restricted drugs for the treatment of gastrointestinal disorders.

Graphical abstract

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A new technique for creating a neo-umbilicus in abdominoplasty

The umbilicus is an essential feature of the abdomen. In this article we describe a new technique for creating a neo-umbilicus in abdominoplasties.

http://ift.tt/2v225lJ

Brazilian Portuguese version of the Female Genital Self Image Scale (FGSIS) for women seeking abdominoplasty

Female body image is a multifaceted construct associated with satisfaction with specific body parts (e.g., abdomen, arms, thighs, among others), body size, and feeling comfortable showing the body to the partner or others1,2. These perceptions and feelings about the body are influenced by socio-cultural aspects and personal views, and may affect sexual performance and satisfaction3. Changes in body image are particularly evident in women who have experienced changes in the body, including pregnancy, weight gain, serious diseases such as cancer, and aging.

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Re: Impact of the Method and Success of Pharyngeal Reconstruction on the Outcome of Treating Laryngeal and Hypopharyngeal Cancers with Pharyngolaryngectomy: A National Analysis

Life expectancy is crucial to evaluate in patients that undergo pharyngolaryngectomy, in order to be able to choose the best reconstructive strategy for each case. Ileocolon free flap represents our preference when voice reconstruction is aimed, especially in patients with long life expectancy.

http://ift.tt/2v1Qao1

Top-down mass spectrometric immunoassay for human insulin and its therapeutic analogs

Publication date: Available online 3 August 2017
Source:Journal of Proteomics
Author(s): Dobrin Nedelkov, Eric E. Niederkofler, Paul E. Oran, Scott Peterman, Randall W. Nelson
Measurement of insulin and its therapeutic analogs is important in diabetes, hypoglycemia, sports anti-doping and toxicology. Commercial insulin immunoassays fail to detect commonly prescribed insulin analogs. Because of their unique sequences and masses, these analogs are readily measured and distinguished with mass spectrometric (MS) assays. Reviewed here is an insulin mass spectrometric immunoassay (MSIA) that combines micro-scale immunoaffinity capture with sensitive MS detection of insulin and its therapeutic analogs. An antibody reactive to all insulin analogs was used to affinity capture the insulin analogs. Following elution, insulins were detected with MALDI-TOF MS or LC-MS analysis. Isotopic resolution for insulin was achieved for both MS techniques, and several insulin analogs were detected at unique m/z signals. Porcine insulin, spiked in all samples, served as an internal reference standard for quantification. Linear standard curves spanning three orders of magnitude were obtained, with limits of detection of 15pM for the MALDI-TOF MS and 1.5pM for the LC-MS. This insulin assay was capable of detecting and quantifying not only human endogenous insulin, but also most of the therapeutic insulin analogs, which could find use in diagnosis of severe hypoglycemia and in sports anti-doping.SignificanceMeasurement of human insulin is critical for proper diagnosis, monitoring, and treatment of diabetes and hypoglycemia. Insulin replacement therapy consists of injection of long- or fast-acting insulin analogs with slightly modified primary sequences compared to human insulin. Assays that are capable of detecting all insulin analogs are desired, not only for medical management of diabetes and severe hypoglycemia but also for sports anti-doping and toxicology. It has been shown that commercial insulin immunoassays fail to detect commonly prescribed insulin analogs. Because of their unique sequences and masses, these analogs could be readily measured and distinguished with MS-based assays. The mass spectrometric immunoassay described here is capable of detecting and quantifying not only human endogenous insulin, but also most of the therapeutic insulin analogs, and can find use in diagnosis of severe hypoglycemia and in sports anti-doping.



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Merging in-silico and in vitro salivary protein complex partners using the STRING database: A tutorial

Publication date: Available online 3 August 2017
Source:Journal of Proteomics
Author(s): Karla Tonelli Bicalho Crosara, Eduardo Buozi Moffa, Yizhi Xiao, Walter Luiz Siqueira
Protein-protein interaction is a common physiological mechanism for protection and actions of proteins in an organism. The identification and characterization of protein-protein interactions in different organisms is necessary to better understand their physiology and to determine their efficacy. In a previous in vitro study using mass spectrometry, we identified 43 proteins that interact with histatin 1. Six previously documented interactors were confirmed and 37 novel partners were identified. In this tutorial, we aimed to demonstrate the usefulness of the STRING database for studying protein-protein interactions. We used an in-silico approach along with the STRING database (http://string-db.org/) and successfully performed a fast simulation of a novel constructed histatin 1 protein-protein network, including both the previously known and the predicted interactors, along with our newly identified interactors. Our study highlights the advantages and importance of applying bioinformatics tools to merge in-silico tactics with experimental in vitro findings for rapid advancement of our knowledge about protein-protein interactions. Our findings also indicate that bioinformatics tools such as the STRING protein network database can help predict potential interactions between proteins and thus serve as a guide for future steps in our exploration of the Human Interactome.SignificanceOur study highlights the usefulness of the STRING protein database for studying protein-protein interactions. The STRING database can collect and integrate data about known and predicted protein-protein associations from many organisms, including both direct (physical) and indirect (functional) interactions, in an easy-to-use interface.



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Psoralidin suppresses osteoclastogenesis in BMMs and attenuates LPS-mediated osteolysis by inhibiting inflammatory cytokines

Publication date: October 2017
Source:International Immunopharmacology, Volume 51
Author(s): Lingbo Kong, Rui Ma, Xiaobin Yang, Ziqi Zhu, Hua Guo, Baorong He, Biao Wang, Dingjun Hao
Psoralidin is a metabolic product from the seed of psoraleacorylifolia, possessed anti-inflammatory and immunomodulatory effects. We speculated that psoralidin might impact osteoclastogenesis and bone loss. By using both in vitro and in vivo studies, we observed psoralidin strongly inhibited RANKL induced osteoclast formation during preosteoclast cultures, suggesting that it acts on osteoclast precursors to inhibit RANKL/RANK signaling. At the molecular level, by using MAPKs specific inhibitors (U-0126, SB-203580 and SP-600125) we demonstrated that psoralidin markedly abrogated the phosphorylation of p38, ERK, JNK. Moreover, the RANKL induced NF-κB/p65 phosphorylation and I-κB degradation were significantly inhibited by psoralidin. Further, psoralidin significantly suppressed osteoclastogenesis marker genes of TRAP, Cathepsin K and OSCAR. These were accompanied by the decreased expression of c-Fos and NFATc1 transcription factors. Consistent with in vitro results, our in vivo and serologic studies showed psoralidin inhibited lipopolysaccharide induced bone resorption by suppressing the inflammatory cytokines: TNF-α and IL-6 expression, as well as the ratio of RNAKL : OPG. These results collectively suggested that psoralidin could represent a novel therapeutic strategy for osteoclast-related disorders, such as rheumatoid arthritis and postmenopausal osteoporosis.



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Object exploration in extremely preterm infants between 6 and 9 months and relation to cognitive and language development at 24 months

Publication date: September 2017
Source:Research in Developmental Disabilities, Volume 68
Author(s): Mariagrazia Zuccarini, Annalisa Guarini, Silvia Savini, Jana M. Iverson, Tiziana Aureli, Rosina Alessandroni, Giacomo Faldella, Alessandra Sansavini
Although early object exploration is considered a key ability for subsequent achievements, very few studies have analyzed its development in extremely low gestational age infants (ELGA- GA <28 weeks), whose early motor skills are delayed. Moreover, no studies have examined its developmental relationship with cognitive and language skills. The present study examined developmental change in Motor Object Exploration (MOE) and different types of MOE (Holding, Oral, Manual and Manual Rhythmic Exploration) in 20 ELGA and 20 full term (FT) infants observed during mother-infant play interaction at 6 and 9 months. It also explored whether specific types of MOE were longitudinally related to 24-month language and cognitive abilities (GMDS-R scores). ELGA infants increased MOE duration from 6 to 9 months, eliminating the initial difference with FT infants. In addition, ELGA infants showed a different pattern of Oral Exploration, that did not increase at 6 months and decrease at 9 months. Oral and Manual Exploration durations at 6 months were longitudinally related to 24-month GMDS-R language and cognitive performance scores respectively. We discuss the relevance of assessing early exploratory abilities in ELGA infants in order to implement customized intervention programs for supporting the development of these skills.



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Technical note: PaGELL v.1.5: A flexible parametric program for the Bayesian analysis of longevity data within the context of animal breeding

Publication date: Available online 2 August 2017
Source:Journal of Dairy Science
Author(s): J. Casellas, L.C. Brito
This technical note presents the program PaGELL v.1.5 (Parametric Genetic Evaluation of Lifespan in Livestock), a flexible software program to analyze (right-censored) longevity data in livestock populations, with a special emphasis on the genetic evaluation of the breeding stock. This software relies on a parametric generalization of the proportional hazard model; more specifically, the baseline hazard function follows a Weibull process and flexibility is gained by including an additional time-dependent effect with the number of change points defined by the user. The program can accommodate 3 different sources of variation (i.e., systematic, permanent environmental, and additive genetic effects) and both fixed and time-dependent patterns (only for systematic and permanent environmental effects). Analyses are performed within a Bayesian context by sampling from the joint posterior distribution of the model, and model fit can be easily determined by the calculation of the deviance information criterion. Although this software has already been used on field data sets, its performance has been double-checked on simulated data set, and results are presented in this technical note. PaGELL v.1.5 was written in Fortran 95 language and, after compiling with the GNU Fortran Compiler v.4.7 and later, it has been tested in Windows, Linux, and MacOS operating systems (both 32- and 64-bit platforms). This program is available at http://ift.tt/2v4aO5o.



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Short communication: The mammalian lignan enterolactone is absorbed by newborn dairy calves fed enterolactone-enriched milk

Publication date: Available online 2 August 2017
Source:Journal of Dairy Science
Author(s): C.P. Ghedini, N.L. Whitehouse, D.C. Moura, A.S. Oliveira, A.F. Brito
Flaxseed is the richest source of the plant lignan secoisolariciresinol diglucoside, which is converted to the mammalian lignans enterolactone (EL) and enterodiol by the gut microbiota of ruminants and humans. Enterolactone has been associated with improved animal and human health due to its antioxidant and anticarcinogenic properties. The objective of this study was to determine the pharmacokinetics of EL in newborn dairy calves fed milk replacer or EL-enriched milk. We hypothesized that newborn Holstein calves fed EL-enriched milk would have greater area under the curve and plasma concentration of EL compared with those fed milk replacer. On d 5 of life, calves were administered 2 L of milk replacer (n = 10; low-EL treatment: 123 nmol/L of EL) or 2 L of EL-enriched milk (n = 10; high-EL treatment: 481 nmol/L of EL) during the morning feeding (0700 h). Blood samples were taken from the jugular vein before (0 h) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, and 48 h after oral administration of treatments. The area under the curve for the plasma concentration of EL was analyzed according to the trapezoidal rule between 0 and 12 h after treatment administration, and it was greater in high- (26 nmol/L × h) than low-EL calves (4.30 nmol/L × h). Similarly, the maximum concentration of EL in plasma was greater in high- (5.06 nmol/L) versus low-EL calves (1.95 nmol/L). Furthermore, the time after treatment intake to reach maximum plasma concentration of EL was faster in high- (4.31 h) compared with low-EL (4.44 h) treatment. Calves were able to absorb EL, indicating that EL-enriched milk can potentially be used as source of EL to pre-weaned ruminants.



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Short communication: Extended-spectrum cephalosporin-resistant Escherichia coli in colostrum from New Brunswick, Canada, dairy cows harbor blaCMY-2 and blaTEM resistance genes

Publication date: Available online 2 August 2017
Source:Journal of Dairy Science
Author(s): B.B. Awosile, J.T. McClure, J. Sanchez, J. VanLeeuwen, J.C. Rodriguez-Lecompte, G. Keefe, L.C. Heider
Dairy calves are colonized shortly after birth by multidrug resistant (MDR) bacteria, including Escherichia coli. The role of dairy colostrum fed to calves as a potential source of MDR bacteria resistance genes has not been investigated. This study determined the recovery rate of extended-spectrum cephalosporin-resistant (ESC-R) E. coli in colostrum from cows. The ESC-R E. coli isolates were further investigated to determine their phenotypic antimicrobial resistance pattern and the genes conferring ESC-R. Fresh colostrum was collected from 452 cows from 8 dairy herds in New Brunswick, Canada. The ESC-R E. coli was isolated from the colostrum by using the VACC agar, a selective media for extended-spectrum β-lactamase producing Enterobacteriaceae. Minimum inhibitory concentration was determined for all the suspected ESC-R E. coli isolates using a commercial gram-negative broth microdilution method. Two multiplex PCR were conducted on all the suspected ESC-R E. coli isolates to determine the presence of the blaCTX-M (groups 1, 2, 9, and 8/25) blaCMY-2, blaSHV, and blaTEM resistance genes. The ESC-R E. coli were detected in 20 (4.43%) of the colostrum samples. At least 1 ESC-R E. coli isolate was detected in 6 (75%) of the dairy herds. All ESC-R E. coli had MDR profiles based on minimum inhibitory concentration testing. No blaCTX-M groups genes were detected; however, the blaCMY-2 gene was detected in 9 or 20 (45%) and blaTEM was detected in 7 of 20 (35%) of the ESC-R E. coli. No ESC-R E. coli had both blaCMY-2 and blaTEM resistance genes. This is the first report of blaCMY-2 and blaTEM genes found in E. coli isolates cultured from dairy colostrum to our knowledge.



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Effect of prepartum exercise, pasture turnout, or total confinement on hoof health

Publication date: Available online 2 August 2017
Source:Journal of Dairy Science
Author(s): R.A. Black, S.R. van Amstel, P.D. Krawczel
Lameness is a major welfare concern in the dairy industry, and access to physical activity during the dry period may improve hoof health. The objective of this study was to determine the effects of forced exercise, pasture turnout, or total confinement of dry cows on horn growth and wear and sole thickness. Twenty-nine primiparous and 31 multiparous, pregnant, nonlactating Holstein (n = 58) and Jersey-Holstein crossbred (n = 2) dairy cows were assigned to either total confinement (n = 20), exercise (n = 20), or pasture (n = 20) treatments at dry-off using rolling enrollment from January to November 2015. Cows were managed with a 60-d dry period (58.5 ± 5.4 d) divided into far-off (dry-off to 2 wk before parturition) and close-up periods (2 wk before projected parturition). Cows were housed in a naturally ventilated, 4-row freestall barn at the University of Tennessee's Little River Animal and Environmental Unit (Walland, TN) with concrete flooring and deep-bedded sand freestalls. Cows assigned to confinement remained in the housing pen. Exercise cows were walked for a targeted 1.5 h at 3.25 km/h, 5 times/wk until calving. Pasture cows were turned out for a targeted 1.5 h, 5 times/wk until calving. Hoof growth and wear and sole thickness of the rear hooves were measured on d 2 and 44, relative to dry-off. Data were analyzed using the MIXED procedure of SAS (SAS Institute Inc., Cary, NC). Cranial and caudal horn wear was greater for exercise cows than confinement and pasture cows. Exercise cows experienced more equal rates of horn growth and wear cranially. Confined cows tended to increase sole thickness from d 2 to 44, relative to dry-off. Frequent, short duration exercise on concrete did not impair the hoof health of late-gestation dry cows. Further, exercise may improve overall hoof health, potentially improving cow welfare.



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Bulk tank milk antibody enzyme-linked immunosorbent assay as a biosecurity tool for detecting dairy herds with past exposure to Mycoplasma bovis

Publication date: Available online 2 August 2017
Source:Journal of Dairy Science
Author(s): A.M. Parker, J.K. House, M.S. Hazelton, K.L. Bosward, J.M. Morton, P.A. Sheehy
In Australia, one of the biosecurity recommendations to help prevent the introduction of Mycoplasma bovis into a dairy herd is to use a PCR assay on bulk tank milk (BTM) samples to evaluate the M. bovis infection status of potential source herds. An alternative approach is to assess the immunological status of the herd with respect to previous exposure to M. bovis via the use of an ELISA that is commercially available for use on cattle milk and serum. The objectives of this study were to (1) evaluate factors potentially associated with variation in the ELISA BTM optical density coefficient (ODC%) in previously exposed herds, (2) evaluate the association between the proportion of cows that are ELISA positive and the BTM ELISA ODC%, (3) assess agreement between the BTM ELISA and PCR and culture, and (4) compare BTM ELISA ODC% between the "hospital" herd and the main lactating herd on the same farm. Bulk tank milk samples (n = 192) were collected from 19 dairy herds with a history of clinical M. bovis disease and from 6 control herds (herds with no known clinical cases of mycoplasmosis). For 28 of the BTM samples collected, blood was also collected from 50 lactating cows contributing to that bulk tank sample. From 1 herd, concurrent paired BTM samples were collected from the main herd and the hospital herd on 16 occasions. All BTM samples were analyzed by ELISA (Bio-X Bio K 302, Bio-X Diagnostics, Rochefort, Belgium), PCR, and culture. The BTM ELISA ODC% was associated with time since initial M. bovis outbreak and time since the start of the herd's calving period. Following an initial outbreak of M. bovis, the BTM ELISA ODC% was highest in the first 8 mo. In split- and seasonal-calving herds, significantly higher BTM ELISA ODC% results were observed 5 to 8 wk after the commencement of the calving period. A significant association was observed between the within-herd seroprevalence for the lactating herd and BTM ELISA ODC%, but within-herd seroprevalence explained little of the variation in BTM ELISA ODC%. When comparing the BTM ELISA with a multiplex probe PCR and culture followed by 16S to 23S rRNA sequencing, there was virtually no agreement above that expected by chance; prevalence-adjusted bias-adjusted kappa values were 0.22 and 0.25 for ELISA category versus PCR category and culture, respectively. Finally, the hospital herd BTM ELISA ODC% mirrored that for the main herd BTM but was significantly higher. This study demonstrates that this commercially available ELISA used on BTM samples may complement the use of BTM PCR or culture in identifying herds from which purchase of animals may pose a higher biosecurity risk for introduction of M. bovis into noninfected herds.



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Prevalence and characterization of methicillin-resistant Staphylococcus aureus carrying mecA or mecC and methicillin-susceptible Staphylococcus aureus in dairy sheep farms in central Italy

Publication date: Available online 2 August 2017
Source:Journal of Dairy Science
Author(s): G. Giacinti, V. Carfora, A. Caprioli, D. Sagrafoli, N. Marri, G. Giangolini, R. Amoruso, M. Iurescia, F. Stravino, S. Dottarelli, F. Feltrin, A. Franco, S. Amatiste, A. Battisti
Between January and May 2012, a total of 286 bulk tank milk samples from dairy sheep farms located in central Italy were tested for the presence of Staphylococcus aureus. One hundred fifty-three samples were positive for S. aureus (53.5%), with an average count of 2.53 log cfu/mL. A total of 679 S. aureus colonies were screened for methicillin resistance by the cefoxitin disk diffusion test, and 104 selected cefoxitin-susceptible isolates were also tested for their susceptibility to other antimicrobials representative of the most relevant classes active against Staphylococcus spp. by using the Kirby-Bauer disk diffusion method. Two methicillin-resistant Staphylococcus aureus (MRSA) isolates, carrying respectively the mecA and the mecC genes, were detected in 2 samples from 2 different farms (prevalence 0.7%). The mecA-positive MRSA isolate was blaZ positive, belonged to spa type t127, sequence type (ST)1, clonal complex (CC)1, carried a staphylococcal cassette chromosome mec (SCCmec) type IVa, and was phenotypically resistant to all the β-lactams tested and to erythromycin, streptomycin, kanamycin, and tetracycline. The mecC-positive MRSA isolate was negative for the chromosomally or plasmid-associated blaZ gene but positive for the blaZ allotype associated with SCCmec XI (blaZ-SCCmecXI), belonged to spa type 843, ST(CC)130, carried a SCCmec type XI, and was resistant only to β-lactams. Both MRSA were negative for the presence of specific immune-evasion and virulence genes such as those coding for the Panton-Valentine leucocidin, the toxic shock syndrome toxin 1, and the immune evasion cluster genes. Regarding the presence of the major S. aureus enterotoxin genes, the mecC-positive MRSA tested negative, whereas the ST (CC)1 mecA-positive MRSA harbored the seh gene. Among the 104 methicillin-susceptible S. aureus isolates examined for antimicrobial susceptibility, 63 (60.58%) were susceptible to all the antimicrobials tested, and 41 (39.42%) were resistant to at least 1 antimicrobial. In particular, 23 isolates (22.12%) were resistant to tetracycline, 16 (15.38%) to sulfonomides, 14 (13.46%) to trimethoprim and sulfamethoxazole, and 9 (8.65%) to ampicillin, whereas only 1 isolate was resistant to both fluoroquinolones and aminoglycosides. The high prevalence of S. aureus found in bulk tank milk samples and the isolation of MRSA, although at a low prevalence, underlines the importance of adopting control measures against S. aureus in dairy sheep farms to minimize the risks for animal and public health. Moreover, this study represents the first report of mecC-positive MRSA isolation in Italy and would confirm that, among livestock animals, sheep might act as a mecC-MRSA reservoir. Although this lineage seems to be rare in dairy sheep (0.35% of farms tested), because mecC-positive MRSA are difficult to detect by diagnostic routine methods employed for mecA-positive livestock-associated MRSA, diagnostic laboratories should be aware of the importance of searching for the mecC gene in all the mecA-negative S. aureus isolates displaying resistance to oxacillin, cefoxitin, or both.



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Whole-body propionate and glucose metabolism of multiparous dairy cows receiving folic acid and vitamin B12 supplements

Publication date: Available online 2 August 2017
Source:Journal of Dairy Science
Author(s): M. Duplessis, H. Lapierre, B. Ouattara, N. Bissonnette, D. Pellerin, J.-P. Laforest, C.L. Girard
This study was undertaken to evaluate the effect of supplementation of folic acid and vitamin B12 on glucose and propionate metabolism. Twenty-four multiparous cows were assigned according to a complete block design in a 2 × 2 factorial arrangement to one of the following treatments: (1) saline 0.9% NaCl, (2) 320 mg of folic acid, (3) 10 mg of vitamin B12, or (4) 320 mg of folic acid and 10 mg of vitamin B12. Intramuscular injections were given weekly from 3 wk before the expected calving date until 9 wk postpartum. At 63 d in milk, d-[6,6-²H2]-glucose (16.5 mmol/h; jugular vein) and [1-¹³C]-sodium propionate (13.9 mmol/h; ruminal vein) were simultaneously infused for 4 h; blood samples were collected from 2 to 4 h of the infusion period. Liver biopsies were carried out the following day. Supplements of folic acid and vitamin B12 respectively increased folate and vitamin B12 concentrations, both in milk and liver. Although dry matter intake was unaffected by treatments, milk and milk lactose yields tended to be lower by 5.0 and by 0.25 kg/d, respectively, for cows receiving the folic acid supplement. Plasma β-hydroxybutyrate concentration with the folic acid supplement followed the same tendency. Hepatic gene expression of methylmalonyl-CoA mutase and S-adenosylhomocysteine hydrolase was higher for cows receiving the combined folic acid and vitamin B12 supplement compared with cows receiving only the supplement of folic acid, whereas no treatment effect was noted for cows not receiving the folic acid supplement. Whole-body glucose rate of appearance and the proportion of whole-body glucose rate of appearance secreted in milk lactose decreased by 229 g/d and 5%, respectively, for animals receiving the folic acid supplement, concomitant with the lower milk lactose synthesis in these cows, indicating that supplementary folic acid may alter energy partitioning in cows. The absence of treatment effect on plasma concentrations of methylmalonic acid as well as on the proportion of glucose synthesized from propionate, averaging 60%, supports the fact that vitamin B12 supply was sufficient in control cows in the current study. Our results suggest that the folic acid supplement reduced glucose-derived lactose synthesis by redirecting glucose for other metabolic activity in the mammary gland or in other tissues.



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Transcript analysis at DGAT1 reveals different mRNA profiles in river buffaloes with extreme phenotypes for milk fat

Publication date: Available online 2 August 2017
Source:Journal of Dairy Science
Author(s): M. Gu, G. Cosenza, I. Nicolae, A. Bota, Y. Guo, L. Di Stasio, A. Pauciullo
Buffalo DGAT1 (diacylglycerol O-acyltransferase 1) was mainly investigated for the characterization of the gene itself and for the identification of the K232A polymorphism, similar to what has been accomplished in cattle, although no information has been reported so far at the mRNA level. The importance of DGAT1 for lipid metabolism led us to investigate the transcript profiles of lactating buffaloes characterized as high (9.13 ± 0.23) and low (7.94 ± 0.29) for milk fat percentage, and to explore the genetic diversity at the RNA and DNA level. A total of 336 positive clones for the DGAT1 cDNA were analyzed by PCR and chosen for sequencing according to the differences in length. The clone assembling revealed a very complex mRNA pattern with a total of 21 transcripts differently represented in the 2 groups of animals. Apart from the correct transcript (17 exons long), the skipping of exon 12 is the most significant in terms of distribution of clones with 11.6% difference between the 2 groups, whereas a totally different mRNA profile was found in approximately 12% of clones. The sequencing of genomic DNA allowed the identification of 10 polymorphic sites at the intron level, which clarify, at least partially, the genetic events behind the production of complex mRNA. Genetic diversity was found also at the exon level. The single nucleotide polymorphism c.1053C>T represents the first example of polymorphism in a coding region for the DGAT1 in the Italian Mediterranean breed. To establish whether this polymorphism is present in other buffalo breeds, a quick method based on PCR-RFLP was set up for allelic discrimination in the Italian Mediterranean and the Romanian Murrah (200 animals in total). The alleles were equally represented in the overall population, whereas the analysis of the 2 breeds showed different frequencies, likely indicating diverse genetic structure of the 2 breeds. The T allele might be considered as the ancestral condition of the DGAT1 gene, being present in the great part of the sequenced species. These data add knowledge at the transcript and genetic levels for the buffalo DGAT1 and open the opportunity for further investigation of other genes involved in milk fat metabolism for the river buffalo, including the future possibility of selecting alleles with quantitative or qualitative favorable effects (or both).



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Changes in animal performance and profitability of Holstein dairy operations after introduction of crossbreeding with Montbéliarde, Normande, and Scandinavian Red

Publication date: Available online 2 August 2017
Source:Journal of Dairy Science
Author(s): C. Dezetter, N. Bareille, D. Billon, C. Côrtes, C. Lechartier, H. Seegers
An individual-based mechanistic, stochastic, and dynamic simulation model was developed to assess economic effects resulting from changes in performance for milk yield and solid contents, reproduction, health, and replacement, induced by the introduction of crossbreeding in Holstein dairy operations. Three crossbreeding schemes, Holstein × Montbéliarde, Holstein × Montbéliarde × Normande, and Holstein × Montbéliarde × Scandinavian Red, were implemented in Holstein dairy operations and compared with Holstein pure breeding. Sires were selected based on their estimated breeding value for milk. Two initial operations were simulated according to the prevalence (average or high) of reproductive and health disorders in the lactating herd. Evolution of operations was simulated during 15 yr under 2 alternative managerial goals (constant number of cows or constant volume of milk sold). After 15 yr, breed percentages reached equilibrium for the 2-breed but not for the 3-breed schemes. After 5 yr of simulation, all 3 crossbreeding schemes reduced average milk yield per cow-year compared with the pure Holstein scheme. Changes in other animal performance (milk solid contents, reproduction, udder health, and longevity) were always in favor of crossbreeding schemes. Under an objective of constant number of cows, margin over variable costs in average discounted value over the 15 yr of simulation was slightly increased by crossbreeding schemes, with an average prevalence of disorders up to €32/cow-year. In operations with a high prevalence of disorders, crossbreeding schemes increased the margin over variable costs up to €91/cow-year. Under an objective of constant volume of milk sold, crossbreeding schemes improved margin over variable costs up to €10/1,000L (corresponding to around €96/cow-year) for average prevalence of disorders, and up to €13/1,000L (corresponding to around €117/cow-year) for high prevalence of disorders. Under an objective of constant number of cows, an unfavorable pricing context (milk price vs. concentrates price) increased slightly crossbreeding positive effects on margin over variable costs. Under an objective of constant volume of milk, only very limited changes in differences of margins were found between the breeding schemes. Our results, obtained conditionally to the parameterization values used here, suggest that dairy crossbreeding should be considered as a relevant option for Holstein dairy operations with a production level until 9,000 kg/cow-year in France, and possibly in other countries.



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Short communication: The role of genotypes from animals without phenotypes in single-step genomic evaluations

Publication date: Available online 2 August 2017
Source:Journal of Dairy Science
Author(s): T. Shabalina, E.C.G. Pimentel, C. Edel, L. Plieschke, R. Emmerling, K.-U. Götz
In a 2-step genomic system, genotypes of animals without phenotypes do not influence genomic prediction of other animals, but that might not be the case in single-step systems. We investigated the effects of including genotypes from culled bulls on the reliability of genomic predictions from single-step evaluations. Four scenarios with a constant amount of phenotypic information and increasing numbers of genotypes from culled bulls were simulated and compared with respect to prediction reliability. With increasing numbers of genotyped culled bulls, there was a corresponding increase in prediction reliability. For instance, in our simulation scenario the reliability for selection candidates was twice as large when all culled bulls from the last 4 generations were included in the analysis. Single-step evaluations imply the imputation of all nongenotyped animals in the pedigree. We showed that this imputation was increasingly more accurate as increasingly more genotypic information from the culled bulls was taken into account. This resulted in higher prediction reliabilities. The extent of the benefit from including genotypes from culled bulls might be more relevant for small populations with low levels of reliabilities.



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Causal effect of prolificacy on milk yield in dairy sheep using propensity score

Publication date: Available online 2 August 2017
Source:Journal of Dairy Science
Author(s): Vera C. Ferreira, David L. Thomas, Bruno D. Valente, Guilherme J.M. Rosa
In animal production, it is often important to investigate causal relationships among variables. The gold standard tool for such investigation is randomized experiments. However, randomized experiments may not always be feasible, possible, or cost effective or reflect real-world farm conditions. Sometimes it is necessary to infer effects from farm-recorded data. Inferring causal effects between variables from field data is challenging because the association between them may arise not only from the effect of one on another but also from confounding background factors. Propensity score (PS) methods address this issue by correcting for confounding in different levels of the causal variable, which allows unbiased inference of causal effects. Here the objective was to estimate the causal effect of prolificacy on milk yield (MY) in dairy sheep using PS based on matched samples. Data consisted of 4,319 records from 1,534 crossbred ewes. Confounders were lactation number (first, second, and third through sixth) and dairy breed composition (<0.5, 0.5–0.75, and >0.75 of East Friesian or Lacaune). The causal variable prolificacy was considered as 2 levels (single or multiple lambs at birth). The outcome MY represented the volume of milk produced in the whole lactation. Pairs of single- and multiple-birth ewes (1,166) with similar PS were formed. The matching process diminished major discrepancies in the distribution of prolificacy for each confounder variable indicating bias reduction (cutoff standardized bias = 20%). The causal effect was estimated as the average difference within pairs. The effect of prolificacy on MY per lactation was 20.52 L of milk with a simple matching estimator and 12.62 L after correcting for remaining biases. A core advantage of causal over probabilistic approaches is that they allow inference of how variables would react as a result of external interventions (e.g., changes in the production system). Therefore, results imply that management and decision-making practices increasing prolificacy would positively affect MY, which is important knowledge at the farm level. Farm-recorded data can be a valuable source of information given its low cost, and it reflects real-world herd conditions. In this context, PS methods can be extremely useful as an inference tool for investigating causal effects. In addition, PS analysis can be implemented as a preliminary evaluation or a hypothesis generator for future randomized trials (if the trait analyzed allows randomization).



http://ift.tt/2hskNyo

Short communication: Prevalence of digital dermatitis in Canadian dairy cattle classified as high, average, or low antibody- and cell-mediated immune responders

Publication date: Available online 2 August 2017
Source:Journal of Dairy Science
Author(s): S.L. Cartwright, F. Malchiodi, K. Thompson-Crispi, F. Miglior, B.A. Mallard
Lameness is a major animal welfare issue affecting Canadian dairy producers, and it can lead to production, reproduction, and health problems in dairy cattle herds. Although several different lesions affect dairy cattle hooves, studies show that digital dermatitis is the most common lesion identified in Canadian dairy herds. It has also been shown that dairy cattle classified as having high immune response (IR) have lower incidence of disease compared with those animals with average and low IR; therefore, it has been hypothesized that IR plays a role in preventing infectious hoof lesions. The objective of this study was to compare the prevalence of digital dermatitis in Canadian dairy cattle that were classified for antibody-mediated (AMIR) and cell-mediated (CMIR) immune response. Cattle (n = 329) from 5 commercial dairy farms in Ontario were evaluated for IR using a patented test protocol that captures both AMIR and CMIR. Individuals were classified as high, average, or low responders based on standardized residuals for AMIR and CMIR. Residuals were calculated using a general linear model that included the effects of herd, parity, stage of lactation, and stage of pregnancy. Hoof health data were collected from 2011 to 2013 by the farm's hoof trimmer using Hoof Supervisor software (KS Dairy Consulting Inc., Dresser, WI). All trim events were included for each animal, and lesions were assessed as a binary trait at each trim event. Hoof health data were analyzed using a mixed model that included the effects of herd, stage of lactation (at trim date), parity (at trim date), IR category (high, average, and low), and the random effect of animal. All data were presented as prevalence within IR category. Results showed that cows with high AMIR had significantly lower prevalence of digital dermatitis than cattle with average and low AMIR. No significant difference in prevalence of digital dermatitis was observed between high, average, and low CMIR cows. These results indicate that having more robust AMIR is associated with lower prevalence of digital dermatitis hoof lesions.



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Environmental life cycle assessment of Italian mozzarella cheese: Hotspots and improvement opportunities

Publication date: Available online 2 August 2017
Source:Journal of Dairy Science
Author(s): A. Dalla Riva, J. Burek, D. Kim, G. Thoma, M. Cassandro, M. De Marchi
The present study investigated a cradle-to-grave life cycle assessment to estimate the environmental impacts associated with Italian mozzarella cheese consumption. The differences between mozzarella produced from raw milk and mozzarella produced from curd were studied, and differences in manufacturing processes have been emphasized in order to provide guidance for targeted improvements at this phase. Specifically, the third-largest Italian mozzarella producer was surveyed to collect site-specific manufacturing data. The Ecoinvent v3.2 database was used for secondary data, whereas SimaPro 8.1 was the modeling software. The inventory included inputs from farm activities to end of life disposal of wasted mozzarella and packaging. Additionally, plant-specific information was used to assign major inputs, such as electricity, natural gas, packaging, and chemicals to specific products; however, where disaggregated information was not provided, milk solids allocation was applied. Notably, loss of milk solids was accounted during the manufacture, moreover mozzarella waste and transport were considered during distribution, retail, and consumption phases. Feed production and animal emissions were the main drivers of raw milk production. Electricity and natural gas usage, packaging (cardboard and plastic), transport, wastewater treatment, and refrigerant loss affected the emissions from a farm gate-to-dairy plant gate perspective. Post-dairy plant gate effects were mainly determined by electricity usage for storage of mozzarella, transport of mozzarella, and waste treatment. The average emissions were 6.66 kg of CO2 equivalents and 45.1 MJ of cumulative energy demand/kg of consumed mozzarella produced directly from raw milk, whereas mozzarella from purchased curd had larger emissions than mozzarella from raw milk due to added transport of curd from specialty manufacturing plants, as well as electricity usage from additional processes at the mozzarella plant that are required to process the curd into mozzarella. Normalization points to ecotoxicity as the impact category most significantly influenced by mozzarella consumption. From a farm gate-to-grave perspective, ecotoxicity and freshwater and marine eutrophication are the first and second largest contributors of mozzarella consumption to average European effects, respectively. To increase environmental sustainability, an improvement of efficiency for energy and packaging usage and transport activities is recommended in the post-farm gate mozzarella supply chain.



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Short communication: Effect of fatty acid supplements on apparent ruminal synthesis of B vitamins in lactating dairy cows

Publication date: Available online 2 August 2017
Source:Journal of Dairy Science
Author(s): D.S. Castagnino, K.J. Harvatine, M.S. Allen, R. Gervais, P.Y. Chouinard, C.L. Girard
The effect of fat supplements (FS) providing different proportions of saturated (SFA) and unsaturated (UFA) fatty acids on supply, apparent ruminal synthesis (ARS), and duodenal flow (DF) of some B vitamins (thiamine, riboflavin, niacin, vitamin B6, folates, and vitamin B12) were evaluated in an experiment using 8 ruminally and duodenally cannulated lactating Holstein cows. The experiment was a replicated 4 × 4 Latin square design with 21-d treatment periods. The 4 treatments were a control diet without fatty acid supplement and 3 diets with 2.5% additional fatty acids from supplements containing (1) SFA, (2) an intermediate mixture of SFA and UFA, or (3) UFA. All diets were served as a total mixed ration once daily at 115% of the expected intake. B-vitamin concentrations were analyzed in feed and duodenal digesta. Apparent ruminal synthesis of each B vitamin was calculated as the DF minus the intake. B-vitamin concentrations were similar among the 4 treatments; consequently, daily intake of the vitamins followed the same pattern as dry matter intake. Adding FS decreased B-vitamin intakes (except vitamin B12), as did increasing the proportion of UFA. Riboflavin and niacin DF and ARS, expressed as total daily amount or per unit of dry matter intake, were not affected by FS, but increasing the proportion of UFA decreased riboflavin and niacin DF and ARS. Fat supplements decreased DF of vitamin B6, expressed either as total daily amount or per unit of dry matter intake. No treatment effects were observed on total daily folate DF and ARS. However, when expressed per unit of dry matter intake, folate DF and ARS were greater when cows were fed FS and they increased linearly with the proportion of UFA in the supplement. Inclusion of fat supplements into the dairy cow diet had a limited effect on the fate of most B vitamins in the rumen although increasing the proportion of UFA in the FS linearly decreased apparent synthesis of riboflavin and niacin in the rumen and the amounts of these vitamins reaching the small intestine.



http://ift.tt/2fdEFV3

Human milk oligosaccharide consumption by probiotic and human-associated bifidobacteria and lactobacilli

Publication date: Available online 2 August 2017
Source:Journal of Dairy Science
Author(s): Taksawan Thongaram, Jennifer L. Hoeflinger, JoMay Chow, Michael J. Miller
Human milk contains high concentrations of nondigestible complex oligosaccharides (human milk oligosaccharides; HMO) that reach the colon and are subsequently fermented by the infant gut microbiota. Using a high-throughput, low-volume growth determination, we evaluated the ability of 12 lactobacilli and 12 bifidobacteria strains, including several commercial probiotics, to ferment HMO and their constituent monomers. Of the 24 strains tested, only Bifidobacterium longum ssp. infantis ATCC 15697 and Bifidobacterium infantis M-63 were able to ferment 3′-sialyllactose, 6′-sialyllactose, 2′-fucosyllactose, and 3′-fucosyllactose. Bifidobacterium infantis M-63 degraded almost 90% of the 2′-fucosyllactose but left most of the fucose in the supernatant, as detected by HPLC. Among bifidobacteria, only the B. infantis strains and Bifidobacterium breve ATCC 15700 were able to ferment lacto-N-neotetraose (LNnT). Among lactobacilli, Lactobacillus acidophilus NCFM was found to be the most efficient at utilizing LNnT. The extracellular β-galactosidase (lacL, LBA1467) of L. acidophilus NCFM cleaves the terminal galactose of LNnT for growth, leaving lacto-N-triose II in the media as detected by HPLC. Inactivation of lacL abolishes growth of L. acidophilus NCFM on LNnT. These results contribute to our knowledge of HMO–microbe interactions and demonstrate the potential for synbiotic combinations of pre- and probiotics.



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The effect of bleaching agents on the degradation of vitamins and carotenoids in spray-dried whey protein concentrate

Publication date: Available online 2 August 2017
Source:Journal of Dairy Science
Author(s): M.A. Stout, C.W. Park, M.A. Drake
Previous research has shown that bleaching affects flavor and functionality of whey proteins. The role of different bleaching agents on vitamin and carotenoid degradation is unknown. The objective of this study was to determine the effects of bleaching whey with traditional annatto (norbixin) by hydrogen peroxide (HP), benzoyl peroxide (BP), or native lactoperoxidase (LP) on vitamin and carotenoid degradation in spray-dried whey protein concentrate 80% protein (WPC80). An alternative colorant was also evaluated. Cheddar whey colored with annatto (15 mL/454 L of milk) was manufactured, pasteurized, and fat separated and then assigned to bleaching treatments of 250 mg/kg HP, 50 mg/kg BP, or 20 mg/kg HP (LP system) at 50°C for 1 h. In addition to a control (whey with norbixin, whey from cheese milk with an alternative colorant (AltC) was evaluated. The control and AltC wheys were also heated to 50°C for 1 h. Wheys were concentrated to 80% protein by ultrafiltration and spray dried. The experiment was replicated in triplicate. Samples were taken after initial milk pasteurization, initial whey formation, after fat separation, after whey pasteurization, after bleaching, and after spray drying for vitamin and carotenoid analyses. Concentrations of retinol, a-tocopherol, water-soluble vitamins, norbixin, and other carotenoids were determined by HPLC, and volatile compounds were measured by gas chromatography-mass spectrometry. Sensory attributes of the rehydrated WPC80 were documented by a trained panel. After chemical or enzymatic bleaching, WPC80 displayed 7.0 to 33.3% reductions in retinol, β-carotene, ascorbic acid, thiamin, α-carotene, and α-tocopherol. The WPC80 bleached with BP contained significantly less of these compounds than the HP- or LP-bleached WPC80. Riboflavin, pantothenic acid, pyridoxine, nicotinic acid, and cobalamin concentrations in fluid whey were not affected by bleaching. Fat-soluble vitamins were reduced in all wheys by more than 90% following curd formation and fat separation. With the exception of cobalamin and ascorbic acid, water-soluble vitamins were reduced by less than 20% throughout processing. Norbixin destruction, volatile compound, and sensory results were consistent with previous studies on bleached WPC80. The WPC80 colored with AltC had a similar sensory profile, volatile compound profile, and vitamin concentration as the control WPC80.



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Evidence that mastitis can cause pregnancy loss in dairy cows: A systematic review of observational studies

Publication date: Available online 2 August 2017
Source:Journal of Dairy Science
Author(s): Mohammad O. Dahl, Fiona P. Maunsell, Albert De Vries, Klibs N. Galvao, Carlos A. Risco, Jorge A. Hernandez
The objective of this study was to conduct a systematic review to identify and assess evidence and knowledge gaps in published observational studies that have investigated the relationship between mastitis and pregnancy loss (PL) in dairy cows. PubMed and ScienceDirect were used to search pertinent peer-reviewed research reports of interest. Screening of research reports was conducted at 3 levels: titles, abstracts, and full-text articles. The search identified 651 records for initial screening. The final screening process identified 8 qualified articles for review after removing 10 duplicate records, 582 titles, 31 abstracts, and 20 full-text articles. Two studies produced strong epidemiologic evidence indicating that (1) exposure to clinical mastitis during early gestation (first 45 d of gestation) is associated with subsequent PL during the following 90 d; and (2) subclinical mastitis 1 to 30 d before artificial insemination (AI) is associated with subsequent PL at 35 to 41 d of gestation. An additional study showed that exposure to clinical mastitis during early lactation in combination with low body condition can increase the risk of PL in dairy cows; however, the interaction effect between clinical mastitis and low body condition on PL was considered weak. Four other studies produced inconclusive evidence indicating that mastitis is a predisposing factor for PL in dairy cows, as the exposure risk period for mastitis overlapped with the follow-up period for diagnosis of PL in dairy cows. Finally, one study failed to identify a relationship between mastitis and PL in dairy cows. Further research is needed to (1) support the hypothesis that mastitis in combination with low body condition score (or other exposure factors) can increase the risk of PL, (2) compare the effect of clinical versus subclinical mastitis on PL, (3) compare the effect of mastitis before breeding and during gestation on PL, and (4) compare the effect of mastitis on PL in dairy cows during different lactations.



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Validation of 2 noninvasive, markerless reconstruction techniques in biplane high-speed fluoroscopy for 3-dimensional research of bovine distal limb kinematics

Publication date: Available online 2 August 2017
Source:Journal of Dairy Science
Author(s): M. Weiss, E. Reich, S. Grund, C.K.W. Mülling, S.M. Geiger
Lameness severely impairs cattle's locomotion, and it is among the most important threats to animal welfare, performance, and productivity in the modern dairy industry. However, insight into the pathological alterations of claw biomechanics leading to lameness and an understanding of the biomechanics behind development of claw lesions causing lameness are limited. Biplane high-speed fluoroscopic kinematography is a new approach for the analysis of skeletal motion. Biplane high-speed videos in combination with bone scans can be used for 3-dimensional (3D) animations of bones moving in 3D space. The gold standard, marker-based animation, requires implantation of radio-opaque markers into bones, which impairs the practicability for lameness research in live animals. Therefore, the purpose of this study was to evaluate the comparative accuracy of 2 noninvasive, markerless animation techniques (semi-automatic and manual) in 3D animation of the bovine distal limb. Tantalum markers were implanted into each of the distal, middle, and proximal phalanges of 5 isolated bovine distal forelimbs, and biplane high-speed x-ray videos of each limb were recorded to capture the simulation of one step. The limbs were scanned by computed tomography to create bone models of the 6 digital bones, and 3D animation of the bones' movements were subsequently reconstructed using the marker-based, the semi-automatic, and the manual animation techniques. Manual animation translational bias and precision varied from 0.63 ± 0.26 mm to 0.80 ± 0.49 mm, and rotational bias and precision ranged from 2.41 ± 1.43° to 6.75 ± 4.67°. Semi-automatic translational values for bias and precision ranged from 1.26 ± 1.28 mm to 2.75 ± 2.17 mm, and rotational values varied from 3.81 ± 2.78° to 11.7 ± 8.11°. In our study, we demonstrated the successful application of biplane high-speed fluoroscopic kinematography to gait analysis of bovine distal limb. Using the manual animation technique, kinematics can be measured with sub-millimeter accuracy without the need for invasive marker implantation.



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Effect of recombinant bovine somatotropin on leukocyte mRNA expression for genes related to cell energy metabolism, cytokine production, phagocytosis, oxidative burst, and adaptive immunity

Publication date: Available online 2 August 2017
Source:Journal of Dairy Science
Author(s): P.R.B. Silva, C.D. Nelson, J.P. Driver, W.W. Thatcher, R.C. Chebel
Objectives of the current experiment were to evaluate the effects of treatment of periparturient dairy cows with recombinant bovine somatotropin (rbST) on mRNA expression in peripheral leukocytes for genes related to the somatotropic axis, cell energy metabolism, and innate and adaptive immune responses. Cows were enrolled in the experiment at 253 ± 3 d of gestation and assigned to an untreated control group (n = 98) or to receive 125 mg of rbST weekly from −21 to 21 d relative to calving (rbST125; n = 98). Data from a subsample of cows (control = 16, rbST125 = 16) are reported herein. Hemogram and polymorphonuclear leukocyte (PMNL) phagocytosis, oxidative burst, and expression of adhesion molecules were determined weekly, from −28 ± 3 to 24 ± 3 d relative to calving. Cows were vaccinated with ovalbumin at −21 ± 3, −7 ± 3, and 7 ± 3 d relative to calving. Serum IgG anti-ovalbumin and haptoglobin optical densities were determined weekly, from −28 ± 3 to 24 ± 3 d relative to calving. Leukocytes were isolated from whole blood on d −21 ± 3, −7 ± 3, and 7 ± 3 relative to calving to determine leukocyte mRNA expression for 66 genes. Cows in the rbST125 treatment had greater concentration of granulocytes 1 wk prepartum (control = 3.7 ± 0.4 vs. rbST125 = 4.6 ± 0.4 × 10⁹ cells/L). Expression of CD18 by PMNL during the prepartum (control = 3,262 ± 280 vs. rbST125 = 3,926 ± 260 geometric mean fluorescence intensity) and percentage of PMNL positive for phagocytosis and oxidative burst 1 wk postpartum (control = 59.2 ± 2.8 vs. rbST125 = 67.6 ± 3.1%) were increased in rbST125 cows. Postpartum IgG anti-ovalbumin optical density was higher in rbST125 cows than control cows (control = 1.5 ± 0.1 vs. rbST125 = 1.9 ± 0.1 optical density). On d −7 relative to calving, leukocyte mRNA expression of IGF1R and JAK1 tended to be downregulated and expression of DEFB3 tended to be upregulated by rbST treatment. Expression of mRNA for STAT1, RELA, and NOD2 tended to be upregulated, expression of RAC2 was downregulated, and expression of JAK3, BLK, and TNFα tended to be downregulated on d 7 relative to calving by rbST treatment. Effects of treatment of periparturient cows with 125 mg of rbST on leukocyte gene expression were minute; thus, additional experiments are necessary to elucidate how rbST-induced increases in growth hormone and insulin-like growth factor-1 concentrations may modulate the immune response of periparturient cows.



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Effect of lignin linkages with other plant cell wall components on in vitro and in vivo neutral detergent fiber digestibility and rate of digestion of grass forages

Publication date: Available online 2 August 2017
Source:Journal of Dairy Science
Author(s): E. Raffrenato, R. Fievisohn, K.W. Cotanch, R.J. Grant, L.E. Chase, M.E. Van Amburgh
The objective of this study was to correlate in vitro and in vivo neutral detergent fiber (NDF) digestibility (NDFD) with the chemical composition of forages and specific chemical linkages, primarily ester- and ether-linked para-coumaric (pCA) and ferulic acids (FA) in forages fed to dairy cattle. The content of acid detergent lignin (ADL) and its relationship with NDF does not fully explain the observed variability in NDFD. The ferulic and p-coumaric acid linkages between ADL and cell wall polysaccharides, rather than the amount of ADL, might be a better predictor of NDFD. Twenty-three forages, including conventional and brown midrib corn silages and grasses at various stages of maturity were incubated in vitro for measurement of 24-h and 96-h NDFD. Undigested and digested residues were analyzed for NDF, acid detergent fiber (ADF), ADL, and Klason lignin (KL); ester- and ether-linked pCA and FA were determined in these fractions. To determine whether in vitro observations of ester- and ether-linked pCA and FA and digestibility were similar to in vivo observations, 3 corn silages selected for digestibility were fed to 6 ruminally fistulated cows for 3 wk in 3 iso-NDF diets. Intact samples and NDF and ADF residues of diet, rumen, and feces were analyzed for ester- and ether-linked pCA and FA. From the in vitro study, the phenolic acid content (total pCA and FA) was highest for corn silages, and overall the content of ester- and ether-linked pCA and FA in both NDF and ADF residues were correlated with NDF digestibility parameters, reflecting the competitive effect of these linkages on digestibility. Also, Klason lignin and ADL were negatively correlated with ether-linked ferulic acid on an NDF basis. Overall, esterified FA and esterified pCA were negatively correlated with all of the measured fiber fractions on both a dry matter and an NDF basis. The lignin content of the plant residues and chemical linkages explained most of the variation in both rate and extent of NDF digestion but not uniformly among forages, ranging from 56 to 99%. The results from the in vivo study were similar to the in vitro data, demonstrating the highest total-tract aNDF digestibility (70%; NDF analysis conducted with α-amylase and sodium sulfite) for cows fed the corn silage with the lowest ester- and ether-linked pCA content in the NDF fraction. In this study, digestibility of forage fiber was influenced by the linkages among lignin and the carbohydrate moieties, which vary by hybrid and species and most likely vary by the agronomic conditions under which the plant was grown.



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Sponsoring Organizations and Liaisons

Publication date: August 2017
Source:The Journal of Prosthetic Dentistry, Volume 118, Issue 2





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Table of Contents

Publication date: August 2017
Source:The Journal of Prosthetic Dentistry, Volume 118, Issue 2





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The Essentials

Publication date: August 2017
Source:The Journal of Prosthetic Dentistry, Volume 118, Issue 2





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Editorial Board

Publication date: August 2017
Source:The Journal of Prosthetic Dentistry, Volume 118, Issue 2





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News and Notes

Publication date: August 2017
Source:The Journal of Prosthetic Dentistry, Volume 118, Issue 2





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Transverse relaxation of cerebrospinal fluid depends on glucose concentration

Publication date: Available online 3 August 2017
Source:Magnetic Resonance Imaging
Author(s): A. Daoust, S. Dodd, G. Nair, N. Bouraoud, S. Jacobson, S. Walbridge, D.S. Reich, A. Koretsky
PurposeTo evaluate the biophysical processes that generate specific T2 values and their relationship to specific cerebrospinal fluid (CSF) content.Materials and methodsCSF T2s were measured ex vivo (14.1T) from isolated CSF collected from human, rat and non-human primate. CSF T2s were also measured in vivo at different field strength in human (3 and 7T) and rodent (1, 4.7, 9,4 and 11.7T) using different pulse sequences. Then, relaxivities of CSF constituents were measured, in vitro, to determine the major molecule responsible for shortening CSF T2 (2s) compared to saline T2 (3s). The impact of this major molecule on CSF T2 was then validated in rodent, in vivo, by the simultaneous measurement of the major molecule concentration and CSF T2.ResultsEx vivo CSF T2 was about 2.0s at 14.1T for all species. In vivo human CSF T2 approached ex vivo values at 3T (2.0s) but was significantly shorter at 7T (0.9s). In vivo rodent CSF T2 decreased with increasing magnetic field and T2 values similar to the in vitro ones were reached at 1T (1.6s). Glucose had the largest contribution of shortening CSF T2in vitro. This result was validated in rodent in vivo, showing that an acute change in CSF glucose by infusion of glucose into the blood, can be monitored via changes in CSF T2 values.ConclusionThis study opens the possibility of monitoring glucose regulation of CSF at the resolution of MRI by quantitating T2.



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The value of ESWAN in diagnosis and differential diagnosis of prostate cancer: Preliminary study

Publication date: Available online 3 August 2017
Source:Magnetic Resonance Imaging
Author(s): Xin Jian-Ying, Gao Shan-Shan, Liu Jin-Gang, Sun Cheng-Feng, Han Yu, Sun Xi-He, Wang Xi-Zhen, Wang Bin
ObjectiveTo evaluate the value of enhanced T2 star-weighted angiography (ESWAN) in diagnosis and differential diagnosis of prostate cancer by comparing the multiple indices of ESWAN in benign prostatic hyperplasia (BPH), prostate cancer (PCa) and the normal peripheral zone (PZ).MethodsTraditional MRI and ESWAN were performed on forty-nine clinically-diagnosed PCa patients, sixty BPH patients, and forty-six normal adult males. The ESWAN indices (magnitude value, phase value, R2* value and T2* value) measured on different regions of interest (ROIs) were analyzed. Additionally, receiver operating characteristic (ROC) analysis was performed to obtain the area under the curve (AUC), sensitivity, specificity, and optimal cut-off points of PCa and BPH, PCa and PZ respectively.ResultsThe magnitude value, phase value, R2* value and T2* value of PZ were 1529.43±254.43, 0.0689±0.1619, 16.57±8.11, 82.75±53.87, respectively; the magnitude value, phase value, R2* value, and T2* value of PCa were 1540.18±338.62, −0.0176±0.0919, 26.93±11.31, and 45.99±17.43, respectively; the magnitude value, phase value, R2* value, and T2* value of BPH were 1579.49±285.28, 0.0209±0.0839, 20.69±3.95, and 51.56±8.90, respectively. Compared with normal PZ, phase value of PCa was lower (t=−3.302, P=0.001), R2* value higher (t=5.326, P=0.000), and T2* value lower (t=−4.570, P=0.000); compared with BPH, phase value of PCa was lower (t=−2.261, P=0.026), R2* value higher (t=3.988, P=0.000), and T2* value lower (t=−2.155, P=0.033). When PCa and PZ were distinguished, the AUC of magnitude value, phase value, R2* value, and T2* value were respectively 0.539 (P=0.510), 0.679 (P=0.0007), 0.811 (P<0.0001), and 0.762 (P<0.0001); the diagnosis efficiency of R2* value was higher than that of T2* value (P=0.037), while the diagnosis efficiency of T2* value was equivalent to phase value (P=0.256). When PCa was differentiated from BPH, the AUC of magnitude value, phase value, R2* value, and T2* value were 0.518 (P=0.752), 0.612 (P=0.039), 0.705 (P=0.0001), and 0.685 (P=0.0006), respectively; there was no statistical difference in the diagnostic efficiency of phase value, R2* value, and T2* value.ConclusionsThe phase value, R2* value and T2* value can distinguish PCa and normal PZ, PCa and BPH, so they are valuable for the diagnosis and differential diagnosis of PCa, moreover, the diagnostic efficiency of R2* value is better than other indices.



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The costal remains of the El Sidrón Neanderthal site (Asturias, northern Spain) and their importance for understanding Neanderthal thorax morphology

Publication date: October 2017
Source:Journal of Human Evolution, Volume 111
Author(s): Daniel García-Martínez, Markus Bastir, Rosa Huguet, Almudena Estalrrich, Antonio García-Tabernero, Luis Ríos, Eugenia Cunha, Marco de la Rasilla, Antonio Rosas
The study of the Neanderthal thorax has attracted the attention of the scientific community for more than a century. It is agreed that Neanderthals have a more capacious thorax than modern humans, but whether this was caused by a medio-lateral or an antero-posterior expansion of the thorax is still debated, and is key to understanding breathing biomechanics and body shape in Neanderthals. The fragile nature of ribs, the metameric structure of the thorax and difficulties in quantifying thorax morphology all contribute to uncertainty regarding precise aspects of Neanderthal thoracic shape. The El Sidrón site has yielded costal remains from the upper to the lower thorax, as well as several proximal rib ends (frequently missing in the Neanderthal record), which help to shed light on Neanderthal thorax shape. We compared the El Sidrón costal elements with ribs from recent modern humans as well as with fossil modern humans and other Neanderthals through traditional morphometric methods and 3D geometric morphometrics, combined with missing data estimation and virtual reconstruction (at the 1st, 5th and 11th costal levels). Our results show that Neanderthals have larger rib heads and articular tubercles than their modern human counterparts. Neanderthal 1st ribs are smaller than in modern humans, whereas 5th and 11th ribs are considerably larger. When we articulated mean ribs (size and shape) with their corresponding vertebral elements, we observed that compared to modern humans the Neanderthal thorax is medio-laterally expanded at every level, especially at T5 and T11. Therefore, in the light of evidence from the El Sidrón costal remains, we hypothesize that the volumetric expansion of the Neanderthal thorax proposed by previous authors would mainly be produced by a medio-lateral expansion of the thorax.



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Rare case of pulmonary involvement in an adult with Kawasaki disease

Publication date: Available online 3 August 2017
Source:Clinical Imaging
Author(s): Joanna G. Escalon, Xiaoping Wu, Ian R. Drexler, Lindsay Lief, Maria Plataki, Michael Bender, James F. Gruden
Kawasaki disease is an acute, self-limited, febrile vasculitis typically seen in early childhood. Pulmonary involvement is uncommon and is not part of the conventional diagnostic criteria. We add to the literature a unique case of a 22year-old male with Kawasaki disease and pulmonary involvement. It illustrates the importance of recognizing unusual presentations of Kawasaki disease and highlights the possibility of pulmonary abnormalities on physical and imaging examination. Awareness of such presentations can help avoid delayed diagnosis, prevent the development of coronary aneurysms, and allow careful observation for imaging resolution.



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Safety and efficacy of topical timolol treatment of infantile haemangioma: A prospective trial

Abstract

Topical timolol therapy is considered a relatively "safer" alternative for the treatment of infantile haemangiomas (IH); however, sufficient supportive pharmacokinetic data does not exist. Most efficacy studies have not evaluated systemic absorption.^1-5 To our knowledge, this is the first prospective trial to assess the clinical response of proliferating IH to topical timolol maleate 0.5% gel-forming solution and to determine if systemic absorption occurred.Twenty-six subjects enrolled in this trial approved by the UCSD IRB.

This article is protected by copyright. All rights reserved.

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TNF antagonist induced lupus: a critically appraised topic

Abstract

TNF antagonist induced lupus is diagnosed upon a temporal relationship of TNF antagonist therapy and the development of four of the 11 American college of rheumatology (ACR) diagnostic criteria for lupus.

We critically appraise the literature on TNF antagonist induced lupus, focusing on the diagnostic criteria, dermatological manifestations, management and outcome.

Eighty cases of TNF antagonist induced lupus that met the ACR criteria were included and analysed. Infliximab was the most commonly reported agent (58.8%, n=47). Cutaneous manifestations were the most common presentation (67.5%, n=54,), specifically malar rash (26.3%, n=21) and photosensitivity (23.4%, n=19). Lupus symptoms resolved in all cases (n=80), withdrawal of the TNF antagonist was sufficient in 18.8% of cases (n=15), additional immunosuppression was required in the remaining cases. Four patients were treated with a second, different TNF antagonist, with no recurrence of symptoms. TNF antagonist induced lupus appears to have a good prognosis and treatment should be tailored to each individual case. As cutaneous features are the most common manifestation it is important that dermatologists are aware of the ACR diagnostic criteria of lupus to ensure accurate diagnoses of TNF antagonist induced lupus.

This article is protected by copyright. All rights reserved.

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Time, PASI and DLQI of psoriasis patients who “drop out” of clinical trials on etanercept due to “lack of efficacy” - a pooled analysis from ten clinical trials

SUMMARY

Background

Patient-reported outcomes in psoriasis studies are assessed at specific study time points. If a treatment has not become effective by a certain time point, it may increase the likelihood of patients being dissatisfied and leaving a clinical study.

Objectives

Generate evidence concerning the number of patients dropping out of etanercept trials over time including PASI and DLQI data.

Methods

Data from psoriasis patients in ten trials with etanercept were pooled. Analyses were performed for a) patients who dropped out due to 'lack of efficacy' b) patients who continued the trial. Psoriasis Area Severity Index (PASI) and Dermatology Life Quality Index (DLQI) data were summarized for different time points. Distribution of dropouts over time, PASI and DLQI and the proportion of patients dropping out with given treatment responses, were calculated.

Results

Of 6119 patients 128 dropped out due to 'lack of efficacy'(or synonym). The highest increase of patients dropping out happened between Day 75 and 85 (46% to 73%). The lowest PASI of patients dropping out was 6.3 within 120 days. Dropouts who achieved ≥ PASI 75 were rare.

Conclusion

A critical time when many patients might have lost their willingness to wait for their treatment with etanercept to show a better effect appeared to be at around Day 80. Most of the patients dropping out showed little improvement, stable disease or worsening of their psoriasis.

This article is protected by copyright. All rights reserved.

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Prognostic importance of a second invasive primary melanoma according to tumor stage

Abstract

It is well known that a considerable proportion of the Caucasian population in many countries are diagnosed with multiple melanomas over time¹. Despite this, most analyses of melanoma survival, including that of the American Joint Committee on Cancer (AJCC), consider only one tumor for every patient and disregard the potential effect of multiple melanomas on outcomes and this is reflected in the lack of specific management guidelines for patients with multiple melanomas beyond those dictated by the clinicopathological features of each tumour^2-4.

Recently we and others have shown that patients with multiple primary invasive melanomas have an increased risk of melanoma death compared to patients with a single melanoma^5,6.

This article is protected by copyright. All rights reserved.

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Engineering Skin with Skinny Genes

Publication date: 3 August 2017
Source:Cell Stem Cell, Volume 21, Issue 2
Author(s): Anika Böttcher, Heiko Lickert, Matthias Tschöp
The increasing prevalence of obesity and diabetes is an urgent worldwide health challenge. Now in Cell Stem Cell, Yue et al. (2017) report a proof-of-concept study using genetically engineered skin transplants that produce the incretin GLP-1 to prevent diet-induced obesity, suggesting a powerful approach for treating metabolic disorders.

Teaser

The increasing prevalence of obesity and diabetes is an urgent worldwide health challenge. Now in Cell Stem Cell, Yue et al. (2017) report a proof-of-concept study using genetically engineered skin transplants that produce the incretin GLP-1 to prevent diet-induced obesity, suggesting a powerful approach for treating metabolic disorders.


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Do Not Adjust Your Mind: The Fault Is in Your Glia

Publication date: 3 August 2017
Source:Cell Stem Cell, Volume 21, Issue 2
Author(s): Robin J.M. Franklin, Edward T. Bullmore
Glia have been implicated in schizophrenia, although whether they play a primary role is uncertain. In this issue of Cell Stem Cell, Windrem et al. (2017) transplant human glial progenitors from schizophrenia patients into mouse brains, which develop abnormalities and behaviors characteristic of schizophrenia, thereby suggesting a primary role for glia in the complex disease pathogenesis.

Teaser

Glia have been implicated in schizophrenia, although whether they play a primary role is uncertain. In this issue of Cell Stem Cell, Windrem et al. (2017) transplant human glial progenitors from schizophrenia patients into mouse brains, which develop abnormalities and behaviors characteristic of schizophrenia, thereby suggesting a primary role for glia in the complex disease pathogenesis.


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A Little Bit of Guidance: Mini Brains on Their Route to Adolescence

Publication date: 3 August 2017
Source:Cell Stem Cell, Volume 21, Issue 2
Author(s): Philipp Koch, Julia Ladewig
Cerebral organoids represent a new model in which to study human brain development outside the human body. Recently in Nature Biotechnology, Lancaster et al. (2017) tackled the lack of reproducibility, tissue homogeneity, and complexity of this system by bioengineering organoids to establish the next generation of human mini brains.

Teaser

Cerebral organoids represent a new model in which to study human brain development outside the human body. Recently in Nature Biotechnology, Lancaster et al. (2017) tackled the lack of reproducibility, tissue homogeneity, and complexity of this system by bioengineering organoids to establish the next generation of human mini brains.


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Cholangiocytes: No Longer Cinderellas to the Hepatic Regenerative Response

Publication date: 3 August 2017
Source:Cell Stem Cell, Volume 21, Issue 2
Author(s): Malcolm R. Alison
Biliary ductal cells proliferate from the portal areas of chronically damaged livers, but their significance to regeneration has been controversial. A recent article in Nature by Raven et al. (2017) now shows that blocking hepatocyte replication is essential for the hepatic differentiation of ductular cells after liver damage.

Teaser

Biliary ductal cells proliferate from the portal areas of chronically damaged livers, but their significance to regeneration has been controversial. A recent article in Nature by Raven et al. (2017) now shows that blocking hepatocyte replication is essential for the hepatic differentiation of ductular cells after liver damage.


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Combining hiPSCs and Human Genetics: Major Applications in Drug Development

Publication date: 3 August 2017
Source:Cell Stem Cell, Volume 21, Issue 2
Author(s): Jin Zhang, Hu Li, Alan Trounson, Joseph C. Wu, Paul Nioi
Merging iPSC models and human genetic research has opened up new avenues in understanding disease mechanisms and target biology, which facilitate exciting translation of this research to many areas of drug development. We highlight recent applications of these combined disciplines and discuss remaining challenges and potential solutions.

Teaser

Merging iPSC models and human genetic research has opened up new avenues in understanding disease mechanisms and target biology, which facilitate exciting translation of this research to many areas of drug development. We highlight recent applications of these combined disciplines and discuss remaining challenges and potential solutions.


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Upstairs, Downstairs: Atrial and Ventricular Cardiac Myocytes from Human Pluripotent Stem Cells

Publication date: 3 August 2017
Source:Cell Stem Cell, Volume 21, Issue 2
Author(s): Michael D. Schneider
Cardiomyocyte creation by human pluripotent stem cells (hPSCs) has generated opportunities for heart repair, disease modeling, and drug development. In this issue of Cell Stem Cell,Lee et al. (2017) report prospective markers of atrial versus ventricular myocyte formation from hPSCs and their use in directed differentiation of cardiac sub-lineages.

Teaser

Cardiomyocyte creation by human pluripotent stem cells (hPSCs) has generated opportunities for heart repair, disease modeling, and drug development. In this issue of Cell Stem Cell, Lee et al. (2017) report prospective markers of atrial versus ventricular myocyte formation from hPSCs and their use in directed differentiation of cardiac sub-lineages.


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Mesenchymal Stem Cells in Fibrotic Disease

Publication date: 3 August 2017
Source:Cell Stem Cell, Volume 21, Issue 2
Author(s): Elie El Agha, Rafael Kramann, Rebekka K. Schneider, Xiaokun Li, Werner Seeger, Benjamin D. Humphreys, Saverio Bellusci
Fibrosis is associated with organ failure and high mortality and is commonly characterized by aberrant myofibroblast accumulation. Investigating the cellular origin of myofibroblasts in various diseases is thus a promising strategy for developing targeted anti-fibrotic treatments. Recent studies using genetic lineage tracing technology have implicated diverse organ-resident perivascular mesenchymal stem cell (MSC)-like cells and bone marrow-MSCs in myofibroblast generation during fibrosis development. In this Review, we give an overview of the emerging role of MSCs and MSC-like cells in myofibroblast-mediated fibrotic disease in the kidney, lung, heart, liver, skin, and bone marrow.

Teaser

Fibrosis is associated with organ failure and is characterized by aberrant myofibroblast accumulation; thus, investigating the cellular origin of myofibroblasts is a promising therapeutic strategy. Here we discuss the emerging role of MSCs and MSC-like cells in myofibroblast-mediated fibrotic disease in the kidney, lung, heart, liver, skin, and bone marrow.


http://ift.tt/2uova7w

Human Pluripotent Stem Cell-Derived Atrial and Ventricular Cardiomyocytes Develop from Distinct Mesoderm Populations

Publication date: 3 August 2017
Source:Cell Stem Cell, Volume 21, Issue 2
Author(s): Jee Hoon Lee, Stephanie I. Protze, Zachary Laksman, Peter H. Backx, Gordon M. Keller
The ability to direct the differentiation of human pluripotent stem cells (hPSCs) to the different cardiomyocyte subtypes is a prerequisite for modeling specific forms of cardiovascular disease in vitro and for developing novel therapies to treat them. Here we have investigated the development of the human atrial and ventricular lineages from hPSCs, and we show that retinoic acid signaling at the mesoderm stage of development is required for atrial specification. Analyses of early developmental stages revealed that ventricular and atrial cardiomyocytes derive from different mesoderm populations that can be distinguished based on CD235a and RALDH2 expression, respectively. Molecular and electrophysiological characterization of the derivative cardiomyocytes revealed that optimal specification of ventricular and atrial cells is dependent on induction of the appropriate mesoderm. Together these findings provide new insights into the development of the human atrial and ventricular lineages that enable the generation of highly enriched, functional cardiomyocyte populations for therapeutic applications.

Graphical abstract

Teaser

Keller, Protze, and colleagues show that atrial and ventricular cardiomyocytes develop from distinct mesoderm populations. Molecular and functional analyses revealed that appropriate mesoderm patterning is required for generating enriched populations of atrial or ventricular cardiomyocytes from hPSCs. These findings provide important new insights for the derivation of populations for future therapeutic applications.


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Long-Term Engraftment of Primary Bone Marrow Stromal Cells Repairs Niche Damage and Improves Hematopoietic Stem Cell Transplantation

Publication date: 3 August 2017
Source:Cell Stem Cell, Volume 21, Issue 2
Author(s): Jean-Paul Abbuehl, Zuzana Tatarova, Werner Held, Joerg Huelsken
Hematopoietic stem cell (HSC) transplantation represents a curative treatment for various hematological disorders. However, delayed reconstitution of innate and adaptive immunity often causes fatal complications. HSC maintenance and lineage differentiation are supported by stromal niches, and we now find that bone marrow stroma cells (BMSCs) are severely and permanently damaged by the pre-conditioning irradiation required for efficient HSC transplantation. Using mouse models, we show that stromal insufficiency limits the number of donor-derived HSCs and B lymphopoiesis. Intra-bone transplantation of primary, but not cultured, BMSCs quantitatively reconstitutes stroma function in vivo, which is mediated by a multipotent NT5E⁺ (CD73)⁺ ENG⁻ (CD105)⁻ LY6A⁺ (SCA1)⁺ BMSC subpopulation. BMSC co-transplantation doubles the number of functional, donor-derived HSCs and significantly reduces clinically relevant side effects associated with HSC transplantation including neutropenia and humoral immunodeficiency. These data demonstrate the potential of stroma recovery to improve HSC transplantation.

Graphical abstract

Teaser

Abbuehl and colleagues show that irradiation required for hematopoietic stem cell (HSC) transplantation permanently damages the bone marrow (BM) stroma, which limits hematopoietic function. They develop protocols for intra-bone transplantation of multipotent BM stroma cells that reconstitute stroma function, thus significantly reducing clinically relevant side effects associated with HSC transplantation.


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