Characteristics of dairy cows with a greater or lower risk of subacute ruminal acidosis: Volatile fatty acid absorption, rumen digestion, and expression of genes in rumen epithelial cells

Publication date: Available online 13 September 2016
Source:Journal of Dairy Science
Author(s): X. Gao, M. Oba
The objective of this study was to examine whether lactating dairy cows with a greater or lower risk of subacute ruminal acidosis (SARA) have differences in volatile fatty acid (VFA) absorption rate, expression of genes involved in VFA metabolism and intracellular pH regulation in rumen epithelial cells, and in situ carbohydrate digestibility in the rumen. We fed 14 ruminally cannulated mid-lactating dairy cows (119 ± 47.2 d in milk; body weight 640 ± 47.9 kg) a high-grain diet consisting of 30% forage ad libitum, with an 18-d diet adaptation and a 7-d sample and data collection period. Eight cows with the lowest acidosis index [area below pH 5.8 normalized for dry matter intake (DMI); 0.10 ± 0.16 pH × min/kg of DMI] and 5 with the highest acidosis index (3.72 ± 0.19 pH × min/kg of DMI) were classified as animals with lower risk (LS) and higher risk (HS) of SARA, respectively. Minimum (5.75 vs. 5.33) and mean rumen pH (6.33 vs. 5.98) were higher for LS than for HS cows. In addition, the duration and area of rumen pH below 5.8 was lower in LS cows (24.9 vs. 481 min/d; 2.94 vs. 102 pH × min/d). Although DMI, milk yield, and milk component yields did not differ, milk fat concentration tended to be higher for LS cows than for HS cows (3.36 vs. 2.93%). However, we observed no difference in VFA absorption rate between LS and HS cows. In situ starch and neutral detergent fiber digestibility were not different between LS and HS cows, but the relative mRNA abundance of lanosterol synthase (LSS) was higher for LS cows than for HS cows. In addition, the mRNA abundance of hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) tended to be higher for LS cows than for HS cows. These results suggested that VFA absorption rate might not explain the difference in rumen pH between LS and HS cows in the current study, even though expression of some genes related to VFA metabolism in rumen epithelium may be associated with variation in the risk of SARA among lactating cows. This variation in the risk of SARA may not be attributed to differences in the capacity of rumen microbes to ferment carbohydrates, because in situ carbohydrate digestibility in the rumen was not different between cows with higher and lower risk of SARA.



http://ift.tt/2cvUmUj

Survey of reproduction management on Canadian dairy farms

Publication date: Available online 13 September 2016
Source:Journal of Dairy Science
Author(s): J. Denis-Robichaud, R.L.A. Cerri, A. Jones-Bitton, S.J. LeBlanc
The objectives of this study were to (1) quantify current reproduction management practices, and (2) assess the association between these practices and herd reproductive performance on dairy farms in Canada. A bilingual survey was developed, validated, and administered from March to May 2014 to collect general and reproduction management and performance measures [annual 21-d pregnancy rate (PR), 21-d insemination rate (IR), and conception risk (CR)]. Associations between management practices and reproductive performance measures were tested using linear regression models. A total of 832 questionnaires were completed online and by mail, representing a response rate of 9%. On average, farms had 77 lactating cows (median = 50) and 13 dry cows (median = 10), and Holstein was the most common breed (92% of herds). Lactating cow housing was tiestall on 61% of the farms, freestall on 37%, and bedded pack on 2%. The average voluntary waiting period was 58 d in milk (DIM). The main reproduction management practice per farm was defined as the means employed for >50% of inseminations. Farms reported their main reproduction management practice for first and subsequent inseminations, respectively, as visual estrus detection (51 and 44% of herds), timed AI (21 and 23% of herds), automated activity monitoring (AAM; 10 and 10% of herds), other management practice (bulls; 2 and 2% of herds), and a combination of management practices (16 and 21% of herds). On farms using visual estrus detection, cows were observed for signs of estrus on average 3.5 times per day, for an average total of 36 min/d. The most common use of reproductive hormones was to synchronize ovulation using Ovsynch (58% of the farms). Average PR, IR, and CR were 17.6, 44.1, and 40.5%, respectively. In linear regression analyses adjusted for confounders, pregnancy rate was significantly associated with geographic region, housing (tiestall: PR = 15.4%, freestall: PR = 17.6%), herd size (<50 lactating cows: PR = 16.2%, 50–100 cows: PR = 16.5%, >100 cows: PR = 17.8%), voluntary waiting period (≤60 DIM: PR = 17.6%, >60 DIM: PR = 15.9%), and frequency of insemination per day (once daily: PR = 16.6%, twice or more daily: PR = 18.1%). The main reproduction management practice at first and subsequent inseminations was divergently associated with IR and CR, but not with PR (visual heat detection: PR = 17.4%, timed AI: PR = 18.4%, AAM: PR = 17.1%, combined practices: PR = 18.2%).



http://ift.tt/2cXbW1O

Effect of dried nut fortification on functional, physicochemical, textural, and microbiological properties of yogurt

Publication date: Available online 13 September 2016
Source:Journal of Dairy Science
Author(s): S. Ozturkoglu-Budak, C. Akal, A. Yetisemiyen
In this study, walnut, hazelnut, almond, and pistachio were incorporated to produce functional yogurt. The effects on physicochemical and instrumental textural characteristics, syneresis, folic acid, selenium, tocopherols, omega fatty acid contents, and viable counts of Streptococcus thermophilus and Lactobacillus bulgaricus were evaluated during storage. Fortified yogurts demonstrated higher protein and total solid contents and lower syneresis compared with control yogurt on d 21. Addition of nuts also increased S. thermophilus and L. bulgaricus counts except for walnut. The concentrations of folic acid, α-tocopherol, selenium, and omega fatty acids were determined to be higher in fortified yogurts compared with the levels found in nut types. However, a decreasing trend was observed in all components during storage. As a consequence, each nut could be incorporated into yogurt because of a specific functional property. For instance, walnut could be preferred for omega acid enrichment.



http://ift.tt/2cvVfvT

Prediction of fat globule particle size in homogenized milk using Fourier transform mid-infrared spectra

Publication date: Available online 13 September 2016
Source:Journal of Dairy Science
Author(s): Larissa Di Marzo, Patrick Cree, David M. Barbano
Our objective was to develop partial least square models using data from Fourier Transform mid-infrared (MIR) spectra to predict the particle size distributions d(0.5) and d(0.9), surface volume mean diameter D[3,2], and volume moment mean diameter D[4,3] of milk fat globules and validate the models. The goal of the study was to produce a method built into the MIR milk analyzer that could be used to warn the instrument operator that the homogenizer is near failure and needs to be replaced to ensure quality of results. Five homogenizers with different homogenization efficiency were used to homogenize pasteurized modified unhomogenized milks and farm raw bulk milks. Homogenized milks were collected from the homogenizer outlet and then run through an MIR milk analyzer without an in-line homogenizer to collect a MIR spectrum. A separate portion of each homogenized milk was analyzed with a laser light-scattering particle size analyzer to obtain reference values. The study was replicated 3 times with 3 independent sets of modified milks and bulk tank farm milks. Validation of the models was done with a set of 34 milks that were not used in the model development. Partial least square regression models were developed and validated for predicting the following milk fat globule particle size distribution parameters from MIR spectra: d(0.5) and d(0.9), surface volume mean diameter D[3,2], and volume moment mean diameter D[4,3]. The basis for the ability to model particle size distribution of milk fat emulsions was hypothesized to be the result of the partial least square modeling detecting absorbance shifts in MIR spectra of milk fat due to the Christiansen effect. The independent sample validation of particle size prediction methods found more variation in d(0.9) and D[4,3] predictions than the d(0.5) and D[3,2] predictions relative to laser light-scattering reference values, and this may be due to variation in particle size among different pump strokes. The accuracy of the d(0.9) prediction for routine quality assurance, to determine if a homogenizer within an MIR milk analyzer was near the failure level [i.e., d(0.9) >1.7 μm] and needed to be replaced, is fit-for-purpose. The daily average particle size performance [i.e., d(0.9)] of a homogenizer based on the mean for the day could be used for monitoring homogenizer performance.



http://ift.tt/2cIy4gR

Tiotropium in asthma: what is the evidence and how does it fit in?

Despite current therapeutic approaches asthma remains uncontrolled in a significant proportion of patients. Short-acting anticholinergic bronchodilators have a very long history of use in asthma, and recent da...

http://ift.tt/2c84QFA

Ten years results of the Canadian breast intensity modulated radiation therapy (IMRT) randomized controlled trial

Publication date: Available online 13 September 2016
Source:Radiotherapy and Oncology
Author(s): Jean-Philippe Pignol, Pauline Truong, Eileen Rakovitch, Margriet G. Sattler, Timothy J. Whelan, Ivo A. Olivotto
Background and purposeWe report the long-term outcomes in patients enrolled in a multicenter randomized controlled trial comparing Intensity Modulated Radiation Therapy (IMRT) with standard wedge radiotherapy.Materials and methodsTrial participants were assessed to compare long-term side effects between treatment arms. The primary endpoint was chronic breast pain assessed by trained observers blinded to treatment allocation. Secondary endpoints included cosmesis and quality of life measures.ResultsMedian follow-up time was 9.8years and 241 patients were available for assessment. There was no significant difference in chronic pain between treatment arms (OR=0.74, range 0.432–1.271). There were also no differences for the secondary endpoints. Univariate and multivariate analyses identified young age (p=0.013) and pain during RT (p<0.001) to be associated with chronic pain. Acute moist desquamation was associated with late subcutaneous fibrosis (p=0.003) and telangiectasia (p=0.039). Pain during RT was associated with a long-term poorer self-assessed cosmetic outcome (p<0.001) and quality of life (p<0.001).ConclusionsBreast IMRT cannot be recommended for all patients to reduce long-term side effects. However, late toxicities were significantly correlated with acute side effects, which are increased in patients having poor dose distribution. Breast IMRT may hence be useful for selected patients.



http://ift.tt/2cvV803

Benefit of particle therapy in re-irradiation of head and neck patients. Results of a multicentric in silico ROCOCO trial

Publication date: Available online 14 September 2016
Source:Radiotherapy and Oncology
Author(s): Daniëlle B.P. Eekers, Erik Roelofs, Urszula Jelen, Maura Kirk, Marlies Granzier, Filippo Ammazzalorso, Peter H. Ahn, Geert O.R.J. Janssens, Frank J.P. Hoebers, Tobias Friedmann, Timothy Solberg, Sean Walsh, Esther G.C. Troost, Johannes H.A.M. Kaanders, Philippe Lambin
Background and PurposeIn this multicentric in silico trial we compared photon, proton, and carbon-ion radiotherapy plans for re-irradiation of patients with squamous cell carcinoma of the head and neck (HNSCC) regarding dose to tumour and doses to surrounding organs at risk (OARs).Material and MethodsTwenty-five HNSCC patients with a second new or recurrent cancer after previous irradiation (70Gy) were included. Intensity-modulated proton therapy (IMPT) and ion therapy (IMIT) re-irradiation plans to a second subsequent dose of 70Gy were compared to photon therapy delivered with volumetric modulated arc therapy (VMAT).ResultsWhen comparing IMIT and IMPT to VMAT, the mean dose to all investigated 22 OARs was significantly reduced for IMIT and to 15 out of 22 OARs (68%) using IMPT. The maximum dose to 2% volume (D2) of the brainstem and spinal cord were significantly reduced using IMPT and IMIT compared to VMAT. The data are available on http://ift.tt/2cUTYB5 this ROCOCO in silico trial, a reduction in mean dose to OARs was achieved using particle therapy compared to photons in the re-irradiation of HNSCC. There was a dosimetric benefit favouring carbon-ions above proton therapy. These dose reductions may potentially translate into lower severe complication rates related to the re-irradiation.



http://ift.tt/2cdTQKb

Transplantation of allogenic chondrocytes with chitosan hydrogel-demineralized bone matrix hybrid scaffold to repair rabbit cartilage injury

Publication date: November 2016
Source:Biomaterials, Volume 108
Author(s): Zhentao Man, Xiaoqing Hu, Zhenlong Liu, Hongjie Huang, Qingyang Meng, Xin Zhang, Linghui Dai, Jiying Zhang, Xin Fu, Xiaoning Duan, Chunyan Zhou, Yingfang Ao
Cartilage tissue engineering is the hotspot of cartilage repair. The allogenic chondrocytes appear to be a promising source of seed cells in cartilage tissue engineering. In this study, we aimed to transplant allogenic chondrocytes with chitosan hydrogel (CS)-demineralized bone matrix (DBM) hybrid scaffold (CS/DBM) to repair rabbit cartilage injury with one-step operation. After the CS/DBM scaffold was successfully fabricated, it showed that the porous CS filled the large pores of DBM, which improved the distribution of seed cells in the CS/DBM scaffold. The allogenic chondrocytes at second passage were transplanted with different scaffolds to repair rabbit cartilage injury. Twenty-four weeks after surgery, the cartilage defect in the CS/DBM group was successfully filled as shown by MRI. Moreover, the histological score of CS/DBM group was significantly higher than that of the other groups. On the aspect of biomechanical property, the regenerated cartilage in the CS/DBM group were superior to those in the other groups as determined by nanoindentation. Meanwhile, no obvious inflammatory response was observed after the transplantation of allogenic chondrocytes at 24 weeks post-surgery. Furtherly, gene expression profile for cells within the repair tissue was compared with the allogenic chondrocytes before transplantation using Agilent microarray and RT-qPCR. The results showed that some genes beneficial to cartilage regeneration, such as BMP-7, HGF, and IGF-1, were upregulated one month after transplantation. Consequently, our study demonstrated that the transplantation of allogenic chondrocytes with CS/DBM scaffold successfully repaired rabbit cartilage injury with only one-step operation, thereby providing new insights into cartilage tissue engineering.



http://ift.tt/2cpnbRx

Immunomodulatory nanoparticles ameliorate disease in the Leishmania (Viannia) panamensis mouse model

Publication date: November 2016
Source:Biomaterials, Volume 108
Author(s): Alyssa L. Siefert, Allison Ehrlich, María Jesús Corral, Karen Goldsmith-Pestana, Diane McMahon-Pratt, Tarek M. Fahmy
Leishmania (Viannia) panamensis (L. (V.) panamensis) is a species of protozoan parasites that causes New World leishmaniasis, which is characterized by a hyper-inflammatory response. Current treatment strategies, mainly chemotherapeutic, are suboptimal due to adverse effects, long treatment regimens, and increasing drug resistance. Recently, immunotherapeutic approaches have shown promise in preclinical studies of leishmaniasis. As NPs may enable broad cellular immunomodulation through internalization in phagocytic and antigen-presenting cells, we tested the therapeutic efficacy of biodegradable NPs encapsulating a pathogen-associated molecular pattern (PAMP), CpG-rich oligonucleotide (CpG; NP-CpG), in mice infected with L. (V.) panamensis. NP-CpG treatment reduced lesion size and parasite burden, while neither free CpG nor empty NP showed therapeutic effects. NP-encapsulation led to CpG persistence at the site of infection along with an unexpected preferential cellular uptake by myeloid derived suppressor cells (MDSCs; CD11b⁺Ly6G⁺Ly6C⁻) as well as CD19⁺ dendritic cells. This corresponded with the suppression of the ongoing immune response measured by the reduction of pathogenic cytokines IL-10 and IL-13, as well as IL-17 and IFNγ, in comparison to other treatment groups. As chronic inflammation is generally associated with the accumulation of MDSCs, this study may enable the rational design of cost-effective, safe, and scalable delivery systems for the treatment of inflammation-mediated diseases.



http://ift.tt/2cUUb7m

Atractylone, an active constituent of KMP6, attenuates allergic inflammation on allergic rhinitis in vitro and in vivo models

Publication date: October 2016
Source:Molecular Immunology, Volume 78
Author(s): Hee-Yun Kim, Sun-Young Nam, Sung-Yeoun Hwang, Hyung-Min Kim, Hyun-Ja Jeong
KMP6 (Pyeongwee-San) is a Korean Medicine used to treat gastrointestinal disorders. Recently, we reported KMP6 had beneficial effects on allergic inflammatory diseases. The aim of this study was to evaluate the effects of atractylone (Atr), a constituent of KMP6, on allergic rhinitis (AR) and to identify the mechanism responsible for these effects. The anti-allergic inflammatory effects of Atr were evaluated on phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-stimulated human mast cell line, HMC-1 cells and in an ovalbumin (OVA)-induced AR animal model using Western blotting, quantitative real-time PCR, ELISA, and immunohistochemistry methods. In HMC-1 cells, Atr and KMP6 attenuated PMACI-caused proinflammatory cytokine production and mRNA expression. We found that PMACI induced caspase-1/nuclear factor (NF)-κB/mitogen activated protein kinases (MAPKs) activation. PMACI-caused caspase-1/NF-κB/MAPKs activations were attenuated by Atr and KMP6. In AR animal model, Atr and KMP6 reduced AR clinical symptoms and biomarkers including rub scores, total IgE, histamine, prostaglandin D2, thymic stromal lymphopoietin, interleukin (IL)-1β, IL-4, IL-5, IL-6, IL-13, tumor necrosis factor-α, cyclooxygenase-2, intercellular adhesion molecule-1, and macrophage inflammatory protein-2. In addition, Atr and KMP6 attenuated eosinophils and mast cells invasions into nasal mucosa tissues and diminished mast cell-derived caspase-1 activation. These results indicate that Atr is an active constituent of KMP6 and a potential therapeutic agent for AR.



http://ift.tt/2ce1yDZ

Tiotropium in asthma: what is the evidence and how does it fit in?

Despite current therapeutic approaches asthma remains uncontrolled in a significant proportion of patients. Short-acting anticholinergic bronchodilators have a very long history of use in asthma, and recent da...

http://ift.tt/2c84QFA

Patient Experiences of Life Years After Severe Civilian Lower Extremity Trauma With Vascular Injury

Publication date: Available online 13 September 2016
Source:European Journal of Vascular and Endovascular Surgery
Author(s): K. Bernhoff, M. Björck, J. Larsson, E. Jangland
ObjectiveSevere lower limb trauma with arterial injury is often devastating for the individual. Many studies describe how to manage these injuries when they occur. Short-term functional outcome is quite well described, but the patients are often young, and their suffering is physical, mental, and social from a lifelong perspective. The aim of this study was to report patient experiences of their lives several years after their accidents, and to explore mechanisms of how to improve management.MethodThe Swedvasc registry was searched for participants from 1987 to 2011, living in the region of Uppsala, Sweden. Some amputated participants were added from the Walking Rehabilitation Center. There were five reconstructed patients with an intact limb, and three with amputations. In depth interviews were conducted and systematically analyzed, using A Giorgi's descriptive phenomenological method.ResultsEight patients participated, five with reconstructed and three with amputated limbs. Life affecting functional impairments were described by all patients. The patients undergoing amputation had received more structured follow up and support through the Walking Rehabilitation Center. The satisfaction with the cosmetic result was poorer than expected. All patients had developed strategies of how to cope with their impairments and stated they now lived "normal lives."ConclusionsDespite substantial physical, psychological, and cosmetic impairments years after severe lower limb trauma, the participants described life as "normal" and mainly satisfactory. Transition to the new situation could have been facilitated by more frequent and continuous follow up after discharge from hospital, in particular among the non-amputated patients who tend to be lost to follow up. Findings also indicate that family members have to be acknowledged, strengthened, and supported.



http://ift.tt/2cIjRkc

Deep Rtms for Neuropsychiatric Symptoms of Huntington's Disease: Case Report

Publication date: Available online 13 September 2016
Source:Brain Stimulation
Author(s): Molly Davis, Angela Phillips, Aron Tendler, Angela Oberdeck




http://ift.tt/2cdUcjK

Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum Reproducibly Improves Symptoms of Body Dysmorphic Disorder

Publication date: Available online 13 September 2016
Source:Brain Stimulation
Author(s): Juan Carlos Baldermann, Sina Kohl, Veerle Visser-Vandewalle, Martin Klehr, Daniel Huys, Jens Kuhn




http://ift.tt/2cvWiZB

The Difficult Journey from Genome-wide Association Studies to Pathophysiology: The Melatonin Receptor 1B (MT2) Paradigm

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Amélie Bonnefond, Angeliki Karamitri, Ralf Jockers, Philippe Froguel




http://ift.tt/2cMzPIB

Never Waste a Good Crisis: Confronting Reproducibility in Translational Research

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Daniel J. Drucker
The lack of reproducibility of preclinical experimentation has implications for sustaining trust in and ensuring the viability and funding of the academic research enterprise. Here I identify problematic behaviors and practices and suggest solutions to enhance reproducibility in translational research.

Teaser

Reproducibility challenges in preclinical research threaten the integrity and viability of our research enterprise. Here Drucker discusses the complexity of methodological, technical, and ethical issues contributing to lack of reproducibility and suggests options for discussion that may enhance the reproducibility and translational relevance of preclinical studies.


http://ift.tt/2cDNTas

Physiological Regulation: How It Really Works

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Douglas S. Ramsay, Stephen C. Woods
Contrary to dogma, much physiological regulation utilizes learning from past experience to make responses that preemptively and effectively neutralize anticipated regulatory challenges. Understanding physiological regulation therefore requires expanding explanatory models beyond homeostasis and allostasis to emphasize the prominence of conditioning.

Teaser

Contrary to dogma, much physiological regulation utilizes learning from past experience to make responses that preemptively and effectively neutralize anticipated regulatory challenges. Understanding physiological regulation therefore requires expanding explanatory models beyond homeostasis and allostasis to emphasize the prominence of conditioning.


http://ift.tt/2cMyxgS

Pharma and Academia: What We Have Here Is a Failure to Communicate

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Morris J. Birnbaum
In recent years, there has been substantial interest in the potential value of collaboration between academia and the pharmaceutical industry. In this Crosstalk, I discuss obstacles to these relationships being optimally productive.

Teaser

In recent years, there has been substantial interest in the potential value of collaboration between academia and the pharmaceutical industry. In this Crosstalk, Birnbaum discusses obstacles to these relationships being optimally productive.


http://ift.tt/2cDNbK0

The Irony of Tumor-Induced Inflammation

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Florian R. Greten
Increased dietary iron intake and elevated systemic iron levels are associated with increased cancer risk. In this issue, Xue et al. (2016) have identified an unexpected link between intracellular iron accumulation and pro-inflammatory signaling that provides, at least in part, a molecular explanation for the tumor-promoting effects of iron.

Teaser

Increased dietary iron intake and elevated systemic iron levels are associated with increased cancer risk. In this issue, Xue et al. have identified an unexpected link between intracellular iron accumulation and pro-inflammatory signaling that provides, at least in part, a molecular explanation for the tumor-promoting effects of iron.


http://ift.tt/2cMywJQ

Weeding Out the Bad Apples

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Nikla Emambokus, Anne Granger




http://ift.tt/2cDN3dN

Beige Communication through Gap Junctions and Adaption by Autophagy

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Sven Enerbäck
How thermogenic stimuli activate and control beige adipocytes is not fully understood. In this issue, Zhu et al. (2016) and Altshuler-Keylin et al. (2016) provide insights into these important issues by demonstrating roles for connexin 43 (Cx43) atg5 and atg12 in signal propagation and phenotypic adaptation in beige adipocytes.

Teaser

How thermogenic stimuli activate and control beige adipocytes is not fully understood. In this issue, Zhu et al. (2016) and Altshuler-Keylin et al. (2016) provide insights into these important issues by demonstrating roles for connexin 45 (Cx45) atg5 and atg12 in signal propagation and phenotypic adaptation in beige adipocytes.


http://ift.tt/2cMzQMJ

Specialized Hub Beta Cells Trade Maximal Insulin Production for Perfect Timing

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Jelena Kolic, James D. Johnson
The pulsatility of insulin release is disturbed early in type 2 diabetes, but it is not clear whether specialized pacemaker cells drive islet oscillations. In this issue of Cell Metabolism, Johnston et al. (2016) show that specialized hubs, identified as 1%–10% of beta cells with more active mitochondria and less insulin, synchronize beta cell oscillations.

Teaser

The pulsatility of insulin release is disturbed early in type 2 diabetes, but it is not clear whether specialized pacemaker cells drive islet oscillations. In this issue of Cell Metabolism, Johnston et al. (2016) show that specialized "hubs," identified as 1%–10% of beta cells with more active mitochondria and less insulin, synchronize beta cell oscillations.


http://ift.tt/2cDNDYY

Fueling Performance: Ketones Enter the Mix

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Brendan Egan, Dominic P. D'Agostino
Ketone body metabolites serve as alternative energy substrates during prolonged fasting, calorie restriction, or reduced carbohydrate (CHO) availability. Using a ketone ester supplement, Cox et al. (2016) demonstrate that acute nutritional ketosis alters substrate utilization patterns during exercise, reduces lactate production, and improves time-trial performance in elite cyclists.

Teaser

Ketone body metabolites serve as alternative energy substrates during prolonged fasting, calorie restriction, or reduced carbohydrate (CHO) availability. Using a ketone ester supplement, Cox et al. demonstrate that acute nutritional ketosis alters substrate utilization patterns during exercise, reduces lactate production, and improves time-trial performance in elite cyclists.


http://ift.tt/2cMyQbI

Mitochondrial Transfer from Astrocytes to Neurons following Ischemic Insult: Guilt by Association?

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Michael V. Berridge, Remy T. Schneider, Melanie J. McConnell
Intercellular mitochondrial transfer has been shown in tumor models, following lung injury and in xenotransplants of leukemic cells, but trafficking between cells in the brain remains unexplored. A suggestion that mitochondria move from astrocytes to neurons in a model of ischemia in a recent article in Nature by Hayakawa et al. (2016) should be interpreted with caution.

Teaser

Intercellular mitochondrial transfer has been shown in tumor models, following lung injury and in xenotransplants of leukemic cells, but trafficking between cells in the brain remains unexplored. A suggestion that mitochondria move from astrocytes to neurons in a model of ischemia in a recent article in Nature by Hayakawa et al. (2016) should be interpreted with caution.


http://ift.tt/2cDNXH7

Food Fight: Role of Itaconate and Other Metabolites in Antimicrobial Defense

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Harding H. Luan, Ruslan Medzhitov
Itaconate is a newly discovered mammalian metabolite bearing significant implications for our understanding of cellular immunometabolism and antimicrobial defense. Here, we explore recent findings regarding the role of itaconate in the innate immune response and highlight the emerging principle that metabolites can have distinct immunological functions independent of bioenergetics.

Teaser

In this Minireview, Luan and Medzhitov discuss the newly discovered mammalian metabolite itaconate as both a regulator and effector of immunity. More generally, they explore the emerging concept that metabolites have distinct immunological functions that could be employed as antimicrobial therapeutics.


http://ift.tt/2cMBn5k

Connexin 43 Mediates White Adipose Tissue Beiging by Facilitating the Propagation of Sympathetic Neuronal Signals

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Yi Zhu, Yong Gao, Caroline Tao, Mengle Shao, Shangang Zhao, Wei Huang, Ting Yao, Joshua A. Johnson, Tiemin Liu, Aaron M. Cypess, Olga Gupta, William L. Holland, Rana K. Gupta, David C. Spray, Herbert B. Tanowitz, Lei Cao, Matthew D. Lynes, Yu-Hua Tseng, Joel K. Elmquist, Kevin W. Williams, Hua V. Lin, Philipp E. Scherer
"Beige" adipocytes reside in white adipose tissue (WAT) and dissipate energy as heat. Several studies have shown that cold temperature can activate pro-opiomelanocortin-expressing (POMC) neurons and increase sympathetic neuronal tone to regulate WAT beiging. WAT, however, is traditionally known to be sparsely innervated. Details regarding the neuronal innervation and, more importantly, the propagation of the signal within the population of "beige" adipocytes are sparse. Here, we demonstrate that beige adipocytes display an increased cell-to-cell coupling via connexin 43 (Cx43) gap junction channels. Blocking of Cx43 channels by 18α-glycyrrhetinic acid decreases POMC-activation-induced adipose tissue beiging. Adipocyte-specific deletion of Cx43 reduces WAT beiging to a level similar to that observed in denervated fat pads. In contrast, overexpression of Cx43 is sufficient to promote beiging even with mild cold stimuli. These data reveal the importance of cell-to-cell communication, effective in cold-induced WAT beiging, for the propagation of limited neuronal inputs in adipose tissue.

Graphical abstract

Teaser

Cold activates the "beiging" of white adipocytes through a sympathetic neuronal signal. White adipose tissue, however, is sparsely innervated. Here, Zhu et al. (2016) show that connexin 43 (Cx43) cell-to-cell gap junction channels are necessary for the propagation of sympathetic signals leading to the beiging of white adipocyte clusters.


http://ift.tt/2cDNbtu

Sex and Gender: Critical Variables in Pre-Clinical and Clinical Medical Research

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Eugenia Morselli, Aaron P. Frank, Roberta S. Santos, Luciana A. Fátima, Biff F. Palmer, Deborah J. Clegg




http://ift.tt/2cDOGIq

MATERNAL EXPOSURE TO BISPHENOL-A DURING PREGNANCY INCREASES PANCREATIC Β-CELL GROWTH DURING EARLY LIFE IN MALE MICE OFFSPRING

Endocrinology, Early Release.


http://ift.tt/2cYRYGG

Ghrelin octanoylation is completely stabilized in biological samples by alkyl fluorophosphonates

Endocrinology, Early Release.


http://ift.tt/2cIkutK

Caregivers’ perception of factors associated with a healthy diet among people with intellectual disability living in community residences: A Concept mapping method

Publication date: December 2016
Source:Research in Developmental Disabilities, Volume 59
Author(s): Marte Pilskog Ruud, Ruth Kjærsti Raanaas, Mona Bjelland
BackgroundMany people with intellectual disabilities (ID) living in community-based residences have been found to have unhealthy diet and weight disturbances. In Norway, a majority of people with ID live in such residences.AimsThe aim of the study was to examine factors affecting the caregivers' opportunity to promote a healthy diet among the residents.Methods and proceduresA concept mapping methodology was adopted, including group-based brainstorming, idea synthesising, sorting, rating and analysis of the results. Informants were caregivers in four different community residences for people with mild to moderate ID in the southeast of Norway. A total of 13 informants were recruited (12 females and 1 male), and 10 informants completed two sessions.ResultsEight clusters were identified as affecting the caregivers' ability to promote a healthy diet: "Availability and accessibility", "Guidance and autonomy", "Competence among staff", "Planning and involvement", "Customization", "External conditions affecting staff", "Legislation, rules and structure" and "Everyday challenges", each including both barriers and facilitators.Conclusions and implicationsMultiple factors affect the caregivers' ability to promote a healthy diet. Caregivers' opportunity to promote a healthy diet is complex. Availability and accessibility of healthy food is crucial, but a healthy diet also requires time and competence among the caregivers.

Graphical abstract

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Psychometric properties of the Arabic self-report version of the strengths and difficulties questionnaire

Publication date: December 2016
Source:Research in Developmental Disabilities, Volume 59
Author(s): Mahmoud Mohamed Emam, Maher M. Abu Hilal, Ali Mahdi Kazem, Suad Juma Alkharousi
Students in middle school tend to display emotional and behavioural difficulties (EBDs) compared to other forms of psychopathology. Early identification of EBDs is therefore a priority in order to prevent the chronic co-morbidity with other forms of psychopathology which may affect students' academic achievement. Assessment of EBDs has been traditionally undertaken via proxy reporting; but psychometrically rigorous instruments are needed so that children and adolescents can report on their own emotions and behaviours. Such need increases in the Omani context given the lack of EBDs adequate assessment instruments. In the current study the factor structure of the Arabic self-report version of the Strengths and Difficulties Questionnaire (A-SDQ) was examined in a sample of 815 middle school students (mean age=14 years). The study tested the SDQ original five-factor model which received considerable empirical support. Responses on the A-SDQ were compared to responses obtained via proxy reports from teachers and parents through confirmatory factor analyses (CFAs). Results showed a reasonable fit for the three informant forms. Nevertheless, there were differences in item loadings across the three informant forms. Additionally, participants' self-report responses were tested for invariance across gender. CFAs provided support to the invariance hypothesis for item loadings, indicating that the items were similarly valid indices of the five factors for males and females. Factor correlations, factor variances and item residuals were not invariant across gender.What this paper addsThis paper, to our knowledge, is the first research paper that provides empirical evidence on the Arabic self report version of the Strengths and Difficulties Questionnaire (A-SDQ) within a school-based sample. Though the focus was on the self-report version we collected data from the proxy versions for parents and teachers to provide additional evidence on the construct validity of the (A-SDQ) through cross informant data.



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Age- and Gender-Specific Risk of Thyroid Cancer in Patients with Familial Adenomatous Polyposis

The Journal of Clinical Endocrinology &Metabolism, Early Release.


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Age-dependent increases in adrenal cytochrome b5 and serum 5-androstenediol-3-sulfate

The Journal of Clinical Endocrinology &Metabolism, Early Release.


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Exploring Inpatient Hospitalizations and Morbidity in Patients with Adrenal Insufficiency

The Journal of Clinical Endocrinology &Metabolism, Early Release.


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Most cleaved anti-Müllerian hormone binds its receptor in human follicular fluid but little is competent in serum

The Journal of Clinical Endocrinology &Metabolism, Early Release.


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Prospective Case Series of Cutaneous Adverse Effects Associated With Dabrafenib and Trametinib

Background:

Dabrafenib, a novel selective small-molecule inhibitor of BRAF, has been shown to increase overall survival in patients with unresectable metastatic melanoma harboring the BRAF V600E mutation. The development of resistance has led to combination therapy with selective MEK inhibitor trametinib. Compared with vemurafenib, dabrafenib is a more recent BRAF inhibitor approved by the Food and Drug Administration in May 2013 for metastatic melanoma; fewer data are available in the current literature regarding cutaneous toxicity.

Objectives:

We sought to present additional cutaneous side effects of dabrafenib and trametinib and follow their evolution and management.

Methods:

We carried out a prospective study of 14 patients treated with dabrafenib alone or with trametinib. Patients were followed every 4 weeks, and we collected detailed cutaneous symptoms, photos, and biopsy specimens.

Results:

All patients presented with at least 1 adverse skin reaction. The mean duration of treatment was 24 weeks. The most common adverse effect was papillomas (7/14), followed by palmoplantar hyperkeratosis (5/14), alopecia (5/14), and seborrheic dermatitis-like eruption (2/14). Three patients who received trametinib developed an acneiform eruption (3/5). One patient developed a keratoacanthoma-like squamous cell carcinoma. Side effects presented as early as 2 weeks after starting therapy, with a mean time of onset of 9 weeks.

Conclusion:

Selective BRAF inhibitor dabrafenib and MEK inhibitor trametinib are associated with multiple skin adverse effects. Given their recent approval and the potential for malignant lesions to develop on treatment, awareness of potential adverse effects and their management is necessary.

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A Case of Squamous Cell Carcinoma Developing Within a Red-Ink Tattoo

Cutaneous reactions to tattoos are well reported and include allergic reactions, infections, and foreign body granuloma or may be a presenting sign of sarcoidosis. There have been very few reported cases of squamous cell carcinoma (SCC) arising in tattoo-treated skin. We report a case of SCC arising within a red-ink tattoo and discuss the potential the role of chronic low-grade inflammation in pathogenesis. This should serve to raise awareness of potential tattoo-related serious adverse effects.

http://ift.tt/2cFQYHX

Diagnostic roles of MUC1 and GLUT1 in differentiating thymic carcinoma from type B3 thymoma

Publication date: Available online 13 September 2016
Source:Pathology - Research and Practice
Author(s): Jun Du, Qin Shen, Honglin Yin, Qiu Rao, Xiaojun Zhou
MUC1 is a transmembrane mucin that has been related to tumor progression and outcome in various malignancies. GLUT1 is a member of the mammalian facilitative glucose transporter (GLUT) family of passive carriers that functions as an energy-independent system for transporting glucose. Both of them are useful markers for the diagnosis, progression, and prognosis of various tumors, especially those that are cancerous. However, the clinical significance of MUC1 and GLUT1 in thymic epithelial tumors remains uncertain due to a lack of quality specimen and studies at sufficient scale, both owing, in part, to the rarity of the tumors. The aim of this article is to study the expression patterns of MUC1 and GLUT1 in thymic carcinoma and type B3 thymoma, and to evaluate their diagnostic value for these two types of tumors via immunohistochemistry. Forty-three patients were included in the study, including twenty-two with thymic carcinoma and twenty-one with type B3 thymoma. Tumor issue sections were immunohistochemically stained for MUC1 and GLUT1; meanwhile, some tumors were also stained with CKpan, TDT, CD5, and CD117. MUC1 was expressed in a total of 17 cases, with a positive rate of 77.27% (17/22) in thymic carcinoma and 9.52% (2/21) in type B3 thymoma, revealing a significant difference (p<0.0001). A significant difference (p<0.0001) was also shown for GLUT1, where the positive rates for thymic carcinoma and type B3 thymoma were 100% (22/22) and 42.86% (9/21), respectively. The expression of MUC1 was significantly correlated with GLUT1 (p<0.0001). Furthermore, GLUT1 staining sensitivity and specificity for thymic carcinoma were 100% (22/22) and 70.97% (22/31), respectively, while MUC1 staining sensitivity and specificity were 77.27% (17/22) and 89.47% (17/19), respectively.In conclusion, our study shows that MUC1 and GLUT1 staining may play a useful role in differentiating thymic carcinoma from type B3 thymoma, with high sensitivity and specificity.



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Salivary gland-like breast carcinomas: an infrequent disease

Publication date: Available online 13 September 2016
Source:Pathology - Research and Practice
Author(s): Santiago Sherwell-Cabello, Antonio Maffuz-Aziz, Nina Paola Ríos-Luna, Verónica Bautista-Piña, Sergio Rodríguez-Cuevas
ObjectiveTo show the incidence, as well as the clinical and histopathological characteristics, of patients diagnosed with mammary salivary gland-like carcinomas at our institution.Materials and MethodsA retrospective study was conducted in all women diagnosed with breast cancer at our institution from January 2005 to February 2016. Patients with diagnosis of salivary gland-like breast carcinomas were included.ResultsIn this period, 6,384 patients were diagnosed with breast cancer at our institution; salivary gland-like carcinomas were found in 7 patients (0.1%), adenoid cystic carcinoma was diagnosed in 5 patients (0.07%), acinic cell carcinoma in 1 patient (0.015%) and mucoepidermoid carcinoma in 1 patient (0.015%). The triple-negative subtype was found in all of the tumors. Median follow-up was 66.3 months (range, 1–108 months). No patient developed local or distant recurrence.ConclusionsSalivary gland-like breast tumors are extremely rare. We found a global incidence of 0.1%. Adenoid cystic, acinic cell and mucoepidermoid carcinomas were the three histologic types diagnosed. Although the triple-negative subtype is mainly found, good prognosis is expected.

Graphical abstract

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Selective Staining of Gastric Biopsies for H. Pylori Does Not Affect Detection Rates or Turnaround Time and Improves Cost Compared to Reflexive Staining

Publication date: Available online 13 September 2016
Source:Pathology - Research and Practice
Author(s): Lauren Decker, Joshua Keith Routh, Jessica Sara Snider, Joshua Anspach Hanson
AimsTo evaluate how reflexive versus selective H. pylori stains affect detection rates, turnaround time (TAT), and cost savings in a real life practice environment following an institutional policy change.MethodsThe aforementioned parameters were evaluated in all cases in the year preceding and the year following an institutional policy change from reflexive to selective staining.Results1,497 patients comprised the reflexive stain (RS) group of which 228 (15.2%) were H. pylori positive. 1,629 patients comprised the selective stain (SS) group of which 237 (14.5%) were H. pylori positive. There was no significant difference in H. pylori detection rates between the RS and SS groups (OR=0.95, 95% CI=0.78-1.15, p=0.59). TATs were similarly equivalent with a mean of 52.4hours for the RS cohort and 53.7hours for the SS cohort (p=0.344), both of which included a resident preview day. We calculated an average laboratory cost savings of $11.68 per case, which saved our department over $15,000 (37%) in the year following the policy change.ConclusionsOur results support a policy of selective staining for H. pylori as opposed to reflexive staining and go on to show that laboratories that change their policy can expect to generate cost savings without compromising detection rates or TAT.



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NCI embraces scientific road map to achieve Cancer Moonshot goals

National Cancer Institute Acting Director Douglas Lowy, M.D., today accepted, with revisions that reflect NCAB's discussion, the recommendations of a Blue Ribbon Panel (BRP) on 10 approaches most likely to make a decade's worth of progress against cancer in five years, a key goal of the White House Cancer Moonshot.

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Oxygen can impair cancer immunotherapy in mice

Researchers have identified a mechanism in mice by which anticancer immune responses are inhibited within the lungs, a common site of metastasis for many cancers.

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Uncovering a new principle in chemotherapy resistance in breast cancer

A laboratory study has revealed an entirely unexpected process for acquiring drug resistance that bypasses the need to re-establish DNA damage repair in breast cancers that have mutant BRCA1 or BRCA2 genes.

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International collaboration to create new cancer models to accelerate research

An international project to develop a large, globally accessible bank of new cancer cell culture models for the research community launched today.

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NCI launches largest-ever study of breast cancer genetics in black women

The Breast Cancer Genetic Study in African-Ancestry Populations initiative is a collaborative research project that will identify genetic factors that may underlie breast cancer disparities. It is the largest study ever to investigate how genetic and biological factors contribute to breast cancer risk among black women.

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Significant expansion of data available in the Genomic Data Commons

The recently launched Genomic Data Commons will get a dramatic increase in the power and utility of its resources with the signing today of a data sharing agreement between the NCI and Foundation Medicine, Inc. (FMI), a molecular information company.

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Newly launched Genomic Data Commons to facilitate data and clinical information sharing

The Genomic Data Commons (GDC), a unified data system that promotes sharing of genomic and clinical data between researchers, launched today with a visit from Vice President Joe Biden to the operations center at the University of Chicago.

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NIH study visualizes proteins involved in cancer cell metabolism

Scientists using cryo-electron microscopy have broken through a technological barrier in visualizing proteins with an approach that may have an impact on drug discovery and development, capturing images of an enzyme found in cells at a resolution of 1.8 angstroms.

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Increased Physical Activity Associated with Lower Risk of 13 Types of Cancer

A new study of the relationship between physical activity and cancer has shown that greater levels of leisure-time physical activity were associated with a lower risk of developing 13 different types of cancer; the risk of developing seven cancer types was 20 percent lower among the most active participants as compared with the least active participants.

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Analysis of rare endocrine cancer reveals novel genetic alterations

A molecular characterization of adrenocortical carcinoma, a rare cancer of the adrenal cortex, analyzed 91 cases for alterations in the tumor genomes and identified several novel genetic mutations as likely mechanisms driving the disease as well as whole genome doubling as a probable driver of the disease.

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