Head and Neck Diseases by Alexandros G.Sfakianakis: 07/07/17

Παρασκευή 7 Ιουλίου 2017

Comparison of Different Hearing Aid Prescriptions for Children.

Objectives: To assess whether there are significant differences between speech scores for different hearing aid prescription methods, specifically DSL i/o, DSL V, and NAL-NL1, using age-appropriate closed- and open-set speech tests with young children, designed to avoid floor and ceiling effects. Design: Participants were 44 children with moderate or severe bilateral hearing loss, 8 aged 2 to 3 years, 15 aged 4 to 5 years, and 21 aged 6 to 9 years. Children wore bilateral hearing aids fitted with each prescription method in turn in a balanced double-blind design. The speech tests used with each child (and for some tests the levels) were chosen so as to avoid floor and ceiling effects. For the closed-set tests, the level used was selected for each child based on their hearing loss. The tests used were: (1) The closed-set Consonant Confusion Test of word identification; (2) The closed-set Chear Auditory Perception Test (CAPT) of word identification. This has separate sections assessing discrimination of consonants and vowels and detection of consonants; (3) The open-set Cambridge Auditory Word Lists for testing word identification at levels of 50 and 65 dBA, utilizing 10 consonant-vowel-consonant real words that are likely to be familiar to children aged 3 years or older; (4) The open-set Common Phrases Test to measure the speech reception threshold in quiet; (5) Measurement of the levels required for identification of the Ling 5 sounds, using a recording of the sounds made at the University of Western Ontario. Results: Scores for the Consonant Confusion Test and CAPT consonant discrimination and consonant detection were lower for the NAL-NL1 prescription than for the DSL prescriptions. Scores for the CAPT vowel-in-noise discrimination test were higher for DSL V than for either of the other prescriptions. Scores for the Cambridge Auditory Word Lists did not differ across prescriptions for the level of 65 dBA, but were lower for the NAL-NL1 prescription than for either of the DSL prescriptions for the level of 50 dBA. The speech reception threshold measured using the Common Phrases Test and the levels required for identification of the Ling 5 sounds were higher (worse) for the NAL-NL1 prescription than for the DSL prescriptions. Conclusions: The higher gains prescribed by the DSL i/o and DSL V prescription methods relative to NAL-NL1 led to significantly better detection and discrimination of low-level speech sounds. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Reversal learning in C58 mice: Modeling higher order repetitive behavior

Publication date: 14 August 2017
Source:Behavioural Brain Research, Volume 332
Author(s): Cristina M. Whitehouse, Lisa S. Curry-Pochy, Robin Shafer, Joseph Rudy, Mark H. Lewis
Restricted, repetitive behaviors are diagnostic for autism and prevalent in other neurodevelopmental disorders. These behaviors cluster as repetitive sensory-motor behaviors and behaviors reflecting resistance to change. The C58 mouse strain is a promising model for these behaviors as it emits high rates of aberrant repetitive sensory-motor behaviors. The purpose of the present study was to extend characterization of the C58 model to resistance to change. This was done by comparing C58 to C57BL/6 mice on a reversal learning task under either a 100% or 80%/20% probabilistic reinforcement schedule. In addition, the effect of environmental enrichment on performance of this task was assessed as this rearing condition markedly reduces repetitive sensory-motor behavior in C58 mice. Little difference was observed between C58 and control mice under a 100% schedule of reinforcement. The 80%/20% probabilistic schedule of reinforcement generated substantial strain differences, however. Importantly, no strain difference was observed in acquisition, but C58 mice were markedly impaired in their ability to reverse their pattern of responding from the previously high density reinforcement side. Environmental enrichment did not impact acquisition under the probabilistic reinforcement schedule, but enriched C58 mice performed significantly better than standard housed C58 mice in reversal learning. Thus, C58 mice exhibit behaviors that reflect both repetitive sensory motor behaviors as well as behavior that reflects resistance to change. Moreover, both clusters of repetitive behavior were attenuated by environmental enrichment. Such findings, along with the reported social deficits in C58 mice, increase the translational value of this mouse model to autism.

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Environmental enrichment attenuates behavioral abnormalities in valproic acid-exposed autism model mice

Publication date: 30 August 2017
Source:Behavioural Brain Research, Volume 333
Author(s): Hiroshi Yamaguchi, Yuta Hara, Yukio Ago, Erika Takano, Shigeru Hasebe, Takanobu Nakazawa, Hitoshi Hashimoto, Toshio Matsuda, Kazuhiro Takuma
We recently demonstrated that prenatal exposure to valproic acid (VPA) at embryonic day 12.5 causes autism spectrum disorder (ASD)-like phenotypes such as hypolocomotion, anxiety-like behavior, social deficits and cognitive impairment in mice and that it decreases dendritic spine density in the hippocampal CA1 region. Previous studies show that some abnormal behaviors are improved by environmental enrichment in ASD rodent models, but it is not known whether environmental enrichment improves cognitive impairment. In the present study, we examined the effects of early environmental enrichment on behavioral abnormalities and neuromorphological changes in prenatal VPA-treated mice. We also examined the role of dendritic spine formation and synaptic protein expression in the hippocampus. Mice were housed for 4 weeks from 4 weeks of age under either a standard or enriched environment. Enriched housing was found to increase hippocampal brain-derived neurotrophic factor mRNA levels in both control and VPA-exposed mice. Furthermore, in VPA-treated mice, the environmental enrichment improved anxiety-like behavior, social deficits and cognitive impairment, but not hypolocomotion. Prenatal VPA treatment caused loss of dendritic spines in the hippocampal CA1 region and decreases in mRNA levels of postsynaptic density protein-95 and SH3 and multiple ankyrin repeat domains 2 in the hippocampus. These hippocampal changes were improved by the enriched housing. These findings suggest that the environmental enrichment improved most ASD-like behaviors including cognitive impairment in the VPA-treated mice by enhancing dendritic spine function.

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MMP-2: A modulator of neuronal precursor activity and cognitive and motor behaviors

Publication date: 30 August 2017
Source:Behavioural Brain Research, Volume 333
Author(s): Qi Li, Michael Michaud, Ravi Shankar, Sandra Canosa, Michael Schwartz, Joseph A. Madri
Matrix Metalloproteinase2, (MMP2, gelatinase A) is a zinc-containing enzyme with a broad substrate specificity including components of the extracellular matrix, cell surface molecules and a wide range bioactive molecules. MMP2 is known to play important roles in a variety of signaling pathways and processes in a wide range of cell types and tissues.In this report we elucidate the effects of the absence of MMP2 in Neural Precursor Cells (NPC) derived from C57BL/6 MMP2 KO mice and in primary and secondary neurosphere formation. We observed smaller neurosphere numbers and sizes, decreased NPC numbers, PCNA expression, DNA and Akt activation in MMP2 KO NPC compared to WT NPC. We also found decreased neurosphere formation and NPC migration outward from adherent neurospheres, decreased CXCR4 and nestin expression and increased GFAP and neuro-filament expression in MMP2 KO NPC compared to Wt NPC. MMP2 KO mice were found to exhibit increased anxiety manifested in open field activity assays compared to Wt mice. MMP2 KO mice also exhibited differences in motor activities manifested by decreased balance and endurance during Rota-rod testing.These studies illustrate an important role of MMP2 in cognitive and motor behaviors and confirm its importance in NPC activities crucial to brain development, growth and response to and recovery from injury.

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Disruption of GluA2 phosphorylation potentiates stress responsivity

Publication date: 30 August 2017
Source:Behavioural Brain Research, Volume 333
Author(s): Alexandra S. Ellis, Anne Q. Fosnocht, Kelsey E. Lucerne, Lisa A. Briand
Cocaine addiction is characterized by persistent craving and addicts frequently relapse even after long periods of abstinence. Exposure to stress can precipitate relapse in humans and rodents. Stress and drug use can lead to common alterations in synaptic plasticity and these commonalities may contribute to the ability of stress to elicit relapse. These common changes in synaptic plasticity are mediated, in part, by alterations in the trafficking and stabilization of AMPA receptors. Exposure to both cocaine and stress can lead to alterations in protein kinase C–mediated phosphorylation of GluA2 AMPA subunits and thus alter the trafficking of GluA2-containing AMPARs. However, it is not clear what role AMPAR trafficking plays in the interactions between stress and cocaine. The current study utilized a mouse with a point mutation within the GluA2 subunit c-terminus resulting in a disruption of PKC-mediated GluA2 phosphorylation to examine stress responsivity. Although no differences were seen in the response to a forced swim stress in naïve mice, GluA2 K882A knock-in mice exhibited an increased stress response following cocaine self-administration. Furthermore, we demonstrated that disrupting GluA2 phosphorylation increases vulnerability to stress-induced reinstatement of both cocaine seeking and cocaine-conditioned reward. Finally, GluA2 K882A knock-in mice exhibit an increased vulnerability to social defeat as indicated by increased social avoidance. Taken together these results indicate that disrupting GluA2 phosphorylation leads to increased responsivity to acute stress following cocaine exposure and increased vulnerability to chronic stress. These results highlight the GluA2 phosphorylation site as a novel target for the stress-related disorders.

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Dopamine transporter (DAT1/SLC6A3) polymorphism and the association between being born small for gestational age and symptoms of ADHD

Publication date: 30 August 2017
Source:Behavioural Brain Research, Volume 333
Author(s): K.E. Waldie, C.M. Cornforth, R.E. Webb, J.M.D. Thompson, R. Murphy, D. Moreau, R. Slykerman, A.R. Morgan, L.R. Ferguson, E.A. Mitchell
Being small for gestational age (SGA) has been established as a risk factor for Attention Deficit Hyperactivity Disorder (ADHD). Likewise, several molecular genetic studies have found a link between DAT1 and ADHD. This study investigated whether SGA moderates the effect of dopamine transporter gene variants on the risk of ADHD. A total of 546 children of European descent were genotyped at age 11 for seven DAT1 SNPs (rs6347, rs11564774, rs40184, rs1042098, rs2702, rs8179029 and rs3863145). The Strengths and Difficulties Questionnaire was used to measure symptoms of ADHD at ages 3.5, 7 and 11. We found significant gene-environment interactions between birth weight and DAT1 SNPs (rs6347, rs40184, rs1042098, rs3863145) on ADHD symptoms at 3.5 years only. Results suggest that genotypic variation of DAT1 may confer a relative protective effect against ADHD in SGA individuals. This study supports the idea that being born SGA moderates the effect of the DAT1 gene on ADHD symptoms in the preschool years and may help to explain some of the heterogeneity in ADHD outcomes.

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Editorial Board

Publication date: August 2017
Source:Critical Reviews in Oncology/Hematology, Volume 116

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Bullous pemphigoid following the replacement of vildagliptin with anagliptin

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WHO position on the use of fractional doses – June 2017, addendum to vaccines and vaccination against yellow fever WHO: Position paper – June 2013

Publication date: Available online 6 July 2017
Source:Vaccine
Author(s): World Health Organization
This article presents the World Health Organization's (WHO) recommendations on the use of fractional doses of yellow fever vaccines excerpted from the "Yellow fever vaccine: WHO position on the use of fractional doses – June 2017, Addendum to Vaccines and vaccination against yellow fever WHO: Position Paper – June 2013″, published in the Weekly Epidemiological Record [1,2].This addendum to the 2013 position paper pertains specifically to use of fractional dose YF (fYF) vaccination (fractional dose yellow fever vaccination refers to administration of a reduced volume of vaccine dose, which has been reconstituted as usual per manufacturer recommendations) in the context of YF vaccine supply shortages beyond the capacity of the global stockpile. The current WHO position on the use of yellow fever (YF) vaccine is set out in the 2013 WHO position paper on vaccines and vaccination against YF and those recommendations are unchanged.Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence, and to the evidence-to-recommendation table. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. Recommendations on the use of Yellow Fever vaccines were discussed by SAGE in October 2016; evidence presented at these meetings can be accessed at: http://ift.tt/2tSR86g.

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Replicon Particle Expressing the E2 Glycoprotein of Bovine Viral Diarrhea Virus Immunization and Evaluation of Antibody Response

Viral Immunology , Vol. 0, No. 0.

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Thymic Hyperplasia Associated with Graves' Disease: Pathophysiology and Proposed Management Algorithm

Thyroid , Vol. 0, No. 0.

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Thymic Hyperplasia Associated with Graves' Disease: Pathophysiology and Proposed Management Algorithm

Thyroid , Vol. 0, No. 0.

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Hypothesis of Improved Visualization of Microstructures in the Interventricular Septum with Ultrasound and Adaptive Beamforming

Publication date: Available online 6 July 2017
Source:Ultrasound in Medicine & Biology
Author(s): Ole Marius Hoel Rindal, Svend Aakhus, Sverre Holm, Andreas Austeng
In this work, in vivo ultrasound cardiac images created with Capon's minimum variance adaptive beamformer are compared with images acquired with the conventional delay-and-sum beamformer. Specifically, we provide three views of a human heart imaged through the parasternal short-axis, the parasternal long-axis and the apical four-chamber views. The minimum variance beamformer produced images with improved lateral resolution, resulting in better resolved speckle structure and improved edges, especially on close investigation of the interventricular septum. These improvements in image quality might possibly improve the visualization of microstructures in the human heart.

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Impact of the pretreatment Glasgow prognostic score on treatment tolerance, toxicities, and survival in patients with advanced head and neck cancer undergoing concurrent chemoradiotherapy

Abstract

Background

The purpose of this study was to evaluate the impact of the pretreatment Glasgow prognostic score on treatment-related toxicities, tolerance, and survival in patients with advanced head and neck cancers undergoing concurrent chemoradiotherapy (CRT).

Methods

We retrospectively analyzed and compared the clinical characteristics, toxicities, and survival of 143 patients with stages III, IVA, and IVB head and neck cancer treated with concurrent CRT according to their Glasgow prognostic score between 2007 and 2010.

Results

The Glasgow prognostic score was correlated with advanced tumor stage and T/N classification. Patients with a higher Glasgow prognostic score were less likely to tolerate concurrent CRT, experienced more weight loss, required tube feeding support more frequently, and had higher percentage of grade ≥3 hematological toxicities, sepsis, and toxic death. Patients with a Glasgow prognostic score of 0 had better overall and recurrence-free survival than those with a Glasgow prognostic score of 1 or 2.

Conclusion

Pretreatment Glasgow prognostic score predicts treatment tolerance, toxicity, and survival in patients with advanced head and neck cancer undergoing concurrent CRT.

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Role of oxidative stress in cardiovascular disease outcomes following exposure to ambient air pollution

Publication date: September 2017
Source:Free Radical Biology and Medicine, Volume 110
Author(s): Frank J. Kelly, Julia C. Fussell
Exposure to ambient air pollution is associated with adverse cardiovascular outcomes. These are manifested through several, likely overlapping, pathways including at the functional level, endothelial dysfunction, atherosclerosis, pro-coagulation and alterations in autonomic nervous system balance and blood pressure. At numerous points within each of these pathways, there is potential for cellular oxidative imbalances to occur. The current review examines epidemiological, occupational and controlled exposure studies and research employing healthy and diseased animal models, isolated organs and cell cultures in assessing the importance of the pro-oxidant potential of air pollution in the development of cardiovascular disease outcomes. The collective body of data provides evidence that oxidative stress (OS) is not only central to eliciting specific cardiac endpoints, but is also implicated in modulating the risk of succumbing to cardiovascular disease, sensitivity to ischemia/reperfusion injury and the onset and progression of metabolic disease following ambient pollution exposure. To add to this large research effort conducted to date, further work is required to provide greater insight into areas such as (a) whether an oxidative imbalance triggers and/or worsens the effect and/or is representative of the consequence of disease progression, (b) OS pathways and cardiac outcomes caused by individual pollutants within air pollution mixtures, or as a consequence of inter-pollutant interactions and (c) potential protection provided by nutritional supplements and/or pharmacological agents with antioxidant properties, in susceptible populations residing in polluted urban cities.

Graphical abstract

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Using Simulation to Improve Systems

Attempts to understand and improve health care delivery often focus on the characteristics of the patient and the characteristics of the health care providers, but larger systems surround and integrate with patients and providers. Components of health care delivery systems can support or interfere with efforts to provide optimal health care. Simulation in situ, involving real teams participating in simulations in real care settings, can be used to identify latent safety threats and improve the work environment while simultaneously supporting participant learning. Thoughtful planning and skilled debriefing are essential.

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Regulation of inflammation by members of the formyl-peptide receptor family

Publication date: Available online 6 July 2017
Source:Journal of Autoimmunity
Author(s): Keqiang Chen, Zhiyao Bao, Wanghua Gong, Peng Tang, Teizo Yoshimura, Ji Ming Wang
Inflammation is associated with a variety of diseases. The hallmark of inflammation is leukocyte infiltration at disease sites in response to pathogen- or damage-associated chemotactic molecular patterns (PAMPs and MAMPs), which are recognized by a superfamily of seven transmembrane, Gi-protein-coupled receptors (GPCRs) on cell surface. Chemotactic GPCRs are composed of two major subfamilies: the classical GPCRs and chemokine GPCRs. Formyl-peptide receptors (FPRs) belong to the classical chemotactic GPCR subfamily with unique properties that are increasingly appreciated for their expression on diverse host cell types and the capacity to interact with a plethora of chemotactic PAMPs and MAMPs. Three FPRs have been identified in human: FPR1–FPR3, with putative corresponding mouse counterparts. FPR expression was initially described in myeloid cells but subsequently in many non-hematopoietic cells including cancer cells. Accumulating evidence demonstrates that FPRs possess multiple functions in addition to controlling inflammation, and participate in the processes of many pathophysiologic conditions. They are not only critical mediators of myeloid cell trafficking, but are also implicated in tissue repair, angiogenesis and protection against inflammation-associated tumorigenesis. A series recent discoveries have greatly expanded the scope of FPRs in host defense which uncovered the essential participation of FPRs in step-wise trafficking of myeloid cells including neutrophils and dendritic cells (DCs) in host responses to bacterial infection, tissue injury and wound healing. Also of great interest is the FPRs are exploited by malignant cancer cells for their growth, invasion and metastasis. In this article, we review the current understanding of FPRs concerning their expression in a vast array of cell types, their involvement in guiding leukocyte trafficking in pathophysiological conditions, and their capacity to promote the differentiation of immune cells, their participation in tumor-associated inflammation and cancer progression. The close association of FPRs with human diseases and cancer indicates their potential as targets for the development of therapeutics.

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Prospective comparison of 18F-NaF PET/CT versus 18F-FDG PET/CT imaging in mandibular extension of head and neck squamous cell carcinoma with dedicated analysis software and validation with surgical specimen. A preliminary study

: The aim of this study is to propose a new method to quantify radioactivity with PET/CT imaging in mandibular extension in head and neck squamous cell carcinoma (HNSCC), using innovative software, and to compare results with microscopic surgical specimens.

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Clinical accuracy of waferless maxillary positioning using customized surgical guides and patient specific osteosynthesis in bimaxillary orthognathic surgery

Computer-assisted planning and surgery for the treatment of orthognathic deformities have been extensively documented over the last decade. Computerized and customized wafers have lacked to improve the accuracy of maxillary positioning, resulting in a draw back of computer-assisted orthognathic surgery. The aim of this study was to determine the accuracy of a new technique of waferless maxillary positioning using customized surgical guides and patient specific osteosynthesis implants in bimaxillary orthognathic surgery.

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Total lower lip and chin reconstruction with radial forearm free flap: A novel approach

The management of large chin and lower lip defects is challenging due to this facial subunit's tremendous functional and aesthetic importance. Specific methods for total lower lip and mentum reconstruction are not well chronicled. Aesthetic and functional goals of this reconstruction include restoration of oral competence by maintaining lower lip height, vermilion reestablishment, color-matched skin introduction to the chin, sensation restoration, and ideally restoration of dynamic activity to the lower lip.

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Associations between subclinical hypocalcemia and postparturient diseases in dairy cows

Publication date: Available online 6 July 2017
Source:Journal of Dairy Science
Author(s): E.M. Rodríguez, A. Arís, A. Bach
Dairy cows suffer blood Ca losses as lactation begins and might be affected by hypocalcemia in its clinical (total serum Ca concentration <1.50 mM) or subclinical form (total serum Ca concentration ≤2.14 mM). Several studies have suggested that hypocalcemia is associated with different health problems of the cow but results from different studies are not consistent. The objective of this study was to assess potential associations between subclinical hypocalcemia (SCHC) and displaced abomasum, intramammary infections, metritis, retained placenta, and ketosis. Also, the associations between SCHC and milk yield and reproductive function were evaluated. After discarding cows (32) with clinical hypocalcemia, a total of 764 cows from 6 different commercial farms were enrolled in this study. Blood samples were collected at 24 to 48 h postcalving and analyzed for total Ca concentration. Odds ratios of the different afflictions potentially associated with SCHC were calculated. Seventy-eight percent of the analyzed cows incurred SCHC. The occurrence of displaced abomasum, ketosis, retained placenta, and metritis was 3.7, 5.5, 3.4, and 4.3 times more likely, respectively, in cows that had SCHC than in cows with normocalcemia. Furthermore, the risk of incurring retained placenta or metritis increased in multiparous cows as serum Ca concentrations decreased compared with that in primiparous cows. Normocalcemic cows, independent of parity, were more likely to show their first estrus sooner after calving than SCHC cows, but no correlation was found between SCHC and other reproductive parameters. Different serum Ca concentration cutoffs were identified for several postpartum afflictions (≤1.93, ≤2.05, ≤2.05, and ≤2.10 mM for ketosis, retained placenta, metritis, and displaced abomasum, respectively). In conclusion, SCHC, defined as serum Ca ≤2.14 mM, is a frequent illness affecting the majority of the dairy cows with important repercussions on health. However, if SCHC were to be used to predict postpartum disease, different serum Ca cutoff points are likely to be needed because best predictive cutoff values varied among postpartum ketosis, displaced abomasum, retained placenta, and metritis.

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Technical note: Nontargeted detection of adulterated plant proteins in raw milk by UPLC-quadrupole time-of-flight-mass spectrometric proteomics combined with chemometrics

Publication date: Available online 6 July 2017
Source:Journal of Dairy Science
Author(s): Weiying Lu, Jie Liu, Boyan Gao, Xiaxia Lv, Liangli (Lucy) Yu
We built and validated a chemometric model to detect possible milk adulteration with plant proteins. Specifically, we extracted proteins in raw milk, treated with tryptic digestion, and obtained peptide fingerprints by UPLC-quadrupole time-of-flight-mass spectrometry with proteomics to differentiate authentic milks from their counterparts adulterated with nonmilk proteins. This approach is able to detect soybean and pea powder-adulterated milks at as low as 1% (wt/wt). Additionally, we obtained the characteristic peptide sequences for milk authentication by principal component analysis. The prediction accuracies for milk authentication by partial least-squares-discriminant analysis were greater than 95%. These results indicated that peptide fingerprints with the chemometric analysis could be successfully applied for milk quality control.

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Effects of depleting ionic strength on 31P nuclear magnetic resonancespectra of micellar casein during membrane separation and diafiltration of skim milk

Publication date: Available online 6 July 2017
Source:Journal of Dairy Science
Author(s): Mattia Boiani, Padraig McLoughlin, Mark A.E. Auty, Richard J. FitzGerald, Phil M. Kelly
Membrane separation processes used in the concentration and isolation of micellar casein-based milk proteins from skim milk rely on extensive permeation of its soluble serum constituents, especially lactose and minerals. Whereas extensive literature exists on how these processes influence the gross composition of milk proteins, we have little understanding of the effects of such ionic depletion on the core structural unit of micellar casein [i.e., the casein phosphate nanocluster (CPN)]. The ³¹P nuclear magnetic resonance (NMR) is an analytical technique that is capable of identifying soluble and organic forms of phosphate in milk. Thus, our objective was to investigate changes to the ³¹P NMR spectra of skim milk during microfiltration (MF) and diafiltration (DF) by tracking movements in different species of phosphate. In particular, we examined the peak at 1.11 ppm corresponding to inorganic phosphate in the serum, as well as the low-intensity broad signal between 1.5 and 3.0 ppm attributed to casein-associated phosphate in the retentate. The MF concentration and DF using water caused a shift in the relevant ³¹P NMR peak that could be minimized if orthophosphate was added to the DF water. However, this did not resolve the simultaneous change in retentate pH and increased solubilization of micellar casein protein. The addition of calcium in combination with orthophosphate prevented micellar casein solubilization and simultaneously contributed to preservation of the CPN structure, except for overcorrection of retentate pH in the acidic direction. A more complex DF solution, involving a combination of phosphate, calcium, and citrate, succeeded in both CPN and micellar casein structure preservation while maintaining retentate pH in the region of the original milk pH. The combination of ³¹P NMR as an analytical technique and experimental probe during MF/DF processes provided useful insights into changes occurring to CPN while retaining the micellar state of casein.

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Experimental evidence for previously unclassified calcium phosphate structures in the casein micelle

Publication date: Available online 6 July 2017
Source:Journal of Dairy Science
Author(s): J.P. Hindmarsh, P. Watkinson
¹H-³¹P Cross-polarization magic angle spinning (CP-MAS) measurements of 40-d-old Mozzarella cheese and 20 mM EDTA-treated casein micelles revealed that each sample had immobile phosphorus with the same spectral pattern, which did not match that of native casein micelles. To identify the immobile phosphorus bodies, ¹H-³¹P CP-MAS spectra and cross-polarization kinetics measurements were undertaken on native casein micelles, EDTA-chelated casein micelles, and reference samples of β-casein and hydroxyapatite. The results showed that the immobile phosphorus bodies in the mature Mozzarella cheese had the following characteristics: they are immobile phosphoserine residues (not colloidal calcium phosphate); they are not the product of phosphoserine to colloidal calcium phosphate bridging; the phosphate is complexed to calcium; their rigidity is localized to a phosphorus site; their rigidity and bond coupling is unaffected by protein hydration; and the immobile bodies share a narrow range of bond orientations. Combining these observations, the best explanation of the immobile phosphorus bodies is that bonding structures of phosphorus-containing groups and calcium exist within the casein micelle that are not yet clearly classified in the literature. The best candidate is a calcium-bridged phosphoserine-to-phosphoserine linkage, either intra- or inter-protein.

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Influence of food deprivation on intravenous glucose tolerance test traits in Holstein Friesian heifers

Publication date: Available online 6 July 2017
Source:Journal of Dairy Science
Author(s): L. Antonio González-Grajales, Laura Pieper, Joachim Kremer, Rudolf Staufenbiel
Glucose is essential for numerous cellular functions due to its involvement in energy supply from early development to adulthood. In the lactating cow, glucose demands by the mammary gland significantly increase to support milk production when compared with other tissues. Thus, insufficient blood glucose levels might predispose dairy cows to metabolic disturbances. The intravenous glucose tolerance test (ivGTT) is a suitable tool to characterize glucose metabolism and insulin responses, but results must be reliable and repeatable. One factor influencing ivGTT is food deprivation period, which has been considered as an obligatory requirement before conduction of glucose tolerance studies in monogastric species, whereas it has been permissive in ruminants. The objective of this study was to determine the influence of 5 fasting periods (0, 12, 24, 36, and 48 h) on ivGTT traits and insulin responses in German Holstein heifers. A total of 140 tests were conducted in 28 females aged 12 to 19 mo. Blood samples were collected every 7 min within 1 h. Assessed glucose and insulin parameters included basal serum glucose and insulin concentration, maximum glucose and insulin concentration obtained between min 7 to 21, and concentrations at min 63 (last sampling) relative to glucose administration, glucose area equivalent (GA), glucose area under the curve (GAUC), insulin area equivalent (InsA), insulin area under the curve (InsAUC), and blood glucose half-life time (GHLT). Serum glucose and insulin concentration were measured according to the hexokinase colorimetric method and solid phase radio immunoassay, respectively. The generalized linear mixed model was used to test for significant differences in all glucose traits and insulin responses at different fasting periods. The model used season and weight as confounding variables. Glucose and insulin concentrations at 0, 7 to 21 (maximum concentration), and 63 min were affected by the duration of food deprivation. The GA, InsA, GAUC, InsAUC, and especially GHLT were also affected by fasting period. A positive linear relationship between GHLT and length of food deprivation was found. Significantly higher GA, GAUC, GHLT values, and glucose and insulin concentration at min 63 were obtained at increasing fasting periods. High intraclass correlation coefficient (0.48) was found for GHLT. The results demonstrate that GHLT might be used to reliably characterize an individual's glucose metabolism and the importance of standardizing food deprivation schedules when performing an ivGTT in nongestating Holstein heifers.

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Effects of replacing maize silage with lucerne silage and lucerne silage chop length on rumen function and milk fatty acid composition

Publication date: Available online 6 July 2017
Source:Journal of Dairy Science
Author(s): A.L. Thomson, D.J. Humphries, K.E. Kliem, M.T. Dittmann, C.K. Reynolds
The objective of this study was to investigate whether higher lucerne (Medicago sativa; alfalfa) silage inclusion rate and longer lucerne chop length improves rumen function through increased provision of physically effective fiber, when included in a maize and lucerne silage-based total mixed ration. Diets were formulated to contain a 50:50 forage:concentrate ratio [dry matter (DM) basis] and be isonitrogenous and contain equal levels of neutral detergent fiber (320 g/kg). The forage portion of the offered diets was composed of maize and lucerne silage DM in proportions (wt/wt) of either 25:75 (high lucerne; HL) or 75:25 (low lucerne; LL). Second-cut lucerne was harvested and conserved as silage at either a long (L) or a short (S) chop length (geometric mean particle lengths of 9.0 and 14.3 mm, respectively). These variables were combined in a 2 × 2 factorial arrangement to give 4 treatments (HLL, HLS, LLL, LLS), which were fed in a 4 × 4 Latin square design study to 4 rumen-cannulated, multiparous, Holstein dairy cows in mid lactation. Effects on DM intake, chewing behavior, rumen volatile fatty acid concentration, rumen pH, rumen and fecal particle size, milk production, and milk fatty acid profile were measured. Longer chop length increased rumination times per kilogram of DM intake (+2.8 min/kg) relative to the S chop length, with HLL diets resulting in the most rumination chews. Rumen concentrations of total volatile fatty acids, acetate, and n-valerate were higher for the HLS diet than the other 3 diets, whereas rumen propionate concentration was lowest for the HLL diet. Physically effective fiber (particles >4 mm) percentage in the rumen mat was increased when L chop length was fed regardless of lucerne inclusion rate. No effect of treatment was observed for milk yield, although milk protein concentration was increased by L for the LL diet (+1.6 g/kg) and decreased by L for the HLL diet (−1.4 g/kg). Milk fat concentrations of total cis-18:1 (+3.7 g/100 g of fatty acids) and 18:3 n-3 (+0.2 g/100 g of fatty acids) were greater with HL. In conclusion, longer lucerne silage chop length increased time spent ruminating per kilogram of DM intake, but had no effect on rumen pH in the present study. Increasing dietary lucerne inclusion rate had no effects on rumination activity or rumen pH, but decreased the ratio of n-6:n-3 polyunsaturated fatty acid concentrations in milk fat.

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The relationship between Norwegian Red heifer growth and their first-lactation test-day milk yield: A field study

Publication date: Available online 6 July 2017
Source:Journal of Dairy Science
Author(s): K.S. Storli, G. Klemetsdal, H. Volden, R. Salte
Today's Norwegian Red (NR) is markedly different from the one that existed 25 yr ago due to the continuous genetic improvement of economically important traits. Still, current national recommendations on replacement heifer rearing largely are based on results from Danish studies from the late 1980s to the mid 1990s. The objectives of the present study were to gain information on (1) growth and growth profiles of modern NR replacement heifers in commercial dairy herds and (2) how growth during the rearing period affects the heifers' milk yield during their first lactation. To this end, we conducted a field study on 5 high-producing and 5 low-producing commercial dairy farms from each of 3 geographical regions in Norway. On these 30 farms, we combined repeated onsite registrations of growth on all available females from newborn to calving with registrations deriving from the Norwegian Dairy Herd Recording System. Each herd was visited 6 to 8 times over a period of 2 yr. At each visit, heart girth circumference on all available young females was measured. Registrations were made on a total of 3,110 heifers. After imposing restrictions on the data, growth parameters were estimated based on information from 536 animals, whereas 350 of these animals had the required information needed to estimate the relationship between growth and test-day milk yield. Our findings pointed toward an optimal ADG of 830 g/d from 10 to 15 mo of age that would optimize first-lactation yield of heifers in an average Norwegian dairy herd. The optimum will likely increase from selection over time. Utilizing simple proportionality, the ADG between 5 and 10 mo of age ideally should be 879 g/d, taking into account the fact that animal growth rate is higher at low ages and that a high prepubertal growth rate had no negative effect on first-lactation yield. When such a rearing practice is used to meet the requirements of today's genetically improved NR heifer, heifers can both optimize production in their first lactation and enter the milking herd earlier than the current average age of 24.8 mo.

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Bovine miR-146a regulates inflammatory cytokines of bovine mammary epithelial cells via targeting the TRAF6 gene

Publication date: Available online 6 July 2017
Source:Journal of Dairy Science
Author(s): Xing-Ping Wang, Zhuo-Ma Luoreng, Lin-Sen Zan, Feng Li, Na Li
It has been reported previously that bovine miR-146a (bta-miR-146a) is significantly differentially expressed in mammary glands infected with mastitis, compared with healthy udders. This suggests that bta-miR-146a plays an important role in the regulation of mammary inflammation. However, the specifics of this function have yet to be elucidated. Bovine mammary epithelial cells (bMEC) represent the first line of defense against pathogens and have important roles in initiating and regulating inflammatory responses and innate immunity during infection. In this study, a double luciferase reporter assay was used to confirm that bta-miR-146a directly targets the 3′ UTR of the tumor-necrosis factor receptor-associated factor 6 (TRAF6) gene. To elucidate the role of bta-miR-146a in innate immune responses, either a mimic or inhibitor of bta-miR-146a was transfected into bMEC stimulated with lipopolysaccharide, which activates the innate immune response through the toll-like receptor (TLR) 4/nuclear factor (NF)-κB signaling pathway. Forty-eight hours posttransfection, quantitative real-time PCR and Western blots were used to detect the expressions of the related genes and proteins, respectively. An ELISA was used to measure the quantity of inflammatory factors in culture supernatants. The results showed that bta-miR-146a significantly inhibits both mRNA and protein expression levels of bovine TRAF6, and ultimately suppresses downstream expression of NF-κB mRNA and protein. As a result, production of NF-κB-dependent inflammatory mediators such as tumor necrosis factor α, IL-6, and IL-8 are suppressed following lipopolysaccharide stimulation of bMEC. Thus, we concluded that bta-miR-146a acts as a negative feedback regulator of bovine inflammation and innate immunity through downregulation of the TLR4/TRAF6/NF-κB pathway. This study presents a potential regulatory mechanism of bta-miR-146a on immune responses in bovine mammary infection and may provide a potential therapeutic target for mastitis.

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Flow cytometric assessment of myeloperoxidase in bovine blood neutrophils and monocytes

Publication date: Available online 6 July 2017
Source:Journal of Dairy Science
Author(s): Elke Depreester, Evelyne Meyer, Kristel Demeyere, Mieke Van Eetvelde, Miel Hostens, Geert Opsomer
Myeloperoxidase (MPO) is a lysosomal peroxidase enzyme mainly stored in the azurophilic granules of neutrophils playing an important role in innate immunity for first-line protection against microorganisms in many species including cattle. As such, determination of MPO has become of great interest for the diagnosis of infectious and inflammatory diseases in multiple species such as humans. In cattle, MPO determination is rarely done because methods to assess MPO in this species are limited: functional assays have been described earlier, but so far, the quantification of MPO at the single cell level has not been done yet. In the present paper, an innovative flow cytometric method to assess MPO in blood leukocytes of dairy cattle is described. A commercial anti-bovine MPO was used following density gradient separation to isolate polymorphonuclear (PMN) and mononuclear (MN) leukocytes from blood. Identification of PMN and MN, subdivided in monocytes and lymphocytes, was based on the expression of the surface markers CH138A and CD172A. The optimized protocol was subsequently evaluated on blood samples of 17 Holstein Friesian heifers. Myeloperoxidase expression was measured flow cytometrically and visualized by fluorescence microscopic imaging of sorted PMN and MN populations. We suggest this innovative method to be useful in the field for early detection of cows at higher risk for inflammatory diseases such as mastitis and metritis during the transition period.

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Genetically modified Lactococcus lactis producing a green fluorescence protein–bovine lactoferrin fusion protein suppresses proinflammatory cytokine expression in lipopolysaccharide-stimulated RAW 264.7 cells

Publication date: Available online 6 July 2017
Source:Journal of Dairy Science
Author(s): S. Shigemori, F. Namai, Y. Yamamoto, S. Nigar, T. Sato, T. Ogita, T. Shimosato
Lactoferrin (LF), an iron-binding glycoprotein distributed widely in the biological fluids of mammals, is believed to play an important role in host defenses against infection. Previous studies in animal models and humans demonstrated that combined administration of LF and probiotic lactic acid bacteria (LAB) can prevent sepsis. In this study, we genetically engineered a probiotic LAB strain, Lactococcus lactis, to produce recombinant bovine LF based on the green fluorescence protein (GFP)-fused expression system. Western blotting confirmed that the genetically modified L. lactis strain (designated NZ-GFP-bLF) produced a protein corresponding to a fusion of GFP and bLF in the presence of nisin, an inducer of target gene expression. The protein synthesized by NZ-GFP-bLF was fluorescent and thus we monitored the time-dependent change in the production level of the recombinant protein using fluorometric analysis. The utility of NZ-GFP-bLF in preventing sepsis was determined by investigating its anti-inflammatory property in lipopolysaccharide (LPS)-stimulated mouse macrophage RAW 264.7 cells. Pretreatment of RAW 264.7 cells with NZ-GFP-bLF significantly attenuated the LPS-induced mRNA expression and protein production of 3 proinflammatory cytokines (IL-1α, IL-6, and tumor necrosis factor-α) compared with pretreatment with a vector control strain of L. lactis. Our results suggest that NZ-GFP-bLF holds promise for the development of a new prophylaxis for sepsis.

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Kallmann syndrome in pediatric otorhinolaryngology practice – Case report and literature review

Kallmann syndrome (KS) is an isolated form of hypogonadotrophic hypogonadism (HH) in combination with a defect in olfactory function. The diagnosis of KS before maturation is often difficult to make due to the broad spectrum of presentation and genetic heterogeneities. ENT examination including smell test is essential for proper diagnosis of olfactory disturbances and non olfactory abnormalities in craniofacial region which may also be existent in KS.

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Diagnosing Subtle Palatal Anomalies: Validation of Video-Analysis and Assessment Protocol for Diagnosing Occult Submucous Cleft Palate

Submucous cleft palate (SMCP) classically involves bifid uvula, zona pellucida, and notched hard palate. However, patients may present with more subtle anatomic abnormalities. The ability to detect these abnormalities is important for surgeons managing velopharyngeal dysfunction (VPD) or considering adenoidectomy.

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Total lower lip and chin reconstruction with radial forearm free flap: A novel approach

Phase II Trial of Sorafenib in Combination with Capecitabine in Patients with Hepatocellular Carcinoma: INST 08‐20

AbstractLessons Learned. There continues to be a lack of systemic options for advanced hepatocellular carcinoma (HCC); sorafenib and, very recently, regorafenib are the only approved options. There exists a potential to combine sorafenib with chemotherapeutic agents shown to be active in HCC, such as capecitabine, safely.Good tumor response was observed, with objective improvement in a few patients seldom seen by single agent sorafenib; however, because of the limited number of patients, meaningful conclusions on survival cannot be drawn.Background.Sorafenib is the currently approved first‐line treatment for hepatocellular carcinoma (HCC). Capecitabine has antitumor activity in hepatobiliary cancers. The combination of the two, if tolerated, could possibly improve antitumor response, and survival.Methods.Patients with advanced HCC ineligible for locoregional therapy, Eastern Cooperative Oncology Group performance status of ≤2, Child‐Pugh class A or B‐7 cirrhosis, hemoglobin ≥8.5 g/dL, platelets ≥50,000/μL, absolute neutrophil count (ANC) ≥1500 cells/μL, and serum creatinine of ≤2.0 mg/dL were recruited. All subjects received a combination of sorafenib and capecitabine, on a 14‐day 7‐days on 7‐days off schedule. The primary end point was safety and secondary end points were overall survival (OS) and disease control rate.Results.A total of 15 out of 47 patients met inclusion criteria. Median age was 64 years (56–79) and 77% were male. With a median follow‐up of 12 months, median OS was 12.7 months (95% confidence interval [CI], 8.5–23.4). Disease control rate was 77% (complete response 8%, partial response 8%, and stable disease 61%). Common adverse events were as follows: (a) thrombocytopenia (64%); (b) anemia (14%); (c) hypophosphatemia (21%); (d) hypomagnesemia (14%); (e) hyperbilirubinemia (21%); (f) increased aspartate transaminase (AST) (14%); (g) hand‐foot syndrome (21%); and (h) deep vein thrombosis (21%).Conclusion.At tolerable doses, the combination of sorafenib and capecitabine seems an active and safe palliative treatment for HCC in class A and B‐7 patients with cirrhosis. The small sample size does not allow comparison with single‐agent sorafenib.

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Antiemetic Corticosteroid Rotation from Dexamethasone to Methylprednisolone to Prevent Dexamethasone‐Induced Hiccup in Cancer Patients Treated with Chemotherapy: A Randomized, Single‐Blind, Crossover Phase III Trial

AbstractBackground.To assess whether the rotation of dexamethasone to methylprednisolone decreases the intensity of dexamethasone‐induced hiccup (DIH) in cancer patients treated with chemotherapy.Materials and Methods.Adult patients who experienced DIH within 3 days after the administration of dexamethasone as an antiemetic were screened. Eligible patients were randomly assigned to receive dexamethasone (n = 33) or methylprednisolone (n = 32) as an antiemetic (randomization phase). In the next cycle of chemotherapy, the dexamethasone group received methylprednisolone and vice versa in the methylprednisolone group (crossover phase). The primary endpoint was the difference in hiccup intensity as measured using the numeric rating scale (NRS) between two groups.Results.No female patients were enrolled, although the study did not exclude them. At the randomization phase, hiccup frequency was 28/33 (84.8%) in the dexamethasone group versus 20/32 (62.5%) in the methylprednisolone group (p = .04). Intensity of hiccup was significantly higher in the dexamethasone group than that in the methylprednisolone group (mean NRS, 3.5 vs. 1.4, p < .001). At the crossover phase, hiccup intensity was further decreased after the rotation of dexamethasone to methylprednisolone in the dexamethasone group (mean NRS, 3.5 to 0.9, p < .001), while it was increased by rotating methylprednisolone to dexamethasone in the methylprednisolone group (mean NRS, 1.4 to 3.3, p = .025). There were no differences in emesis intensity between the two groups at either the randomization or crossover phases. Clinicaltrials.gov identifier: NCT01974024.Conclusion.Dexamethasone‐induced hiccup is a male‐predominant phenomenon that can be ameliorated by rotating dexamethasone to methylprednisolone without compromising the antiemetic efficacy.Implications for Practice.In this randomized, multicenter, phase III trial, hiccup intensity was significantly lower when the antiemetic corticosteroid was rotated from dexamethasone to methylprednisolone without a change in emesis intensity than that when dexamethasone was maintained. At the crossover phase, hiccup intensity was increased again if dexamethasone was readministered instead of methylprednisolone. The present study demonstrated that dexamethasone‐induced hiccup can be improved by rotating from dexamethasone to methylprednisolone without compromising its antiemetic efficacy.

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A Phase II Trial Evaluating the Safety of Rapid Infusion of Ofatumumab in Patients with Previously Treated Chronic Lymphocytic Leukemia

AbstractLessons Learned. Ofatumumab infusion reactions can be diminished by escalating the dose rate in individual patients in sequential infusions.Background.Ofatumumab (OFA) is a fully humanized, anti‐CD20 antibody approved for use in chronic lymphocytic leukemia (CLL). The recommended administration requires long infusion times. We evaluated an accelerated infusion regimen of 2 hours.Methods.The first dose of OFA (300 mg) was given on week 1 day 1 starting at 3.6 mg/hour and doubling every 30 minutes until a rate of 240 mg/hour was reached. If tolerated, the second dose (1,000 mg) was given on week 1 day 3 starting at 50 mg/hour and doubling every 30 minutes until a rate of 800 mg/hour was reached. If tolerated, the third dose (2,000 mg) was given on week 2 day 1 at 800 mg/hour over the first 30 minutes and, if tolerated, at 1,068 mg/hour over the next 90 minutes (goal infusion time: 120 minutes). Subsequent OFA infusions were administered weekly in the same manner for 8 weeks, and then monthly for 4 months.Results.Thirty‐four patients were treated. Most infusion‐related reactions occurred during the first and second infusion. Eighty‐seven percent (87%) of patients finished the third infusion within 15 minutes of the planned 2 hours and only one had an infusion reaction.Conclusion.Using this stepped‐up dosing regimen, a rapid infusion of OFA is safe and well tolerated.

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Selection of effective cocrystals former for dissolution rate improvement of active pharmaceutical ingredients based on lipoaffinity index

Publication date: 30 September 2017
Source:European Journal of Pharmaceutical Sciences, Volume 107
Author(s): Piotr Cysewski, Maciej Przybyłek
New theoretical screening procedure was proposed for appropriate selection of potential cocrystal formers possessing the ability of enhancing dissolution rates of drugs. The procedure relies on the training set comprising 102 positive and 17 negative cases of cocrystals found in the literature. Despite the fact that the only available data were of qualitative character, performed statistical analysis using binary classification allowed to formulate quantitative criterions. Among considered 3679 molecular descriptors the relative value of lipoaffinity index, expressed as the difference between values calculated for active compound and excipient, has been found as the most appropriate measure suited for discrimination of positive and negative cases. Assuming 5% precision, the applied classification criterion led to inclusion of 70% positive cases in the final prediction. Since lipoaffinity index is a molecular descriptor computed using only 2D information about a chemical structure, its estimation is straightforward and computationally inexpensive. The inclusion of an additional criterion quantifying the cocrystallization probability leads to the following conjunction criterions Hmix<−0.18 and ΔLA>3.61, allowing for identification of dissolution rate enhancers. The screening procedure was applied for finding the most promising coformers of such drugs as Iloperidone, Ritonavir, Carbamazepine and Enthenzamide.

Graphical abstract

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Design, synthesis, and biological evaluation of 2,4-dihydropyrano[2,3-c]pyrazole derivatives as autotaxin inhibitors

Publication date: 30 September 2017
Source:European Journal of Pharmaceutical Sciences, Volume 107
Author(s): Tatu Pantsar, Prosanta Singha, Tapio J. Nevalainen, Igor Koshevoy, Jukka Leppänen, Antti Poso, Juha M.A. Niskanen, Sanna Pasonen-Seppänen, Juha R. Savinainen, Tuomo Laitinen, Jarmo T. Laitinen
Inhibition of Autotaxin (ATX) is a potential treatment strategy for several diseases, including tumors with elevated ATX-lysophosphatidic acid (LPA) signaling. Combining structure-based virtual screening together with hen egg-white Autotaxin (ewATX) activity assays enabled the discovery of novel small-molecule ATX inhibitors with a 2,4-dihydropyrano[2,3-c]pyrazole scaffold. These compounds are suggested to bind to the lipophilic pocket, leaving the active site unrestrained. Our most potent compound, (S)-6-amino-4-(3,4-dichlorophenyl)-3-(4-[(4-fluorobenzyl)oxy]phenyl)-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile [(S)-25], inhibited human ATX (hATX) with an IC50-value of 134nM. It also blocked ATX-evoked but not LPA-mediated A2058 melanoma cell migration. Noteworthy, molecular modeling correctly predicted the biologically active enantiomer of 2,4-dihydropyrano[2,3-c]pyrazoles, as verified by compound crystallization and activity assays. Our study established the ewATX activity assay as a valid and affordable tool in ATX inhibitor discovery. Overall, our study offers novel insights and approaches into design of novel ATX inhibitors targeting the hydrophobic pocket instead of the active site.

Graphical abstract

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Tritium forms discrimination in ryegrass under constant tritium exposure: From seed germination to seedling autotrophy

Publication date: October 2017
Source:Journal of Environmental Radioactivity, Volume 177
Author(s): H. Renard, D. Maro, S. Le Dizès, A. Escobar-Gutiérrez, C. Voiseux, L. Solier, D. Hébert, M. Rozet, C. Cossonnet, R. Barillot
Uncertainties remain regarding the fate of atmospheric tritium after it has been assimilated in grasslands (ryegrass) in the form of TFWT (Tissue Free Water Tritium) or OBT (Organically Bound Tritium). One such uncertainty relates to the tritium forms discrimination during transfer from TFWT to OBT resulting from photosynthesis (OBTphoto), corresponding to the OBTphoto/TFWT ratio. In this study, the OBT/TFWT ratio is determined by experiments in the laboratory using a ryegrass model and hydroponic cultures, with constant activity of tritium in the form of tritiated water (denoted as HTO) in the "water" compartment (liquid HTO) and "air" compartment (HTO vapour in the air). The OBTphoto/TFWT ratio and the exchangeable OBT fraction are measured for three parts of the plant: the leaf, seed and root. Plant growth is modelled using dehydrated biomass measurements taken over time in the laboratory and integrating physiological functions of the plant during the first ten days after germination. The results suggest that there is no measurable discrimination of tritium in the plant organic matter produced by photosynthesis.

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Erratum to: Do epinephrine auto-injectors have an unsuitable needle length in children and adolescents at risk for anaphylaxis from food allergy?

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Erratum to: Do epinephrine auto-injectors have an unsuitable needle length in children and adolescents at risk for anaphylaxis from food allergy?

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