Gastric submucosal haematoma caused by an amyloidoma in the setting of multiple myeloma

Publication date: Available online 15 December 2017
Source:Arab Journal of Gastroenterology
Author(s): Stella C. Pak, John-Phillip T. Markovic
This is a case of a 67-year-old woman with a history of multiple myeloma with amyloidosis who presented with massive hematemesis. Emergent upper endoscopy revealed a mass on the greater curvature of the stomach, which measured approximately 3 cm in width and 7 cm in length. The patient underwent a wedge resection of the gastric mass without complication. Microscopic examination of the gastric mass revealed amorphous deposits that were congophilic in nature and stained positive with Alcian blue. These findings are consistent with amyloidosis. The patient had a favourable postoperative recovery and was discharged from the hospital. This case highlights the need for clinicians to be aware of the possibility of spontaneous gastric haemorrhage secondary to light chain (AL) amyloidosis, especially in patients with a known bone marrow disorder.



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Protective effects of curcumin against doxorubicin-induced toxicity and resistance: a review

Publication date: Available online 14 December 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Mohammad Mohajeri, Amirhossein Sahebkar
Doxorubicin (DOX)-induced toxicity and resistance are major obstacles in chemotherapeutic approaches. Despite effective in the treatment of numerous malignancies, some clinicians have voiced concern that DOX has the potential to cause debilitating consequences in organ tissues, especially the heart. The mechanisms of toxicity and resistance are respectively related to induction of reactive oxygen species (ROS) and up-regulation of ATP-binding cassette (ABC) transporter. Curcumin (CUR) with several biological and pharmacological properties is expected to restore DOX-mediated impairments to tissues. This review is intended to address the current knowledge on DOX adverse effects and CUR protective actions in the heart, kidneys, liver, brain, and reproductive organs. Coadministration of CUR and DOX is capable of ameliorating DOX toxicity pertained to antioxidant, apoptosis, autophagy, and mitochondrial permeability.



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Metachronous solitary metacarpal bone metastasis from rectal cancer

Abstract

Metachronous solitary metacarpal bone metastasis from rectal cancer has not been reported previously. Here, we describe a 54-year-old woman who underwent abdominoperineal resection for rectal cancer following neoadjuvant chemoradiotherapy. The resected specimen contained adenocarcinoma with no lymph node metastases (Stage II, T3N0M0); no adjuvant chemotherapy was administered. Fifteen months after surgery, the patient presented with pain and swelling of the right thumb. Radiography revealed metacarpal bone destruction, and fluorine-18 fluorodeoxyglucose positron emission tomography showed uptake only in the metacarpal bone. Open biopsy revealed an adenocarcinoma, and a right thumb resection was performed. Histological examination indicated features of adenocarcinoma similar to the findings of a rectal lesion, leading to a diagnosis of metachronous solitary metacarpal bone metastasis from rectal cancer. The patient remains free of disease after 6 years of follow-up. Our findings suggest that surgical resection may lead to favorable outcomes in patients with resectable solitary bone metastases.

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Novel technique using a bioabsorbable prosthesis with fibrin glue fixation to prevent a Petersen’s space hernia

Abstract

Introduction

Laparoscopic Roux-en-Y gastric bypass is a bariatric operation that is effective for long-term weight loss. Although rare, one serious complication is an internal hernia through Petersen's space, which may result in bowel strangulation. Although the incidence of internal hernia can be reduced through closing the Petersen's defect, it does not eliminate the risk. This case describes a novel and reliable method to close Petersen's defect. We report the case of a 30-year-old female who underwent a laparoscopic Roux-en-Y gastric bypass for the management of morbid obesity. Following her Roux-en-Y reconstruction, a prosthetic bioabsorbable mesh was placed in Petersen's space and reinforced with fibrin glue to prevent internal herniation through Petersen's defect. The use of a bioabsorbable mesh in Petersen's space is a novel and easy technique that could be used to reduce the incidence of an internal hernia through Petersen's defect.

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Extra peritoneal giant pelvic hibernoma: a case report

Abstract

Abdominal hibernoma is a rare slow-growing tumor originating from brown adipose tissue. Due to its rarity, only a few case reports have been published so far. Pelvic localization is anedoctal and preoperative differential diagnosis with other malignancies may be challenging. We present the case of a woman who, due to a lower abdominal pain, underwent an abdominal ultrasonography with diagnosis of a 15 cm hyperechogenous pelvic mass. A subsequent MRI showed a 16 × 5.8 × 7.8 cm³ lesion anterior to the left iliacus muscle, with an intra- and extrapelvic component longitudinally extending from the left anterior superior iliac spine until the lesser trochanter. Surgical resection was performed and final histopathology was consistent with hibernoma. This report emphasizes the necessity to include hibernoma among differential diagnosis when a retroperitoneal abdominal mass is diagnosed and the difficulty to perform preoperatively this diagnosis due to the extreme rarity of these neoplasms.

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Phyllodes tumor masquerading as a fungating breast mass

Abstract

Phyllodes tumor of the breast is an uncommonly encountered disease. The tumor presenting as fungating breast mass or 'ruptured' breast is an even more rare presentation of an unusual disease. This report documents the case of a 60-year-old female with delayed presentation of a large exophytic mass of the left breast. Biopsy of this lesion was non-diagnostic, so excision via left total mastectomy was performed. The final pathology was consistent with malignant phyllodes tumor. This report highlights the features of a rare breast cancer, the challenges in obtaining a definitive diagnosis, and the treatment of this disease, in an effort to provide clinicians with an example of the management of such a peculiar entity.

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Pulmonary Mycobacterium Avium-Intracellulare Complex Infection in an Infant: A Silent and Coincidental Finding

Pediatric Allergy, Immunology, and Pulmonology Dec 2017, Vol. 30, No. 4: 257-259.


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Comparison of Blood Eosinophil Numbers Between Acute Asthma and Stable Disease in Children with Preschool Wheeze

Pediatric Allergy, Immunology, and Pulmonology Dec 2017, Vol. 30, No. 4: 210-217.


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Personalized Medicine in Preschool Children with Asthma

Pediatric Allergy, Immunology, and Pulmonology Dec 2017, Vol. 30, No. 4: 260-262.


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Cocaine-induced pseudo-Wellens syndrome: a Wellens phenocopy

Wellens' syndrome represents critical occlusion of the proximal left anterior descending coronary artery. Electrocardiographic changes similar to Wellens' wave are not exceptional to acute coronary occlusion and can also be seen in cardiac and non-cardiac conditions, such as left ventricular hypertrophy, persistent juvenile T wave, bundle branch blocks, cerebral haemorrhage, pulmonary oedema, pulmonary embolism, pheochromocytoma, Takotsubo syndrome, digitalis and cocaine-induced coronary vasospasm. Cocaine-induced pseudo-Wellens' syndrome should be considered as one of the differentials, since cocaine is used frequently by young adults and can cause left anterior descending coronary vasospasm mimicking Wellens' syndrome. Initiation of the beta-blocking agent in pseudo-Wellens' syndrome as a part of acute coronary syndrome management can be disastrous. We illustrated a case of cocaine-induced pseudo-Wellens' syndrome presented with typical chest pain associated with Wellenoid ECG.

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Iatrogenic propagation of coronary dissection during diagnostic coronary angiography: an uncommon but important procedural consideration

Spontaneous coronary artery dissection is an uncommon cause of acute myocardial infarction in the general population but is relatively more common in the peripartum period. Regardless of clinical setting, the management strategy is individualised, ranging from conservative to invasive. We report a case of peripartum myocardial infarction due to spontaneous coronary dissection that propagated during diagnostic angiography and ultimately required emergent bypass surgery.

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Congenital scoliosis: an anomalous association with endosulfan

Endosulfan is an organochlorine pesticide that is used extensively across the world to kill insects. Incidence of acute and chronic toxicity with endosulfan poisoning has been reported, and nearly 80 countries have banned its use. However, it is still being used in many low-income/middle-income countries. One of the most severe tragedies because of endosulfan poisoning has taken place in the Indian state of Kerala due to persistent aerial spraying of endosulfan. Even though there are reports of skeletal and other congenital abnormalities in humans and experimental animals following exposure to endosulfan, very few have been documented. We report two cases of congenital scoliosis in siblings living in a community affected by high levels of endosulfan in the environment. High index of suspicion is essential during the screening of school children exposed to endosulfan. Congenital scoliosis is a progressive deformity that leads to severe disability, unless detected and corrected at an early stage.

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Stent extrusion on the external surface of the transplanted kidney: unusual occurrence

Here we present the case of a 40-year-old man, who underwent deceased donor renal transplantation. Towards the end of this operation, open-ended double J stent was inserted in the transplanted kidney. Modified Lich–Gregoir ureterovesical anastomosis was performed. Prior to the abdominal closure, it was discovered that proximal end of the stent had pierced the renal parenchyma and extruded on the external surface of the transplanted kidney. We contemplated removing the stent and reinserting it but decided against that due to various reasons. The stent was left as such. The patient was managed conservatively with satisfactory outcome in the postoperative period. To the best of our knowledge, this is first such report of conservative management of stent extrusion in transplanted kidney in the literature.

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Periosteal desmoid tumour: a rare finding in the oral cavity

A 55-year-old female patient reported with an intraoral well-localised asymptomatic swelling on the right side of the mandible in relation to the right mandibular first molar along with a history of trauma 6 months back. Panoramic radiograph revealed normal trabecular bone pattern in relation to the lesion. The lesion was excised along with the associated buccal cortical plate and tooth. The microscopic examination revealed a well-circumscribed lesion consisting of spindle cells arranged in storiform pattern associated with the buccal cortical plate. The key feature to note was presence of reactive periosteum, which was in continuum with the lesion. Immunohistochemistry (IHC) revealed faint nuclear positivity for β-catenin. The above findings led to our diagnosis of periosteal desmoid, which is rarely reported in the head-and-neck region. The major challenge in the diagnosis of such lesions is good clinicopathological correlation as the differential diagnosis of spindle-cell lesions is vast and needs IHC confirmation.

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Left ventricular pseudoaneurysm formation in a patient presenting with a subacute myocardial infarction

Left ventricular pseudoaneurysm is a rare mechanical complication of acute myocardial infarction. In the present case, an 80-year-old man presenting with a subacute non-ST segment elevation myocardial infarction was found to have an occluded second obtuse marginal branch of the left circumflex coronary artery. Following the implantation of two drug-eluting stents, the patient developed no-reflow phenomenon. Coronary angiography 6 weeks later revealed persistence of the no-reflow phenomenon. During the left ventriculogram, a massive pseudoaneurysm was diagnosed and the patient successfully underwent emergency surgery. The persistence of no-reflow was likely due to the fact that the myocardial territory supplied by the infarct-related artery was completely necrosed resulting in persistent flow impairment through the vessel.

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Pneumatosis intestinalis with extensive intrahepatic portal venous gas secondary to intra-abdominal sepsis: a rare occurrence

Description

A 32-year-old man presented with a 3-day history of abdominal pain, vomiting and diarrhoea. He was afebrile and haemodynamically stable (saturating at 97% on air with a respiratory rate of 15, his blood pressure was 117/65 with a heart rate of 78 bpm). Clinical examination revealed right iliac fossa tenderness with localised guarding. His inflammatory markers were raised (white cell count 21 x10⁹/L , neutrophils 16 and C-reactive protein 26). He was diagnosed with acute appendicitis and had an emergency open appendectomy. The operative findings were a periappendicular mass with a necrotic tip of appendix and pus within the abdomen.

Unfortunately he had a complex postoperative course. He developed paralytic ileus by day 3 and was managed conservatively via insertion of a nasogastric tube, rehydration with intravenous fluid and correction of his electrolyte imbalance. By day 6 he became febrile (39°), increasingly short of breath with a grossly distended non-tender...

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Sarcoidosis-lymphoma syndrome: a diagnostic dilemma

Sarcoidosis and lymphoma are generally thought of as being two mutually exclusive diseases that need to be considered in the differential diagnosis of patients with hilar/mediastianal lymphadenopathy. However, there are rare patients in whom both of these diseases coexist. These patients constitute a diagnostic challenge because their presentation (ie, clinical symptoms, imaging abnormalities and even pathology) may all be atypical when each individual disease is considered separately. In this report, we describe a patient who presented with such atypical features and was eventually diagnosed as having both sarcoidosis and a B-cell lymphoma with features of splenic marginal zone lymphoma (SMZL) simultaneously. To our knowledge, this is only the second reported case of SMZL and sarcoidosis in the same patient.

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Table of Contents

Publication date: January–February 2018
Source:American Journal of Otolaryngology, Volume 39, Issue 1





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Guidelines for Contributing Authors

Publication date: January–February 2018
Source:American Journal of Otolaryngology, Volume 39, Issue 1





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Editorial Board

Publication date: January–February 2018
Source:American Journal of Otolaryngology, Volume 39, Issue 1





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Voice and swallowing outcomes following hypoglossal nerve stimulation for obstructive sleep apnea

Publication date: Available online 15 December 2017
Source:American Journal of Otolaryngology
Author(s): Andrew J. Bowen, Amy S. Nowacki, Alan H. Kominsky, Douglas K. Trask, Michael S. Benninger, Paul C. Bryson
ObjectiveHypoglossal nerve stimulation is an effective treatment for a subset of patients with Obstructive Sleep Apnea (OSA). Although multiple clinical trials demonstrate its efficacy, no previous literature explores the potential impact the stimulator has on swallowing and voice. Our primary objective is to evaluate patient reported post-operative changes in voice or swallowing following hypoglossal nerve stimulator placement.Study designProspective cohort study.SettingTertiary care hospital.Subject and methodsPatients scheduled to receive a hypoglossal stimulator were enrolled. Participants completed baseline Voice Handicap Index-10 (VHI-10) and Eating Assessment Tool-10 (EAT-10) questionnaires preoperatively and again at 1week, 3months, and 6months post-operatively following placement of a hypoglossal nerve stimulator.Results9 males and 5 females completed the study. The mean pre-operative VHI-10 and EAT-10 score was 3 and 0.8 respectively. Using linear mixed models, a clinically and statistically significant increase in the mean EAT-10 score was observed post-operatively at 1week (p=0.007), which was not observed at the time points the stimulator was active. A clinically and statistically significant decrease in VHI-10 score was observed following 2months of active stimulator use (p=0.02), which was not observed at any other time point.ConclusionThe implantation and use of the hypoglossal nerve stimulator over 5months did not demonstrate any sustained, patient reported changes in voice handicap and swallowing function. While larger studies are warranted, our findings can be used to provide further informed consent for hypoglossal nerve stimulator implantation.



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A novel method to measure the external auditory canal: Normative data and practical implications

Publication date: Available online 14 December 2017
Source:American Journal of Otolaryngology
Author(s): Jason Barnes, Roy T. Sabo, Daniel H. Coelho
PurposeTo accurately measure external auditory canal (EAC) dimensions by high resolution computed tomography (CT), and compare results with a traditional method of EAC measurement.MethodsUsing an advanced multidimensional open source digital imaging and communications in medicine (DICOM) analysis program (OsiriX, Pixmeo, Geneva, Switzerland) 91 adult EACs were analyzed on a previously obtained temporal bone CT scan. Tympanometric data were also recorded for each ear. The methods were compared using a linear mixed effect model.ResultsEAC volume was compared between tympanometrically calculated volumes and CT measured volumes. It was found that CT measured volumes are, on average, smaller (1.12cm³, SE=0.04) than tympanometry volumes (1.27cm³, SE=0.04cm³). There was a significant difference in CT measured volume between genders (p=0.0125), with males having larger measured volumes (1.23cm³, SD=0.28cm³) than females (1.06cm³, SD=0.20cm³). There was a significant difference in average circumference between ear laterality (p=0.0071), with the right ear having a slightly larger average circumference (2.49cm, SD=0.23cm) than the left ear (2.44cm, SD=0.50cm).There was also a significant difference in minimum circumference between age groups (p=0.0448), with patients younger than 60years having larger minimum circumferences (1.89cm, SD=0.21cm) than older patients (1.78cm, SD=0.25cm).ConclusionsThis study demonstrates that CT analysis can provide more information about EAC dimensions than traditional techniques. Moreover, slight but statistically significant differences are associated with age, gender and laterality. Accurate estimation of EAC dimensions is important for the development of hearing aids and personal protective equipment and can also be helpful for surgical planning, specifically otoendoscopy. Future research will focus on simplifying computation, developing cross-cultural cohort comparisons, and application to otoendoscopic procedures.



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Molecular characterization, RNA interference and recombinant protein approach to study the function of the putative Molt Inhibiting Hormone (FmMIH1) gene from the shrimp Fenneropenaeus merguiensis

Publication date: Available online 14 December 2017
Source:Peptides
Author(s): Huafang Liang, Yin Lau, Ting Ting Zhou, Xiaoyuan Li, Bin Li, Siuming F. Chan
The Molt Inhibiting Hormone gene and cDNA of the banana shrimp Fenneropenaeus merguiensis (FmMIH1) has been cloned and characterized. FmMIH1 possesses most of the characteristics of the eyestalk CHH/MIH/GIH family subtype-II neuropeptides. FmMIH1 open reading frame consists of 315 bp encoding for 105 amino acid residues. The mature peptide of FmMIH1 consists of 76 amino acid residues, a glycine residue at position 11 of the mature peptide and 6 cysteine residues located in the conserved position. In addition to eyestalk, high levels of FmMIH1 transcript could also be detected in the intestine. FmMIH1 transcript level is low throughout the post-molt, early to mid-intermolt and premolt. However, a sharp increase could be observed in late intermolt (C3 stage). Both alignment and phylogenetic analysis reveal that FmMIH1 is most similar to the MIH1 of other shrimps. For functional assay, RNA interference results show that a significant 2.3 days (P < 0.05) reduction in molt cycle duration could be observed in shrimp receiving dsFmMIH1 injection. Surprisingly, injection of recombinant FmMIH1 could also cause a significant reduction of the molt cycle (average 1.9 days, P < 0.05). We hypothesize that the recombinant protein is biological inactive but it competes with the endogenous MIH for carrier protein binding and consequently reduces the amount of biological MIH that could reach the targets. In conclusion, the result of this study will provide us new insight to manipulate molting/growth in crustaceans.



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Vasodilator and hypotensive effects of the spider peptide Lycosin-I in vitro and in vivo

Publication date: Available online 14 December 2017
Source:Peptides
Author(s): Binbin Ma, Zhouhuan Xi, Jiahui Li, Tianqi Gao, Runzhi Liao, Shuhang Wang, Xianyao Li, Yaqin Tang, Zheng Wang, Shengjie Hou, Jinying Jiang, Meichun Deng, Zhigui Duan, Xing Tang, Liping Jiang
Lycosin-I, a spider peptide isolated from the venom of the spider Lycosa singoriensis, has anti-bacteria and anti-cancer properties in organisms. However, cardiovascular effects of Lycosin-I have not been studied. In this study, we investigated for the first time the vasodilator and hypotensive effects of Lycosin-I and the possible mechanisms, in order to develop a promising treatment for hypertension-related diseases. For in vitro experiments, thoracic aortas were isolated, and divided into two groups, endothelium-intact and endothelium-denuded aortic rings. Lycosin-I induced a remarkable dose-dependent relaxation in endothelium-intact aortic rings pre-treated with phenylephrine (p < 0.05), while it showed no obvious vasodilator effects in endothelium-denuded aortic rings (p > 0.05). The vasodilator effects of Lycosin-I were significantly weakened by a nitric oxide synthase (NOS) inhibitor, L-NAME (p < 0.001) and a selective inhibitor of nitric oxide (NO)-sensitive soluble guanylate cyclase (sGC), ODQ (p < 0.05), respectively. The levels of endothelial nitric oxide synthase (eNOS) phosphorylation and the NO production were significantly higher in human umbilical vascular endothelial cells pre-cultured with Lycosin-I than the control (p < 0.001), determined via western blot analysis and ozone-chemiluminescence technology. For in vivo experiments, arterial and venous catheters were inserted for mean arterial pressure (MAP) recording and drug administration in anaesthetized spontaneously hypertensive rats. Lycosin-I caused a transient drop of MAP 2 minutes after the administration compared with the saline control (p < 0.001). In conclusion, Lycosin-I has the potential to be an anti-hypertensive drug by endothelium-dependent vasodilatation, in which eNOS and NO-sensitive sGC are two main involved factors.



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outside front cover

Publication date: June 2017
Source:Seminars in Oncology, Volume 44, Issue 3





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Masthead

Publication date: June 2017
Source:Seminars in Oncology, Volume 44, Issue 3





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Editorial Board

Publication date: June 2017
Source:Seminars in Oncology, Volume 44, Issue 3





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Table of Contents

Publication date: June 2017
Source:Seminars in Oncology, Volume 44, Issue 3





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Future Meetings

Thyroid Dec 2017, Vol. 27, No. 12: 1586-1586.


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Iodized Salt Intake and Its Association with Urinary Iodine, Thyroid Peroxidase Antibodies, and Thyroglobulin Antibodies Among Urban Chinese

Thyroid Dec 2017, Vol. 27, No. 12: 1566-1573.


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Validation of Three Scoring Risk-Stratification Models for Thyroid Nodules

Thyroid Dec 2017, Vol. 27, No. 12: 1550-1557.


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Diastolic Dysfunction is Common in Survivors of Pediatric Differentiated Thyroid Carcinoma

Thyroid Dec 2017, Vol. 27, No. 12: 1481-1489.


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Reduced Retinoblastoma Protein Expression Is Associated with Decreased Patient Survival in Medullary Thyroid Cancer

Thyroid Dec 2017, Vol. 27, No. 12: 1523-1533.


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Urinary Iodine, Perchlorate, and Thiocyanate Concentrations in U.S. Lactating Women

Thyroid Dec 2017, Vol. 27, No. 12: 1574-1581.


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Death by Suicide in Graves' Disease and Graves' Orbitopathy: A Nationwide Danish Register Study

Thyroid Dec 2017, Vol. 27, No. 12: 1475-1480.


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Laboratory Services for Managing Thyroid Disease: Different and Common Viewpoints of American Thyroid Association Members and of Members of the Endocrine Division of the American Association for Clinical Chemistry

Thyroid Dec 2017, Vol. 27, No. 12: 1583-1585.


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Individualizing Surgery in Papillary Thyroid Carcinoma Based on a Detailed Sonographic Assessment of Extrathyroidal Extension

Thyroid Dec 2017, Vol. 27, No. 12: 1544-1549.


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Clinical Characteristics and Outcomes of Propylthiouracil-Induced Antineutrophil Cytoplasmic Antibody-Associated Vasculitis in Patients with Graves' Disease: A Median 38-Month Retrospective Cohort Study from a Single Institution in China

Thyroid Dec 2017, Vol. 27, No. 12: 1469-1474.


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Selected Radiation Safety Aspects Including Transportation and Lodging After Outpatient 131I Therapy for Differentiated Thyroid Cancer

Thyroid Dec 2017, Vol. 27, No. 12: 1558-1565.


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Chronic nasal dysfunction

Publication date: Available online 14 December 2017
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): R. Jankowski, D.T. Nguyen, A. Russel, B. Toussaint, P. Gallet, C. Rumeau
Chronic nasal dysfunction is a clinical concept in the diagnostic and therapeutic management of sinonasal diseases, based on the evo-devo theory of formation of the nose according to which the nose is not a single organ but rather an association of three organs: olfactory nose, respiratory nose and paranasal sinuses. In chronic nasal dysfunction theory, etiological diagnosis takes account of the possible pathophysiological independence of nasal symptoms, in accordance with the different origins and physiology of the three organs constituting the nose. The diagnostic approach of the chronic nasal dysfunction concept breaks down the pathology so as to propose treatment(s) adapted to the diseased organ(s) and to the capacity for physiological resolution of dysfunction induced in one organ by pathology in a neighboring nasal organ. The ethmoid is not a sinus according to evo-devo, and therefore functional endoscopic endonasal surgery (FEES) cannot be restricted to functional endoscopic sinus surgery (FESS). Evo-devo theory and the chronic nasal dysfunction concept offer an alternative to the concept of chronic rhinosinusitis with or without polyps for the management of sinonasal diseases.



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The neonatal window of opportunity – early priming for life

Publication date: Available online 14 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Harald Renz, Becky D. Adkins, Sina Bartfeld, Richard S. Blumberg, Donna L. Farber, Johan Garssen, Peter Ghazal, David J. Hackam, Benjamin J. Marsland, Kathy D. McCoy, John Penders, Immo Prinz, Valerie Verhasselt, Erika von Mutius, Jeffrey N. Weiser, Duane R. Wesemann, Mathias W. Hornef
The concept of the neonatal window of opportunity assigns the early postnatal period a critical role for life-long host-microbial and immune homeostasis. It is supported by epidemiological evidence that links postnatal environmental exposure with disease susceptibility and mechanisms in the neonate host that facilitate the postnatal transposition, establish a stable microbiome and promote immune maturation. During the conference on "The neonatal window of opportunity – early priming for life", postnatal microbiome and immune maturation, epidemiological evidence and fundamental mechanisms were discussed to identify new targets for future preventive and interventional measures.



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Multifaceted roles of basophils in health and disease

Publication date: Available online 14 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Hajime Karasuyama, Kensuke Miyake, Soichiro Yoshikawa, Yoshinori Yamanishi
Until recently, basophils had often been neglected in immunological studies because of their minority status among immune cells, or confused with tissue-resident mast cells due to some phenotypic similarities between them in spite of different anatomical localization. It is now appreciated that basophils and mast cells are distinct cell lineages, and that basophils play important and non-redundant roles distinct from those played by mast cells. On the one hand, basophils contribute beneficially to protective immunity, particularly against parasitic infections. On the other hand, basophils are involved in the development of various disorders, including allergy and autoimmune disease. Basophils interact with other immune cells and non-hematopoietic cells through cell to cell contact or basophil-derived factors such as cytokines and proteases, contributing to the regulation of immune and allergic responses. In this review article, we highlight recent advances in our understanding of basophil pathophysiology in humans and animal models by consolidating research findings reported during the past five years. Further studies on basophils and their products will help identify suitable targets for novel therapeutics in allergy and effective vaccines against parasitic infection.



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S1PR5 is essential for human NK cell migration towards sphingosine-1 phosphate

Publication date: Available online 14 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Annabelle Drouillard, Anne-Laure Mathieu, Antoine Marçais, Alexandre Belot, Sébastien Viel, Michaël Mingueneau, Kevin Guckian, Thierry Walzer




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Isotype-Specific Agglutination-PCR (ISAP): a sensitive and multiplex method for measuring allergen-specific IgE

Publication date: Available online 14 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Cheng-ting Tsai, Kaori Mukai, Peter V. Robinson, Melissa A. Gray, Malika B. Waschmann, Shu-Chen Lyu, Mindy Tsai, Rebecca S. Chinthrajah, Kari C. Nadeau, Carolyn R. Bertozzi, Stephen J. Galli




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TNFAIP3/A20 acts as master switch in TNFα blockade-driven IL-17A expression

Publication date: Available online 14 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Paulo CM. Urbano, Raúl Aguirre-Gamboa, Angel Ashikov, Bennie van Heeswijk, Anja Krippner-Heidenreich, Henk Tijssen, Yang Li, Valderilio F. Azevedo, Lisa JT. Smits, Frank Hoentjen, Irma Joosten, Hans JPM. Koenen
BackgroundAnti-TNF inhibitors successfully improve life quality of patients suffering from inflammatory disease. Unfortunately, not all patients respond to anti-TNF therapy and some patients show paradoxical immune side-effects, which is poorly understood. Surprisingly, anti-TNF agents were shown to promote IL-17A production, with as yet unknown clinical implications.ObjectiveTo investigate the molecular mechanism underlying anti-TNF driven IL-17A expression and the clinical implications of this phenomenon.MethodsFACS, RNA-sequencing, RT-qPCR, western blotting, siRNA interference and kinase-inhibitors, were used to study the molecular mechanism in isolated human CD4⁺ T cells from healthy donors. The clinical implication was studied in blood samples of inflammatory bowel disease (IBD) patients under anti-TNF therapy.ResultsHere we show that anti-TNF treatment results in inhibition of the anti-inflammatory molecule TNFAIP3/A20 in memory CD4⁺ T cells. We found an inverse relationship between TNFAIP3/A20 expression levels and IL-17A production. Inhibition of TNFAIP3/A20 promotes kinase activity of p38-MAPK and PKC, which drives IL-17A expression. Regulation of TNFAIP3/A20 expression and cognate IL-17A production in T cells is specifically mediated via TNFR2-signaling. Ex vivo, in IBD patients treated with anti-TNF, we found further evidence for an inverse relationship between TNFAIP3/A20 expression levels and IL-17A producing T cells.ConclusionAnti-TNF treatment interferes in the TNFAIP3/A20 mediated anti-inflammatory feedback-loop in CD4⁺ T cells and promotes kinase activity. This puts TNFAIP3/A20, combined with IL-17A expression, on the map as a potential tool in predicting therapy responsiveness or side effects of anti-TNF therapy. Moreover, it provides novel targets, related to TNFAIP3/A20 activity, for superior therapeutic regimens in IBD patients.



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Airway exposure initiates peanut allergy by involving the IL-1 pathway and T follicular helper cells in mice

Publication date: Available online 14 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Joseph J. Dolence, Takao Kobayashi, Koji Iijima, James Krempski, Li Y. Drake, Alexander L. Dent, Hirohito Kita
BackgroundLittle is currently known regarding the immunological mechanism(s) that initiate peanut allergy. Notably, peanut proteins have been detected in house dust, and their levels correlate with peanut allergy prevalence.ObjectiveThis study aimed to develop a new mouse model for peanut allergy and to investigate the immunological mechanisms involved in peanut allergen sensitization.MethodsTo mimic environmental exposure, naïve mice were exposed to peanut flour by inhalation for up to 4 weeks. We then analyzed serum levels of IgE antibody and challenged mice with peanut proteins. Immunological mechanisms involved in sensitization were analyzed using cytokine reporter mice, an adoptive cell transfer model, and gene knockout mice.ResultsWhen exposed to peanut flour by inhalation, both BALB/c and C57BL/6 mice developed peanut allergy, as demonstrated by the presence of peanut-specific IgE antibodies and manifestation of acute anaphylaxis upon challenge. A large number of follicular helper T (Tfh) cells were also detected in draining lymph nodes of allergic mice. These cells produced IL-4 and IL-21, and more robustly promoted peanut-specific IgE production than Th2 cells. Genetic depletion of Tfh cells decreased IgE antibody levels and protected mice from anaphylaxis, without affecting Th2 cells. Furthermore, peanut flour exposure increased lung levels of IL-1α and IL-1β, and mice deficient in the receptor for these cytokines showed a significant decrease in Tfh cells compared to wild-type mice.ConclusionTfh cells play a key role in peanut allergy, and the IL-1 pathway is involved in the Tfh response to peanut allergen exposure.

Graphical abstract

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Genetic analysis of predicted fatty acid profiles of milk from Danish Holstein and Danish Jersey cattle populations

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): L. Hein, L.P. Sørensen, M. Kargo, A.J. Buitenhuis
The objective of this paper was to assess the genetic variability of the detailed fatty acid (FA) profiles of Danish Holstein (DH) and Danish Jersey (DJ) cattle populations. We estimated genetic parameters for 11 FA or groups of FA in milk samples from the Danish milk control system between May 2015 and October 2016. Concentrations of different FA and FA groups in milk samples were measured by mid-infrared spectroscopy. Data used for parameter estimation were from 132,732 first-parity DH cows and 21,966 first-parity DJ cows. We found the highest heritabilities for test day measurements in both populations for short-chain FA (DH = 0.16; DJ = 0.16) and C16:0 (DH = 0.14; DJ = 0.16). In DH, the highest heritabilities were also found for saturated FA and monounsaturated FA (both populations: 0.15). Genetic correlations between the fatty acid traits showed large differences between DH and DJ for especially short-chain FA with the other FA traits measured. Furthermore, genetic correlations of total fat with monounsaturated FA, polyunsaturated FA, short-chain FA, and C16:0 differed markedly between DH and DJ populations. In conclusion, we found genetic variation in the mid-infrared spectroscopy-predicted FA and FA groups of the DH and DJ cattle populations. This finding opens the possibility of using genetic selection to change the FA profiles of dairy cattle.



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Calf management risk factors on dairy farms associated with male calf mortality on veal farms

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): D.L. Renaud, D.F. Kelton, S.J. LeBlanc, D.B. Haley, T.F. Duffield
The objective of this cross-sectional herd-level study was to assess the association of calf management practices on source dairy farms with mortality risk on veal farms. From April to October 2016, 52 source dairy farms supplying male calves to 2 veal operations were visited once. A questionnaire was administered that covered all areas of calf management, calves between 1 and 10 d of age were examined using a standardized health scoring system, and blood was taken to evaluate passive transfer of immunoglobulins. The mortality risk for calves from each dairy farm was calculated based on the number of male calves sold from the dairy farm and that died during 2016 at the veal operations. The mean mortality risk was calculated for both veal farms and, based on the veal facility-adjusted mortality risk, dairy farms were classified as high- or low-mortality source farms. Using the information gathered at the 52 source dairy farms, a logistic regression model was used to assess factors associated with being a high-mortality source farm. Suppliers to veal farm 1 had a mean mortality risk of 9.6% and suppliers to veal farm 2 had a mean mortality risk of 4.2%. The lower mortality risk at veal farm 2 was partially influenced by a shorter period of observation. Of the 182 calves examined during the single visit to the source dairy farms, 41% of male calves and 29% of female calves had at least one identifiable health abnormality. The risk of failure of passive transfer on source dairy farms was low, with only 13% of calves tested having <10 mg of IgG/mL of serum. The subset of calves examined at the source dairy farm was not followed prospectively to the veal farms. Using a tube feeder or pail to feed colostrum, bedding male calves on wood shavings or chopped straw at the source dairy farm, and the herd veterinarian not routinely and actively inquiring about the health and performance of calves during regular herd visits were significantly associated with the farm being classified as a high-mortality source dairy farm. Checking the calving pen at an interval of every 3 h or more during the day was associated with a lower probability of being classified as a high-mortality source dairy farm. The results of this study suggest that there are management practices on the source farm that contribute to the risk of mortality on veal farms.



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Heritabilities and genetic correlations in the same traits across different strata of herds created according to continuous genomic, genetic, and phenotypic descriptors

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): Tong Yin, Sven König
The most common approach in dairy cattle to prove genotype by environment interactions is a multiple-trait model application, and considering the same traits in different environments as different traits. We enhanced such concepts by defining continuous phenotypic, genetic, and genomic herd descriptors, and applying random regression sire models. Traits of interest were test-day traits for milk yield, fat percentage, protein percentage, and somatic cell score, considering 267,393 records from 32,707 first-lactation Holstein cows. Cows were born in the years 2010 to 2013, and kept in 52 large-scale herds from 2 federal states of north-east Germany. The average number of genotyped cows per herd (45,613 single nucleotide polymorphism markers per cow) was 133.5 (range: 45 to 415 genotyped cows). Genomic herd descriptors were (1) the level of linkage disequilibrium (r²) within specific chromosome segments, and (2) the average allele frequency for single nucleotide polymorphisms in close distance to a functional mutation. Genetic herd descriptors were the (1) intra-herd inbreeding coefficient, and (2) the percentage of daughters from foreign sires. Phenotypic herd descriptors were (1) herd size, and (2) the herd mean for nonreturn rate. Most correlations among herd descriptors were close to 0, indicating independence of genomic, genetic, and phenotypic characteristics. Heritabilities for milk yield increased with increasing intra-herd linkage disequilibrium, inbreeding, and herd size. Genetic correlations in same traits between adjacent levels of herd descriptors were close to 1, but declined for descriptor levels in greater distance. Genetic correlation declines were more obvious for somatic cell score, compared with test-day traits with larger heritabilities (fat percentage and protein percentage). Also, for milk yield, alterations of herd descriptor levels had an obvious effect on heritabilities and genetic correlations. By trend, multiple trait model results (based on created discrete herd classes) confirmed the random regression estimates. Identified alterations of breeding values in dependency of herd descriptors suggest utilization of specific sires for specific herd structures, offering new possibilities to improve sire selection strategies. Regarding genomic selection designs and genetic gain transfer into commercial herds, cow herds for the utilization in cow training sets should reflect the genomic, genetic, and phenotypic pattern of the broad population.



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Influence of ad libitum milk replacer feeding and butyrate supplementation on the systemic and hepatic insulin-like growth factor I and its binding proteins in Holstein calves

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): D. Frieten, C. Gerbert, C. Koch, G. Dusel, K. Eder, A. Hoeflich, B. Mielenz, H.M. Hammon
Ad libitum milk feeding and butyrate (B) supplementation have the potential to stimulate postnatal growth and development in calves. The somatotropic axis is the main endocrine regulator of postnatal growth and may be affected by both ad libitum milk replacer (MR) feeding and B supplementation in calves. We hypothesized that ad libitum MR feeding and B supplementation stimulate systemic and hepatic insulin-like growth factor (IGF)-I and IGF binding proteins (IGFBP) in preweaning calves. Sixty-four (32 male, 32 female) Holstein calves were examined from birth until wk 11 of life. Calves received MR either ad libitum (Adl) or restrictively (6 L/d; Res). In each feeding group half of the calves received a MR with 0.24% butyrate and the other half received same MR without butyrate. Ad libitum MR feeding was performed from d 4 until wk 8 of age. From wk 9 to 10, Adl and Res calves were gradually weaned and were fed 2 L/d until the end of the trial. Concentrate, hay, and water were freely available. Feed intake was measured daily and body weight weekly. Blood samples for analyzing plasma concentrations of glucose, insulin, IGF-I, and IGFBP-2, −3, and −4 were taken on d 1, 2, 4, and 7, then weekly or every other week (IGFBP) until wk 11 of life. Liver samples were taken on d 50 and at the end of the study (d 80) to measure gene expression of the growth hormone receptor 1A (GHR1A), IGF1, IGFBP1-4, and of the IGF Type 1 and insulin receptor in the liver. Intake of MR and body weight were greater, but concentrate intake was lower in Adl than in Res. Plasma concentrations of IGF-I and IGFBP-3 were greater and plasma concentration of IGFBP-2 was lower in Adl than in Res during the ad libitum milk feeding period. After reduction of MR in both groups to 2 L/d plasma concentrations of IGF-I and IGFBP-4 were lower and plasma concentration of IGFBP-2 was higher in Adl than in Res. Supplementation of B depressed plasma IGF-I from wk 1 to 4 and in wk 9. On d 50, mRNA abundance of the GHR1A and IGF1 was greater and of IGFBP2 mRNA was lower in Adl than in Res. At d 80, IGFBP2 mRNA was greater in Adl than in Res, and IGFBP2 mRNA increased with B supplementation. Ad libitum MR feeding stimulated the systemic and hepatic IGF system and mirrored the greater growth rate during the ad libitum MR feeding, whereas butyrate supplementation partly reduced the systemic and hepatic IGF system.



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Effect of aluminized reflective hutch covers on calf health and performance

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): D. Manriquez, H. Valenzuela, S. Paudyal, A. Velasquez, P.J. Pinedo
The effect of polyethylene hutches wrapped in aluminized reflective covers (ARC) on health and performance of pre-weaned Holstein heifers during summer was evaluated. Ambient and hutch temperature and temperature-humidity index (THI) were also assessed. The study was conducted from June to October 2016 where temperature, humidity, and THI ranged from −1.3 to 38.4°C, 9.8 to 99.7%, and 33.6 to 81.1 units, respectively. Heifers enrolled at 1 d of life and housed in individual polyethylene hutches with (covered) or without (control) ARC were monitored until 60 d of life in 2 study groups (SG1, n = 94, monitored from June to September; and SG2, n = 101, monitored from August to October 2016). Calves were assessed twice per week for health status, behavior, rectal temperature, and respiratory rate. Similarly, hutch inner wall and sand bedding temperatures were determined for comparison between covered and control hutches housing calves. Four empty hutches per treatment group were continuously monitored for temperature and THI. The odds (95% confidence interval) of presenting diarrhea were 1.30 (1.01–1.60) times greater for calves housed in covered hutches than for those in the control group. Similarly, the odds of an abnormal ear score were 1.40 (1.03–2.00) times greater for calves in covered hutches compared with calves in control hutches. The odds of nasal discharge, eye discharge, and clinical dehydration did not differ between treatment groups. Rectal temperatures and respiratory rates were also similar in both groups. No differences were found in average daily gain between calves housed in covered and control hutches. Calf location determined at a fixed time during the day (starting at 1200 h) was associated with the use of ARC. The odds of remaining inside the hutch were 1.33 (1.03–1.70) times greater for calves housed in control compared with covered hutches. Overall, the average of hutch interior temperature was higher in covered compared with control hutches in both studies (SG1, 23.2 ± 0.06 vs. 22.8 ± 0.06°C; SG2, 17.1 ± 0.07 vs. 16.9 ± 0.07°C). Hutch THI was higher in covered empty hutches compared with control hutches in both study groups (SG1: 68.6 ± 0.06 vs. 67.6 ± 0.06°C; SG2: 60.2 ± 0.08 vs. 59.6 ± 0.08°C). Average temperature (measured at 1200 h) of the inner surface of the hutch wall was lower in covered compared with control hutches by 1°C (24.4 ± 0.13 vs. 25.4 ± 0.13°C), whereas the temperature of the sand bedding did not differ between groups. Our results suggest that the use of ARC did not generate a hutch microclimate that resulted in significant improvements on health and performance of pre-weaned dairy calves under these specific study settings.



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Lactobacillus casei asp23 gene contributes to gentamycin resistance via regulating specific membrane-associated proteins

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): Wenyi Zhang, Chenxia Cao, Jie Zhang, Lai-Yu Kwok, Heping Zhang, Yongfu Chen
Lactobacillus casei Zhang is a probiotic strain originally isolated from koumiss. Previously, we showed that an alkaline shock protein (encoded by asp23) was involved in the adaptation of L. casei Zhang to gentamycin. In the present study, we compared the proteomes of the asp23 mutant and its parent strain grown in the presence of gentamycin. The results showed that 22 and 21 proteins were significantly up- and downregulated, respectively (>1.5-fold difference). By parallel reaction monitoring analysis, we further validated that specific membrane-associated proteins were important in regulating the antibiotics-induced cell wall stress. The findings provide insight into the physiological role of the asp23 gene in the growth response of L. casei when exposed to antibiotic stress.



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Varying the ratio of Lys:Met while maintaining the ratios of Thr:Phe, Lys:Thr, Lys:His, and Lys:Val alters mammary cellular metabolites, mammalian target of rapamycin signaling, and gene transcription

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): X. Dong, Z. Zhou, B. Saremi, A. Helmbrecht, Z. Wang, J.J. Loor
Amino acids are not only precursors for but also signaling molecules regulating protein synthesis. Regulation of protein synthesis via AA occurs at least in part by alterations in the phosphorylation status of mammalian target of rapamycin (mTOR) pathway proteins. Although the ideal profile of Lys:Met to promote milk protein synthesis during established lactation in dairy cows has been proposed to be 3:1, aside from being the most-limiting AA for milk protein synthesis, the role of Met in other key biologic pathways such as methylation is not well characterized in the bovine. The objective of this study was to determine the influence of increasing supplemental Met, based on the ideal 3:1 ratio of Lys to Met, on intracellular metabolism related to protein synthesis and mTOR pathway phosphorylation status. MAC-T cells, an immortalized bovine mammary epithelial cell line, were incubated (n = 5 replicates/treatment) for 12 h with 3 incremental doses of Met while holding Lys concentration constant to achieve the following: Lys:Met 2.9:1 (ideal AA ratio; IPAA), Lys:Met 2.5:1 (LM2.5), and Lys:Met 2.0:1 (LM2.0). The ratios of Thr:Phe (1.05:1), Lys:Thr (1.8:1), Lys:His (2.38:1), and Lys:Val (1.23:1) were the same across the 3 treatments. Applying gas chromatography–mass spectrometry metabolomics revealed distinct clusters of differentially concentrated metabolites in response to Lys:Met. Lower Phe, branched-chain AA, and putrescine concentrations were observed with LM2.5 compared with IPAA. Apart from greater intracellular Met concentrations, further elevations in Met level (LM2.0) led to greater intracellular concentrations of nonessential AA (Pro, Glu, Gln, and Gly) compared with IPAA and greater essential AA (EAA; Met, Ile, and Leu) and nonessential AA (Pro, Gly, Ala, Gln, and Glu) compared with LM2.5. However, compared with IPAA, mRNA expression of β-casein and AA transporters (SLC7A5, SLC36A1, SLC38A2, SLC38A9, and SLC43A1) and mTOR phosphorylation were lower in response to LM2.5 and LM2.0. Overall, the results of this study provide evidence that increasing Met while Lys and the ratios of Phe, Thr, His, and Val relative to Lys were held constant could increase the concentration and utilization of intracellular EAA, in particular branched-chain AA, potentially through improving the activity of AA transporters partly controlled by mTOR signaling. Because EAA likely are metabolized by other tissues upon absorption, a question for future in vivo studies is whether formulating diets for optimal ratios of EAA in the metabolizable protein is sufficient to provide the desired levels of these AA to the mammary cells.



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Reproductive performance and herd exit dynamics of lactating dairy cows managed for first service with the Presynch-Ovsynch or Double-Ovsynch protocol and different duration of the voluntary waiting period

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): M.L. Stangaferro, R. Wijma, M. Masello, J.O. Giordano
The objective of this experiment was to evaluate the reproductive performance and herd exit dynamics of dairy cows managed for first service with programs varying in method of submission for insemination and voluntary waiting period (VWP) duration. Holstein cows from a commercial farm in New York were randomly allocated to receive timed artificial insemination (TAI) after the Double-Ovsynch protocol (GnRH, 7 d later PGF2α, 3 d later GnRH, 7 d later GnRH, 7 d later PGF2α, 56 h later GnRH, and 16 to 18 h later TAI) at 60 ± 3 d in milk (DIM) (DO60 = 458), TAI after Double-Ovsynch at 88 ± 3 DIM (DO88 = 462), or a combination of AI at detected estrus (starting at 50 ± 3 d in milk) and TAI with the Presynch-Ovsynch protocol (PGF2α, 14 d later PGF2α, 12 d later GnRH, 7 d later PGF2α, 56 h later GnRH, and 16 to 18 h later TAI; PSOv = 450). Subsequent artificial insemination (AI) services were conducted at detected estrus or the Ovsynch protocol (32 ± 3 d after AI GnRH, 7 d later PGF2α, 56 h later GnRH, and 16 to 18 h later TAI) for cows not reinseminated at detected estrus. In a subgroup of cows, cyclicity (based on progesterone concentration), uterine health (vaginal discharge and uterine cytology), and BCS were evaluated at baseline (DO60 and DO88 = 33 ± 3 DIM; PSOv = 34 ± 3 DIM), beginning of the synchronization protocol (DO60 = 33 ± 3 DIM; DO88 = 61 ± 3 DIM; PSOv = 34 ± 3 DIM), and within −5 (PSOv) or −10 d (DO) of the VWP end (DO60 = 50 ± 3 DIM; DO88 = 78 ± 3 DIM; PSOv = 45 ± 3 DIM). Effects of treatments were assessed with multivariable statistical methods relevant for each outcome variable. Cows in the DO88 treatment had delayed time to pregnancy during lactation (DO60 vs. DO88 hazard ratio = 1.53, 95% confidence interval = 1.32 to 1.78; PSOv vs. DO88 hazard ratio = 1.37, 95% confidence interval = 1.19 to 1.61) and, within multiparous cows, the DO88 and PSOv treatments had greater risk of leaving the herd than cows in the DO60 treatment (DO88 vs. DO60 hazard ratio = 1.49, 95% confidence interval = 1.11 to 2.00; PSOv vs. DO60 hazard ratio = 1.39, 95% confidence interval = 1.03 to 1.85). Cows in the DO88 treatment had improved uterine health, greater BCS, and reduced incidence of anovulation than cows in DO60 and PSOv; however, overall pregnancy per AI 39 ± 3 d after AI was similar for the 3 treatment groups. In summary, reproductive management strategies that led to similar average DIM to the first service (∼60 d) through a combination of AI at estrus with TAI (PSOv) or all TAI (DO60) resulted in reduced time to pregnancy after calving when compared with an all TAI program (DO88) with a VWP of 88 d. Within the multiparous cow group, those that received all TAI with a VWP duration of 60 d were less likely to leave the herd than cows in the other treatments.



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Inclusion of calcium hydroxide-treated corn stover as a partial forage replacement in diets for lactating dairy cows

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): Brittany A. Casperson, Aimee E. Wertz-Lutz, Jim L. Dunn, Shawn S. Donkin
Chemical treatment may improve the nutritional value of corn crop residues, commonly referred to as corn stover, and the potential use of this feed resource for ruminants, including lactating dairy cows. The objective of this study was to determine the effect of prestorage chopping, hydration, and treatment of corn stover with Ca(OH)2 on the feeding value for milk production, milk composition, and dry matter intake (DMI). Multiparous mid-lactation Holstein cows (n = 30) were stratified by parity and milk production and randomly assigned to 1 of 3 diets. Corn stover was chopped, hydrated, and treated with 6% Ca(OH)2 (as-fed basis) and stored in horizontal silo bags. Cows received a control (CON) total mixed ration (TMR) or a TMR in which a mixture of treated corn stover and distillers grains replaced either alfalfa haylage (AHsub) or alfalfa haylage and an additional portion of corn silage (AH+CSsub). Treated corn stover was fed in a TMR at 0, 15, and 30% of the diet DM for the CON, AHsub, and AH+CSsub diets, respectively. Cows were individually fed in tiestalls for 10 wk. Milk production was not altered by treatment. Compared with the CON diet, DMI was reduced when the AHsub diet was fed and tended to be reduced when cows were fed the AH+CSsub diet (25.9, 22.7, and 23.1 ± 0.88 kg/d for CON, AHsub, and AH+CSsub diets, respectively). Energy-corrected milk production per unit of DMI (kg/kg) tended to increase with treated corn stover feeding. Milk composition, energy-corrected milk production, and energy-corrected milk per unit of DMI (kg/kg) were not different among treatments for the 10-wk feeding period. Cows fed the AHsub and AH+CSsub diets had consistent DMI over the 10-wk treatment period, whereas DMI for cows fed the CON diet increased slightly over time. Milk production was not affected by the duration of feeding. These data indicate that corn stover processing, prestorage hydration, and treatment with calcium hydroxide can serve as an alternative to traditional haycrop and corn silage in diets fed to mid-lactation dairy cows.



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Effect of leaving milk trucks empty and idle for 6 h between raw milk loads

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): Eva Kuhn, Lisbeth Meunier-Goddik, Joy G. Waite-Cusic
The US Pasteurized Milk Ordinance (PMO) allows milk tanker trucks to be used repeatedly for 24 h before mandatory clean-in-place cleaning, but no specifications are given for the length of time a tanker can be empty between loads. We defined a worst-case hauling scenario as a hauling vessel left empty and dirty (idle) for extended periods between loads, especially in warm weather. Initial studies were conducted using 5-gallon milk cans (pilot-scale) as a proof-of-concept and to demonstrate that extended idle time intervals could contribute to compromised raw milk quality. Based on pilot-scale results, a commercial hauling study was conducted through partnership with a Pacific Northwest dairy co-op to verify that extended idle times of 6 h between loads have minimal influence on the microbiological populations and enzyme activity in subsequent loads of milk. Milk cans were used to haul raw milk (load 1), emptied, incubated at 30°C for 3, 6, 10, and 20 h, and refilled with commercially pasteurized whole milk (load 2) to measure cross-contamination. For the commercial-scale study, a single tanker was filled with milk from a farm known to have poorer quality milk (farm A, load 1), emptied, and refilled immediately (0 h) or after a delay (6 h) with milk from a farm known to have superior quality milk (farm B, load 2). In both experiments, milk samples were obtained from each farm's bulk tank and from the milk can or tanker before unloading. Each sample was microbiologically assessed for standard plate count (SPC), lactic acid bacteria (LAB), and coliform counts. Selected isolates were assessed for lipolytic and proteolytic activity using spirit blue agar and skim milk agar, respectively. The pilot-scale experiment effectively demonstrated that extended periods of idle (>3 h) of soiled hauling vessels can significantly affect the microbiological quality of raw milk in subsequent loads; however, extended idle times of 6 h or less would not measurably compromise milk quality in subsequent loads in commercial tankers. Current tanker sanitation practices appear to be sufficient for maintaining raw milk SPC, LAB, and coliform levels, which are important measures of milk quality.



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Breastfeeding-associated microbiota in human milk following supplementation with Lactobacillus rhamnosus GG, Lactobacillus acidophilus La-5, and Bifidobacterium animalis subspecies lactis Bb-12

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): Melanie Rae Simpson, Ekaterina Avershina, Ola Storrø, Roar Johnsen, Knut Rudi, Torbjørn Øien
Breastfeeding is one of the major factors affecting the early development of the infant gut microbiota, and weaning is associated with a shift in the gut microbiota toward a more adult composition. Through breastfeeding, infants receive bioactive components that shape their microbiota while also being exposed to the breast milk and breast surface microbial communities. Recent studies have suggested the possibility of an entero-mammary route of microbial transfer, opening the possibility of infant gut microbiota modulation through maternal probiotic supplementation. In this study, we have analyzed breast milk samples collected at 10 d and 3 mo postpartum from women participating in the Probiotics in the Prevention of Allergy among Children in Trondheim placebo controlled trial. Women who were randomized to the probiotic arm of the Probiotics in the Prevention of Allergy among Children in Trondheim trial received a fermented milk supplemented with Lactobacillus rhamnosus GG, Lactobacillus acidophilus La-5, and Bifidobacterium animalis ssp. lactis Bb-12, consuming this daily from 4 wk before their expected due date until 3 mo after birth. In total, 472 breast milk samples were assessed for the administered bacteria using quantitative real-time PCR and the microbiota transferred during breastfeeding was analyzed using 16S ribosomal RNA gene sequencing of 142 samples. We found that breastfeeding is unlikely to be a significant source of L. rhamnosus GG, L. acidophilus La-5, and B. animalis ssp. lactis Bb-12 for infants in the probiotic arm of the trial. Furthermore, maternal supplementation did not significantly affect the overall composition of the breast milk microbiota transferred during breastfeeding. We also present a descriptive analysis of this microbiota, which was largely dominated by Streptococcus and Staphylococcus genera at both 10 d and 3 mo postpartum. Samples collected at 3 mo postpartum had a statistically significant lower presence and relative abundance of the Staphylococcus genus. These samples also had a greater number of observed species and diversity, including more operational taxonomic units from the Rothia, Veillonella, Granulicatella, and Methylbacterium genera.



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Computed tomography study of the fetal development of the dairy cow stomach complex

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): S. Al Masri, R. Reincke, H. Huenigen, O. Gemeinhardt, K.C. Richardson, J. Plendl
In the fetal development of animals, critical physiological and anatomical events influence the long-term health and performance of the offspring. To identify the critical growth phases of the fetal bovine stomach, we used computed tomography imaging on 30 German Holstein fetuses to examine the fetal bovine stomach in situ. Computed tomography allows the study of diverse parameters such as the volume of the stomach chambers in situ without the need for sophisticated filling preparation techniques. The absolute volume, relative volume, and monthly volume increase of each stomach chamber were determined. Computed tomography was a reliable method for in situ examination of the fetal bovine stomach complex from the third month of gestation onward. It was able to detect an abnormal position of the abomasum in 2 fetuses. The crown-rump length of the fetuses studied ranged from 9.5 to 89 cm (from 2.2 to 8.3 mo of gestation). Over this timeline, the changes in the relative volumes of the ruminoreticulum and abomasum were inversely related. Until mo 5 of gestation, the relative volume of the ruminoreticulum increased steadily, whereas that of the abomasum decreased. Thereafter, the relative volume of the ruminoreticulum became gradually smaller, and that of the abomasum became larger; by mo 8, the abomasum was larger than the ruminoreticulum. All stomach chambers had large increases in volume over the gestation period and we observed differences in development patterns and volume changes of the individual stomach chambers over this period. The largest monthly volume increase of the stomach complex was between mo 4 and 5 of gestation. In this period, the volume of the ruminoreticulum increased 43.8 times, that of the omasum 38.9 times, and that of the abomasum 30.03 times. Between mo 5 and 6 of gestation, the abomasum had another growth spurt, with a monthly volume increase of 10.4 times. These 2 time points in the gestation period may be critical phases of fetal development that should be considered in the management of pregnant cattle.



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Temperature modulates the production and activity of a metalloprotease from Pseudomonas fluorescens 07A in milk

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): Maura P. Alves, Rafael L. Salgado, Monique R. Eller, Roberto Sousa Dias, Sérgio Oliveira de Paula, Antonio Fernandes de Carvalho
This work evaluated the expression and activity of a metalloprotease released by Pseudomonas fluorescens 07A in milk. Low relative expression of the protease by the strain was observed after incubation for 12 h at 25°C while the strain was in the logarithmic growth phase. After 24 h, protease production significantly increased (P < 0.05) and remained constant for up to 48 h, a time range during which the strain remained in the stationary phase. Conversely, at refrigeration temperatures, at 12 h the strain was still in the lag phase and expressed the protease at higher levels than when the logarithmic phase was reached. Casein fractions were highly degraded by P. fluorescens 07A, the purified protease, and the bacterial pellet on d 7 of incubation at 25°C and to a lesser extent at 10°C for the sample incubated with the bacterium. Heat treatment at 90°C for 5 min completely inactivated the proteolytic activity of the purified protease and the bacterial pellet. This work contributes to the knowledge about the conditions of milk storage that influence the production and activity of this extracellular metalloprotease. The results demonstrate the need to find alternative strategies to control the synthesis and activity of proteolytic enzymes in the dairy industry to ensure the quality of processed products.



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Reliability of sampling strategies for measuring dairy cattle welfare on commercial farms

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): Jennifer M.C. Van Os, Christoph Winckler, Julia Trieb, Soraia V. Matarazzo, Terry W. Lehenbauer, John D. Champagne, Cassandra B. Tucker
Our objective was to evaluate how the proportion of high-producing lactating cows sampled on each farm and the selection method affect prevalence estimates for animal-based measures. We assessed the entire high-producing pen (days in milk <100; range = 81–241 cows) on 10 California farms using measures from the Welfare Quality Protocol for Cattle. Cows were restrained in head locks and visually evaluated for body condition, dirtiness, skin alterations (hair loss, lesions, or swelling), discharge (ocular, nasal, vulvar), diarrhea, and impaired respiration. Lameness was scored upon release. Prevalence was calculated as a percentage of assessed cows. The most common conditions were dirty hindquarters (33.5 ± 10.7%, mean ± standard deviation) and lesions or swelling on the carpal joint (34.4 ± 7.0%) and hock (26.4 ± 16.7%). Diarrhea (8.0 ± 5.8%), lameness (moderate = 7.3 ± 4.7%, severe = 2.2 ± 2.2%), and neck (5.8 ± 12.6%), flank (4.5 ± 5.0%), or hindquarter alterations (5.5 ± 3.9%) were less common. Very fat cows, vulvar discharge, and impaired respiration were rare (≤1%) and were excluded from further analysis. Four sampling strategies were used to generate 20 estimates for each animal-based measure. The strategies were (1) selecting every 10th, 5th, 4th, 3rd, 2nd, 2 of 3, or 3 of 4 cows at the feed bunk (7 estimates/measure); (2) randomly selecting 7 matching proportions of the pen; (3) randomly selecting cows using 3 sample size calculations from the Welfare Quality Protocol; and (4) selecting the first, middle, or final third of cows exiting the milking parlor. Estimates were compared with true values using regression analysis and were considered accurate if they met 3 criteria: the coefficient of determination was ≥0.9 and the slope and intercept did not differ significantly from 1 and 0, respectively. All estimates met the slope and intercept criteria, whereas the coefficient of determination increased when more cows were sampled. All estimates were accurate for neck alterations, ocular discharge (22.2 ± 27.4%), and carpal joint hair loss (14.1 ± 17.4%). Selecting a third of the milking order or using the Welfare Quality sample size calculations failed to accurately estimate all measures simultaneously. However, all estimates were accurate when selecting at least 2 of every 3 cows locked at the feed bunk. Using restraint position at the feed bunk did not differ systematically from computer-selecting the same proportion of cows randomly, and the former may be a simpler approach for welfare assessments.



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Dynamics of methanogenesis, ruminal fermentation, and alfalfa degradation during adaptation to monensin supplementation in goats

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): Z.J. Li, H. Ren, S.M. Liu, C.J. Cai, J.T. Han, F. Li, J.H. Yao
This study aimed to examine the temporal (hourly within a day and daily over the long term) effects of monensin on CH4 emissions, ruminal fermentation, and in situ alfalfa degradation in dairy goats during dietary monensin supplementation by controlling the confounding effects of feed intake and ambient temperature. Six ruminally cannulated dairy goats were used, and they were housed in environmental chambers and fed a restricted amount of ration throughout the experiment. The experiment included a baseline period of 20 d followed by a treatment period of 55 d with 32 mg of monensin/d. During the whole experiment, CH4 production was measured every 5 d, whereas fermentation characteristics and in situ alfalfa degradation were analyzed every 10 d. The CH4-depressing effect of monensin was time dependent on the duration of treatment, highly effective at d 5 but thereafter decreased gradually until d 55 even though CH4-suppressing effect still remained significant. The decreasing effects of monensin on ruminal acetate proportion and acetate to propionate ratio also faded over days of treatment, and the acetate proportion returned up to the pre-supplementation level on d 50. Monensin supplementation elevated ruminal propionate proportion and decreased the effective ruminal degradability of alfalfa NDF, but both measurements tended to recover over time. The postprandial increase rate of hourly CH4 emissions was reduced, whereas that of propionate proportion was enhanced by monensin supplementation. However, the postprandial responses to monensin in CH4 emission rates, ruminal VFA profiles, and in situ degradation kinetics declined with both hours after feeding and days of treatment. Our results suggest that the CH4-suppressing effect of monensin supplementation in goats was attributed to reductions in both ruminal feed degradation and acetate to propionate ratio, but those reductions faded with time, hours after feeding, and days of treatment.



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Influence of conjugated linoleic acids and vitamin E on biochemical, hematological, and immunological variables of dairy cows during the transition period

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): S. Schäfers, D. von Soosten, U. Meyer, C. Drong, J. Frahm, A. Tröscher, W. Pelletier, H. Sauerwein, S. Dänicke
The objective of this experiment was to determine the effects of conjugated linoleic acid (CLA) and vitamin E as well as their interaction on biochemical and hematological variables and on leukocyte populations and their functionality. We assigned 59 German Holstein cows between the 2nd and 9th lactation to 4 dietary groups in a 2 × 2 factorial design with the factors CLA and vitamin E. Six weeks before calving the cows had a BCS of 3.7 to provoke a higher risk of developing ketosis, which might impair their immune function. Blood samples for analyses were taken on d −42, −14, −7, −3, 1, 3, 7, 10, 14, 21, 28, 35, 42, 56, and 70 relative to parturition. Furthermore, peripheral blood mononuclear cells were cultured on d −42, −7, 1, 7, 14, 28, and 70 relative to calving. Most variables were characterized by a high variation between d 7 antepartum and d 7 postpartum. Treatments did not elicit any effect, with the exception of vitamin E, which increased serum urea concentrations and decreased monocyte percentages. Haptoglobin, aspartate-aminotransferase, red blood cell count, leukocyte percentage and populations, as well as peripheral blood mononuclear cells were influenced by parity. In conclusion, the impairment of immune function caused by calving was more severe in cows in ≥3rd parity than in younger cows. However, neither vitamin E nor CLA supplementation was successful to stabilize parity or parturition related variance in hematological and immunological traits.



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Method comparison and validation of a prototype device for measurement of ionized calcium concentrations cow-side against a point-of-care instrument and a benchtop blood-gas analyzer reference method

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): R.C. Neves, T. Stokol, K.D. Bach, J.A.A. McArt
The objective of this study was to assess an optimized ion-selective electrode Ca-module prototype as a potential cow-side device for ionized Ca (iCa) measurements in bovine blood. A linearity experiment showed no deviation from linearity over a range of iCa concentrations compared with a commercial point-of-care (POC) device commonly used in the field (POCVS; VetScan i-STAT, Abaxis North America, Union City, CA) and a laboratory gold standard benchtop blood-gas analyzer [reference analyzer (RA); ABL-800 FLEX, Radiometer Medical, Copenhagen, Denmark]. Coefficient of variation on 3 samples with high, within-range, and low iCa concentrations ranged from 1.0 to 3.9% for the prototype. A follow-up validation experiment was performed, in which our objectives were to (1) assess the performance of the prototype cow-side against the POCVS (farm gold-standard) using fresh non-anticoagulated whole-blood samples; (2) assess the performance of the prototype and the POCVS against the RA in a diagnostic laboratory using blood collected in a heparin-balanced syringe; and (3) assess the agreement of the prototype and POCVS on-farm (fresh non-anticoagulated whole blood) against the RA on heparin-balanced blood. Finally, sensitivity and specificity of the results obtained by the prototype and the POCVS cow-side compared with the results obtained by the laboratory RA using 3 different iCa cut points for classification of subclinical hypocalcemia were calculated. A total of 101 periparturient Holstein cows from 3 dairy farms in New York State were used for the second experiment. Ionized Ca results from the prototype cow-side were, on average, 0.06 mmol/L higher than the POCVS. With heparin-balanced samples under laboratory conditions, the prototype and POCVS measured an average 0.04 mmol/L higher and lower, respectively, compared with the RA. Results from the prototype and POCVS cow-side were 0.01 mmol/L higher and 0.05 mmol/L lower, respectively, compared with results from the laboratory RA on heparinized blood. Sensitivity and specificity for the prototype and the POCVS under farm conditions at 3 potential subclinical hypocalcemia cut points were 100 and ≥93.5%, respectively. This novel ion-selective electrode Ca-module could become a rapid low-cost tool for assessing iCa cow-side, while qualitatively allowing classification of subclinical hypocalcemia on-farm.



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Replacing maize silage plus soybean meal with red clover silage plus wheat in diets for lactating dairy cows

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): Franziska Schulz, Edwin Westreicher-Kristen, Karin Knappstein, Joachim Molkentin, Andreas Susenbeth
The objectives of this study were to evaluate the effects of replacing maize silage plus soybean meal with red clover silage (RCS) plus wheat on feed intake, diet digestibility, N partitioning, urinary excretion of purine derivatives, and milk production in dairy cows. Forty-four lactating German Holstein cows were used in a 4 × 4 Latin square design with 21-d periods composed of a 13-d adaptation phase followed by an 8-d sampling phase. Experimental diets offered as total mixed ration consisted of a constant forage-to-concentrate ratio (75:25) with targeted proportions of RCS-to-maize silage of 15:60 (RCS15), 30:45 (RCS30), 45:30 (RCS45), and 60:15 (RCS60) on a dry matter (DM) basis. Increasing the proportion of RCS plus wheat in the diet decreased linearly the intake of DM from 22.4 to 19.8 kg/d, and of organic matter from 21.1 to 18.1 kg/d. The apparent total tract digestibility (ATTD) of DM and organic matter did not differ across diets and averaged 68.4 and 70.5%, respectively. However, ATTD of N decreased linearly from 68.5 to 63.2%, whereas ATTD of neutral detergent fiber and acid detergent fiber increased linearly from 50.4 to 59.6% and from 48.4 to 57.7%, respectively, when increasing the proportion of RCS plus wheat. Fecal N excretion increased from 31.6 (RCS15) to 37.2% (RCS60) of N intake, whereas urinary N excretion was the lowest (32.8% of N intake) with RCS45. Hence, N efficiency (milk N/N intake) decreased linearly with incremental levels of RCS plus wheat, being the lowest when feeding RCS60 (25.4%), probably due to increased nonprotein N proportion in total dietary N. Urinary excretion of purine derivatives decreased linearly from 378 to 339 mmol/d, which suggests that increasing levels of RCS plus wheat reduced the microbial crude protein flow at the duodenum. Milk yield and milk protein concentration declined linearly from 35.9 to 30.2 kg/d and from 3.20 to 3.01%, respectively, when increasing the proportion of RCS plus wheat. In conclusion, caution should be taken before introducing high levels of RCS plus wheat in diets of high-yielding dairy cows. However, RCS plus wheat can be included up to 30% of the dairy cow diet (DM basis) without a reduction in lactation performance.



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Economic costs of recorded reasons for cow mortality and culling in a pasture-based dairy industry

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): J.I. Kerslake, P.R. Amer, P.L. O'Neill, S.L. Wong, J.R. Roche, C.V.C. Phyn
The objective of this study was to determine the economic costs associated with different reasons for cow culling or on-farm mortality in a pasture-based seasonal system. A bioeconomic model was developed to quantify costs associated with the different farmer-recorded reasons and timing of cow wastage. The model accounted for the parity and stage of lactation at which the cows were removed as well as the consequent effect on the replacement rate and average age structure of the herd. The costs and benefits associated with the change were quantified, including animal replacement cost, cull salvage value, milk production loss, and the profitability of altered genetic merit based on industry genetic trends for each parity. The total cost of cow wastage was estimated to be NZ$23,628/100 cows per year (NZ$1 = US$0.69) in a pasture-based system. Of this total cost, NZ$14,300/100 cows worth of removals were for nonpregnancy and unknown reasons, and another NZ$3,631/100 cows was attributed to low milk production, mastitis, and udder problems. The total cost for cow removals due to farmer-recorded biological reasons (excluding unknown, production, and management-related causes) was estimated to be NZ$13,632/100 cows per year. Of this cost, an estimated NZ$10,286/100 cows was attributed to nonpregnancy, mastitis, udder problems, calving trouble, and injury or accident. There is a strong economic case for the pasture-based dairy industries to invest in genetic, herd health, and production management research focused on reducing animal wastage due to reproductive failure, mastitis, udder problems, injuries or accidents, and calving difficulties.



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Multi-year evaluation of stocking rate and animal genotype on milk production per hectare within intensive pasture-based production systems

Publication date: Available online 14 December 2017
Source:Journal of Dairy Science
Author(s): E.L. Coffey, L. Delaby, C. Fleming, K.M. Pierce, B. Horan
The objective of this experiment was to evaluate the effect of stocking rate (SR) and animal genotype (BR) on milk production, body weight (BW), and body condition score (BCS) within intensive pasture-based systems. A total of 533 lactation records, from 246 elite genetic merit dairy cows were available for analysis; 68 Holstein-Friesian (HF) and 71 Jersey × Holstein-Friesian (JxHF) crossbred cows in each of 4 consecutive years (2013–2016, inclusive). Cows from each BR were randomly allocated to 1 of 3 whole-farm comparative SR treatments, low (LSR; 1,200 kg of BW/ha), medium (MSR; 1,400 kg of BW/ha), and high (HSR; 1,600 kg of BW/ha), and remained in the same SR treatments for the duration of the experiment. The effects of SR, BR, and their interaction on milk production/cow and per hectare, BW, BCS, and grazing characteristics were analyzed. Total pasture utilization per hectare consumed in the form of grazed pasture increased linearly as SR increased: least in LSR (10,237 kg of dry matter/ha), intermediate in MSR (11,016 kg of dry matter/ha), and greatest in HSR (11,809 kg of dry matter/ha). Milk and milk solids (MS) yield per hectare was greatest for HSR (15,942 and 1,354 kg, respectively), intermediate for MSR (14,191 and 1,220 kg, respectively), and least for LSR (13,186 and 1,139 kg, respectively) with similar trends evident for fat, protein, and lactose yield/ha. At higher SR (MSR and HSR), MS yield per kg of BW per ha was reduced (0.85 and 0.82 kg of MS/kg of BW, respectively) compared with LSR (0.93 kg of MS/kg of BW/ha). Holstein-Friesian cows achieved fewer grazing days per hectare (−37 d), and produced more milk (+561 kg/ha) but less fat plus protein (−57 kg/ha) compared with JxHF cows; the JxHF cows were lighter. At similar BW per hectare, JxHF cows produced more fat plus protein/ha during the grazing season at low (1,164 vs. 1,113 kg), medium (1,254 vs. 1,185 kg), and high (1,327 vs. 1,380 kg) SR. In addition, JxHF cows produced more fat plus protein per kg of BW/ha (0.90 kg) compared with HF cows (0.84 kg). The results highlight the superior productive efficiency of high genetic potential crossbred dairy cows within intensive pasture-based production systems.



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Evaluation of Large-Aperture Imaging Through the ex Vivo Human Abdominal Wall

Publication date: Available online 14 December 2017
Source:Ultrasound in Medicine & Biology
Author(s): Nick Bottenus, Will Long, Matthew Morgan, Gregg Trahey
Current clinical abdominal imaging arrays are designed to maximize angular field of view rather than the extent of the coherent aperture. We illustrate, in ex vivo experiments, the use of a large effective aperture to perform high-resolution imaging, even in the presence of abdominal wall-induced acoustic clutter and aberration. Point and lesion phantom targets were imaged through a water path and through three excised cadaver abdominal walls to create different clinically relevant clutter effects with matched imaging targets. A 7.36-cm effective aperture was used to image the targets at a depth of 6.4 cm, and image quality metrics were measured over a range of aperture sizes using synthetic aperture techniques. In all three cases, although degradation compared with the control was observed, lateral resolution improved with increasing aperture size without loss of contrast. Spatial compounding of the large-aperture data drastically improved lesion detectability and produced contrast-to-noise ratio improvements of 83%–106% compared with the large coherent aperture. These studies indicate the need for the development of large arrays for high-resolution abdominal diagnostic imaging.



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FDA Benefit‐Risk Assessment of Osimertinib for the Treatment of Metastatic Non‐Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor T790M Mutation

AbstractOn March 30, 2017, the U.S. Food and Drug Administration (FDA) approved osimertinib for the treatment of patients with metastatic, epidermal growth factor receptor (EGFR) T790M mutation‐positive, non‐small cell lung cancer (NSCLC), as detected by an FDA‐approved test, whose disease has progressed following EGFR tyrosine kinase inhibitor (TKI) therapy. Approval was based on demonstration of a statistically significant difference in the primary endpoint of progression‐free survival (PFS) when comparing osimertinib with chemotherapy in an international, multicenter, open‐label, randomized trial (AURA3). In this confirmatory trial, which enrolled 419 patients, the PFS hazard ratio for osimertinib compared with chemotherapy per investigator assessment was 0.30 (95% confidence interval 0.23–0.41), p < .001, with median PFS of 10.1 months in the osimertinib arm and 4.4 months in the chemotherapy arm. Supportive efficacy data included PFS per blinded independent review committee demonstrating similar PFS results and an improved confirmed objective response rate per investigator assessment of 65% and 29%, with estimated median durations of response of 11.0 months and 4.2 months, in the osimertinib and chemotherapy arms, respectively. Patients received osimertinib 80 mg once daily and had a median duration of exposure of 8 months. The toxicity profile of osimertinib compared favorably with the profile of other approved EGFR TKIs and chemotherapy. The most common adverse drug reactions (>20%) in patients treated with osimertinib were diarrhea, rash, dry skin, nail toxicity, and fatigue. Herein, we review the benefit‐risk assessment of osimertinib that led to regular approval, for patients with metastatic NSCLC harboring EGFR TKI whose disease has progressed on or after EGFR TKI therapy.Implications for Practice.Osimertinib administered to metastatic non‐small cell lung cancer (NSCLC) patients harboring an EGFR T790M mutation, who have progressed on or following EGFR TKI therapy, demonstrated a substantial improvement over platinum‐based doublet chemotherapy as well as durable intracranial responses. The ability to test for the T790M mutation in plasma using the FDA‐approved cobas EGFR Mutation Test v2 (Roche, Basel, Switzerland) identifies patients with NSCLC tumors not amenable to biopsy. Since a 40% false‐negative rate has been observed with the circulating tumor DNA test, re‐evaluation of the feasibility of tissue biopsy is recommended to identify patients with a false‐negative plasma test result who may benefit from osimertinib.

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Phase II Study of BEZ235 versus Everolimus in Patients with Mammalian Target of Rapamycin Inhibitor‐Naïve Advanced Pancreatic Neuroendocrine Tumors

AbstractLessons Learned. Treatment with BEZ235 has not been shown to demonstrate increased efficacy compared with everolimus and may be associated with a poorer tolerability profile.The hypothesis of dual targeting of the phosphatidylinositol 3‐kinase and mammalian target of rapamycin pathways in patients with advanced pancreatic neuroendocrine tumors may warrant further study using other agents.Background.This phase II study investigated whether targeting the phosphatidylinositol 3‐kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway via PI3K, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) inhibition using BEZ235 may be more effective than mTORC1 inhibition with everolimus in patients with advanced pancreatic neuroendocrine tumors (pNET) who are naïve to mTOR inhibitor therapy.Methods.Patients with advanced pNET were randomized (1:1) to oral BEZ235 400 mg twice daily or oral everolimus 10 mg once daily on a continuous dosing schedule. The primary endpoint was progression‐free survival (PFS). Secondary endpoints included safety, overall response rate (ORR), overall survival (OS), and time to treatment failure.Results.Enrollment in this study was terminated early (62 enrolled of the 140 planned). The median PFS was 8.2 months (95% confidence interval [CI]: 5.3 to not evaluable [NE]) with BEZ235 versus 10.8 months (95% CI: 8.1–NE) with everolimus (hazard ratio 1.53; 95% CI: 0.72–3.25). The most commonly reported all‐grade adverse events (>50% of patients regardless of study treatment relationship) with BEZ235 were diarrhea (90.3%), stomatitis (74.2%), and nausea (54.8%).Conclusion.BEZ235 treatment in mTOR inhibitor‐naïve patients with advanced pNET did not demonstrate increased efficacy compared with everolimus and may be associated with a poorer tolerability profile.

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Patient‐Reported Comorbidity and Survival in Older Adults with Cancer

AbstractBackground.Our ability to optimize the care of older adults with cancer and comorbid illnesses is insufficient because most clinical trials lack systematic measurement. The primary purpose of this study was to evaluate the association between patient‐reported comorbidity and all‐cause mortality using various comorbidity scoring algorithms.Materials and Methods.The Carolina Senior Registry was linked with the North Carolina Central Cancer Registry to obtain mortality data. Comorbidity was assessed using the patient‐reported Older Americans Resources and Services Questionnaire subscale that assesses 13 specific conditions and the degree to which each impairs activities. Multivariable Cox proportional hazard regression models were used to evaluate the association between comorbidities and all‐cause mortality.Results.The study sample included 539 patients; the median age was 72 years, 72% were female, and 47% had breast cancer. Overall, 92% reported ≥1 comorbid condition, with a mean of 2.7 conditions (range 0–10), with arthritis and hypertension the most common (52% and 50%, respectively). Approximately 60% reported a functional limitation related to comorbidity. After adjusting for time from diagnosis to geriatric assessment, age, cancer type, and stage, the risk of death increased by 5% for each unit increase in comorbidity burden score (adjusted hazard ratio [HR] = 1.05, 95% confidence interval [CI]: 1.01–1.10) and 12% for each comorbid condition impacting function (HR = 1.12, 95% CI: 1.02–1.23).Conclusion.Comorbid conditions in older adults with cancer are highly prevalent and associated with all‐cause mortality, particularly those conditions that impair function. Routine comorbidity assessment should be included in clinical trials and can be measured via a simple one‐page patient‐reported questionnaire.Implications for Practice.In order to optimize and personalize the care of older adults with cancer, systematic measurement of comorbidities is necessary in both clinical trials and routine practice. Patient‐reported comorbid conditions in older adults with cancer are highly prevalent and are associated with increased risk of all‐cause mortality, particularly for those conditions that impair function. Comorbidity can be systematically measured via a one‐page patient‐reported questionnaire and should be incorporated into future clinical trials and considered for use in oncology clinics to aid in assessing older adults with cancer.

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Results of Fertility‐Sparing Surgery for Expansile and Infiltrative Mucinous Ovarian Cancers

AbstractBackground.No series had been reported focusing on the results of fertility‐sparing surgery in stage I mucinous ovarian cancers according to histotype (infiltrative vs. expansile). Investigating such outcomes was the aim of the present study.Materials and Methods.The present study was a retrospective analysis of patients treated conservatively with preservation of the uterus and contralateral ovary from 1976 to 2016. The pathology of the tumors was reviewed by two expert pathologists according to the 2014 World Health Organization (WHO) classification criteria. Oncologic and fertility results were analyzed.Results.Twenty‐one patients fulfilled the inclusion criteria, twelve with expansile and nine with infiltrative cancer. All patients had a unilateral tumor and underwent unilateral salpingo‐oophorectomy in one‐step (n = 6) or two‐step (n = 15) surgeries. All but one had complete peritoneal staging surgery based on cytology, omentectomy, and random peritoneal biopsies. Ten had nodal staging surgery. The International Federation of Gynecology and Obstetrics stages were IA (n = 9), IC1 (n = 6), and IC2 (n = 6); the nuclear grades were grade 1 (n = 9), grade 2 (n = 5), and grade 3 (n = 1). Two patients recurred (one expansile and one infiltrative type) 19 and 160 months after surgery, respectively. One stage IA, nuclear grade 2 expansile tumor recurred on the spared ovary; the patient remains alive. The other stage IA infiltrative tumor recurred as peritoneal spread; the patient is alive with disease. Six patients became pregnant; four with expansile tumors and two with infiltrative tumors.Conclusion.The type of mucinous cancer has no impact on the oncologic outcome in this series of patients treated conservatively. Fertility‐sparing surgery should be considered for early‐stage infiltrative‐type tumors.Implications for Practice.According to the most recently updated World Health Organization classification guidelines, mucinous cancers should be classified as either expansile or infiltrative. The infiltrative type has a poorer prognosis, but there are no data about the safety of fertility‐sparing surgery (FSS) in this context. A collection of 21 cases reviewed by two expert pathologists this study is the first devoted to the conservative treatment of mucinous tumors according to both subtypes. The key result was that the type of mucinous cancer has no impact on the oncologic outcome; thus, FSS may be considered in both subtypes.

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Molecular Biomarkers of Primary and Acquired Resistance to T‐Cell‐Mediated Immunotherapy in Cancer: Landscape, Clinical Implications, and Future Directions

AbstractThe emergence of immunotherapy has revolutionized cancer treatment in recent years. Inhibitors of immune checkpoints, including antibodies against cytotoxic T‐lymphocyte‐associated protein 4, programmed cell death protein 1, and programmed death ligand 1, have demonstrated notable efficacy in certain advanced cancers. Unfortunately, many patients do not benefit from these therapies and either exhibit primary resistance to treatment or develop acquired mechanisms of resistance after initially responding to therapy. Here, we review the genomic and immune traits that may promote resistance to T‐cell‐mediated immunotherapy, with a focus on identifying potential biomarkers that could eventually be used in the clinical setting to guide treatment selection. We summarize the clinical evidence for these markers and discuss how current understanding of resistance mechanisms can inform future studies and aid clinical decision‐making in order to derive maximum benefit from immunotherapy.Implications for Practice.Immunotherapy has rapidly progressed as a treatment modality for multiple cancers, but it is still unclear which patients are likely to benefit from these therapies. Studies of resistance mechanisms have only recently started to identify biomarkers that can help predict patient outcomes. This review summarizes the available clinical data in regard to immunotherapy resistance, with a focus on molecular biomarkers that may be useful in guiding clinical decision‐making. It discusses possible applications of these biomarkers and highlights opportunities for further clinical discovery.

http://ift.tt/2jWqMtS

Disentangling the effects of parental food restriction on child's risk of overweight

Publication date: 1 April 2018
Source:Appetite, Volume 123
Author(s): Valérie Godefroy, Camille Champel, Laura Trinchera, Natalie Rigal
The links between parental restriction of food intake, child's eating behaviour and child's adiposity are still unclear. Our aim was to validate a model suggesting an underlying mechanism for the impact of parental restriction on child's adiposity through a broad dimension of child's eating temperament entitled the appetite reactivity (including both appetite arousal and appetite persistence). Using an online questionnaire administered at home to children aged between 8 and 11 years (N = 414) with one or both of their parents, we measured: based on child's reports, the perceived maternal restriction of child's food intake, the appetite reactivity and both the desired and the eaten mean food portion sizes; based on parental reports, the mean food portion size given to the child and the child's BMI. Structural equation modelling was used to test a model linking measured variables. A well-fitting structural model (AGFI = 0.91; RMSEA = 0.07; SRMR = 0.08) was identified, showing that: (i) perceived maternal restriction of child's food intake negatively impacts child's appetite arousal and food portion size but positively influences child's appetite persistence; (ii) the two components of appetite reactivity have a positive effect on child's adiposity which is partly mediated by child's actual food portion size. Results suggest an explanation for the controversy surrounding the links between parental food restriction and child's adiposity: through its negative impact on child's appetite arousal and food portion size, parental control may protect against overweight, but because of its positive effect on appetite persistence, it can also be detrimental.



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Life in the Emergency Department.

Life in the Emergency Department.

Mil Med. 2017 Dec 11;:

Authors: Goldenberg W

PMID: 29237022 [PubMed - as supplied by publisher]

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Systemic treatment in adult uterine sarcomas

Publication date: Available online 14 December 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): I.M.E. Desar, P.B. Ottevanger, C. Benson, W.T.A. van der Graaf
Uterine sarcomas (US) are rare mesenchymal tumours of the uterus and are divided mainly into uterine leiomyosarcoma (uLMS), low grade endometrial stromal sarcoma (LG-ESS), high grade endometrial stromal sarcoma (HG-ESS), adenosarcomas and high grade undifferentiated sarcoma (HGUS). US are often high-grade tumours with a high local recurrence rate and metastatic risk. We here discuss the current standard of care and knowledge of systemic therapy for adult uterine sarcomas, in particular uLMS, LG-ESS, HG-ESS and HGUS, in both the adjuvant as well as the metastatic setting.



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Cytosolic sensing of immuno-stimulatory DNA, the enemy within

Rekha Dhanwani | Mariko Takahashi | Sonia Sharma

http://ift.tt/2yuV4sp

Developmental control of macrophage function

Johnny Bonnardel | Martin Guilliams

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