Treatment of spinal cord injury by an advanced cell transplantation technology using brain-derived neurotrophic factor-transfected mesenchymal stem cell spheroids

Publication date: December 2016
Source:Biomaterials, Volume 109
Author(s): Satoshi Uchida, Kentaro Hayakawa, Toru Ogata, Sakae Tanaka, Kazunori Kataoka, Keiji Itaka
Curing spinal cord injury (SCI) is challenging because of the onset of multiple and irreversible pathological responses to such injury. To suppress the responses, we employed an advanced cell transplantation technology integrating three-dimensional spheroid cell transplantation with non-viral gene transfection using biodegradable polycations. Brain-derived neurotrophic factor (BDNF)-transfected mesenchymal stem cell (MSC) spheroids were transplanted at thoraces level (Th9) to SCI region in mice. BDNF-transfected MSC spheroid transplantation led to a significantly enhanced recovery of hindlimb motor function in acute phase of SCI with myelinated axons preserved at the SCI region, while use of either technology in isolation, BDNF transfection or spheroid culture, exerted only a limited therapeutic effect, demonstrating the importance of integrated approaches. Secretion of endogenous therapeutic proteins, such as anti-inflammatory factors, was greater in MSC spheroids than in monolayer culture MSCs, and these factors appeared to act synergistically alongside BDNF secretion in SCI treatment. This study forms a basis for cell therapy regulating complex pathophysiologic processes.



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Commentary on ‘Monitoring of Foot Oxygenation with Near-infrared Spectroscopy in Patients with Critical Limb Ischemia Undergoing Percutaneous Transluminal Angioplasty: A Pilot Study’

Publication date: Available online 15 September 2016
Source:European Journal of Vascular and Endovascular Surgery
Author(s): N. De Luccia




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Racial differences in association of serum calcium with mortality and incident cardio- and cerebrovascular events

The Journal of Clinical Endocrinology &Metabolism, Early Release.


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The role of microRNAs in the pathogenesis of autoimmune diseases

Publication date: Available online 15 September 2016
Source:Autoimmunity Reviews
Author(s): Ji-Qing Chen, Gábor Papp, Péter Szodoray, Margit Zeher
MicroRNAs (miRNAs) are single-stranded, endogenous non-coding small RNAs, ranging from 18 to 25 nucleotides in length. Growing evidence suggests that miRNAs are essential in regulating gene expression, cell development, differentiation and function. Autoimmune diseases are a family of chronic systemic inflammatory diseases. Recent findings on miRNA expression profiles have been suggesting their role as biomarkers in autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and Sjögren's syndrome. In this review, we summarize the characteristics of miRNAs and their functional role in the immune system and autoimmune diseases including systemic lupus erythematosus, primary Sjögren's syndrome, rheumatoid arthritis, systemic sclerosis, multiple sclerosis and psoriasis; moreover, we depict the advantages of miRNAs in modern diagnostics.



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Dry eye disease and uveitis: a closer look at immune mechanisms in animal models of two ocular autoimmune diseases

Publication date: Available online 15 September 2016
Source:Autoimmunity Reviews
Author(s): Tanima Bose, Maria Diedrichs-Moehring, Gerhild Wildner
Understanding the immunopathogenesis of autoimmune and inflammatory diseases is a prerequisite for specific and effective therapeutical intervention. This review focuses on animal models of two common ocular inflammatory diseases, dry eye disease (DED), affecting the ocular surface, and uveitis with inflammation of the inner eye. In both diseases autoimmunity plays an important role, in idiopathic uveitis immune reactivity to intraocular autoantigens is pivotal, while in dry eye disease autoimmunity seems to play a role in one subtype of disease, Sjögren's syndrome (SjS). Comparing the immune mechanisms underlying both eye diseases reveals similarities, and significant differences. Studies have shown genetic predispositions, T and B cell involvement, cytokine and chemokine signatures and signaling pathways as well as environmental influences in both DED and uveitis. Uveitis and DED are heterogeneous diseases and there is no single animal model, which adequately represents both diseases. However, there is evidence to suggest that certain T cell-targeting therapies can be used to treat both, dry eye disease and uveitis. Animal models are essential to autoimmunity research, from the basic understanding of immune mechanisms to the pre-clinical testing of potential new therapies.



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Psoriasis and autoimmunity

Publication date: Available online 15 September 2016
Source:Autoimmunity Reviews
Author(s): Michael Sticherling
Psoriasis is one of the most common chronic inflammatory human skin diseases. Though clinically well characterized, the exact etiological and pathogenic mechanisms are still not known in detail. Current knowledge indicates distinct overlap to other inflammatory as well as autoimmune disorders. However, the one or more relevant autoantigens could not be characterized so-far. On the other side, several autoimmune diseases were shown to be associated with psoriasis. In addition, serological autoimmune phenomena, namely diverse circulating specific autoantibodies could be demonstrated in the past. A matter of current debate is if psoriasis is a primary autoimmune disease or secondarily evolving into autoimmunity as seen in other chronic inflammatory diseases. Related to this aspect is the concept of autoinflammation versus autoimmunity where psoriasis shares mechanisms of both entities. Though T-cells remain among the most important cellular players in the pathogenesis of psoriasis and current therapeutic strategies successfully target these cells or their products irrespective of these concepts, autoimmunity if relevant will add to the treatment armamentarium by using protective and prophylactic antigen-specific modalities.



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Cognitive Disorders and Antiphospholipid Antibodies

Publication date: Available online 15 September 2016
Source:Autoimmunity Reviews
Author(s): Cécile M. Yelnik, Elizabeth Kozora, Simone Appenzeller
Cognitive disorders have frequently been described in the field of antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). Nevertheless, the relationship between those disorders and antiphospholipid antibodies (aPL) remains unclear and seems to involve various mechanisms. Overlap with systemic lupus erythematosus, the small sample size of studies, and discrepancies in antiphospholipid antibodies and cognitive impairment determinations complicate analyzes of the literature data. In this paper, we summarize current knowledge on epidemiologic, clinical data, imaging findings and treatment of cognitive dysfunction associated with aPL. We analyzed separately data on aPL-positive carriers without history of clinical feature of APS; APS patients without overlaps autoimmune disease; and SLE associated aPL patients.



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Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT): Characteristics, treatment and outcome in 251 cases from the literature

Publication date: Available online 15 September 2016
Source:Autoimmunity Reviews
Author(s): Charlotte Laurent, Jean Capron, Bluenn Quillerou, Guy Thomas, Sonia Alamowitch, Olivier Fain, Arsène Mekinian
BackgroundSteroid-responsive encephalopathy and associated autoimmune thyroiditis (SREAT) is characterized by encephalopathy and the presence of antithyroid antibodies. We describe the clinical presentation, outcome and treatments for SREAT by a systematic review of the literature.MethodsMEDLINE via PubMed, Web of Science and the Cochrane Library were searched for articles published until 2015. Inclusion criteria were unexplained encephalopathy with antithyroid antibodies.ResultsWe found reports of 251 patients (median age 52years [range 18–86], 73% females, 80 [32%] with preexisting thyroiditis). Patients presented encephalitis signs with convulsions (n=117; 47%), confusion (n=115, 46%), speech disorder (n=91, 37%), memory impairment (n=107, 43%), gait disturbance (n=67, 27%) and persecutory delusions (n=61, 25%). Twenty-eight patients (11%) presented progressive memory impairment and 26 (10%) isolated psychiatric disorders. In serum, 34% of patients were positive for anti-thyroid peroxidase (TPO) antibodies, 7% for anti-thyroglobulin (TG) antibodies, and 69% both. Thyroid-stimulating hormone levels were usually normal, at 2 UI/ml [0.001–205]. Cerebrospinal fluid from 10/53 patients (19%) was positive for anti-TPO antibodies, 2/53 (4%) anti-TG antibodies and 28 (53%) both. Electroencephalography findings were abnormal for 82% of patients, showing diffuse slowing consistent with encephalopathy (70%) or epileptic activity (14%). The first-line treatment was steroids in 193 patients and other immunosuppressive drugs in 10 cases. At a median follow-up of 12months [range 0.2–110], 91% of patients showed complete or partial neurological response, with anti-TPO and -TG antibody titers at 347 UI/ml [0–825000] and 110 UI/ml [0–50892], respectively. During follow-up, 40 patients (16%) experienced at least one relapse. Relapse was more frequent in patients with initial coma (26% vs 13%, p=0.08).ConclusionThe diagnosis of SREAT should be suspected in case of encephalopathy without obvious cause, to quickly start corticosteroid treatment. The exact modalities of treatment must be defined.



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Catastrophic antiphospholipid syndrome (CAPS): Descriptive analysis of 500 patients from the International CAPS Registry

Publication date: Available online 15 September 2016
Source:Autoimmunity Reviews
Author(s): Ignasi Rodríguez-Pínto, Marta Moutinho, Irene Santacreu, Yehuda Shoenfeld, Doruk Erkan, Gerard Espinosa, Ricard Cervera
ObjectiveTo analyze the clinical and immunologic manifestations of patients with catastrophic antiphospholipid syndrome (CAPS) from the "CAPS Registry".MethodsThe demographic, clinical and serological features of 500 patients included in the website-based "CAPS Registry" were analyzed. Frequency distribution and measures of central tendency were used to describe the cohort. Comparison between groups regarding qualitative variables was undertaken by chi-square or Fisher exact test while T-test for independent variables was used to compare groups regarding continuous variables.Results500 patients (female: 343 [69%]; mean age 38±17) accounting for 522 episodes of CAPS where included in the analysis. Forty percent of patients had an associated autoimmune disease, mainly systemic lupus erythematosus (SLE) (75%). The majority of CAPS episodes were triggered by a precipitating factor (65%), mostly infections (49%). Clinically, CAPS was characterized by several organ involvement affecting kidneys (73%), lungs (60%), brain (56%), heart (50%), and skin (47%). Lupus anticoagulant, IgG anticardiolipin and IgG anti-β2-glycprotein antibodies were the most often implicated antiphospholipid antibodies (83%, 81% and 78% respectively). Mortality accounted for 37% of episodes of CAPS.Several clinical differences could be observed based on the age of presentation and its association to SLE. Those cases triggered by a malignancy tended to occur in older patients, while CAPS episodes in young patients were associated with an infectious trigger and peripheral vessels involvement. Additionally, CAPS associated with SLE were more likely to have severe cardiac and brain involvement leading to a higher mortality (48%).ConclusionAlthough the presentation of CAPS is characterized by multiorgan thrombosis and failure, clinical differences among patients exist based on age and underlying chronic diseases, e.g. malignancy, SLE.



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The association of other autoimmune diseases in patients with autoimmune thyroiditis: Review of the literature and report of a large series of patients

Publication date: Available online 15 September 2016
Source:Autoimmunity Reviews
Author(s): Poupak Fallahi, Silvia Martina Ferrari, Ilaria Ruffilli, Giusy Elia, Marco Biricotti, Roberto Vita, Salvatore Benvenga, Alessandro Antonelli
We have evaluated prospectively the prevalence of other autoimmune disorders in outpatient clinic in 3069 consecutive patients with diagnosed chronic autoimmune thyroiditis (AT), with respect to two age- and sex-matched control groups: a) a control group of 1023 subjects, extracted from a random sample of the general population without thyroid disorders; b) 1023 patients with non-toxic multinodular goiter extracted from the same random sample of the general population, with similar odine intake. The results of our study demonstrate a significant increase of the prevalence of autoimmune disorders in AT patients (with respect to both controls), for the following diseases: chronic autoimmune gastritis (CAG), vitiligo (Vit), rheumatoid arthritis, polymialgia rheumatica (Polym), celiac disease, diabetes, sjogren disease, multiple sclerosis, systemic lupus erythematosus, sarcoidosis, alopecia, psoriathic arthritis, systemic sclerosis, HCV-related cryoglobulinemia. While the statistical analysis reached near the significance for Addison's disease and ulcerative colitis. Interestingly, the association of three autoimmune disorders was observed almost exclusively in AT patients, and the most frequent associations were AT+CAG+Vit and AT+CAG+Polym.We suggest that patients with AT who remain unwell, or who develop new not specific symptoms (despite adequate treatment) should be screened for other autoimmune disorders, avoiding the delay in the diagnosis of these disorders.



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Prevalence and predictors of valvular heart disease in patients with systemic lupus erythematosus

Publication date: Available online 15 September 2016
Source:Autoimmunity Reviews
Author(s): Florencia Vivero, Cristina Gonzalez-Echavarri, Beatriz Ruiz, Irene Maderuelo, Guillermo Ruiz-Irastorza
ObjectivesWe aimed to study the frequency, severity and predictors of valvular heart disease (VHD) in our lupus cohort.Material and Methods211 patients were included. A transthoracic echocardiogram was used for this study. Significant valvular lesions were classified into two groups: valvular thickening and valvular dysfunction. Univariate logistic regression was performed in order to find associations with valvular thickening and dysfunction. Those variables with a p value ≤0.1 in the univariate analysis were subsequently included in multiple logistic regression models.ResultsSignificant valve lesions were found in 53 patients (25%). The independent predictors of valvular thickening were the age at the time of the echocardiogram (OR 1.05, 95% CI 1.02–1.7), lymphopenia (OR 3.6, 95%CI 1.4–9.5), thrombocytopenia (OR 2.65, 95%CI 1.24–5.72), and anti-Sm antibodies (OR 3.28, 95%CI 1.44–7.33). The independent predictors of valvular dysfunction were age at the time of the echocardiogram (OR 1.045, 95%CI 1.009–1.083), thrombocytopenia (OR 5, 95%CI 1.66–14.86), hypertension (OR 6.2, 95%CI 2.1–18.4) and aPL (OR 6.2, 95%CI 2.1–18.4). Regarding the latter, the independent relation with valvular dysfunction was only seen for the double positivity aCL/LA, (OR 13.2, 95%CI 3.8–45.2, p<0.0001).ConclusionsOur study confirms the high prevalence of significant VHD in SLE patients. Clinical variables related with persistent inflammatory activity were associated with VHD. The association between VHD and aPL positivity was confirmed. Double-positive aCL/LA patients were most likely to suffer from valvular dysfunction.



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Inactivation of p27kip1 promoted nonspecific inflammation by enhancing macrophage proliferation in islet transplantation

Endocrinology, Early Release.


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Foxo1 is Required for Normal Somatotrope Differentiation

Endocrinology, Early Release.


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The Bone Sparing Effects of 2-methoxyestradiol are Mediated via Estrogen Receptor-α in Male Mice

Endocrinology, Early Release.


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Timed Inhibition of Orexin System by Suvorexant Improved Sleep and Glucose Metabolism in Type 2 Diabetic db/db Mice

Endocrinology, Early Release.


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Operative Techniques in Otolaryngology-Head and Neck Surgery: Sep-2016 (Volume 27, Issue 3)

Please add journals@mail.elsevierhealth.com to your Safe Senders list. If you have trouble viewing this message, click here to view it online.

JOURNAL HOME      |         RSS      |      SUBSCRIBE TO JOURNAL     Editorial Board      Contents      Future and recent issues      Information for authors      Preface  David Goldenberg, Brian Saunders      Anatomy and embryology of the parathyroid gland  Joseph Scharpf, Natalia Kyriazidis, Dipti Kamani, Gregory Randolph      Essentials of parathyroid imaging  Andrew J. Redmann, David L. Steward      Surgical exploration for hyperparathyroidism  Shivani Shah-Becker, David Goldenberg      Surgery for secondary hyperparathyroidism  Brian D. Saunders      Surgical management of parathyroid carcinoma  Phillip K. Pellitteri      Minimally invasive parathyroidectomy  Shivani Shah-Becker, David Goldenberg      Focused lateral approach for targeted parathyroidectomy  Maisie Shindo      Parathyroid surgery for inherited endocrinopathies  Joshua Davies, Gerard M. Doherty      Robot-assisted parathyroidectomy  Daniah Bu Ali, Fadi Murad, Sang-Wook Kang, Emad Kandil      Revision parathyroid surgery  Alfred A. Simental, Robert L. Ferris      Nuances in parathyroid evaluation and management  David J. Terris, William S. Duke      Frontmatter     Masthead

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Physical activity and lifestyle improvement in the management of psoriasis

http://ift.tt/2crvHxl

Tyrosinase inhibitors from marine algae

Linked Article: Kwak et al. Br J Dermatol 2016; 175:501–511.

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Editor's Choice

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Worth more than their weight in gold?

Summary

The cost of many topical prescription medications has increased in recent years. We have calculated that the cost per unit now exceeds that of many ?valuable' consumer items.

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Suicide and psoriasis: no longer an association

Linked Article: Egeberg et al. Br J Dermatol 2016; 175:493–500.

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Protein kinases and phophodiesterases in psoriasis: time to refocus on biochemistry

Linked Article: Snape et al. Br J Dermatol 2016; 175:479–486.

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Repigmentation patterns in vitiligo: where do we stand?

Linked Article: Gan et al. Br J Dermatol 2016; 175:555–560.

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Turning up the heat: mechanistic insights into thermal photodynamic therapy

Linked Article: Mamalis et al. Br J Dermatol 2016; 175:512–519.

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Case reports in dermatology: loved by clinicians, loathed by editors, and occasionally important

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Another guardian against alopecia areata?

Linked Article: Bertolini et al. Br J Dermatol 2016; 175:531–541.

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Image Gallery: Amyloidosis of the tongue associated with haemodialysis

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Heat urticaria – easy to diagnose but also to misdiagnose

Linked Article: Pezzolo et al. Br J Dermatol 2016; 175:473–478.

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Plain language summaries

Linked Article: Quist et al. Br J Dermatol 2016; 175:520–530.

Linked Article: Rencz et al. Br J Dermatol 2016; 175:561–571.

Linked Article: Egeberg et al. Br J Dermatol 2016; 175:487–492.

Linked Article: Bobotsis et al. Br J Dermatol 2016; 175:464–472.

Linked Article: van Lee et al. Br J Dermatol 2016; 175:549–554.

Linked Article: Egeberg et al. Br J Dermatol 2016; 175:493–500.

Linked Article: Gan et al. Br J Dermatol 2016; 175:555–560.

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Stem cell markers of skin appendages in human skin tumours

Linked Article: Quist et al. Br J Dermatol 2016; 175:520–530.

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A changing treatment paradigm: the role of palliative care in metastatic melanoma

Linked Article: Gallais Sérézal et al. Br J Dermatol 2016; 175:583–592.

http://ift.tt/2cZrCFQ

Promoter DNA methylation of CDO1 gene and its clinical significance in esophageal squamous cell carcinoma

Summary

We have demonstrated that CDO1 methylation is frequently found in various cancers, including esophageal squamous cell carcinoma (ESCC), but its clinical relevance has remained elusive. CDO1 methylation was investigated in 169 ESCC patients who underwent esophagectomy between 1996 and 2007. CDO1 methylation was assessed by Q-MSP (quantitative methylation specific PCR), and its clinical significance, including its relationship to prognosis, was analyzed. (i) The median TaqMeth value of CDO1 methylation was 9.4, ranging from 0 to 279.5. CDO1 methylation was significantly different between cStage I and cStage II/III (P = 0.02). (ii) On the log-rank plot, the optimal cut-off value was determined to be 8.9; ESCC patients with high CDO1 methylation showed a significantly worse prognosis than those with low CDO1 methylation (P = 0.02). (iii) A multivariate Cox proportional hazards model identified only CDO1 hypermethylation as an independent prognostic factor (HR 2.00, CI 1.09–3.78, P = 0.03). (iv) CDO1 hypermethylation stratified ESCC patients' prognosis in cStage II/III for both neoadjuvant chemo(radio)therapy (NAC)-positive and NAC-negative cases. Moreover, the CDO1 methylation level was significantly lower in cases with Grade 2/3 than in those with Grade 0/1 (P = 0.02) among cStage II/III ESCC patients with NAC. Promoter DNA hypermethylation of CDO1 could be an independent prognostic factor in ESCC; it may also reflect NAC eradication of tumor cells in the primary tumors.

http://ift.tt/2cgESmq

Systematic review of the use of endo-luminal topical negative pressure in oesophageal leaks and perforations

Summary

Topical negative pressure is widely used in the management of superficial wounds. The use of this technology in the management of oesophageal perforations is becoming increasingly common. This systematic review aims to capture available evidence about its use in this setting. Medline and Embase were searched using MeSH terms and free text: esophageal perforation; esophageal injury; vacuum assisted closure; vacuum therapy device; esophagus; wounds penetrating; esophageal perforation; wound healing; negative pressure wound therapy. Searches were carried out between April and November 2015. Case series, cohort trials and controlled trials were included. Additional studies were found by hand searching reference lists. Eleven studies met the inclusion criteria with 180 patients. Nine of the studies were case series and two were retrospective comparisons of negative pressure with stents or clips. Healing of the perforation occurred in 163/179 patients and the overall mortality was 12.8%. Compared with published data on mortality from oesophageal perforation, the application of negative pressure appears to be beneficial. The studies are, however, limited to case series and retrospective cohort studies. The number of patients in each study is small and in the absence of randomized trials demonstrating a lack of bias firm conclusions cannot be made.

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Comparison of three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, and volumetric-modulated arc therapy in the treatment of cervical esophageal carcinoma

Summary

The aim of this study was to evaluate the effectiveness and toxicities of three-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), and volumetric-modulated arc therapy (VMAT) in patients with cervical esophageal cancer. Specifically, we asked whether technological advances conferred an advantage with respect to the clinical curative effect. Seventy-eight patients with cervical esophageal cancer treated with definitive radiotherapy with or without concomitant chemotherapy at our institution between 2007 and 2014 were enrolled in the study: 26 received 3DCRT, 30 were treated with IMRT, and 22 underwent VMAT. Kaplan–Meier analysis and the Cox proportional hazard model were used to analyze overall survival (OS) and failure-free survival (FFS). Treatment-related toxicity was also assessed. For all patients, the 2-year OS and FFS rates were 56.2 and 53.9%, respectively. The 2-year OS for the 3DCRT, IMRT, and VMAT groups was 53.6, 55.6, and 60.6%, respectively (P = 0.965). The corresponding 2-year FFS rates were 49.5, 56.7, and 60.1% (P = 0.998). A univariate analysis of the complete response to treatment showed an advantage of treatment modality with respect to OS (P < 0.001). The development of acute hematologic toxicity was not significantly different among the three groups. The survival rates of patients treated with IMRT and VMAT were comparable to the survival of patients administered 3DCRT, while lower lung mean dose, V20, maximum dose of brachial plexus and spinal cord. Grade 1 radiation pneumonitis occurred significantly less in patients treated with IMRT and VMAT than with 3DCRT (P = 0.011). A complete response was the most important prognostic factor of the patients with cervical esophageal cancer.

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Nasogastric decompression following esophagectomy: a systematic literature review and meta-analysis

Summary

Routine use of nasogastric tubes for gastric decompression has been abolished in nearly all types of gastro-intestinal surgery after introduction of enhanced recovery after surgery programs. However, in esophagectomy the routine use of nasogastric decompression is still a matter of debate. To determine the effects of routine nasogastric decompression following esophagectomy compared with early or peroperative removal of the nasogastric tube on pulmonary complications, anastomotic leakage, mortality, and postoperative recovery. A systematic literature review and meta-analysis of studies comparing early or peroperative versus late removal of nasogastric tubes. A total of seven comparative studies were included (n = 608). In two randomized trials, and one retrospective cohort study, peroperative removal of the nasogastric tube was compared with routine nasogastric decompression. In one randomized trial early removal of the nasogastric tube (on postoperative day 2) was compared with removal of the nasogastric tube on the 6th–10th postoperative day. In the remaining three trials a fast-track protocol without a nasogastric tube was compared with conventional care with a nasogastric tube during the first postoperative days. Peroperative or early removal of the nasogastric tube did not result in a significantly different rate of anastomotic leakage, pulmonary complications or mortality in individual studies, nor in the meta-analysis. In the meta-analysis, hospital stay was significantly shorter with peroperative or early removal of the nasogastric tube when all studies were included, but not when the meta-analysis was limited to randomized trials. This systematic review did not find a difference in adverse outcomes between nasogastric decompression or no nasogastric decompression following esophagectomy.

http://ift.tt/2cAcZmG

Searching for the most effective thyrotropin (TSH) threshold to rule-out autonomously functioning thyroid nodules in iodine deficient regions

Abstract

The purpose of this study is to evaluate the distribution of thyrotropin (TSH) values in patients with autonomously functioning thyroid nodules and to set a TSH threshold above which thyroid scintigraphy would be obviated. Four hundred fifty one patients were included in the present study. Inclusion criteria were age > 18 years, TSH levels between 0.40 and 4.0 mIU/L, detection of a single solid or predominantly solid thyroid nodule >10 mm in the longest diameter. Thyroid ultrasound and thyroid scintigraphy with ^99mTc-pertechnetate were performed concurrently in all patients. Among 451 enrolled patients, 173 (38 %) had an autonomously functioning thyroid nodules, of which 137 (79 %) with a normal TSH level. Demographic data and nodules' volume were not significantly different in patients with autonomously functioning thyroid nodules and non-functioning nodules, respectively. However, TSH levels were nonetheless significantly lower in patients with autonomously functioning thyroid nodules compared to those with non-functioning nodules (p < 0.001). Adopting a TSH cutoff level at 2.38 mUI/L, all autonomously functioning thyroid nodules were correctly identified (i.e., 100 % sensitivity) with a 100 % negative predictive value. Our study showed a very high prevalence of autonomously functioning thyroid nodules in mildly iodine-deficient regions and confirmed that serum TSH is not an effective screening test to diagnose an autonomously functioning thyroid nodules. Our data add arguments in favor of the first-line use of thyroid scintigraphy to assess thyroid nodules, at least in iodine deficient areas. As all scintigraphically detected autonomously functioning thyroid nodules had a TSH level below 2.38 mUI/L, a thyroid scintigraphy should be omitted when higher TSH values are found in patients carrying a thyroid nodule.

http://ift.tt/2cAbVPW

Distinct subpopulations of hepatitis C virus infectious cells with different levels of intracellular hepatitis C virus core protein

Publication date: Available online 14 September 2016
Source:The Kaohsiung Journal of Medical Sciences
Author(s): Shu-Chi Wang, Jeng-Fu Yang, Chao-Ling Wang, Chung-Feng Huang, Yu-Yin Lin, Yi-You Chen, Chung-Ting Lo, Po-Yen Lee, Kuan-Ta Wu, Chia-I. Lin, Meng-Hsuan Hsieh, Hung-Yi Chuang, Chi-Kung Ho, Ming-Lung Yu, Chia-Yen Dai
Chronic infection by hepatitis C virus (HCV) is a major risk factor for the development of hepatocellular carcinoma (HCC). Despite the clear clinical importance of virus-associated HCC, the underlying molecular mechanisms remain largely unclarified. Oxidative stress, in particular, DNA lesions associated with oxidative damage, plays a major role in carcinogenesis, and is strongly linked to the development of many cancers, including HCC. However, in identifying hepatocytes with HCV viral RNA, estimates of the median proportion of HCV-infected hepatocytes have been found as high as 40% in patients with chronic HCV infection. In order to explore the gene alternation and association between different viral loads of HCV-infected cells, we established a method to dissect high and low viral load cells and examined the expression of DNA damage-related genes using a quantitative polymerase chain reaction array. We found distinct expression patterns of DNA damage-related genes between high and low viral load cells. This study provides a new method for future study on virus-associated gene expression research.



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The Multiscale Entropy: guidelines for use and interpretation in brain signal analysis

Publication date: Available online 14 September 2016
Source:Journal of Neuroscience Methods
Author(s): Julie Courtiol, Dionysios Perdikis, Spase Petkoski, Viktor Müller, Raoul Huys, Rita Sleimen-Malkoun, Viktor K. Jirsa
BackgroundMultiscale Entropy (MSE) estimates the predictability of a signal over multiple temporal scales. It has been recently applied to study brain signal variability, notably during aging. The grounds of its application and interpretation remain unclear and subject to debate.MethodWe used both simulated and experimental data to provide an intuitive explanation of MSE and to explore how it relates to the frequency content of the signal, depending on the amount of (non)linearity and stochasticity in the underlying dynamics.ResultsThe scaling and peak-structure of MSE curves relate to the scaling and peaks of the Power Spectrum in the presence of linear autocorrelations. MSE also captures nonlinear autocorrelations and their interactions with stochastic dynamical components. The previously reported crossing of young and old adults' MSE curves for EEG data, appears to be mainly due to linear stochastic processes, and relates to young adults' EEG dynamics exhibiting a slower time constant.Comparison with existing methodsWe make the relationship between MSE curve and Power Spectrum as well as with a linear autocorrelation measure, namely Multiscale Root-Mean-Square-Successive-Difference, more explicit. MSE allows gaining insight into the time-structure of brain activity fluctuations. Its combined use with other metrics could prevent any misleading interpretations with regard to underlying stochastic processes.ConclusionsAlthough not straightforward, when applied to brain signals, the features of MSE curves can be linked to their power content and provide information about both linear and nonlinear autocorrelations that are present therein.



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The path to economic independence among survivors of intimate partner violence: A critical review of the literature and courses for action

Publication date: Available online 14 September 2016
Source:Aggression and Violent Behavior
Author(s): Einat Peled
Public policy encourages women, including survivors of intimate partner violence (IPV), to develop economic independence. However, a critical review of the literature in this field reveals that IPV survivors face unique obstacles in doing so: active and violent intervention by the perpetrator; damage to the survivor's health due to prolonged subjection to violence; and structural obstacles. A background of gendered violence, low socioeconomic status, and belonging to a marginalized ethnic or racial group, may further intersect with the direct and indirect influences of that violence, resulting in even greater obstacles to the development of economic independence. The article concludes with a discussion of how existing intervention programs for developing economic independence among survivors of IPV meet those obstacles, and a framework for intervention in this domain. (126 words)



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Role and therapeutic potential of CDK12 in human cancers

Publication date: Available online 14 September 2016
Source:Cancer Treatment Reviews
Author(s): Rosaria Chilà, Federica Guffanti, Giovanna Damia
Phosphorylation of the RNA polymerase II C-terminal domain by cyclin-dependent kinases (CDK) is important for productive transcription. Deregulated transcription-CDKs have been reported in different human cancers. Until recently CDK9 was the only transcription-CDK with a causative role in cancer, but evidence is cumulating of the importance of CDK12. This review summarizes the role of CDK12 in transcription and RNA processing, in maintaining genomic stability/integrity and in tumorigenesis. CDK12 mutations have been reported in many cancers and have been suggested as a cause of defective DNA repair in ovarian carcinoma. CDK12 may have a role as a new therapeutic target in oncology.



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Novel antioxidant capability of titanium induced by UV light treatment

Publication date: November 2016
Source:Biomaterials, Volume 108
Author(s): Takeshi Ueno, Takayuki Ikeda, Naoki Tsukimura, Manabu Ishijima, Hajime Minamikawa, Yoshihiko Sugita, Masahiro Yamada, Noriyuki Wakabayashi, Takahiro Ogawa
The intracellular production of reactive oxygen species (ROS) is a representative form of cellular oxidative stress and plays an important role in triggering adverse cellular events, such as the inflammatory reaction and delayed or compromised differentiation. Osteoblastic reaction to titanium with particular focus on ROS production remains unknown. Ultraviolet (UV) light treatment improves the physicochemical properties of titanium, specifically the induction of super hydrophilicity and removal of hydrocarbon, and eventually enhances its osteoconductivity. We hypothesized that there is a favorable regulatory change of ROS production within osteoblasts in contact with UV-treated titanium. Osteoblasts were cultured on titanium disks with or without UV-pretreatment. The intracellular production of ROS was higher on acid-etch-created rough titanium surfaces than on machine-prepared smooth ones. The ROS production was reduced by 40–50% by UV pretreatment of titanium regardless of the surface roughness. Oxidative DNA damage, as detected by 8-OHdG expression, was alleviated by 50% on UV-treated titanium surfaces. The expression of inflammatory cytokines was consistently lower in osteoblasts cultured on UV-treated titanium. ROS scavenger, glutathione, remained more without being depleted in osteoblasts on UV-treated titanium. Bio-burden test further showed that culturing osteoblasts on UV-treated titanium can significantly reduce the ROS production even with the presence of hydrogen peroxide, an oxidative stress inducer. These data suggest that the intracellular production of ROS and relevant inflammatory reaction, which unavoidably occurs in osteoblasts in contact with titanium, can be significantly reduced by UV pretreatment of titanium, implying a novel antioxidant capability of the particular titanium.



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Aqueous synthesized quantum dots interfere with the NF-κB pathway and confer anti-tumor, anti-viral and anti-inflammatory effects

Publication date: November 2016
Source:Biomaterials, Volume 108
Author(s): Zhilin Hu, Bin Song, Lei Xu, Yiling Zhong, Fei Peng, Xiaoyuan Ji, Fang Zhu, Chengkui Yang, Jinying Zhou, Yuanyuan Su, Suning Chen, Yao He, Sudan He
The NF-κB pathway plays crucial roles in inflammatory responses and cell survival. Aberrant constitutive NF-κB activation is associated with various human diseases including cancer and inflammatory and auto-immune diseases. Consequently, it is highly desirable to develop new kinds of inhibitors, which are highly efficacious for blocking the NF-κB pathway. In this study, by using a typical kind of aqueous synthesized quantum dots (QDs), i.e., CdTe QDs, as a model, we for the first time demonstrated that the QDs could selectively affect the cellular nuclear factor-κB (NF-κB) signaling pathway, but do not affect the AKT or ERK pathways. Typically, the QDs efficiently inhibited the activation of IKKα and IKKβ, resulting in the suppression of both the canonical and the non-canonical NF-κB signaling pathways. Inhibition of NF-κB by QDs downregulates anti-apoptotic genes and promotes apoptosis in cancer cells. The QDs induced NF-κB inhibition and cytotoxicity could be blocked by N-acetylcysteine due to the reduced cellular uptake of QDs. Importantly, inhibition of NF-κB by QDs displayed promising effects against the viral replication and in vivo bacterial endotoxin-induced inflammatory responses. These data suggest the QDs as potent inhibitors of the NF-κB signaling pathway, both in vitro and in vivo. Our findings highlight the potential of using QDs in the development of anti-cancer, anti-viral, and anti-inflammatory approaches, and also facilitate better understanding of QDs-related cellular behavior under the molecular level.



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ADSA Member News . . .

Publication date: October 2016
Source:Journal of Dairy Science, Volume 99, Issue 10





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Chemical and ruminal in vitro evaluation of Canadian canola meals produced over 4 years1

Publication date: October 2016
Source:Journal of Dairy Science, Volume 99, Issue 10
Author(s): Glen A. Broderick, Stefania Colombini, Sara Costa, Mehmet A. Karsli, Antonio P. Faciola
To test the effects of year and processing plant on the nutritional value of canola meal (CM), 3 CM samples/yr were collected from each of 12 Canadian production plants over 4yr (total=144). Samples of CM were analyzed for differences in chemical composition and for in vitro ruminal protein degradability using the Michaelis-Menten inhibitor in vitro (MMIIV) method. In the MMIIV method, protein degradation rate (kd) was estimated by 2 methods: from net release (i.e., blank corrected) of (1) ammonia plus AA determined by o-phthaldialdehyde fluorescence (OPAF) assay or (2) ammonia, AA, plus oligopeptides determined by o-phthaldialdehyde absorbance (OPAA) assay; rumen-undegradable protein (RUP) was computed assuming passage rates of 0.16 and 0.06/h for, respectively, soluble and insoluble protein. Casein, solvent soybean meal (SSBM), and expeller soybean meal (ESBM) were included in all incubations as standard proteins. Differences among years and plants were assessed using the mixed procedures of SAS. Small but significant differences were found in CM among years for chemical composition, including N solubility; some of these differences may have been related to changes in our analytical methods over time. However, adjustment of degradation activity of individual in vitro incubations based on the mean degradation activity over all incubations yielded kd and RUP that did not differ by year using either assay. Simultaneously incubating CM samples from 2yr in the same in vitro runs confirmed that no year effects existed for kd or RUP. Differences existed in chemical composition of CM among the 12 processing plants over the 4yr of sample collection. Moreover, consistent differences in kd and RUP were observed among plants: kd ranged from 0.069 to 0.113/h (OPAA assay) and 0.075 to 0.120/h (OPAF assay), and RUP estimates ranged from 51 to 43% (OPAA assay) and 49 to 41% (OPAF assay). Regression of kd on insoluble N content of CM yielded correlation coefficients (R²)=0.40 (OPAA assay) and 0.42 (OPAF assay), and regressions of kd on NDIN and N-fraction B3 yielded R²<0.02. Mean estimates from both OPAA and OPAF assays for casein, SSBM, ESBM, and CM were, respectively, kd=0.764, 0.161, 0.050, and 0.093/h and RUP=18, 33, 56, and 45%. A range of 8 percentage units from lowest to highest RUP suggests that substantial differences exist in metabolizable protein content of CM produced by different processing plants.



http://ift.tt/2d06r26

Using protein-fatty acid complexes to improve vitamin D stability

Publication date: October 2016
Source:Journal of Dairy Science, Volume 99, Issue 10
Author(s): Jannik Nedergaard Pedersen, Henriette Søster Frislev, Jan Skov Pedersen, Daniel E. Otzen
Liprotides are complexes between lipids and partially denatured proteins in which the protein forms a stabilizing shell around a fatty acid micelle core. We have previously shown that liprotides stabilize small aliphatic molecules such as retinal and tocopherol by sequestering these molecules in the fatty acid core. This opens up the use of liprotides to formulate food additives. Here, we expand our investigations to the large and bulky molecule vitamin D3 (vitD), motivated by the population-wide occurrence of vitD deficiency. We prepared liprotides using different proteins and fatty acids and evaluated their ability to protect vitD upon exposure to heating or intense UV light. Additionally, we determined the stability of liprotides toward pH, Ca²⁺, and BSA. The best results were obtained with liprotides made from α-lactalbumin and oleate. These liprotides were able to completely solubilize vitD, increase the stability toward UV light 9-fold, and increase the long-term stability at 37°C up to 1,000-fold. Native α-lactalbumin binds Ca²⁺, making Ca²⁺ potentially disruptive toward liprotides. However, liprotides prepared by incubation at 80°C were stable toward Ca²⁺, in contrast to those made at 20°C. Nevertheless, the fatty acid binding protein BSA reduced the ability of both liprotides to protect vitD; the amount of vitD remianing after 20d at 20°C decreased from 79±3% in the absence of BSA to 49±4 and 23±3% in the presence of BSA for liprotides made at 80 and 20°C, respectively. Both classes of liprotides were able to release their vitD content, as demonstrated by the transfer of vitD encapsulated in liprotides to phospholipid vesicles. Importantly, liprotides were not stable at pH 6 and below, limiting the useful pH range of the liprotides to >pH 6. Our results indicate that vitD may be encapsulated and stabilized for enrichment of clear beverages at neutral pH to improve the intake and bioavailability of vitD.



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Interpretive Summaries, October 2016

Publication date: October 2016
Source:Journal of Dairy Science, Volume 99, Issue 10





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Assessment of dietary ratios of red clover and corn silages on milk production and milk quality in dairy cows

Publication date: October 2016
Source:Journal of Dairy Science, Volume 99, Issue 10
Author(s): J.M. Moorby, N.M. Ellis, D.R. Davies
Twenty-four multiparous Holstein-Friesian dairy cows were used in a replicated 3×3 Latin square changeover design experiment to test the effects of changing from corn (Zea mays) silage to red clover (Trifolium pratense) silage in graded proportions on feed intakes, milk production, and whole-body N and P partitioning. Three dietary treatments with ad libitum access to 1 of 3 forage mixtures plus a standard allowance of 4kg/d dairy concentrates were offered. The 3 treatment forage mixtures were, on a dry matter (DM) basis: (1) R10: 90% corn silage and 10% red clover silage, (2) R50: 50% corn silage and 50% red clover silage, and (3) R90: 10% corn silage and 90% red clover silage. In each of 3 experimental periods, there were 21d for adaptation to diets, and 7d for measurements. Diet crude protein intakes increased, and starch intakes decreased, as the silage mixture changed from 90% corn to 90% red clover, although the highest forage DM intakes and milk yields were achieved on diet R50. Although milk fat yields were unaffected by diet, milk protein yields were highest with the R 0250 diet. Whole-body partitioning of N was measured in a subset of cows (n=9), and both the daily amount and proportion of N consumed that was excreted in feces and urine increased as the proportion of red clover silage in the diet increased. However, the apparent efficiency of utilization of feed N for milk protein production decreased from 0.33g/g for diet R10 to 0.25g/g for diet R90. The urinary excretion of purine derivatives (sum of allantoin and uric acid) tended to increase, suggesting greater flow of microbial protein from the rumen, as the proportion of red clover silage in the diet increased, and urinary creatinine excretion was affected by diet. Fecal shedding of E. coli was not affected by dietary treatment. In conclusion, even though microbial protein flow may have been greatest from the R 0450 diet, optimum feed intakes and milk yields were achieved on a diet that contained a 1:1 DM mixture of corn and red clover silages.



http://ift.tt/2cyVaI8

Effect of standardizing the lactose content of cheesemilk on the properties of low-moisture, part-skim Mozzarella cheese

Publication date: October 2016
Source:Journal of Dairy Science, Volume 99, Issue 10
Author(s): A.C. Moynihan, S. Govindasamy-Lucey, M. Molitor, J.J. Jaeggi, M.E. Johnson, P.L.H. McSweeney, J.A. Lucey
The texture, functionality, and quality of Mozzarella cheese are affected by critical parameters such as pH and the rate of acidification. Acidification is typically controlled by the selection of starter culture and temperature used during cheesemaking, as well as techniques such as curd washing or whey dilution, to reduce the residual curd lactose content and decrease the potential for developed acidity. In this study, we explored an alternative approach: adjusting the initial lactose concentration in the milk before cheesemaking. We adjusted the concentration of substrate available to form lactic acid. We added water to decrease the lactose content of the milk, but this also decreased the protein content, so we used ultrafiltration to help maintain a constant protein concentration. We used 3 milks with different lactose-to-casein ratios: one at a high level, 1.8 (HLC, the normal level in milk); one at a medium level, 1.3 (MLC); and one at a low level, 1.0 (LLC). All milks had similar total casein (2.5%) and fat (2.5%) content. We investigated the composition, texture, and functional and sensory properties of low-moisture, part-skim Mozzarella manufactured from these milks when the cheeses were ripened at 4°C for 84d. All cheeses had similar pH values at draining and salting, resulting in cheeses with similar total calcium contents. Cheeses made with LLC milk had higher pH values than the other cheeses throughout ripening. Cheeses had similar moisture contents. The LLC and MLC cheeses had lower levels of lactose, galactose, lactic acid, and insoluble calcium compared with HLC cheese. The lactose-to-casein ratio had no effect on the levels of proteolysis. The LLC and MLC cheeses were harder than the HLC cheese during ripening. Maximum loss tangent (LT), an index of cheese meltability, was lower for the LLC cheese until 28d of ripening, but after 28d, all treatments exhibited similar maximum LT values. The temperature where LT=1 (crossover temperature), an index of softening point during heating, was higher for MLC and LLC cheese at 56 and 84d of ripening. The LLC cheese also had lower blister color and less stretch than MLC and HLC cheese. Adjusting the lactose content of milk while maintaining a constant casein level was a useful technique for controlling cheese pH, which affected the texture, functionality, and sensory properties of low-moisture, part-skim Mozzarella cheese.



http://ift.tt/2d056Zl

Enhancing flora balance in the gastrointestinal tract of mice by lactic acid bacteria from Chinese sourdough and enzyme activities indicative of metabolism of protein, fat, and carbohydrate by the flora

Publication date: October 2016
Source:Journal of Dairy Science, Volume 99, Issue 10
Author(s): Dong Yang, Xiaomin Yu, Yaoping Wu, Xingxing Chen, Hua Wei, Nagendra P. Shah, Feng Xu
In this study, we investigated the effect of administration of 5 strains of lactic acid bacteria (LAB) isolated from traditional Chinese sourdough on the flora balance of gastrointestinal tract of mice. We specifically measured Enterococcus, Enterobacter, Bacteroides, and Lactobacillus by plate count and real-time PCR methods, and α-glucosidase, lactate dehydrogenase, esterase, and aminopeptidase activities as indicative of metabolism of sugar, fat, and protein from LAB isolated from feces of mice in vitro. The results showed that administration of Lactobacillus acidophilus LAC0201 and Lactobacillus fermentum LFE0302 lowered the uricacid index of serum. Lactobacillus acidophilus LAC0201, L. fermentum LFE0302, as well as Lactobacillus curvatus LCU0401 administration resulted in a reduction in the opportunistic pathogens (i.e., Enterococcus and Enterobacter), meanwhile, administration of L. fermentum LFE0302 and Lactobacillus sp. ULA0104 resulted in an increase in the counts of Lactobacillus. Lactobacillus fermentum LFE0302 administration increased starch digestion of intestinal flora after 4wk of feeding and also resulted in increased α-glucosidase activity in the intestinal flora after 3wk of feeding. We found a similar trend in esterase activity after administration of L. acidophilus LAC0201 for 3wk. Hence, our study suggested that LAB from Chinese sourdough might be used as potential probiotics to strengthen the flora balance in gastrointestinal tract and positively change the metabolism of nutrients through bacterial enzyme activities.



http://ift.tt/2cyV6Ig

Rapid, sensitive, and reproducible screening of liquid milk for adulterants using a portable Raman spectrometer and a simple, optimized sample well

Publication date: October 2016
Source:Journal of Dairy Science, Volume 99, Issue 10
Author(s): M.K. Nieuwoudt, S.E. Holroyd, C.M. McGoverin, M.C. Simpson, D.E. Williams
We have developed a powerful general spectroscopic method for rapidly screening liquid milk for adulterants by combining reflective focusing wells simply fabricated in aluminum with a small, portable Raman spectrometer with a focusing fiber optic probe. Hemispherical aluminum sample wells were specially designed to optimize internal reflection and sampling volume by matching the focal length of the mirror to the depth of focus of the laser probe. The technique was tested on milk adulterated with 4 different nitrogen-rich compounds (melamine, urea, dicyandiamide, and ammonium sulfate) and sucrose. No sample preparation of the milk was needed, and the total analysis time was 4min. Reliable sample presentation enabled average reproducibility of 8% residual standard deviation. The limit of detection interval measured from partial least squares calibrations ranged between 140 and 520mg/L for the 4 N-rich compounds and between 7,000 and 36,000mg/L (0.7–3.6%) for sucrose. The portability of the system and the reliability and reproducibility of this technique open opportunities for general, reagentless screening of milk for adulterants at the point of collection.



http://ift.tt/2d052ZB

Bacterial microbiota compositions of naturally fermented milk are shaped by both geographic origin and sample type

Publication date: October 2016
Source:Journal of Dairy Science, Volume 99, Issue 10
Author(s): Z. Zhong, Q. Hou, L. Kwok, Z. Yu, Y. Zheng, Z. Sun, B. Menghe, H. Zhang
Naturally fermented dairy products contain a rich microbial biodiversity. This study aimed to provide an overview on the bacterial microbiota biodiversity of 85 samples, previously collected across a wide region of China, Mongolia, and Russia. Data from these 85 samples, including 55 yogurts, 18 naturally fermented yak milks, 6 koumisses, and 6 cheeses, were retrieved and collectively analyzed. The most prevalent phyla shared across samples were Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria, which together accounted for 99% of bacterial sequences. The predominant genera were Lactobacillus, Lactococcus, Streptococcus, Acetobacter, Acinetobacter, Leuconostoc, and Macrococcus, which together corresponded to 96.63% of bacterial sequences. Further multivariate statistical analyses revealed significant differences in the microbiota structure across sample geographic origin and type. First, on the principal coordinate score plot, samples representing the 3 main sample collection regions (Russia, Xinjiang, and Tibet) were mostly located respectively in the upper left, lower right, and lower left quadrants, although slight overlapping occurred. In contrast, samples from the minor sampling areas (Inner Mongolia, Mongolia, Gansu, and Sichuan) were predominantly distributed in the lower left quadrant. These results suggest a possible association between sample geographical origin and microbiota composition. Second, bacterial microbiota structure was stratified by sample type. In particular, the microbiota of cheese was largely distinct from the other sample types due to its high abundances of Lactococcus and Streptococcus. The fermented yak milk microbiota was most like that of the yogurts. Koumiss samples had the lowest microbial diversity and richness. In conclusion, both geographic origin and sample type shape the microbial diversity of naturally fermented milk.



http://ift.tt/2cyTzBQ

Fish oil-induced milk fat depression and associated downregulation of mammary lipogenic genes in dairy ewes

Publication date: October 2016
Source:Journal of Dairy Science, Volume 99, Issue 10
Author(s): D. Carreño, G. Hervás, P.G. Toral, T. Castro-Carrera, P. Frutos
Several studies in dairy cows have shown a relationship between milk fat depression (MFD) and alterations caused in lipogenic gene expression by dietary nutrients. However, information on small ruminants is not only scarce but also inconsistent. Therefore, this experiment was conducted in dairy ewes to study the effect of a diet known to induce MFD on milk fatty acid (FA) composition and mRNA abundance of key candidate genes involved in mammary lipogenesis. Twelve lactating Assaf ewes (on average 63d in milk) were randomly assigned to 2 treatments consisting of a total mixed ration based on alfalfa hay and concentrates (50:50), supplemented with 0 (control) or 17g of fish oil/kg of diet dry matter (FO). Profiles of milk FA and mRNA abundance of candidate genes in biopsied mammary tissue were examined before starting the treatments and after 1 and 4.5wk on the diets. As expected, FO induced MFD and modified milk FA composition. Compared with the control, reductions in milk fat concentration and yield were not detected on d 7, but reached up to 25 and 22%, respectively, on d 30. However, increases in confirmed or putative antilipogenic FA (trans-10,cis-12 and trans-9,cis-11 18:2, cis-9 16:1, cis-11 18:1, and oxo-FA) were already established on the early stage of the treatment and lasted until the end of the feeding period. These changes were accompanied by decreases in the mRNA abundance of genes encoding lipogenic enzymes. The coordinated nature of the downregulation, which tended to affect most studied metabolic pathways, including FA activation (ACSS1), de novo synthesis (ACACA and FASN), uptake and transport (LPL and FABP3), desaturation (SCD1), and esterification (AGAPT6), supports the involvement of a central regulator of milk fat synthesis. In this regard, without ruling out the potential contribution of PPARG, our results suggest that SREBF1 would have a relevant role in the MFD syndrome in sheep fed FO. Among the other studied transcription factors, the tendency to a downregulation of INSIG1 was associated with that of SREBF1, whereas no variation was detected for SCAP or THRSP. Fish oil had no significant effects on the transcript abundance of CD36, GPAM, DGAT1, LPIN1, and XDH. Overall, changes in potential antilipogenic FA and mRNA abundance of candidate lipogenic genes support a relationship between them and suggest that FO-induced MFD in dairy ewes would be mediated by transcriptional mechanisms.



http://ift.tt/2d05LtG

The effects of increasing amounts of milk replacer powder added to whole milk on feed intake and performance in dairy heifers

Publication date: October 2016
Source:Journal of Dairy Science, Volume 99, Issue 10
Author(s): R.A. Azevedo, F.S. Machado, M.M. Campos, P.M. Furini, S.R.A. Rufino, L.G.R. Pereira, T.R. Tomich, S.G. Coelho
The aim of this study was to evaluate the effects on feed intake, heifer performance, and health of increasing the total solids (TS) content of liquid feed (whole milk) by adding increasing amounts of milk replacer powder during the pre- and postweaning periods. Crossbred Holstein-Gyr heifers (n=60) were assigned to 1 of 4 treatments (n=15 per group), which consisted of different TS concentrations: 12.5, 15.0, 17.5, and 20.0% of liquid feed. Heifers received 6 L of liquid feed per day, divided into 2 equal meals (0800 and 1600h) and provided in buckets, from 5 to 55d of age. From 56 to 59d of age, the total amount of liquid feed was reduced by half, maintaining only morning feedings. Heifers were weaned at 60d and monitored until 90d of age. Water and starter were provided ad libitum during the entire experiment. Corn silage was included in the diet during the postweaning period (70d of age). Feed intake and health scores were evaluated daily. Body weight and body frame development were recorded weekly. Starting at 14d, ruminal pH was measured every other week. Laboratory analysis determined that the actual TS contents of the liquid feed were 13.5, 16.1, 18.2, and 20.4%, for the proposed 12.5, 15.0, 17.5, and 20.0% TS treatments, respectively. The osmolality of liquid feed treatments was 265 to 533mOsm/L. Intake of liquid feed was similar among treatments from 4wk of age. During the preweaning period, starter intake, fecal score, and days with diarrhea were similar among treatments. Ruminal pH at weaning averaged 6.2 and was similar among treatments. Increasing concentrations of TS in the liquid feed were associated with linear increases in average daily gain, final body weight, and growth performance, but linear decreases in feed efficiency. During the postweaning period, intake of starter, corn silage, and water were similar among treatments, as well as average daily gain and feed efficiency. Final body weight and growth performance during the postweaning period also increased linearly with concentration of TS in liquid feed. Increasing the concentration of TS in liquid feed up to 20.4% increased performance and body frame development in dairy heifers during the pre- and postweaning periods and had no effects on solid feed intake or health.



http://ift.tt/2cyU52S

Genetic correlations between type and test-day milk yield in small dual-purpose cattle populations: The Aosta Red Pied breed as a case study

Publication date: October 2016
Source:Journal of Dairy Science, Volume 99, Issue 10
Author(s): Serena Mazza, Nadia Guzzo, Cristina Sartori, Roberto Mantovani
This study aimed at estimating the relationships between linear type traits and milk production in the dual-purpose Aosta Red Pied (ARP) cattle breed, by expressing type traits as factor scores with the same biological meaning of the individual traits. Factor analysis was applied to individual type traits for muscularity and udder of 32,275 first-parity ARP cows, obtaining 3 factor scores for individual muscularity (F1), udder side (F2), and udder conformation (F3). Data from 169,008 test-day records of milk, fat, and protein yield (kg), belonging to the first 3 lactations of 16,605 cows, were also analyzed. After obtaining genetic parameters for both morphological factors and milk production traits through a series of AIREML single-trait models, bivariate analyses were performed on a data set accounting for 201,283 records of 35,530 cows, to assess the phenotypic and genetic correlations among all factor scores and milk yield traits. The heritability estimates obtained proved to be moderate for both groups of traits, ranging from 0.132 (fat) to 0.314 (F1). Muscularity factor showed moderate and negative genetic correlations (ra) with udder size (−0.376) and udder conformation (0.214) factors. A low and negative ra was found between udder factors. Strong and positive ra were found among all the 3 milk production traits and F 0010 (ra≥0.597). Negative ra with milk traits were obtained for both F 0005 and F3, ranging from −0.417 to −0.221. Phenotypic correlations were lower than the genetic ones, and sometimes close to zero. The antagonism between milk production and meat attitude traits suggests that great attention should be paid in assigning proper weight to the traits, comprising functional traits such as udder conformation, included in selection indices for the dual-purpose breed. The ra obtained for factor scores are consistent with previous estimates for the corresponding individual type traits, and this confirms the possible use of factor analysis to improve type traits relevant to beef attitude.



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Meta-analysis of postruminal microbial nitrogen flows in dairy cattle. I. Derivation of equations

Publication date: October 2016
Source:Journal of Dairy Science, Volume 99, Issue 10
Author(s): Yairanex Roman-Garcia, Robin R. White, Jeffrey L. Firkins
The objective was to summarize the literature and derive equations that relate the chemical composition of diet and rumen characteristics to the intestinal supply of microbial nitrogen (MicN), efficiency of microbial protein synthesis (EMPS), and flow of nonammonia nonmicrobial N (NANMN). In this study, 619 treatment means from 183 trials were assembled for dairy cattle sampled from the duodenum or omasum. Backward elimination multiple regression was used to derive equations to estimate flow of nitrogenous components over a large range of dietary conditions. An intercept shift for sample location revealed that omasal sampling estimated greater MicN flow relative to duodenal sampling, but sample location did not interact with any other variables tested. The ruminal outflow of MicN was positively associated with dry matter intake (DMI) and with dietary starch percentage at a decreasing rate (quadratic response). Also, MicN was associated with DMI and rumen-degraded starch and neutral detergent fiber (NDF). When rumen measurements were included, ruminal pH and ammonia-N were negatively related to MicN flow along with a strong positive association with ruminal isovalerate molar proportion. When evaluating these variables with EMPS, isovalerate interacted with ammonia such that the slope for EMPS with increasing isovalerate increased as ammonia-N concentration decreased. A similar equation with isobutyrate confirms the importance of branched-chain volatile fatty acids to increase growth rate and therefore assimilation of ammonia-N into microbial protein. The ruminal outflow of NANMN could be predicted by dietary NDF and crude protein percentages, which also interacted. This result is probably associated with neutral detergent insoluble N contamination of NDF in certain rumen-undegradable protein sources. Because NANMN is calculated by subtracting MicN, sample location was inversely related compared with the MicN equation, and omasal sampling underestimated NANMN relative to duodenal sampling. As in the MicN equation, sampling location did not interact with any other variables tested for NANMN. Equations derived from dietary nutrient composition are robust across dietary conditions and could be used for prediction in protein supply-requirement models. These empirical equations were supported by more mechanistic equations based on the ruminal carbohydrate degradation and ruminal variables related to dietary rumen degradable protein.



http://ift.tt/2cyUYZq

Whole-genome scan to detect quantitative trait loci associated with milk protein composition in 3 French dairy cattle breeds

Publication date: October 2016
Source:Journal of Dairy Science, Volume 99, Issue 10
Author(s): M.P. Sanchez, A. Govignon-Gion, M. Ferrand, M. Gelé, D. Pourchet, Y. Amigues, S. Fritz, M. Boussaha, A. Capitan, D. Rocha, G. Miranda, P. Martin, M. Brochard, D. Boichard
In the context of the PhénoFinLait project, a genome-wide analysis was performed to detect quantitative trait loci (QTL) that affect milk protein composition estimated using mid-infrared spectrometry in the Montbéliarde (MO), Normande (NO), and Holstein (HO) French dairy cattle breeds. The 6 main milk proteins (α-lactalbumin, β-lactoglobulin, and αS1-, αS2-, β-, and κ-caseins) expressed as grams per 100g of milk (% of milk) or as grams per 100g of protein (% of protein) were estimated in 848,068 test-day milk samples from 156,660 cows. Genotyping was performed for 2,773 MO, 2,673 NO, and 2,208 HO cows using the Illumina BovineSNP50 BeadChip (Illumina Inc., San Diego, CA). Individual test-day records were adjusted for environmental effects and then averaged per cow to define the phenotypes analyzed. Quantitative trait loci detection was performed within each breed using a linkage disequilibrium and linkage analysis approach. A total of 39 genomic regions distributed on 20 of the 29 Bos taurus autosomes (BTA) were significantly associated with milk protein composition at a genome-wide level of significance in at least 1 of the 3 breeds. The 9 most significant QTL were located on BTA2 (133 Mbp), BTA6 (38, 47, and 87 Mbp), BTA11 (103 Mbp), BTA14 (1.8 Mbp), BTA20 (32 and 58 Mbp), and BTA29 (8 Mbp). The BTA6 (87 Mbp), BTA11, and BTA20 (58 Mbp) QTL were found in all 3 breeds, and they had highly significant effects on κ-casein, β-lactoglobulin, and α-lactalbumin, expressed as a percentage of protein, respectively. Each of these QTL explained between 13% (BTA14) and 51% (BTA11) of the genetic variance of the trait. Many other QTL regions were also identified in at least one breed. They were located on 14 additional chromosomes (1, 3, 4, 5, 7, 15, 17, 19, 21, 22, 24, 25, 26, and 27), and they explained 2 to 8% of the genetic variance of 1 or more protein composition traits. Concordance analyses, performed between QTL status and sequence-derived polymorphisms from 13 bulls, revealed previously known causal polymorphisms in LGB (BTA11) and GHR (BTA20 at 32 Mbp) and excluded some other previously described mutations. These results constitute a first step in identifying causal mutations and using routinely collected mid-infrared predictions in future genomic selection programs to improve bovine milk protein composition.



http://ift.tt/2d07f75

Meta-analysis of postruminal microbial nitrogen flows in dairy cattle. II. Approaches to and implications of more mechanistic prediction

Publication date: October 2016
Source:Journal of Dairy Science, Volume 99, Issue 10
Author(s): Robin R. White, Yairanex Roman-Garcia, Jeffrey L. Firkins
Several attempts have been made to quantify microbial protein flow from the rumen; however, few studies have evaluated tradeoffs between empirical equations (microbial N as a function of diet composition) and more mechanistic equations (microbial N as a function of ruminal carbohydrate digestibility). Although more mechanistic approaches have been touted because they represent more of the biology and thus might behave more appropriately in extreme scenarios, their precision is difficult to evaluate. The objective of this study was to derive equations describing starch, neutral detergent fiber (NDF), and organic matter total-tract and ruminal digestibilities; use these equations as inputs to equations predicting microbial N (MicN) production; and evaluate the implications of the different calculation methods in terms of their precision and accuracy. Models were evaluated based on root estimated variance σˆe and concordance correlation coefficients (CCC). Ruminal digestibility of NDF was positively associated with DMI and concentrations of NDF and CP and was negatively associated with concentration of starch and the ratio of acid detergent fiber to NDF (CCC=0.946). Apparent ruminal starch digestibility was increased by omasal sampling (compared with duodenal sampling), was positively associated with forage NDF and starch concentrations, and was negatively associated with wet forage DMI and total dietary DMI (CCC=0.908). Models were further evaluated by calculating fit statistics from a common data set, using stochastic simulation, and extreme scenario testing. In the stochastic simulation, variance in input variables were drawn from a multi-variate random normal distribution reflective of input measurement errors and predicting MicN while accounting for the measurement errors. Extreme scenario testing evaluated each MicN model against a data subset. When compared against an identical data set, predicting MicN empirically had the lowest prediction error, though differences were slight (σˆe 23.3% vs. 23.7 or 24.3%), and highest concordance (0.52 vs. 0.48 or 0.44) of any approach. Minimal differences were observed between empirical MicN prediction (σˆe 25.3%; CCC 0.530) and MicN prediction (σˆe 25.3%; CCC 0.532) from rumen carbohydrate digestibility in the stochastic analysis or extreme scenario testing. Despite the hypothesized benefits of a more mechanistic prediction approach, few differences between the calculation approaches were identified.



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Morphological abnormalities in Japanese red pine (Pinus densiflora) at the territories contaminated as a result of the accident at Fukushima Dai-Ichi Nuclear Power Plant

Publication date: December 2016
Source:Journal of Environmental Radioactivity, Volume 165
Author(s): Vasyl Yoschenko, Kenji Nanba, Satoshi Yoshida, Yoshito Watanabe, Tsugiko Takase, Natsumi Sato, Koji Keitoku
Our research, carried out in 2014–2016 at eight sites in the radioactive contaminated territories of Fukushima Prefecture, showed that the young trees of Japanese red pine (Pinus densiflora) are sensitive to radiation. Irradiation induced cancellation of the apical dominance in this species. The effect is similar to that observed in young trees of Scots pine growing in the Chernobyl zone. At the same time, we did not observed any morphological abnormalities in mature trees of Japanese red pine. The probability of cancelling the apical dominance in Japanese red pine increased to 0.11 and 0.14 in the two less irradiated populations, and to 0.5 and 0.9 at sites were the absorbed dose rates were approximately 14 and 25 μGy h⁻¹, respectively. Most of the observed abnormalities appeared in the second whorl after the beginning of exposure. No new abnormalities were observed in the fifth whorl. This temporal pattern is similar to those reported for Scots pine in Chernobyl and for Japanese fir in Fukushima. Additional detailed studies are necessary for interpretation of the observed temporal pattern and, in general, for explanation of the mechanism of formation of the morphological abnormalities.



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MT1-MMP and its potential role in the vertebrate intestinal morphogenesis

Publication date: Available online 14 September 2016
Source:Acta Histochemica
Author(s): K.C. Camargo, J.R. Gomes, M.M. Loddi, R. de Sordi, C.L.S. Costa-Ayub, M.A. de M. Soares
Membrane type 1-matrix metalloproteinase (MT1-MMP) is involved in numerous biological processes, including morphogenesis. However, the role of MT1-MMP in the development of the vertebrate intestine is poorly understood. This study aimed to evaluate the expression of MT1-MMP in the intestine of rats and chickens along the embryonic and postnatal periods using immunohistochemistry. Results revealed a remarkable spatiotemporal correlation between MT1-MMP expression and intestinal villi morphogenesis in both vertebrates. However, the villi morphogenesis process was found to be different in chickens to that of rats. Moreover, extensive MT1-MMP labeling was observed in the entire villus epithelium from birth until the complete maturation of the small intestinal mucosa in both vertebrates. From these results, we suggest that MT1-MMP contributes to intestinal development, particularly to villi morphogenesis, in both vertebrates. However, further studies are necessary to confirm the role of MT1-MMP in this cellular process. In addition, we performed validation of the primary antibody against human MT1-MMP for adult chickens.



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MiR-143-3p controls TGF-β1-induced cell proliferation and extracellular matrix production in airway smooth muscle via negative regulation of the nuclear factor of activated T cells 1

Publication date: October 2016
Source:Molecular Immunology, Volume 78
Author(s): Wei Cheng, Kun Yan, Li-Yi Xie, Feng Chen, Hong-Chuan Yu, Yan-Xia Huang, Cheng-Xue Dang
MicroRNAs (miRNAs) are small noncoding RNAs that function in diverse biological processes. However, little is known about the precise role of microRNAs in the functioning of airway smooth muscle cells (ASMCs). Here, we investigated the potential role and mechanisms of the miR-143 -3p on proliferation and the extracellular matrix (ECM) protein production of ASMCs. We demonstrated that miR-143-3p was aberrantly lower in ASMCs isolated from individuals with asthma than in individuals without asthma. Meanwhile, TGF-β1 caused a marked decrease in a time-dependent manner in miR-143-3p expression in ASMCs from asthmatics. Additionally, the overexpression of miR- 143-3p robustly reduced TGF-β1-induced ASMCs proliferation and downregulated CDK and cyclin expression, whereas the inhibition of miR-143-3p significantly enhanced ASMCs proliferation and upregulated the level of CDKs and cyclins. Re-expression of miR-143-3p attenuated ECM protein deposition reflected as a marked decrease in the expression of type I collagen and fibronectin, whereas miR-143-3p downregulation caused an opposite effect on the expression of type I collagen and fibronectin. Moreover, qRT-PCR and western blot analysis indicated that miR-143-3p negatively regulated the expression of nuclear factor of activated T cells 1 (NFATc1). Subsequent analyses demonstrated that NFATc1 was a direct and functional target of miR-143-3p, which was validated by the dual luciferase reporter assay. Most importantly, the overexpression of NFATc1 effectively reversed the inhibition of miR-143-3p on TGF-β1-induced proliferation, and strikingly abrogated the effect of miR-143-3p on the expression of CDK4 and Cyclin D1. Together, miR-143-3p may function as an inhibitor of asthma airway remodeling by suppressing proliferation and ECM protein deposition in TGF-β1-mediated ASMCs via the negative regulation of NFATc1 signaling, suggesting miR-143-3p as a potential therapeutic target for asthma.



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Improved protocol for the isolation of naïve follicular dendritic cells

Publication date: October 2016
Source:Molecular Immunology, Volume 78
Author(s): Kazuki Sato, Shin-ichiro Honda, Akira Shibuya, Kazuko Shibuya
Follicular dendritic cells (FDCs) in lymphoid organs play an important role in the humoral immune response. However, because the isolation of FDCs is difficult due to their very small population size and fragility under mechanical and chemical stresses, the genetic and biochemical characteristics of FDCs remain unclear. Previously, we identified FDCs as ICAM-1⁺ cells in the CD45⁻ non-hematopoietic cell fraction from naïve mouse spleen after cell separation by means of digestion with a combination of enzymes. In the present study, using a new combination of enzymes, we found that FDCs are highly enriched in the CD45⁻ICAM-1⁺CD21/35⁺ cell fraction. CD45⁻ICAM-1⁺CD21/35⁺ cells in the mouse spleen retained an antigen administered in vivo for more than 7 days. Moreover, CD45⁻ICAM-1⁺CD21/35⁺ cells isolated from the spleen of mice administered with a cognate antigen enhanced the survival and proliferation of antigen-specific B cells in vitro. Our improved protocol for the isolation of naïve FDCs will be useful for the analysis of FDCs in vitro and in vivo.



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