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Πέμπτη, 11 Μαΐου 2017

The Changing Profile of Hypercalcemia in Hospital Populations

Abstract

Hypercalcemia is a relatively common condition in hospitalized patients. Malignancy is still the most common etiology for hypercalcemia in hospitalized populations. Much insight has been gained into the pathogenesis of malignancy-associated hypercalcemia (MAHC) over the last three decades. The classical primary hyperparathyroidism (PHPT) used to be a severe debilitating disease, usually involving bones and kidneys, needing hospital-based management. However, over the past five decades in the Western world and one decade in the Eastern countries, more and more cases of asymptomatic PHPT are being diagnosed. This population is detected with mild hypercalcemia on routine biochemical screening without any overt clinical features. Overzealous correction of asymptomatic vitamin D deficiency has led to the emergence of another type of hypercalcemia, called vitamin D toxicosis. This is not uncommonly seen, especially in countries where megadoses of injectable vitamin D preparations are easily accessible. Hypercalcemia of advanced chronic liver disease (CLD), a poorly understood and uncommonly reported condition is usually seen in hospitals having large volume hepatological services. Hypercalcemia due to chronic infective granulomatous diseases (like tuberculosis) in underdeveloped nations and granulomatous reactions to cosmetic filling materials in developed nations contribute significantly to non-parathyroid group of hypercalcemia. In conclusion, the pattern of hypercalcemia in hospitalized patients has changed considerably over the last five decades. Clinicians should be aware of these changing patterns so that appropriate diagnosis and treatment can be offered to the patients.



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Title Page/Sections Editors

Publication date: June 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1860, Issue 6





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Determination of disease phenotypes and pathogenic variants from exome sequence data in the CAGI 4 gene panel challenge

ABSTRACT

The use of gene panel sequence for diagnostic and prognostic testing is now widespread, but there are so far few objective tests of methods to interpret these data. We describe the design and implementation of a gene panel sequencing data analysis pipeline (VarP) and its assessment in a CAGI4 community experiment. The method was applied to clinical gene panel sequencing data of 106 patients, with the goal of determining which of 14 disease classes each patient has and the corresponding causative variant(s). The disease class was correctly identified for 36 cases, including 10 where the original clinical pipeline did not find causative variants. For a further seven cases, we found strong evidence of an alternative disease to that tested. Many of the potentially causative variants are missense, with no previous association with disease, and these proved the hardest to correctly assign pathogenicity or otherwise. Post analysis showed that three-dimensional structure data could have helped for up to half of these cases. Over-reliance on HGMD annotation led to a number of incorrect disease assignments. We used a largely ad hoc method to assign probabilities of pathogenicity for each variant, and there is much work still to be done in this area.

This article is protected by copyright. All rights reserved



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Current FDA-approved injection pattern versus targeted peripheral nerve–directed injection pattern. The current FDA-approved injection pattern includes chemodenervation of 7 head and neck muscle groups (A–C). The total units of BOTOX injected for each site bilaterally include: corrugators 10U, procerus 5U, frontalis 20U (A), temporalis 40U (B), occipitalis 30U, cervical paraspinal 20U, and trapezius 30U (C). By comparison, peripheral nerve–directed BOTOX injection targets fewer sites with a smaller total quantity of BOTOX (D–F). The total units of BOTOX injected for each site bilaterally include: supraorbital nerve/supratrochlear nerve 25U (D), zygomaticotemporal nerve 37.5U (E), and greater occipital nerve 50U (F). Source Targeted Peripheral Nerve-directed Onabotulinumtoxin A Injection for Effective Long-term Therapy for Migraine Headache






Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Autologous Platelet-rich Plasma Glue : Seroma and hematoma formations are the most common complications after plastic surgery. The aim of this study was to assess the efficacy of autologous platelet-rich plasma (A-PRP) glue to reduce postoperative wound complications and improve surgical outcomes.

http://otorhinolaryngology-crete.blogspot.com/2017/05/autologous-platelet-rich-plasma-glue.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Therapie der Migräne

Zusammenfassung

Die Akuttherapie der Migräne kann mit Analgetika, nichtsteroidalen Antirheumatika und Triptanen erfolgen. Die gute Wirkung der Akuttherapie ist auch im Hinblick auf eine mögliche Kopfschmerzchronifizierung bedeutsam. Zur Prophylaxe stehen Betablocker, trizyklische Antidepressiva, Flunarizin, Antikonvulsiva und Botulinumtoxin A zur Verfügung. Weitere Substanzen wie Sartane haben einen Wirksamkeitsbeleg erbracht. In der Therapie spielen neben den medikamentösen die nichtmedikamentösen therapeutischen Ansätze eine zentrale Rolle. Durch Edukation und rechtzeitigen Einsatz einer Migräneprophylaxe sollte das Risiko eines Medikamentenübergebrauchs reduziert werden. Neu zur Prophylaxe stehen nichtinvasive Neurostimulationsverfahren (Supraorbitalisstimulation, transkutane Nervus-vagus-Stimulation) zur Verfügung. In klinischen Studien werden ein oraler CGRP („calcitonin gene-related peptide") -Antagonist zur Akuttherapie und mehrere monoklonale Antikörper gegen CGRP bzw. CGRP-Rezeptoren auf ihre Wirksamkeit und Verträglichkeit untersucht.



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Pharmakotherapie des Morbus Parkinson

Zusammenfassung

Hintergrund

Diese Übersicht widmet sich den Aspekten der Arzneimitteltherapiesicherheit in der Pharmakotherapie des Morbus Parkinson, einer der häufigsten chronischen Erkrankungen des Nervensystems. Die Pharmakotherapie des Morbus Parkinson ist beispielhaft für die Komplexität im typischerweise neurogeriatrischen Patientenkollektiv.

Ziel der Arbeit

Herausstellung potenzieller Risiken und von Aspekten der Arzneimitteltherapiesicherheit in der Pharmakotherapie des Morbus Parkinson.

Material und Methoden

Selektive Literatur- und Leitlinienrecherche unter Zuhilfenahme von Pubmed sowie der wissenschaftlich-klinischen Erfahrungen der Autoren.

Ergebnisse

Da Parkinson-Patienten meist ältere Menschen sind, die infolge von Komorbiditäten mit weiteren Medikamenten therapiert werden, kommt es häufig zu einer komplexen Medikation mit mehr als fünf Arzneimitteln. Diese Polymedikation erhöht das Risiko unerwünschter Arzneimittelereignisse, sodass die Medikation der Patienten auf Interaktionen überprüft und Kontraindikationen ausgeschlossen werden müssen. Damit besteht vermehrter Aufklärungsbedarf bezüglich möglicher arzneimittelbezogener Probleme. Die Komorbiditäten oder die verordneten Arzneimittel können Kontrolluntersuchungen erforderlich machen, um arzneimittelbezogene Probleme zu erkennen und die Arzneimitteltherapiesicherheit zu gewährleisten.

Schlussfolgerung

Um die gesundheitsbezogene Lebensqualität und die Qualität der Arzneimitteltherapie von Parkinson-Patienten zu gewährleisten, muss die individuell beste Therapie unter Berücksichtigung aller Kontraindikationen, Nebenwirkungen, Kontrolluntersuchungen und Interaktionen gefunden werden. Aufklärungsarbeit kann die Compliance der Patienten erhöhen und zur Steigerung der Arzneimitteltherapiesicherheit beitragen.



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Akutes fokal-neurologisches Defizit in der Notaufnahme

Zusammenfassung

Ein akut aufgetretenes oder rasch zunehmendes fokal-neurologisches Defizit ist ein alarmierender Befund, der auf eine akut behandlungspflichtige Funktionsstörung des Nervensystems hinweist. In der Notaufnahme ist es unter begrenzten zeitlichen Ressourcen erforderlich, das fokal-neurologische Defizit rasch syndromal einzuordnen und eine Verdachtsdiagnose zu formulieren, um darauf beruhend die klärende Akutdiagnostik und oft zeitnah notwendige Akuttherapie einzuleiten. In dem vorliegenden Artikel sollen vor allem den noch nicht sehr erfahrenen Kollegen häufige und typische neurologische Krankheitsbilder in der Notaufnahme und ihr charakteristisches fokales Defizit dargestellt werden. Darüber hinaus soll ein vorgeschlagener Algorithmus erleichtern, orientierend am Leitsymptom rasch die zielführende Diagnostik durchzuführen und die notwendige Akuttherapie häufiger und relevanter neurologischer Erkrankungen in der Notaufnahme einzuleiten.



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Cardio-Protective effects of Qishen Granule (芪参颗粒) on sarcoplasmic reticulum Ca 2+ handling in heart failure rats

Abstract

Objectives

To assess the effects of Qishen Granule (芪参颗粒, QSG) on sarcoplasmic reticulum (SR) Ca2+ handling in heart failure (HF) model of rats and to explore the underlying molecular mechanisms.

Methods

HF rat models were induced by left anterior descending coronary artery ligation surgery and high-fat diet feeding. Rats were randomly divided into sham (n=10), model (n=10), QSG (n=12, 2.2 g/kg daily) and metoprolol groups (n=12, 10.5 mg/kg daily). The therapeutic effects of QSG were evaluated by echocardiography and blood lipid testing. Intracellular Ca2+ concentration and sarco-endoplasmic reticulum ATPase 2a (SERCA2a) activity were detected by specifific assay kits. Expressions of the critical regulators in SR Ca2+ handling were evaluated by Western blot and real-time quantitative polymerase chain reaction.

Results

HF model of rats developed ventricular remodeling accompanied with calcium overload and defective Ca2+ releaseuptake cycling in cardiomyocytes. Treatment with QSG improved contractive function, attenuated ventricular remodeling and reduced the basal intracellular Ca2+ level. QSG prevented defective Ca2+ leak by attenuating hyperphosphorylation of ryanodine receptor 2, inhibiting expression of protein kinase A and up-regulating transcriptional expression of protein phosphatase 1. QSG also restored Ca2+ uptake by up-regulating expression and activity of SERCA2a and promoting phosphorylation of phospholamban.

Conclusions

QSG restored SR Ca2+ cycling in HF rats and served as an ideal alternative drug for treating HF.



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Effect of Lang-Chuang-Ding Decoction (狼疮定汤) on DNA methylation of CD70 gene promoter in peripheral blood mononuclear cells of female patients with systemic lupus erythematosus

Abstract

Objectives

To investigate the effect of Lang-chuang-ding Decoction (狼疮定汤, LCD) on the expression of DNA methylation of CD70 gene promoter in peripheral blood mononuclear cells (PBMCs) of females with systemic lupus erythematosus (SLE).

Methods

PBMCs isolated from female patients with SLE or healthy donors were cultured and treated with LCD medicated serum or normal serum for 24 or 48 h. The mRNA expressions of CD70 gene in PBMCs were detected by reverse transcription polymerase chain reaction (PCR); the DNA methylation of the CD70 gene promoter region was detected by methylation-specific PCR.

Results

After treated with medicated serum for 48 h, the mRNA expression levels of CD70 in PBMCs of SLE patients were signifificantly higher than those of healthy donors (P<0.05); the DNA methylation levels of CD70 promoter region in PBMCs of SLE patients treated with medicated serum for 48 h were signifificantly higher than those treated with fetal bovine serum (P<0.01).

Conclusions

LCD could inhibit CD70 gene expression in PBMCs of SLE patients by promoting the DNA methylation of CD70 gene promoter.



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Embolic effects of Bletilla striata microspheres in renal artery and transplanted VX2 liver tumor model in rabbits

Abstract

Objectives

To evaluate the characteristics of Bletilla striata microspheres (BSMs) and its effects as an embolic agent in a rabbit model.

Methods

BSMs were prepared with an emulsifification-cool condensation-chemical cross-linking method. The characteristics of BSMs in vitro were observed. Embolization experiments were performed in renal artery of rabbit and in a rabbit liver VX2 carcinoma model. Seventy-two New Zealand rabbits were divided into 2 groups, and the right renal artery was embolized with BSMs (200 μm in diameter) in the experimental group and with polyvinyl alcohol (PVA) of the same size in the control group. The pathological findings were examined with hematoxylin-eosin and Masson stainings. Liver and renal functions were tested before and after embolization. VX2 tumor was transplanted in 15 New Zealand rabbits, which were randomly divided into 3 groups (n=5). Group A were treated with saline, group B with a mixture of doxorubicin and lipiodol, and group C with hepatic arterial infusion of BSMs (200 μm in diameter). Tumor growth rate was evaluated by magnetic resonance imaging scan. Apoptosis-related factors (bax, bcl-2) and tumor vascular endothelial cell growth factor (VEGF) were evaluated through immunohistochemical staining.

Results

The characteristics of BSMs in vitro were in full compliance with the requirements for use in interventional procedures. In the renal artery embolization experiment, after BSMs intervention, it was more diffificult to form collateral circulation than that with PVAs, and the kidney manifested atrophy and calcifification. There were no signifificant difference of liver and renal functions in rabbits between groups. In the liver VX2 carcinoma embolization experiment, compared with group A, the growth rate of VX2 liver tumor and Bcl-2 levels was reduced, while apoptosis index, Bax, and VEGF were increased in group B (P<0.05). There were no signifificant difference between groups B and C (P>0.05).

Conclusions

The characteristics of BSMs in vitro and in vivo meet the requirements for its use as an embolic agent in interventional approaches.



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Xuebijing Injection (血必净注射液) increases early survival rate by alleviating pulmonary vasopermeability in rats subjected to severe burns

Abstract

Objectives

To investigate the effects of Xuebijing Injection (血必净注射液, XBJ) on survival rate and pulmonary vasopermeability in a rat model of severe scald injury.

Methods

Rats were divided into two experiments: experiment 1 was monitored for 12 h post-injury for survival analysis after severe burns; in experiment 2, rats were killed for determination of pulmonary vascular permeability and pro-inflflammatory mediators. In both experiments, rats were subject to third-degree 50% total body surface area (TBSA) burns or sham injury followed by XBJ or normal saline (NS) treatment. In addition, rat pulmonary microvascular endothelium cells (PMECs) were pretreated with either XBJ or phosphate buffer saline (PBS), and then subjected to sham serum or scald serum stimulation for 2 or 6 h, followed by transwell examination for the permeability of PMECs. Meanwhile, pro-inflflammatory mediators in PMECs culture supernatant were also investigated.

Results

The average survival time in the scald+XBJ group was 582.1±21.2 min, which was signifificantly longer than that in the scald + NS group (345.8±25.4 min, P<0.01). Plasma levels of tumor necrosis factor-alpha (TNF-α), E-selectin, interleukin-6 (IL-6), vascular permeability and water content of lung tissues were signifificantly increased in animals after severe burns (P<0.01). However, administration of XBJ signifificantly decreased these levels in plasma and lung tissue. In in vitro cell experiments, XBJ markedly attenuated permeability in PMECs monolayer and reduced the levels of TNF-α, IL-6 and soluble E-selectin after stimulation with scald serum (P<0.01).

Conclusions

XBJ increases early survival rate by alleviating pulmonary vasopermeability and inhibiting pro-inflflammatory mediators in rats subjected to lethal scald injury. XBJ may be a potent drug in treatment of severe burns.



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Progressive muscle relaxation combined with Chinese medicine five-element music on depression for cancer patients: A randomized controlled trial

Abstract

Objectives

To evaluate the effects of progressive muscle relaxation training (PMRT) combined with fifive elements music therapy of Chinese medicine (CM) for improving anxiety and depression of cancer patients.

Methods

From June 2015 to March 2016, 60 cancer patients were included into the study. The patients were randomly assigned to a control group and a treatment group by envelope randomization, receiving PMRT and PMRT plus CM five elements music therapy, respectively, for 8 weeks. Hospital Anxiety and Depression Scale (HADS), Benefit Finding Scales (BFS), Functional Assessment of Chronic Illness Therapy-Spiritual (FACIT-Sp), and Intervention Expectations Questionnaire (IEQU) were adopted to assess the depression of the two groups before and after the treatment.

Results

Four cases dropped out during the study, and 29 cases in the treatment group and 27 in the control group were included in the fifinal analysis. Prior to the treatments, the baselines of the 4 questionnaires in the two groups showed no difference. After the 8-week treatment, the treatment group presented better levels of HADS, BFS and FACIT-Sp scores compared with the control group (P<0.05). Among the single items of HADS, 4 items involving vexation, feeling fifidgeted, pleasure and prospecting the future in the treatment group were improved compared with the control group (P<0.05).

Conclusions

As a simple and reliable and effective intervention, PMRT combined with fifive elements music therapy mitigated anxiety and depression of cancer patients. Cancer patients have been found to respond well to psychological intervention in areas regarding stabilisation of emotions, disease awareness, and therapeutic compliance. This brings about a great difference in improving their quality of life and psychological state, offers an effective approach to better self-management in cancer treatment.



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Xuebijing Injection (血必净注射液) and resolvin D1 synergize to regulate leukocyte adhesion and improve survival rate in mice with sepsis-induced lung injury

Abstract

Objectives

To investigate the effect of combined application of Xuebijing Injection (血必净注 射液, XBJ) and resolvin D1 (RvD1) on survival rate and the underlying mechanisms in mice with sepsisinduced lung injury.

Methods

The cecal ligation and puncture (CLP) method was used to develop a mouse sepsis model. Specifific pathogen free male C57BL/6 mice were randomly divided into 5 groups (n=20 each): sham, CLP, CLP+XBJ, CLP+RvD1 and CLP+XBJ+RvD1. After surgery, mice in the CLP+XBJ, CLP+RvD1 and CLP+XBJ+RvD1 groups were given XBJ (25 μL/g body weight), RvD1 (10 ng/g body weight), and their combination (the same dose of XBJ and RvD1), respectively. In each group, 12 mice were used to observe 1-week survival rate, while the rest were executed at 12 h. Whole blood was collected for flow cytometric analysis of leukocyte adhesion molecules CD18, lung tissues were harvested for observing pathological changes, and testing the activity of myeloperoxidase (MPO) and the expression of intercellular cell adhesion molecule 1 (ICAM-1).

Results

Compared with the CLP group, the histopathological damage of the lung tissues was mitigated, MPO activity was decreased in the CLP+XBJ and CLP+RvD1 groups (P<0.05). In addition, the 1-week survival rate was improved, proportion of CD18-expressing cells in whole blood and ICAM-1 protein expression in lung tissue were decreased in the CLP+XBJ+RvD1 group (P<0.05 or P<0.01).

Conclusions

XBJ together with RvD1 could effectively inhibit leukocyte adhesion, reduce lung injury, and improve the survival rate of mice with sepsis.



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Effect of Miscanthus sinensis var. purpurascens flower extract on proliferation and molecular regulation in human dermal papilla cells and stressed C57BL/6 mice

Abstract

Objectives

To investigate the hair growth-promoting effect of Miscanthus sinensis var. purpurascens (MSP) flower extracton on in vitro and in vivo models.

Methods

MSP flower extract was extracted in 99.9% methanol and applied to examine the proliferation of human dermal papilla cells (hDPCs) in vitro at the dose of 3.92–62.50 μg/mL and hair growth of C57BL/6 mice in vivo at the dose of 1000 μg/mL. The expression of transforming growth factor β1 (TGF-β1), hepatocyte growth factor (HGF), β-catenin, substance P was measured by relative quantitative realtime polymerase chain reaction. Histopathological and immunohistochemical analysis were performed.

Results

MSP (7.81 μg/mL) down-regulated TGF-β1 and up-regulated HGF and β-catenin in hDPCs (P<0.01). MSP (1000 μg/mL)-treated mice showed the earlier transition of hair follicles from the telogen to the anagen phase. The number of mast cells was lower in the MSP-treated mice than in other groups (P<0.05 vs. NCS group). Substance P and TGF-β1 were expressed in hair follicles and skin of the MSP group lower than that in negative control. Stem cell factor in hair follicles was up-regulated in the MSP-treated mice (P<0.01).

Conclusions

The MSP flflower extract may have hair growth-promotion activities.



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Garlicin post-conditioning suppresses adhesion molecules in a porcine model of myocardial ischemia-reperfusion injury

Abstract

Objectives

To evaluate whether garlicin post-conditioning can attenuate myocardial ischemiareperfusion injury in a catheter-based porcine model of acute myocardial infarction (AMI) by affecting adhesion molecules integrin β1/CD29 and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31).

Methods

Twenty-two swine were devided into 3 groups: 6 in a sham-operation group, and 8 each in the model and garlicin groups. AMI porcine model was established in the model and garlicin groups. The distal parts of the left anterior descending coronary artery in the animals of the model and garlicin groups were occluded by dilated balloon for 2 h, followed by reperfusion for 3 h. Garlicin (1.88 mg/kg) was injected over a period of 1 h, beginning just before reperfusion, in the garlicin group. Real-time polymerase chain reaction, immunohistochemistry and Western blot were carried out to detect mRNA and protein expressions of CD29 and CD31 3 h after reperfusion.

Results

Hematoxylin-eosin staining showed a better myocardial structure in the garlicin group after reperfusion. Compared to the model group, garlicin inhibited both the mRNA and protein expression of CD29 and CD31 in reperfusion area and no-reflflow area (P<0.05 respectively).

Conclusions

Garlicin post-conditioning induced cardio-protection against myocardial ischemia-reperfusion injury in this catheter-based porcine model of AMI. The cardio-protective effect of garlicin is possibly owing to suppression of production of CD29 and CD31, by inhibition of the mRNA expression of CD29 and CD31.



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The effect of insulin administration on c-peptide in critically ill patients with type 2 diabetes

In critically ill patients with permissive hyperglycemia, it is uncertain whether exogenous insulin administration suppresses or enhances c-peptide secretion (a marker of pancreatic beta-cell response). We aim...

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Predictors of response to prefabricated foot orthoses or rocker-sole footwear in individuals with first metatarsophalangeal joint osteoarthritis

Abstract

Background

Osteoarthritis of the first metatarsophalangeal joint (1st MTPJ OA) is a common and disabling condition commonly managed with footwear and orthotic interventions. The objective of this study was to identify factors associated with a successful treatment response in people with 1st MTPJ OA provided with prefabricated orthoses or rocker-sole footwear as part of a randomised clinical trial.

Methods

People with 1st MTPJ OA (n = 88) who participated in a randomised trial were allocated to receive prefabricated foot orthoses (n = 47) or rocker-sole footwear (n = 41) and completed a baseline questionnaire including information on demographics, anthropometrics, general health, pain characteristics (including the Foot Health Status Questionnaire [FHSQ] and Foot Function Index [FFI]) and perceptions of the interventions, and a clinical assessment of foot posture, range of motion, radiographic severity and in-shoe plantar pressures. Adherence was documented using diaries. At 12 weeks, participants documented their perception of improvement on a 15-point scale. Those reporting at least moderate improvement on this scale were classified as 'responders'.

Results

There were 29 responders (62%) in the orthoses group and 16 responders (39%) in the rocker-sole group. In the orthoses group, responders had greater baseline pain severity while walking, a higher FFI difficulty score, and wore their orthoses more frequently. In the rocker-sole group, responders had a higher FFI stiffness score and greater radiographic severity. However, the accuracy of these variables in identifying responders in each group was modest (62 and 53%, respectively).

Conclusion

The response to prefabricated orthoses or rocker-sole footwear in people with 1st MTPJ OA is related to measures of increased pain and disease severity. However, the overall classification accuracy associated with these factors is not sufficient for identifying individuals who are most likely to benefit from these interventions.

Trial registration

Australian New Zealand Clinical Trials Registry: ACTRN12613001245785



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Analysis of copy number variations in Holstein-Friesian cow genomes based on whole-genome sequence data

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Publication date: Available online 10 May 2017
Source:Journal of Dairy Science
Author(s): M. Mielczarek, M. Frąszczak, R. Giannico, G. Minozzi, John L. Williams, K. Wojdak-Maksymiec, J. Szyda
Thirty-two whole genome DNA sequences of cows were analyzed to evaluate inter-individual variability in the distribution and length of copy number variations (CNV) and to functionally annotate CNV breakpoints. The total number of deletions per individual varied between 9,731 and 15,051, whereas the number of duplications was between 1,694 and 5,187. Most of the deletions (81%) and duplications (86%) were unique to a single cow. No relation between the pattern of variant sharing and a family relationship or disease status was found. The animal-averaged length of deletions was from 5,234 to 9,145 bp and the average length of duplications was between 7,254 and 8,843 bp. Highly significant inter-individual variation in length and number of CNV was detected for both deletions and duplications. The majority of deletion and duplication breakpoints were located in intergenic regions and introns, whereas fewer were identified in noncoding transcripts and splice regions. Only 1.35 and 0.79% of the deletion and duplication breakpoints were observed within coding regions. A gene with the highest number of deletion breakpoints codes for protein kinase cGMP-dependent type I, whereas the T-cell receptor α constant gene had the most duplication breakpoints. The functional annotation of genes with the largest incidence of deletion/duplication breakpoints identified 87/112 Kyoto Encyclopedia of Genes and Genomes pathways, but none of the pathways were significantly enriched or depleted with breakpoints. The analysis of Gene Ontology (GO) terms revealed that a cluster with the highest enrichment score among genes with many deletion breakpoints was represented by GO terms related to ion transport, whereas the GO term cluster mostly enriched among the genes with many duplication breakpoints was related to binding of macromolecules. Furthermore, when considering the number of deletion breakpoints per gene functional category, no significant differences were observed between the “housekeeping” and “strong selection” categories, but genes representing the “low selection pressure” group showed a significantly higher number of breakpoints.



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Short communication: Nutrient consumption patterns of Lactobacillus acidophilus KLDS 1.0738 in controlled pH batch fermentations

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Publication date: Available online 10 May 2017
Source:Journal of Dairy Science
Author(s): Xuepeng Lv, Gefei Liu, Xiaomei Sun, Hongyu Chen, Jiahui Sun, Zhen Feng
This work focused on elucidating the nutrient consumption patterns of Lactobacillus acidophilus to guide the design of media for high-cell-density culture. We investigated the nutrient consumption patterns of L. acidophilus KLDS 1.0738 in chemically defined media in controlled pH batch fermentations. The most abundantly consumed amino acids, vitamins, ions, and purines and pyrimidines were Glu and Gly, pyridoxine and nicotinamide, K+ and PO43−, and guanine and uracil, respectively. The highest consumption rates for amino acids, vitamins, ions, and purines and pyrimidines were Asp and Arg, folic acid and pyridoxine, Fe2+ and Mn2+, and uracil and thymine, respectively. Furthermore, most of the amino acids, as well as guanine, thymine, pyridoxine, folic acid, nicotinamide, Mg2+, PO43−, and K+ had the highest bioavailability from the end of the lag growth phase to the mid-exponential growth phase. The overall consumption of glucose, adenine nucleotides, 2'-deoxyguanosine monohydrate, calcium pantothenate, Fe2+ and Mn2+ decreased with increasing average growth rate, indicating more effective use of these nutritional components at a higher average growth rate, as biomass yield based on nutritional component consumption increased. Our findings help to formulate complex media for high-cell-density cultivation and provide a theoretical basis for L. acidophilus feeding strategies.



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Understanding the gut microbiome of dairy calves: Opportunities to improve early-life gut health

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Publication date: Available online 10 May 2017
Source:Journal of Dairy Science
Author(s): Nilusha Malmuthuge, Le Luo Guan
Early gut microbiota plays a vital role in the long-term health of the host. However, understanding of these microbiota is very limited in livestock species, especially in dairy calves. Neonatal calves are highly susceptible to enteric infections, one of the major causes of calf death, so approaches to improving gut health and overall calf health are needed. An increasing number of studies are exploring the microbial composition of the gut, the mucosal immune system, and early dietary interventions to improve the health of dairy calves, revealing possibilities for effectively reducing the susceptibility of calves to enteric infections while promoting growth. Still, comprehensive understanding of the effect of dietary interventions on gut microbiota—one of the key aspects of gut health—is lacking. Such knowledge may provide in-depth understanding of the mechanisms behind functional changes in response to dietary interventions. Understanding of host–microbial interactions with dietary interventions and the role of the gut microbiota during pathogenesis at the site of infection in early life is vital for designing effective tools and techniques to improve calf gut health.



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Short communication: Associations between blood glucose concentration, onset of hyperketonemia, and milk production in early lactation dairy cows

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Publication date: Available online 10 May 2017
Source:Journal of Dairy Science
Author(s): J. Ruoff, S. Borchardt, W. Heuwieser
The objectives of this study were to describe the associations between hypoglycemia and the onset of hyperketonemia (HYK) within the first 6 wk of lactation, to evaluate the effects of body condition score at calving on glucose concentration, and to study the effects of hypoglycemia on milk production. A total of 621 dairy cows from 6 commercial dairy farms in Germany were enrolled between 1 and 4 d in milk (DIM). Cows were tested twice weekly using an electronic handheld meter for glucose and β-hydroxybutyrate (BHB), respectively, for a period of 42 d. Hypoglycemia was defined as glucose concentration ≤2.2 mmol/L. Hyperketonemia was defined as a BHB concentration ≥1.2 mmol/L. The onset of HYK was described as early onset (first HYK event within the first 2 wk postpartum) and late onset (first HYK event in wk 3 to 6 postpartum). The effect of ketosis status on blood glucose within 42 DIM was evaluated using a generalized linear mixed model. No effect was observed of HYK on glucose concentration in primiparous cows. Multiparous cows with early-onset HYK had a lower glucose concentration (−0.21 mmol/L) compared with nonketotic cows. Overall, primiparous cows had a lower prevalence and incidence of hypoglycemia than multiparous cows. Hypoglycemia in multiparous cows was associated with higher first test-day milk production and 100 DIM milk production. In conclusion, hypoglycemia mainly occurred in multiparous cows with early-onset HYK, whereas primiparous cows were at a lower risk for hypoglycemia.



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The genetics of antibody response to paratuberculosis in dairy cattle

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Publication date: Available online 10 May 2017
Source:Journal of Dairy Science
Author(s): T. Pritchard, R. Mrode, M. Coffey, K. Bond, E. Wall
Genetic parameters were estimated for antibody response to paratuberculosis (Mycobacterium avium ssp. paratuberculosis) using milk ELISA test results, collected and analyzed by National Milk Records, from Holstein Friesian cows on UK dairy farms in their first 3 lactations. Milk ELISA test results were obtained from 2007 to 2012 and combined with milk recording data and pedigree information. The reduced data set edited for the purposes of genetic parameter estimation consisted of 148,054 milk ELISA records from 64,645 lactations in 40,142 cows of 908 sires, recorded in 641 herds. Milk ELISA test results were loge-transformed and univariate analysis of 3 alternative animal models and equivalent sire models were considered. The most appropriate model included additive genetic and permanent environmental random effects, whereas maternal effects were significant according to likelihood ratio test and Akaike's information criterion but not for Bayesian information criterion. Heritability and repeatability estimates were 0.06 and 0.37, respectively, for the chosen animal model and its equivalent sire model. A subset of the data including herds with greater than 10% positive tests gave a slightly higher heritability of 0.08. Favorable but generally low significant genetic correlations were obtained between antibody response with 305-d milk yield (−0.16), 305-d protein yield (−0.16), loge-transformed lactation-average somatic cell count (0.15), and the number of mastitis episodes (0.22). Thus, selection on the antibody response to paratuberculosis, should not be detrimental to production or udder health traits. Testing cattle for paratuberculosis is important for its use in control programs and although the heritability of antibody response was low, breeding against the disease might be a good prospect as a preventative measure to assist together with other approaches in an overall control strategy.



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Machine-learning-based calving prediction from activity, lying, and ruminating behaviors in dairy cattle

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Publication date: Available online 10 May 2017
Source:Journal of Dairy Science
Author(s): M.R. Borchers, Y.M. Chang, K.L. Proudfoot, B.A. Wadsworth, A.E. Stone, J.M. Bewley
The objective of this study was to use automated activity, lying, and rumination monitors to characterize prepartum behavior and predict calving in dairy cattle. Data were collected from 20 primiparous and 33 multiparous Holstein dairy cattle from September 2011 to May 2013 at the University of Kentucky Coldstream Dairy. The HR Tag (SCR Engineers Ltd., Netanya, Israel) automatically collected neck activity and rumination data in 2-h increments. The IceQube (IceRobotics Ltd., South Queensferry, United Kingdom) automatically collected number of steps, lying time, standing time, number of transitions from standing to lying (lying bouts), and total motion, summed in 15-min increments. IceQube data were summed in 2-h increments to match HR Tag data. All behavioral data were collected for 14 d before the predicted calving date. Retrospective data analysis was performed using mixed linear models to examine behavioral changes by day in the 14 d before calving. Bihourly behavioral differences from baseline values over the 14 d before calving were also evaluated using mixed linear models. Changes in daily rumination time, total motion, lying time, and lying bouts occurred in the 14 d before calving. In the bihourly analysis, extreme values for all behaviors occurred in the final 24 h, indicating that the monitored behaviors may be useful in calving prediction. To determine whether technologies were useful at predicting calving, random forest, linear discriminant analysis, and neural network machine-learning techniques were constructed and implemented using R version 3.1.0 (R Foundation for Statistical Computing, Vienna, Austria). These methods were used on variables from each technology and all combined variables from both technologies. A neural network analysis that combined variables from both technologies at the daily level yielded 100.0% sensitivity and 86.8% specificity. A neural network analysis that combined variables from both technologies in bihourly increments was used to identify 2-h periods in the 8 h before calving with 82.8% sensitivity and 80.4% specificity. Changes in behavior and machine-learning alerts indicate that commercially marketed behavioral monitors may have calving prediction potential.



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Effect of conjugated linoleic acid and acetate on milk fat synthesis and adipose lipogenesis in lactating dairy cows

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Publication date: Available online 10 May 2017
Source:Journal of Dairy Science
Author(s): N. Urrutia, K.J. Harvatine
During biohydrogenation-induced milk fat depression (MFD), nutrients are spared from milk fat synthesis and are available for other metabolic uses. Acetate is the major carbon source spared and it may increase lipid synthesis in adipose tissue during MFD. The objective of this study was to compare the effect of trans-10, cis-12 conjugated linoleic acid (CLA) and the amount of acetate spared during CLA-induced MFD on adipose tissue lipogenesis. Nine multiparous, lactating, ruminally cannulated Holstein cows (244 ± 107 d in milk; 25 ± 8.4 kg of milk/d; mean ± standard deviation) were randomly assigned to treatments in a 3 × 3 Latin square design. Experimental periods were 4 d followed by a 10-d washout. Treatments were control (CON), ruminal infusion of acetate (AC; continuous infusion of 7 mol/d adjusted to pH 6.1 with sodium hydroxide), or abomasal infusion of CLA (10 g/d of both trans-10, cis-12 CLA and cis-9, trans-11 CLA). Dry matter intake, milk yield, and milk protein yield and percentage were not affected by treatments. Compared with CON, milk fat yield decreased 23% and fat percent decreased 28% in CLA, and milk fat yield increased 20% in AC. Concentration and yield of milk de novo synthesized fatty acids (<C16) were reduced and concentration of preformed fatty acids (>C16) was increased by CLA, compared with CON. Yield of de novo synthesized fatty acids and palmitic acid was increased by AC, compared with CON. Lipogenesis capacity of adipose tissue explants was decreased 72% by CLA, but was not affected by AC. Acetate oxidation by adipose explants was not affected by treatments. Treatments had no effect on expression of key lipogenic factors, lipogenic enzymes, and leptin; however, expression of fatty acid binding protein 4 was reduced in CLA compared with CON. Additionally, hormone-sensitive lipase and perilipin 1 were decreased by CLA and acetate. Plasma glucose and glucagon concentrations were not affected by treatments; however, CLA increased nonesterified fatty acids 17.7%, β-hydroxybutyrate 16.1%, and insulin 27.8% compared with CON, and AC increased plasma β-hydroxybutyrate 18%. In conclusion, during CLA-induced MFD in low-producing cow adipose tissue was sensitive to the anti-lipogenic effects of CLA, while spared acetate did not stimulate adipose lipogenesis. However, acetate may play an important role in stimulating lipogenesis and improving energy status in the mammary gland under normal conditions.



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Effect of different fat supplements on performance of dairy calves during cold season

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Publication date: Available online 10 May 2017
Source:Journal of Dairy Science
Author(s): E. Ghasemi, M. Azad-Shahraki, M. Khorvash
The objective of this experiment was to evaluate the effects of starter supplementation with fat sources differing in their fatty acid (FA) profile on performance of dairy calves during cold season. Sixty Holstein calves (3 d of age; 39.7 ± 3.8 kg of body weight) were randomly assigned to 1 of 5 starter diets supplemented with (1) no fat or oil source (control), (2) 3% palm fat (PLF), (3) 3% soybean oil (SBO), (4) 3% tallow (TAL), and (5) a 3.2% mixture (MIX) of PLF, SBO, and fish oil. The fat supplements were substituted for corn in the basal starter diet. Both the control and fat-supplemented diets contained similar amounts of dietary crude protein (19.4%), but the latter had a slightly higher quantity of calculated metabolizable energy (3.17 vs. 3.07 Mcal/kg) than did the former. Calves were reared outdoor in individual pens during the cold of winter with a mean ambient temperature of 5.0°C during the study period. Whole milk was offered twice daily from d 3 to 45 and once from d 46 to 49. The animals were weaned on d 50 and monitored in their individual pens until d 70. Supplementation with SBO and MIX increased both the dietary concentration and ratio of essential FA (n-6 and n-3), whereas supplementation with TAL and PLF made no change in the essential FA profile. Starter intake and average daily gain were not affected by PLF and TAL supplements, but were reduced as a result of feeding MIX. Feeding supplemental SBO did not affect starter intake, but tended to improve average daily gain and final body weight. Fat sources had no effects on body skeletal measurements, fecal score, digestibility, ruminal pH, ammonia, and total volatile FA concentrations; however, feeding MIX increased rumen molar proportion of propionate. No differences were observed in blood metabolites across the treatments during the preweaning period. Plasma concentrations of triacylglycerol and cholesterol increased when fat sources were supplemented and glucose concentration increased when SBO was supplemented during the postweaning period. Overall, addition of 3% PLF or TAL to the diet of young calves failed to improve growth performance. Although addition of SBO and MIX increased the dietary essential FA concentration, calf performance was only improved when SBO was supplemented.



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Effects of dietary crude protein concentration on late-lactation dairy cow performance and indicators of nitrogen utilization

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Publication date: Available online 10 May 2017
Source:Journal of Dairy Science
Author(s): T. Barros, M.A. Quaassdorff, M.A. Aguerre, J. J. Olmos Colmenero, S.J. Bertics, P.M. Crump, M.A. Wattiaux
The objectives of this study were to measure performance responses and to evaluate indictors of N utilization in late-lactation cows fed diets with incremental reductions in crude protein (CP) concentration. Holstein cows (n = 128; 224 ± 54 d in milk) were stratified by parity and days pregnant (86 ± 25 d) and randomly assigned to 1 of 16 pens in a randomized complete block design. For 3 wk, all cows received a covariate diet containing 16.9% CP [dry matter (DM) basis]. For the subsequent 12 wk, pens were randomly assigned to 1 of 4 treatments that contained 16.2, 14.4, 13.1, or 11.8% CP (DM basis). Diets were offered once daily and contained 32.5% corn silage, 32.5% alfalfa silage, 13.5% high-moisture corn, and 21.5% concentrate mix. A reduction in dietary CP was achieved by replacing soybean meal with soy hulls in the concentrate mix (DM basis). Dry matter intake, milk urea N (MUN; mg/dL), and the yield of milk urea N (g/d) decreased linearly with dietary CP. Compared with a 16.2% CP diet, a 14.4% CP diet did not alter milk yield throughout the study, but the 13.1 and 11.8% CP diets reduced milk yield after 4 and 1 wk, respectively. Furthermore, milk protein percentage was reduced for all dietary CP less than 16.2%, but this negative effect was temporary and disappeared after 7 wk for the 14.4% CP diet. In contrast, MUN adjusted to a new steady state within 1 wk for all dietary treatments. Modeling quadratic responses with a plateau led to predictions of no reduction in fat- and protein-corrected milk (32.6 kg/d) and yields of fat (1.31 kg/d), lactose (1.49 kg/d), and true protein (1.12 kg/d) until dietary CP decreased below 15.5, 15.3, 15.9, and 16.2%, respectively. In this study, MUN and the yield of MUN were highly correlated with N intake, milk protein yield, and fat- and protein-corrected milk. Surprisingly, N use efficiency (milk protein N/intake N) was not correlated with any variables related to N utilization and reached an apparent upper limit of approximately 30%. Although this observation may be associated with feeding diets deficient in metabolizable protein, late-lactation cows in this study adjusted to low dietary CP concentration better than anticipated as milk production was 2.6, 3.6, 6.4, and 8.0 kg/d higher than National Research Council (2001)-predicted metabolizable protein-allowable milk for dietary CP of 16.2, 14.4, 13.1, and 11.8%, respectively.



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Effects of dietary energy allowance and decline in dry matter intake during the dry period on responses to glucose and insulin in transition dairy cows

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Publication date: Available online 10 May 2017
Source:Journal of Dairy Science
Author(s): S. Salin, A. Vanhatalo, K. Elo, J. Taponen, R.C. Boston, T. Kokkonen
We assessed whether high energy intake during the early dry period [144% of metabolizable energy (ME) requirements/d] followed by a gradual restriction of energy intake in the close-up dry period (119% of ME/d; HEI) impaired whole-body insulin sensitivity compared with a controlled energy intake (100% of ME/d; CEI) throughout the 6-wk dry period. Multiparous Ayrshire dairy cows (n = 16) were blocked by body weight, body condition score, and expected date of parturition and were used in a randomized complete block design until 10 d after parturition. Cows were fed either HEI or CEI diets based on grass silage during the first 3 wk of the dry period and grass silage supplemented with a commercial concentrate (30% of ME intake) during the final 3 wk of gestation. After calving, all cows were fed grass silage ad libitum and an increasing amount of commercial concentrate (maximum 9 kg at d 10 postpartum). Intravenous glucose tolerance tests (IVGTT) and intravenous insulin challenges were performed −10 ± 5 d (n = 15) and +10 ± 1 d (n = 14) relative to parturition. Following glucose injection, we did not find any treatment effects on glucose and insulin responses. The prepartal nonesterified fatty acid (NEFA) response of the HEI group was blunted, basal NEFA and the decrement of NEFA were smaller, and the area under the response curve (AUC) of NEFA was less negative in HEI cows than in CEI cows. The NEFA response reversed after parturition; the NEFA AUC of the HEI group was more negative than that of the CEI group. We did not find similar responses after insulin injection. Across the treatments, NEFA AUC correlated strongly with the basal NEFA concentration during the IVGTT pre- and postpartum. Calculated and model-based indices characterizing the overall glucose tolerance and β-cell function and the insulin sensitivity were higher after parturition than during the dry period. Consistent with the lower basal insulin, the acute insulin release after the glucose infusion was smaller in postpartal IVGTT than in prepartal IVGTT. The results suggest that whole-body insulin sensitivity of the cows increased after parturition. However, the role of peripheral insulin sensitivity in the regulation of glucose partitioning seems to be minor relative to the major change in insulin secretion and clearance during the periparturient period.



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Effect of inhibiting the lactogenic signal at calving on milk production and metabolic and immune perturbations in dairy cows

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Publication date: Available online 10 May 2017
Source:Journal of Dairy Science
Author(s): N. Vanacker, S. Ollier, F. Beaudoin, R. Blouin, P. Lacasse
During the periparturient period, the abrupt increase in energy demand for milk production often induces metabolic and immunological disturbances in dairy cows. Our previous work has shown that reducing milk output by milking once a day or incompletely in the first few days of lactation reduces these disturbances. The aim of this study was to reduce metabolic and immunological disturbances by limiting milk production during the first week of lactation by inhibiting the lactogenic signal driven by prolactin. Twenty-two fresh cows received 8 i.m. injections of the prolactin-release inhibitor quinagolide (QUIN; 2 mg) or water as a control (CTL). The first injection was given just after calving, and the subsequent 7 injections were given every 12 h. Milk production was measured until d 28 after calving. Blood samples were taken from d 1 (calving) to d 5 and then on d 7, 10, 14, 21, and 28 to measure concentrations of urea, phosphorus, calcium, glucose, nonesterified fatty acids (NEFA), β-hydroxybutyrate, and prolactin. Other blood samples were taken on d 2, 5, 10, and 28 to analyze oxidative burst, phagocytosis, and the effect of the serum on the lymphoproliferation of peripheral blood mononuclear cells from donor cows. Blood prolactin concentration was lower from d 2 to 5 but higher from d 10 to 28 in the QUIN cows than in the CTL cows. Milk production was lower from d 2 to 6 in the QUIN cows than in the CTL cows (24.3 ± 6.4 and 34.8 ± 4.1 kg/d on average, respectively). We observed no residual effect of quinagolide on milk production after d 6. During the first week of lactation, blood glucose and calcium concentrations were higher and β-hydroxybutyrate concentration was lower in the QUIN cows than in the CTL cows. Blood NEFA, urea, and phosphorus concentrations were not affected by the treatment. At d 2 and 5, the phagocytosis ability of polymorphonuclear leukocytes was not affected by treatment; however, quinagolide injection enhanced the proportion of cells that entered oxidative burst, The mitogen-induced proliferation of peripheral blood mononuclear cells was greater when they were incubated with serum harvested from the CTL cows and was negatively correlated with the NEFA concentration in the serum. Reducing the prolactin peak at calving was effective in reducing milk production during the first week of lactation without compromising the dairy cow's overall productivity. Slowing the increase in milk production allowed a more gradual transition from pregnancy to lactation and led to a reduction in metabolic stress and an improvement in some immune system aspects during this period.



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Amino acid composition of rumen bacteria and protozoa in cattle

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Publication date: Available online 10 May 2017
Source:Journal of Dairy Science
Author(s): M. Sok, D.R. Ouellet, J.L. Firkins, D. Pellerin, H. Lapierre
Because microbial crude protein (MCP) constitutes more than 50% of the protein digested in cattle, its AA composition is needed to adequately estimate AA supply. Our objective was to update the AA contributions of the rumen microbial AA flowing to the duodenum using only studies from cattle, differentiating between fluid-associated bacteria (FAB), particle-associated bacteria (PAB), and protozoa, based on published literature (53, 16, and 18 treatment means were used for each type of microorganism, respectively). In addition, Cys and Met reported concentrations were retained only when an adequate protection of the sulfur groups was performed before the acid hydrolysis. The total AA (or true protein) fraction represented 82.4% of CP in bacteria. For 10 AA, including 4 essential AA, the AA composition differed between protozoa and bacteria. The most noticeable differences were a 45% lower Lys concentration and 40% higher Ala concentration in bacteria than in protozoa. Differences between FAB and PAB were less pronounced than differences between bacteria and protozoa. Assuming 33% FAB, 50% PAB, and 17% of protozoa in MCP duodenal flow, the updated concentrations of AA would decrease supply estimates of Met, Thr, and Val originating from MCP and increase those of Lys and Phe by 5 to 10% compared with those calculated using the FAB composition reported previously. Therefore, inclusion of the contribution of PAB and protozoa to the duodenal MCP flow is needed to adequately estimate AA supply from microbial origin when a factorial method is used to estimate duodenal AA flow. Furthermore, acknowledging the fact that hydrolysis of 1 kg of true microbial protein yields 1.16 kg of free AA substantially increases the estimates of AA supply from MCP.



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Milk production and composition, nitrogen utilization, and grazing behavior of late-lactation dairy cows as affected by time of allocation of a fresh strip of pasture

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Publication date: Available online 10 May 2017
Source:Journal of Dairy Science
Author(s): R.E. Vibart, M. Tavendale, D. Otter, B.H. Schwendel, K. Lowe, P. Gregorini, D. Pacheco
Eighty late-lactation dairy cows were used to examine the effects of allocating a new pasture strip of a sward based on ryegrass (Lolium perenne L.) in the morning (a.m.; ∼0730 h) or in the afternoon (p.m.; ∼1530 h) on milk production and composition, nitrogen (N) utilization, and grazing behavior. Cows grazed the same pasture strips for 24 h and were offered the same daily herbage allowance. Herbage composition differed among treatments; p.m. herbage had greater dry matter (DM; 22.7 vs. 19.9%), organic matter (OM; 89.5 vs. 88.9%), and water-soluble carbohydrate (10.9 vs. 7.6%) concentrations and lesser crude protein (20.5 vs. 22.2%) and neutral detergent fiber (48.8 vs. 50.4%) concentrations compared with a.m. herbage. Total fatty acids (FA), α-linolenic acid, and polyunsaturated FA (PUFA) were greater in a.m. herbage, whereas monounsaturated FA were greater in p.m. herbage. Estimates of herbage DM intake did not differ among treatments. Daily milk yields and milk fat and milk protein concentrations were similar among treatments, whereas milk fat (684 vs. 627 g/cow), milk protein (545 vs. 505 g/cow), and milk solids (milk fat + milk protein) yields (1,228 vs. 1,132 g/cow) tended to be greater for cows on p.m. herbage. Rumenic acid and total PUFA in milk were greater for cows on a.m. herbage, whereas oleic acid was greater for cows on p.m. herbage. Estimates of urinary N excretion (g/d) did not differ among treatments, but urinary N concentrations were greater for cows on a.m. herbage (5.85 vs. 5.36 g/L). Initial herbage mass (HM) available (kg of DM/ha) and instantaneous HM disappearance rates (kg of DM/ha and kg of DM/h) did not differ, but fractional disappearance rates (0.56 vs. 0.74 per hour for a.m. vs. p.m., respectively) differed. Under the current conditions, timing of pasture strip allocation altered the herbage nutrient supply to cows; allocating a fresh strip of pasture later in the day resulted in moderate increases in milk and milk solids yields in late-lactation dairy cows. Conversely, a greater concentration of precursor FA in a.m. herbage resulted in a greater concentration of beneficial FA in milk, compared with cows on p.m. herbage.



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Use of calcitriol to maintain postpartum blood calcium and improve immune function in dairy cows

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Publication date: Available online 10 May 2017
Source:Journal of Dairy Science
Author(s): A. Vieira-Neto, I.R.P. Lima, F. Lopes, C. Lopera, R. Zimpel, L.D.P. Sinedino, K.C. Jeong, K. Galvão, W.W. Thatcher, C.D. Nelson, J.E.P. Santos
Our objectives were to determine the effects of an injectable formulation of calcitriol on mineral metabolism and immune function in postpartum Holstein cows that received an acidogenic diet prepartum to minimize hypocalcemia. In experiment 1, cows within 6 h of calving received calcitriol (0, 200, or 300 μg) to determine the dose needed to increase plasma concentrations of Ca; 300 μg was sufficient to sustain Ca for at least 3 d. In experiment 2, multiparous cows were assigned randomly to receive only vehicle (control, n = 25) or 300 μg of calcitriol (n = 25) subcutaneously within the first 6 h after calving. Blood was sampled before treatment and 12 h later, then daily until 15 d in milk (DIM), and analyzed for concentrations of ionized Ca (iCa), total Ca (tCa), total Mg (tMg), and total P (tP), metabolites, and hormones. Urine was sampled in the first 7 DIM and analyzed for concentrations of tCa, tMg, and creatinine. Neutrophil function was evaluated in the first week postpartum. Dry matter intake and production performance were evaluated for the first 36 DIM. Calcitriol administration increased concentrations of calcitriol in plasma within 12 h of application from 51 to 427 pg/mL, which returned to baseline within 5 d. Concentrations of iCa and tCa increased 24 h after treatment with calcitriol. Concentrations of iCa (control = 1.08 vs. calcitriol = 1.20 mM), tCa (control = 2.23 vs. calcitriol = 2.33 mM), and tP (control = 1.47 vs. calcitriol = 1.81 mM) remained elevated in cows treated with calcitriol until 3, 5, and 7 DIM, respectively, whereas concentration of tMg (control = 0.76 vs. calcitriol = 0.67 mM) was less in calcitriol cows than control cows until 3 DIM. Concentrations of parathyroid hormone decreased in calcitriol cows compared with control cows (control = 441 vs. calcitriol = 336 pg/mL). Calcitriol tended to increase plasma concentrations of β-hydroxybutyrate and serotonin, but concentrations of glucose, nonesterified fatty acids, and C-telopeptide of type I collagen in plasma did not differ between treatments. Cows treated with calcitriol excreted more urinary tCa (control = 0.5 vs. calcitriol = 2.1 g/d) and tMg (control = 4.5 vs. calcitriol = 5.0 g/d) in the first 7 and 2 DIM, respectively, than control cows. Compared with control, calcitriol improved the proportion of neutrophils with oxidative burst (control = 31.9 vs. calcitriol = 40.6%), mean fluorescence intensity for oxidative burst (control = 90,900 vs. calcitriol = 99,746), and mean fluorescence intensity for phagocytosis (control = 23,887 vs. calcitriol = 28,080). Dry matter intake, yields of milk, and milk components did not differ between treatments. Administration of 300 μg of calcitriol at calving was safe and effective in increasing blood concentration of iCa and plasma concentrations of calcitriol, tCa, and tP for the first 6 d after treatment, and improved measures of innate immune function in early-lactation Holstein cows.



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Thiamine supplementation facilitates thiamine transporter expression in the rumen epithelium and attenuates high-grain-induced inflammation in low-yielding dairy cows

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Publication date: Available online 10 May 2017
Source:Journal of Dairy Science
Author(s): X.H. Pan, L. Yang, Y. Beckers, F.G. Xue, Z.W. Tang, L.S. Jiang, B.H. Xiong
An experiment was conducted to uncover the effects of increasing dietary grain levels on expression of thiamine transporters in ruminal epithelium, and to assess the protective effects of thiamine against high-grain-induced inflammation in dairy cows. Six rumen-fistulated, lactating Holstein dairy cows (627 ± 16.9 kg of body weight, 180 ± 6 d in milk; mean ± standard deviation) were randomly assigned to a replicated 3 × 3 Latin square design trial. Three treatments were control (20% dietary starch, dry matter basis), high-grain diet (HG, 33.2% dietary starch, DM basis), and HG diet supplemented with 180 mg of thiamine/kg of dry matter intake. On d 19 and 20 of each period, milk performance was measured. On d 21, ruminal pH, endotoxic lipopolysaccharide (LPS), and thiamine contents in rumen and blood, and plasma inflammatory cytokines were detected; a rumen papillae biopsy was taken on d 21 to determine the gene and protein expression of toll-like receptor 4 (TLR4) signaling pathways. The HG diet decreased ruminal pH (5.93 vs. 6.49), increased milk yield from 17.9 to 20.2 kg/d, and lowered milk fat and protein from 4.28 to 3.83%, and from 3.38 to 3.11%, respectively. The HG feeding reduced thiamine content in rumen (2.89 vs. 8.97 μg/L) and blood (11.66 vs. 17.63 μg/L), and the relative expression value of thiamine transporter-2 (0.37-fold) and mitochondrial thiamine pyrophosphate transporter (0.33-fold) was downregulated by HG feeding. The HG-fed cows exhibited higher endotoxin LPS in rumen fluid (134,380 vs. 11,815 endotoxin units/mL), and higher plasma concentrations of lipopolysaccharide binding protein and pro-inflammatory cytokines when compared with the control group. The gene and protein expression of tumor necrosis factor α (TNFα), IL1B, and IL6 in rumen epithelium increased when cows were fed the HG diet, indicating that local inflammation occurred. The depressions in ruminal pH, milk fat, and protein of HG-fed cows were reversed by thiamine supplementation. Thiamine supplementation increased thiamine contents in rumen and blood, and also upregulated the relative expression of thiamine transporters compared with the HG group. Thiamine supplementation decreased ruminal LPS (49,361 vs. 134,380 endotoxin units/mL) and attenuated the HG-induced inflammation response as indicated by a reduction in plasma IL6, and decreasing gene and protein expression of pro-inflammatory cytokines in rumen epithelium. Western bottling analysis showed that thiamine suppressed the protein expression of TLR4 and the phosphorylation of nuclear factor kappa B (NFκB) unit p65. In conclusion, HG feeding inhibits thiamine transporter expression in ruminal epithelium. Thiamine could attenuate the epithelial inflammation during high-grain feeding, and the protective effects may be due to its ability to suppress TLR4-mediated NFκB signaling pathways.



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Effect of feeding strategies and cropping systems on greenhouse gas emission from Wisconsin certified organic dairy farms

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Publication date: Available online 10 May 2017
Source:Journal of Dairy Science
Author(s): D. Liang, F. Sun, M.A. Wattiaux, V.E. Cabrera, J.L. Hedtcke, E.M. Silva
Organic agriculture continues to expand in the United States, both in total hectares and market share. However, management practices used by dairy organic producers, and their resulting environmental impacts, vary across farms. This study used a partial life cycle assessment approach to estimate the effect of different feeding strategies and associated crop production on greenhouse gas emissions (GHG) from Wisconsin certified organic dairy farms. Field and livestock-driven emissions were calculated using 2 data sets. One was a 20-yr data set from the Wisconsin Integrated Cropping System Trial documenting management inputs, crop and pasture yields, and soil characteristics, used to estimate field-level emissions from land associated with feed production (row crop and pasture), including N2O and soil carbon sequestration. The other was a data set summarizing organic farm management in Wisconsin, which was used to estimate replacement heifer emission (CO2 equivalents), enteric methane (CH4), and manure management (N2O and CH4). Three combinations of corn grain (CG) and soybean (SB) as concentrate (all corn = 100% CG; baseline = 75% CG + 25% SB; half corn = 50% CG + 50% SB) were assigned to each of 4 representative management strategies as determined by survey data. Overall, GHG emissions associated with crop production was 1,297 ± 136 kg of CO2 equivalents/t of ECM without accounting for soil carbon changes (ΔSC), and GHG emission with ΔSC was 1,457 ± 111 kg of CO2 equivalents/t of ECM, with greater reliance on pasture resulting in less ΔSC. Higher levels of milk production were a major driver associated with reduction in GHG emission per metric tonne of ECM. Emissions per metric tonne of ECM increased with increasing proportion of SB in the ration; however, including SB in the crop rotation decreased N2O emission per metric tonne of ECM from cropland due to lower applications of organically approved N fertility inputs. More SB at the expense of CG in the ration reduced enteric CH4 emission per metric tonne of ECM (because of greater dietary fat content) but increased N2O emission per metric tonne of ECM from manure (because of greater N content). An increased reliance on pasture for feed at the expense of grain resulted in decreased in milk production, subsequently leading to substantially higher emissions per metric tonne of ECM.



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Acute phase proteins and inflammatory factors: the peri-operative changes in on-pump versus off-pump cardiac surgery

Abstract

Objectives

Off-pump cardiac bypass grafting (OPCABG) has reduced in numbers as some studies suggest no clinical benefit and greater technical difficulty compared to on-pump operations. We examined the inflammatory changes due to extracorporeal circulation and compared the outcomes of patients undergoing OPCABG, on-pump CABG and single cardiac valve replacement with mechanical one.

Methods

Sixty-six elective patients who had severe coronary vessel disease requiring coronary artery bypass were allocated to two groups. The 1st group underwent OPCAB and the other one on-pump coronary artery bypass. A third group of 33 patients presented with single valve disease and underwent mechanical valve replacement were included in our study. Pre- and postoperative serum levels of 15 markers of acute phase inflammatory response were analysed. Postoperative complications were also recorded.

Results

Both on-pump and off-pump coronary bypass techniques provoked biochemical and enzymatic alterations, with more systemic inflammations which correlate with more complications and worse outcome in the on-pump group. Mechanical valve implantation also provoked more systemic inflammation, possibly due to foreign bodies in the systemic circulation.

Conclusion

Our results suggest that off-pump bypass induce a lesser inflammatory response and have better outcomes to on-pump bypass and valve replacement operations.



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Phase II trial of the PI3 kinase inhibitor buparlisib (BKM-120) with or without enzalutamide in men with metastatic castration resistant prostate cancer

Phosphatidylinositol-3-kinase (PI3K) and androgen receptor pathway activation is common in metastatic castration resistant prostate cancer (mCRPC). Buparlisib is an oral, pan-class I PI3 kinase inhibitor.

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Cystic fibrosis transmembrane conductance regulator mediates tenogenic differentiation of tendon-derived stem cells and tendon repair: accelerating tendon injury healing by intervening in its downstream signaling [Research]

Tendons are a mechanosensitive tissue, which enables them to transmit to bone forces that are derived from muscle. Patients with tendon injuries, such as tendinopathy or tendon rupture, were often observed with matrix degeneration, and the healing of tendon injuries remains a challenge as a result of the limited understanding of tendon biology. Our study demonstrates that the stretch-mediated activation channel, cystic fibrosis transmembrane conductance regulator (CFTR), was up-regulated in tendon-derived stem cells (TDSCs) during tenogenic differentiation under mechanical stretching. Tendon tissues in CFTR dysfunctional mice (DF508) exhibited irregular cell arrangement, uneven fibril diameter distribution, weak mechanical properties, and less matrix formation in a tendon defect model. Moreover, both tendon tissues and TDSCs isolated from DF508 mice showed significantly decreased levels of tendon markers, such as scleraxis, tenomodulin, Col1A1 (collagen type I α 1 chain), and decorin. Furthermore, by RNA sequencing analysis, we demonstrated that Wnt/β-catenin signaling was abnormally activated in TDSCs from DF508 mice, thereby further activating the pERK1/2 signaling pathway. Of most importance, we found that intervention in pERK1/2 signaling could promote tenogenic differentiation and tendon regeneration both in vitro and in vivo. Taken together, our study demonstrates that CFTR plays an important role in tenogenic differentiation and tendon regeneration by inhibiting the β-catinin/pERK1/2 signaling pathway. The therapeutic strategy of intervening in the CFTR/β-catenin/pERK1/2 regulatory axis may be helpful for accelerating tendon injury healing, which has implications for tendon injury management.—Liu, Y., Xu, J., Xu, L., Wu, T., Sun, Y., Lee, Y.-W., Wang, B., Chan, H.-C., Jiang, X., Zhang, J., Li, G. Cystic fibrosis transmembrane conductance regulator mediates tenogenic differentiation of tendon-derived stem cells and tendon repair: accelerating tendon injury healing by intervening in its downstream signaling.



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PHD3 is a transcriptional coactivator of HIF-1{alpha} in nucleus pulposus cells independent of the PKM2-JMJD5 axis [Research]

The role of prolyl hydroxylase (PHD)-3 as a hypoxia inducible factor (HIF)-1α cofactor is controversial and remains unknown in skeletal tissues. We investigated whether PHD3 controls HIF-1 transcriptional activity in nucleus pulposus (NP) cells through the pyruvate kinase muscle (PKM)-2-Jumonji domain­–containing protein (JMJD5) axis. PHD3–/– mice (12.5 mo old) showed increased incidence of intervertebral disc degeneration with a concomitant decrease in expression of the HIF-1α targets VEGF-A, glucose transporter-1, and lactate dehydrogenase A. PHD3 silencing decreased hypoxic activation of HIF-1α C-terminal transactivation domain (C-TAD), but not HIF-1α-N-terminal-(N)-TAD or HIF-2α-TAD. Moreover, PHD3 suppression in NP cells resulted in decreased HIF-1α enrichment on target promoters and lower expression of select HIF-1 targets. Contrary to other cell types, manipulation of PKM2 and JMJD5 levels had no effect on HIF-1 activity in NP cells. Likewise, stabilization of tetrameric PKM2 by a chemical approach had no effect on PHD3-dependent HIF-1 activity. Coimmunoprecipitation assays showed lack of association between HIF-1α and PKM2 in NP cells. Results support the role of the PHD3 as a cofactor for HIF-1, independent of PKM2-JMJD5.—Schoepflin, Z. R., Silagi, E. S., Shapiro, I. M., Risbud, M. V. PHD3 is a transcriptional coactivator of HIF-1α in nucleus pulposus (NP) cells independent of PKM2-JMJD5 axis.



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Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model [Research]

Exposure to microgravity leads to alterations in multiple systems, but microgravity-related changes in the gastrointestinal tract and its clinical significance have not been well studied. We used the hindlimb unloading (HU) mouse model to simulate a microgravity condition and investigated the changes in intestinal microbiota and colonic epithelial cells. Compared with ground controls (Ctrls), HU affected fecal microbiota composition with a profile that was characterized by the expansion of Firmicutes and decrease of Bacteroidetes. The colon epithelium of HU mice showed decreased goblet cell numbers, reduced epithelial cell turnover, and decreased expression of genes that are involved in defense and inflammatory responses. As a result, increased susceptibility to dextran sulfate sodium–induced epithelial injury was observed in HU mice. Cohousing of Ctrl mice with HU mice resulted in HU-like epithelial changes in Ctrl mice. Transplantation of feces from Ctrl to HU mice alleviated these epithelial changes in HU mice. Results indicate that HU changes intestinal microbiota, which leads to altered colonic epithelial cell homeostasis, impaired barrier function, and increased susceptibility to colitis. We further demonstrate that alteration in gastrointestinal motility may contribute to HU-associated dysbiosis. These animal results emphasize the necessity of evaluating astronauts’ intestinal homeostasis during distant space travel.—Shi, J., Wang, Y., He, J., Li, P., Jin, R., Wang, K., Xu, X., Hao, J., Zhang, Y., Liu, H., Chen, X., Wu, H., Ge, Q. Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model.



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Transmission electron microscopy artifacts in characterization of the nanomaterial-cell interactions

Abstract

We investigated transmission electron microscopy artifacts obtained using standard sample preparation protocols applied to the investigation of Escherichia coli cells exposed to common nanomaterials, such as TiO2, Ag, ZnO, and MgO. While the common protocols for some nanomaterials result only in known issues of nanomaterial-independent generation of anomalous deposits due to fixation and staining, for others, there are reactions between the nanomaterial and chemicals used for post-fixation or staining. Only in the case of TiO2 do we observe only the known issues of nanomaterial-independent generation of anomalous deposits due to exceptional chemical stability of this material. For the other three nanomaterials, different artifacts are observed. For each of those, we identify causes of the observed problems and suggest alternative sample preparation protocols to avoid artifacts arising from the sample preparation, which is essential for correct interpretation of the obtained images and drawing correct conclusions on cell-nanomaterial interactions. Finally, we propose modified sample preparation and characterization protocols for comprehensive and conclusive investigations of nanomaterial-cell interactions using electron microscopy and for obtaining clear and unambiguous revelation whether the nanomaterials studied penetrate the cells or accumulate at the cell membranes. In only the case of MgO and ZnO, the unambiguous presence of Zn and Mg could be observed inside the cells.



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The sigma-1 receptor modulates dopamine transporter conformation and cocaine binding and may thereby potentiate cocaine self-administration in rats [Molecular Bases of Disease]

The dopamine transporter (DAT) regulates dopamine (DA) neurotransmission by recapturing DA into the presynaptic terminals, and is a principal target of the psychostimulant cocaine. The sigma-1 receptor (σ1R) is a molecular chaperone, and its ligands have been shown to modulate dopamine neuronal signaling, although their effects on DAT activity are unclear. Here, we report that the prototypical σ1R agonist (+)-pentazocine potentiated the dose response of cocaine self-administration in rats, consistent with effects of the σR agonists PRE-084 and DTG reported previously. These behavioral effects appeared to be correlated with functional changes of DAT. Preincubation with (+)-pentazocine or PRE-084 increased the Bmax values of [3H]WIN35428 binding to DAT in rat striatal synaptosomes and transfected cells. A specific interaction between σ1R and DAT was detected by co-immunoprecipitation and bioluminescence resonance energy transfer assays. Mutational analyses indicated that the transmembrane domain of σ1R likely mediated this interaction. Further, cysteine accessibility assays showed that σ1R agonist preincubation potentiated cocaine-induced changes in DAT conformation, which were blocked by the specific σ1R antagonist CM304. Moreover, σ1R ligands had distinct effects on σ1R multimerization. CM304 increased the proportion of multimeric σ1Rs, whereas (+)-pentazocine increased monomeric σ1Rs. Together these results support the hypothesis that σ1R agonists promote dissociation of σ1R multimers into monomers, which then interact with DAT to stabilize an outward-facing DAT conformation and enhance cocaine binding. We propose that this novel molecular mechanism underlies the behavioral potentiation of cocaine self administration by σ1R agonists in animal models.

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Proteolytic Cleavage of the Hydrophobic Domain in the CaV{alpha}2{delta}1 Subunit improves assembly and activity of cardiac CaV1.2 Channels [Molecular Biophysics]

Voltage-gated L-type CaV1.2 channels in cardiomyocytes exist as heteromeric complexes with the pore-forming CaVα1, CaVβ, and CaVα2δ1 subunits. The full complement of subunits is required to reconstitute the native-like properties of L-type Ca2+ currents but the molecular determinants responsible for the formation of the heteromeric complex are still being studied. Enzymatic treatment with PI-PLC, a phospholipase C specific for the cleavage of glycosyl-phosphatidylinositol (GPI)-anchored proteins, disrupted plasma membrane localization of the cardiac CaVα2δ1 prompting us to investigate deletions of its hydrophobic transmembrane domain. Patch-clamp experiments indicated that C-terminally cleaved CaVα2δ1 proteins upregulate CaV1.2 channels. In contrast, deleting the residues before the single hydrophobic segment (CaVα2δ1 Δ1059-1063) impaired current upregulation.CaVα2δ1 mutants G1060I and G1061I near-eliminated the cell-surface fluorescence of CaVα2δ1, indicated by two-color flow cytometry assays and confocal imaging, and prevented CaVα2δ1-mediated increase in peak current density and modulation of the voltage-dependent gating of CaV1.2. These impacts were specific to substitutions with isoleucine residues since functional modulation was partially preserved in CaVα2δ1 G1060A and G1061A proteins. Moreover, C-terminal fragments exhibited significantly altered mobility in denatured immunoblots of CaVα2δ1 G1060I and G1061I, suggesting that these mutant proteins were impaired in proteolytic processing. Finally, CaVα2δ1 Δ1059-1063, but not CaVα2δ1 G1060A, failed to coimmunoprecipitate with CaV1.2. Altogether, our data support a model in which small neutral hydrophobic residues facilitate the post-translational cleavage of the CaVα2δ1 subunit at the predicted membrane interface and further suggest that preventing GPI-anchoring of CaVα2δ1 averts its cell-surface expression, its interaction with CaVα1, and modulation of CaV1.2 currents.

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The uniqueness of subunit {alpha} of mycobacterial F-ATP synthases: An evolutionary variant for niche adaptation [Enzymology]

The F1FO ATP (F-ATP) synthase is essential for growth of Mycobacterium tuberculosis, the causative agent of tuberculosis (TB). In addition to their synthase function most F-ATP synthases possess an ATP-hydrolase activity, which is coupled to proton-pumping activity. However, the mycobacterial enzyme lacks this reverse activity, but the reason for this deficiency is unclear. Here, we report that a Mycobacterium-specific, 36 amino acid long C-terminal domain in the nucleotide-binding subunit α (Mtα) of F-ATP synthase suppresses its ATPase activity and determined the mechanism of suppression. First, we employed vesicles to show that in intact membrane-embedded mycobacterial F-ATP synthases deletion of the C-terminal domain enabled ATPase and proton-pumping activity. We then generated a heterologous F-ATP synthase model system, which demonstrated that transfer of the mycobacterial C-terminal domain to a standard F-ATP synthase α subunit suppresses ATPase activity. Single-molecule rotation assays indicated that the introduction of this Mycobacterium-specific domain decreased the angular velocity of the power-stroke after ATP binding. Solution X-ray scattering data and NMR results revealed the solution shape of Mtα and the 3D structure of the subunit α C-terminal peptide 521PDEHVEALDEDKLAKEAVKV540 of M. tubercolosis (Mtα521-540), respectively. Together with crosslinking studies, the solution structural data lead to a model, in which Mtα521-540 comes in close proximity with subunit γ residues 104-109, whose interaction may influence the rotation of the camshaft-like subunit γ. Finally, we propose that the unique segment Mtα514-549, which is accessible at the C-terminus of mycobacterial subunit α, is a promising drug epitope.

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A systems biology analysis connects insulin receptor signaling with glucose transporter translocation in rat adipocytes [Computational Biology]

Type 2 diabetes is characterized by insulin resistance, which arises from malfunctions in the intracellular insulin signaling network. Knowledge of the insulin signaling network is fragmented and, because of the complexity of this network, little consensus has emerged for the structure and importance of the different branches of the network. To help overcome this complexity, systems biology mathematical models have been generated for predicting both the activation of the insulin receptor (IR) and the redistribution of glucose transporter 4 (GLUT4) to the plasma membrane. Although the insulin signal transduction between IR and GLUT4 has been thoroughly studied with modelling and time-resolved data in human cells, comparable analyses in cells from commonly used model organisms such as rats and mice are lacking. Here, we combined existing data and models for rat adipocytes with new data collected for the signaling network between IR and GLUT4 to create a model also for their inter-connections. To describe all data (>140 data points), the model needed three distinct pathways from IR to GLUT4: i) via protein kinase B (PKB) and Akt substrate of 160 kDa (AS160), ii) via an AS160-independent pathway from PKB, and iii) via an additional pathway from IR, e.g. affecting the membrane constitution. The developed combined model could describe data not used for training the model and was used to generate predictions of the relative contributions of the pathways from IR to translocation of GLUT4. The combined model provides a systems-level understanding of insulin signaling in rat adipocytes, which, when combined with corresponding models for human adipocytes, may contribute to model-based drug development for diabetes.

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Endoplasmic reticulum (ER) Ca2+-channel activity contributes to ER stress and cone death in cyclic nucleotide-gated channel deficiency [Cell Biology]

Endoplasmic reticulum (ER) stress and mislocalization of improperly folded proteins have been shown to contribute to photoreceptor death in models of inherited retinal degenerative diseases. In particular, mice with cone cyclic nucleotide-gated (CNG) channel deficiency, a model for achromatopsia, display both early-onset ER stress and opsin mistrafficking. By 2 weeks, these mice show elevated signaling from all three arms of the ER stress pathway, and by 1 month, cone opsin is improperly distributed away from its normal outer segment location to other retinal layers. This work investigated the role of Ca2+ release channels in ER stress, protein mislocalization, and cone death in a mouse model of CNG channel deficiency. We examined whether preservation of luminal Ca2+ stores through pharmacological and genetic suppression of ER Ca2+ efflux protects cones by attenuating ER stress. We demonstrated that inhibition of ER Ca2+ efflux channels reduced all three arms of ER stress signaling while improving opsin trafficking to cone outer segments and decreasing cone death by 20-35%. Cone-specific gene deletion of the inositol-1,4,5-trisphosphate receptor type I (IP3R1) also significantly increased cone density in the CNG channel-deficient mice, suggesting that IP3R1 signaling contributes to Ca2+ homeostasis and cone survival. Consistent with the important contribution of organellar Ca2+ signaling in this achromatopsia mouse model, significant differences in dynamic intraorganellar Ca2+ levels were detected in CNG channel-deficient cones. These results thus identify a novel molecular link between Ca2+ homeostasis and cone degeneration; thereby revealing novel therapeutic targets to preserve cones in inherited retinal degenerative diseases.

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Pedunculated hemorrhagic cystic swelling: An unusual presentation of polydactyly

Kavita Bisherwal, Archana Singal, Deepika Pandhi, Sonal Sharma

Indian Dermatology Online Journal 2017 8(3):220-221



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Body to scalp: Evolving trends in body hair transplantation

Kuldeep Saxena, Sandeep S Savant

Indian Dermatology Online Journal 2017 8(3):167-175

Follicular unit extraction (FUE) is becoming an increasingly popular method for hair restoration. As FUE leaves behind no linear scars, it is more suitable to harvest from various body areas including beard, chest, and extremities in hirsute individuals. Body hair characteristics such as thickness, length, and hair cycle may not completely match to that of the scalp hair. The techniques of harvesting body hairs are more time consuming, requiring higher degree of skill than regular scalp FUE. Body hair transplantation can be successfully used either alone or in combination with scalp hair in advanced grades of baldness, for improving the cosmetic appearance of hairlines and in scarring alopecia when there is paucity of donor scalp hair. Harvesting of body hairs opens up a new viable donor source for hair restoration surgeons, especially in cases of advanced Norwood grades five and above of androgenetic alopecia.

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A pilot study for the evaluation of pcr as a diagnostic tool in patients with suspected dermatophytoses

Robin Sharma, Samiksha Gupta, Dinesh P Asati, T Karuna, Shashank Purwar, Debasis Biswas

Indian Dermatology Online Journal 2017 8(3):176-180

Context: The conventional diagnostic tools for dermatophytoses suffer from several limitations including low sensitivity, specificity, and long turn-around-time. Aims: The present study was, therefore, performed to evaluate the performance of a polymerase chain reaction (PCR)-based method for the diagnosis of this condition. Settings and Design: The study was conducted in the Dermatology outpatient department of a tertiary care teaching hospital in central India over a period of 3 months from July to September 2015. Materials and Methods: Forty participants, including 25 cases and 15 controls, were recruited in this observational study. Direct microscopy and fungal culture were performed from skin scrapings and nail clippings collected from the participants. PCR was also performed to amplify the chitin synthase 1 and internal transcribed spacer 2 genes from DNA samples extracted from the same clinical materials, using the method reported by Brillowska-Dabrowska et al. The diagnostic performance of fungal culture and PCR was compared using OpenEpi software. Results: We observed a significant male predominance among patients with dermatophytoses. The sensitivity of fungal culture and dermatophyte PCR to diagnose dermatophytoses was 24% and 48%, respectively, whereas the specificity of the two assays was 100% and 93.3%, respectively. The likelihood ratio of a positive PCR assay was 7.2 and the negative likelihood ratio was 0.5. PCR assay also delivered a significant shortening of the time-to-diagnosis, with the mean turn-around-time being 8 hours and 14 days for PCR and culture, respectively. Conclusion: This study, thus, highlights the potential merits of the dermatophyte PCR assay in achieving a rapid diagnosis of dermatophytoses and underscores its utility as a complementary test to improve the sensitivity of the conventional diagnostic tools for this condition, as well as to reliably differentiate this condition from other similar skin conditions.

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SkIndia Quiz 37: A persistent plaque in the pubic region

Lalit Kumar Gupta, Ranjana Beniwal, Ashok Kumar Khare, Asit Mittal, Sharad Mehta, Manisha Balai

Indian Dermatology Online Journal 2017 8(3):227-228



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Occupational dermatoses among cottage industry workers of Kashmir Valley in North India

Saniya Akhtar, Iffat Hassan, Farhan Rasool, Yasmeen J Bhat, Gousia Sheikh

Indian Dermatology Online Journal 2017 8(3):181-185

Introduction: Cottage industry is usually a small-scale industry operated from home by family members using their own equipment. Kashmir has a unique cottage industry of its own which deals with production of many handicrafts, which may lead to a peculiar pattern of skin diseases in these artisans. Aim: The aim of this study was to find out the pattern of skin disorders in the cottage industry workers of Kashmir valley, with primary focus on the occupation-related dermatoses and to identify the most common cutaneous manifestation in these workers. Materials and Methods: This was a cross-sectional descriptive study in which 1062 cottage industry workers engaged in different crafts were screened. A detailed history taking and examination was carried out in each worker and the diagnosis was made on clinical grounds. Wherever deemed necessary, relevant investigations were done to establish the nature of the disease. Results: A total of 1062 workers were evaluated for the presence of skin disorders. The male-to-female ratio was 1:1.5. The mean age of the study group was 30.3 years ± 10.79 years, with maximum number of workers (164) belonging to the crewel embroidery industry. The mean duration of work was 6.4 ± 2.08 hours/day. A total of 953 workers (89.7%) had cutaneous manifestations, with callosities being the most common finding seen in 371 workers (35%), followed by cumulative insult dermatitis seen in 201 workers (19%). Conclusion: Cottage industry of Kashmir valley is a unique occupational group where a high percentage of workers had cutaneous manifestations related to their occupation, with callosities being the most common finding. Information and better knowledge regarding these dermatoses are important in devising strategies to improve the health scenario of these workers. Simple measures such as proper use of instruments, use of protective gloves, guarded use of chemicals, and hand washing may be very beneficial in reducing the burden of health problems in these workers.

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Persistent and generalized purpuric lesions in an adolescent: A rare atypical form of pityriasis rosea

Funda Tamer, Evren Sarifakioglu, Ozge M Orenay, Umran Yildirim

Indian Dermatology Online Journal 2017 8(3):217-218



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Misuse of topical corticosteroids over face: A clinical study

Kajal Manchanda, Sandip Mohanty, Pallavi C Rohatgi

Indian Dermatology Online Journal 2017 8(3):186-191

Introduction: Topical corticosteroids (TCS) have been widely used in various dermatological diseases. However, because of inadvertent use, TCS misuse has become a common problem faced by dermatologists in various parts of the world. Prolonged use over the face can cause various side effects such as steroid rosacea, acneiform eruptions, and hypertrichosis. Aim: To study the effects of TCS misuse and analyze various factors promoting its use on face. Materials and Methods: A total of 100 patients presenting with various facial dermatoses following the misuse of TCS on the face were studied. Detailed history was noted and the various side effects were recorded. Results: Majority of the patients (70%) were females with maximum number of patients belonging to the age group of 11–20 years. Eighty-five percent of the patients were applying TCS for medical conditions, with acne being the most common indication, and the rest were applying as a general face cream. Pruritus and acneiform eruptions were the most common side effects observed and the other reported were erythema, photosensitivity, steroid dependent face, and telangiectasia. Conclusion: TCS misuse especially over the face can lead to a multitude of side effects. It is high time to create awareness among the patients as well as doctors regarding the proper usage of this wonder drug.

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Zinc responsive acrodermatitis in nephrotic syndrome

M Mahalakshmi, L Balamurugan, R Madhu, A Ramesh

Indian Dermatology Online Journal 2017 8(3):224-225



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Disseminated cutaneous trichosporonosis in an adult bone marrow transplant patient

A. M. Y. Yong, SS Yang, KB Tan, SA Ho

Indian Dermatology Online Journal 2017 8(3):192-194

The Trichosporon species are yeast-like opportunistic pathogens in immunocompromised patients. Trichosporon asahii infections have been reported in pediatric bone marrow transplant (BMT) patients. However, its incidence is low in the adult literature. A 52-year-old Chinese woman who was diagnosed with acute myeloid leukemia received induction chemotherapy and underwent allogenic bone marrow transplant, which was complicated by a relapse and required salvage chemotherapy. She developed persistent non-neutropenic fever secondary to presumed hepatosplenic candidiasis. Antifungal therapy with fluconazole and anidulafungin was administered. She remained febrile and tender dusky nodules appeared over all the four limbs. Histopathological examination and fungal culture identified T. asahii. Oral voriconazole was initiated with complete resolution of her lesions. The Trichosporon species is a frequently isolated yeast species from cancer patients. Voriconazole has become the first choice agent against Trichosporon. We highlight the increased awareness and clinical suspicion required for diagnosis and subsequent management in similar adult patients.

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Kaposi's varicelliform eruption in phenytoin-induced erythroderma

Kikkeri N Naveen, D Joshika Bhandary, MD Chandan, SB Athaniker

Indian Dermatology Online Journal 2017 8(3):231-232



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Dermatofibrosarcoma protuberans in a 9-year-old child

Priyanka Patil, Swagata Tambe, Chitra Nayak, C Ramya

Indian Dermatology Online Journal 2017 8(3):195-197

Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue neoplasm of low-to-intermediate grade malignant potential. Childhood onset of DFSP is rare. It is most commonly seen on the trunk and proximal extremities. In children, a high index of suspicion is necessary to avoid delays in diagnosis that can lead to further morbidity. Here, we report a case of DFSP in a 9-year-old female child. Excision biopsy of lesion was performed with 1 cm margin. After confirmation of the diagnosis by histopathology, the patient was observed for recurrence, but there was no recurrence after 1 and half years of follow up.

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Rapp hodgkin syndrome

Manas Chatterjee, Shekhar Neema, Sweta Mukherjee

Indian Dermatology Online Journal 2017 8(3):215-216



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Atypical lichen myxedematosus: A case with remarkable response to low dose melphalan

Mini Gomathy, Beena Sunny, Krishna Anitha, Sukumarakurup Sreekanth, Kunnaruvath Rajeevan, Soni C Das

Indian Dermatology Online Journal 2017 8(3):198-200

A 41-year-old man was referred to our outpatient department with a diagnosis of urticaria with angioedema of 3 months duration. On examination, he had generalized coalescent waxy papules and diffuse periorbital swelling. Systemic examination was unremarkable except for limited finger flexion. Serum electrophoresis and thyroid function tests were normal. Histopathological examination showed normal epidermis and intradermal mucin deposition, which was diagnostic of lichen myxedematosus (LM). The patient showed prompt response to melphalan. Here, we report this case of atypical LM because the patient had generalized eruption with normal thyroid function along with the absence of monoclonal gammopathy.

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