Repeated restraint stress reduces the acquisition and relapse of methamphetamine-conditioned place preference but not behavioral sensitization

Publication date: Available online 5 February 2018
Source:Brain Research Bulletin
Author(s): Jee-Yeon Seo, Yong-Hyun Ko, Shi-Xun Ma, Bo-Ram Lee, Seok-Yong Lee, Choon-Gon Jang
The studies for the effects of stress on drug addiction were mostly obtained using sequential exposure to stress and drugs. However, few studies have been conducted on the effects of simultaneous exposure to stress and methamphetamine (METH) on METH-induced reward effects and behavioral sensitization. Thus, we examined the effects of simultaneous exposure to restraint stress and METH on METH-induced addictive behaviors using conditioned place preference (CPP) in mice. During the conditioning period, the mice were exposed to 2 h restraint stress before administration of METH or saline for 4 days. To investigate the effect of restraint stress on drug relapse, the mice were exposed to 2 h of restraint stress for 4 days during the late period of withdrawal. The results showed that the acquisition of METH CPP was impaired by simultaneous exposure to restraint stress and METH administration and the impairment of METH CPP was retained until METH-induced reinstatement. Additionally, based on locomotor activity data measured during METH reinstatement, simultaneous stress exposure during the conditioning phase increased METH-induced locomotor sensitization. We also found that the magnitude of METH-primed relapse was reduced in mice exposed to restraint stress during the late period of withdrawal. Taken together, these findings suggest that simultaneous exposure to restraint stress and METH can reduce the acquisition and relapse of METH-induced addictive behaviors but not behavioral sensitization.



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Involvement of NO/NMDA-R pathway in the behavioral despair induced by amphetamine withdrawal

Publication date: Available online 5 February 2018
Source:Brain Research Bulletin
Author(s): Arvin Haj-Mirzaian, Shayan Amiri, Hossein Amini-Khoei, Arya Haj-Mirzaian, Arsalan Hashemiaghdam, Kiana Ramezanzadeh, Maria Ghesmati, Khashayar Afshari, Ahmad Reza Dehpour
Abrupt discontinuation of chronic amphetamine consumption leads to withdrawal symptoms including depression, anhedonia, dysphoria, fatigue, and anxiety. These irritating symptoms may result in continuing to take the drug or can lead to suicidal behavior. Past studies have shown the involvement of various biologic systems in depression induced following amphetamine withdrawal (AW). However, there is no evidence about the relation between nitric oxide (NO) with NMDA receptors on depression following AW. In this study, we examined the involvement of the NO/NMDA pathways on depressive-like behaviors after 24 h withdrawal following 5 continuous days of amphetamine administration in male NMRI mice. Behavioral tasks used for depression assessment included the forced swimming test (FST), the Splash test and the open field test (OFT). In order to evaluate the role of NO/NMDA pathways animals treated with MK-801 (NMDA-R antagonist), Aminoguanidine (AG), a selective iNOS inhibitor, Nω-Nitro-L-arginine (L-NNA), a non-selective NOS inhibitor and 7-Nitro indazole (7-NI), a selective nNOS inhibitor. We also measured the level of nitrite in the hippocampus. Our data showed that AW induced the depressive-like effect in the FST and the Splash test. We showed that administration of AG, L-NNA, and MK-801 mitigated AW induced depression, however, 7-NI was failed to decrease depressive-like behaviors. Also, the antidepressant-like effect of co-injection of sub-effective doses of MK-801 with AG suggested that inducible nitric oxide synthase (iNOS) is associated with NMDA-R in AW induced depression. In conclusion, both NO and NMDA-R pathways are involved and related to each other in depression induced following AW.



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Effect of glucagon-like peptide-1 analogue; Exendin-4, on cognitive functions in type 2 diabetes mellitus; possible modulation of brain derived neurotrophic factor and brain Visfatin

Publication date: Available online 5 February 2018
Source:Brain Research Bulletin
Author(s): O.M. Abdelwahed, O.M. Tork, M.M. Gamal el Din, L. Rashed, M. Zickri
BackgroundBrain derived neurotrophic factor (BDNF) is one of the most essential neurotrophic factors in the brain. BDNF is involved in learning, memory and locomotion suggesting it as a target in type 2 diabetes mellitus (T2DM) associated cognitive changes. Visfatin; an adipokine discovered to be expressed in the brain; was found to have multiple effects including its participation in keeping energy supply to the cell and is consequentially involved in cell survival. Its role in cognitive functions in T2DM was not studied before. Recent studies point to the possible neuro-protective mechanisms of glucagon-like peptide 1 analogue: Exendin-4 (Ex-4) in many cognitive disorders, but whether BDNF or Visfatin are involved or not in its neuro-protective mechanisms; is still unknown.Aimsto study the changes in cognitive functions in T2DM, either not treated or treated with Glucagon-like peptide 1 (GLP-1) analogue: Ex-4, and to identify the possible underlying mechanisms of these changes and whether BDNF and brain Visfatin are involved.MethodsA total of 36 adult male wistar albino rats were divided into 4 groups; Control, Exendin-4 control, Diabetic and Exendin-4 treated groups. At the end of the study, Y-maze and open field tests were done the day before scarification to assess spatial working memory and locomotion, respectively. Fasting glucose and insulin, lipid profile and tumor necrosis factor- alpha (TNF-α) were measured in the serum. Homeostasis model assessment insulin resistance was calculated. In the brain tissue, malondialdehyde (MDA) level, gene expression and protein levels of BDNF and Visfatin, area of degenerated neurons, area of glial cells and area % of synaptophysin immunoexpression were assessed.ResultsCompared with the control, the untreated diabetic rats showed insulin resistance, dyslipidemia and elevation of serum TNF-α. The brain tissue showed down-regulation of BDNF gene expression and reduction of its protein level, up-regulation of Visfatin gene expression and elevation of its protein level, increase in MDA, area of degenerated neurons and area of glial cells and reduction in area % of synaptophysin immunoexpression. These changes were paralleled with significant deterioration in spatial working memory and locomotion. Treatment of diabetic rats with Ex-4 reversed all these changes.ConclusionT2DM has a negative impact on cognitive functions through different pathological and subcellular mechanisms. The current study provides evidence for involvement of BDNF and brain Visfatin in T2DM- associated cognitive dysfunction. BDNF and brain Visfatin were also found to contribute to the neuro-protective effect of Ex-4 via modulation of inflammation, oxidative stress, neuro-degeneration and synaptic function.



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Baseline neutrophil to lymphocyte ratio combined with serum LDH level associated with outcome of nivolumab immunotherapy in a Japanese advanced melanoma population

Abstract

Although immune checkpoint inhibitors (ICI) significantly improve the survival of advanced melanoma, more than half of the patients received no benefit. To predict outcomes, efforts to associate baseline peripheral blood biomarkers were started in patients given treatment with ipilimumab. Among the most critical markers is an increased neutrophil-to-lymphocyte ratio (NLR), which negatively correlates with outcome. Although several baseline factors have been reported to correlate with outcome in patients treated with nivolumab/pembrolizumab (eosinophil count, lymphocyte count, lactate dehydrogenase [LDH], and c-reactive protein [CRP]), a positive link between NLR and outcome has yet to be shown.

This article is protected by copyright. All rights reserved.

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Wide skin markings pattern - melanoma descriptor or patient-related factor?

Abstract

We are intrigued by the findings reported in the letter titled "Uncovering the diagnostic dermoscopic features of flat melanomas located on the lower limbs"(1). Bassoli et al investigated the association of the "wider skin marking pattern" with cutaneous melanoma. They state that this feature corresponds to "…linear intercepting furrows, lighter than the lesion's overall pigmentation and wider compared to the surrounding skin. The authors conclude that "recognition of wider skin markings may…prompt the clinician to obtain a biopsy specimen." We respectfully ask the authors to clarify several aspects of their study methodology.

This article is protected by copyright. All rights reserved.

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Application of in vivo reflectance confocal microscopy (RCM) and ex vivo fluorescence confocal microscopy (FCM) in most common subtypes of Basal Cell Carcinoma and correlation with histopathology

Abstract

Basal cell carcinoma (BCC) accounts for 80% of non-melanoma skin cancer. The identification of the histological subtype is crucial for the correct management of the tumor. In vivo reflectance confocal microscopy (RCM) is a novel technique that has demonstrated high sensitivity and specificity in the in vivo diagnosis of BCC. In an effort to determine reliable criteria for preoperative diagnosis of BCC subtypes, Longo et al. and Peppelman et al., described RCM criteria present in different BCC subtypes.

This article is protected by copyright. All rights reserved.

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Hyaluronan metabolism enhanced during epidermal differentiation is suppressed by vitamin C

Abstract

Background

Hyaluronan is a large, linear glycosaminoglycan present throughout the narrow extracellular space of the vital epidermis. Increased hyaluronan metabolism takes place in epidermal hypertrophy, wound healing and cancer. Hyaluronan is produced by hyaluronan synthases (HAS1-3) and catabolized by hyaluronidases (HYAL1 and -2), reactive oxygen species (ROS), and the KIAA1199 protein.

Objectives

To investigate the changes in hyaluronan metabolism during epidermal stratification and maturation, and the impact of vitamin C.

Methods

Hyaluronan synthesis and expression of the hyaluronan-related genes were analyzed during epidermal maturation from a simple epithelium to a fully differentiated epidermis in organotypic cultures of rat epidermal keratinocytes (REK) using qRT-PCR, immunostainings, and western blotting, in the presence and absence of vitamin C.

Results

With epidermal stratification, both the production and the degradation of hyaluronan were enhanced, resulting in an increase of hyaluronan fragments of various sizes. While the mRNA levels of Has3 and KIAA1199 remained stable during the maturation, Has1, Has2, and Hyal2 showed a transient upregulation during stratification, Hyal1 remained permanently increased, and the hyaluronan receptor Cd44 decreased. At maturation, Vitamin C downregulated Has2, Hyal2 and Cd44, while it increased high molecular mass hyaluronan in the epidermis, and reduced small fragments in the medium, suggesting stabilization of epidermal hyaluronan.

Conclusions

Epidermal stratification and maturation is associated with enhanced hyaluronan turnover, and release of large amounts of hyaluronan fragments. The high turnover is suppressed by vitamin C, which is suggested to enhance normal epidermal differentiation in part through its effect on hyaluronan.

This article is protected by copyright. All rights reserved.

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Impact of long-term fertilization practices on the soil aggregation and humic substances under double-cropped rice fields

Abstract

Soil organic matter (SOM) content and soil aggregation are essential components of soil structure, which plays an important role in soil quality and fertility. Also, the SOM content, aggregation, and humus substances in paddy field were affected by application of fertilization practices. However, there is still limited information about the effects of long-term different fertilization practices on soil aggregation and carbon content in the humic acid (C-HAF), fulvic acid (C-FAF), and humin (C-HUM) fractions under double-cropping rice (Oryza sativa L.) system in Southern China paddy fields. Therefore, the effects of long-term fertilizer application on soil aggregation and C-HUM, C-HAF, and C-FAF contents in 0–5-, 5–10-, and 10–20-cm soil depth under double-cropped rice fields in Southern China were investigated. The experiment located at NingXiang County in Hunan Province, China begins in 1986 and the experiment includes five treatments: without fertilizer input (CK), mineral fertilizer alone (MF), rice straw residues and mineral fertilizer (RF), 30% organic matter and 70% mineral fertilizer (LOM), and 60% organic matter and 40% mineral fertilizer (HOM). The results showed that the soil total organic carbon content in paddy soils with RF, LOM, and HOM treatments was significant higher (P < 0.05) than that of the CK treatment at early and late rice maturity stages. The different sizes of soil aggregates with different fertilization treatments were decreased as HOM > LOM > RF > MF > CK. The HOM treatment had the highest percentage of soil aggregates in each size class and the CK treatment had the lowest percentage of soil aggregates in each size class in 0–5-, 5–10-, and 10–20-cm soil depth at early and late rice maturity stages. The soil C-HAF, C-FAF, and C-HUM contents were increased by long-term combined application of manure with mineral fertilizer practices. Meanwhile, the results indicated that the soil C-HAF, C-FAF, and C-HUM contents with RF, LOM, and HOM treatments were significantly higher (P < 0.05) than that of the CK treatment at early and late rice maturity stages. As a result, the soil total organic carbon content, each size class of soil aggregates, and soil C-HAF, C-FAF, and C-HUM contents were increased by long-term combined application of manure with mineral fertilizer in double-cropped rice fields.

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Label-free imaging for T staging of gastric carcinoma by multiphoton microscopy

Abstract

Gastric cancer is one of the most common malignancies worldwide. The accurate diagnosis of tumor invasion depth is critical for therapeutic strategy and prognosis. Without fluorescent labelling, multiphoton microscopy (MPM) imaging could directly reveal tissue architecture based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). In this study, we aimed to explore the feasibility of MPM imaging to assess the gastric tumor morphology and infiltration. Unstained slides of 18 fresh gastric tissues with different T staging were examined by multiphoton microscopy. Morphological and quantitative analyses were both conducted. The nuclear area was defined as the area of nuclear boundary. Collagen content was defined as the ratio of SHG pixels to all pixels. Gastric normal and tumor tissues under different T stages visually presented with cellular and subcellular features on fluorescent imaging. The nuclear areas of normal and cancerous cells were 32.01 ± 2.89 and 58.41 ± 6.06 μm² (P < 0.001), respectively. Collagen content was quantified as 0.087 ± 0.012 in normal mucosa but 0.020 ± 0.007 in cancerous mucosa (P < 0.001). All results were in accord with the paired H&E-stained slides. Our findings suggested the convincing potential of MPM for judging T staging of gastric cancer. Without staining intervention, TPEF and SHG of MPM imaging could objectively and quantitatively indicate the subcellular and molecular changes during carcinogenesis. With the advancement of deep penetration, self-focus imaging and three-dimensional (3D) visualization, label-free MPM imaging compacted with endoscopy could be further introduced to realize the real-time in vivo assessment of tumor invasion clinically.

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Age-related differences in the functional properties of lips compared with skin

Abstract

Background/aims

Lips can easily become dry and rough and their biggest problems are drying and chapping. The cause of those problems is considered to be that the stratum corneum (SC) moisture is small and its barrier function is low. However, those problems decrease in subjects as they approach 40 years of age, after which problems due to their shape and color increase. The purpose of this study was to investigate relationships between SC properties of the lips during aging and to clarify the cause(s) of lip problems.

Methods

One hundred and 38 Japanese female subjects with normal skin ranging in age from 16 to 78 years were enrolled in the study. The capacitance and transepidermal water loss (TEWL) values, viscoelasticity, and color of their lips were measured and compared with their cheeks.

Results

The capacitance values for the lip and the cheek increased and TEWL values for both areas decreased with age. TEWL values for the lip decreased until ~30 years of age and this is considered to be related to the problem of drying. Although the maximum amplitude U_f of the lip increased with age, the U_r/U_f had no correlation with age. As for color, the L* and a* values decreased with age.

Conclusion

Age-related changes with regard to SC functions, viscoelasticity and color of the lips have been clarified for the first time, and it is clear that these changes are related to problems of the lips. Compared with the cheeks, differences with the lips are more apparent.

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Non-invasive evaluation of human mucosal structures by multiphoton laser scanning tomography in vitro

Abstract

Background

Mucous membranes may be affected by various diseases and the diagnostic accessibility is limited. Multiphoton laser tomography (MPT) is a useful tool for in vivo evaluation of superficial skin structures and might also be useful for the imaging of mucosa.

Objectives

In order to investigate the suitability of MPT for the evaluation of mucous membranes, tissue samples of different donors and anatomical localizations have been imaged.

Methods

Human mucosa samples from the urinary bladder, palatine tonsil and ocular conjunctiva were investigated by MPT and subsequently compared with conventional histology.

Results

Horizontal images of the epithelium and the underlying connective tissue were obtained using the autofluorescence and second harmonics generation signals by MPT. The stratification of multilayered epithelium was consistently reproduced. Also inflammatory changes like lymphocytic infiltrates and widened intercellular spaces were imaged in some cases.

Conclusion

Mucous tissue samples were obtained and MPT imaging was successfully performed. In the direct comparison with histology of the same tissue samples, the characteristic morphology of the epithelia was found. Further studies are necessary in order to compare images of healthy and diseased mucosal epithelium and the use of MPT for its evaluation in vivo.

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Plasma exeresis for active acne vulgaris: Clinical and in vivo microscopic documentation of treatment efficacy by means of reflectance confocal microscopy

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Cortisol evaluation during the acute phase of traumatic brain injury – a prospective study

Abstract

Background

Biochemical diagnosis of adrenal insufficiency (AI) is difficult in the context of traumatic brain injury (TBI)

Aim

to assess the frequency and predictive factors of AI in victims of TBI from Algiers.

Methods

Between November 2009 and December 2013, TBI victims had a single 8-9 a.m. serum cortisol measurement during the acute post injury period (0-7 days). AI was defined according to basal cortisol levels of 83, 276 and 414 nmol/L. Variables studied were TBI severity according to Glasgow coma scale, duration of intubation and coma, pupillary status, hypotension, anemia, brain imaging findings, diabetes insipidus and medication. Insulin tolerance test was performed during the recovery phase, defining AI as peak cortisol <500 nmol/L.

Results

Cortisol samples were obtained at median 3 (1-7) days from 277 patients (257M: 20F) aged 32 (18-65) years. Acute AI frequency was 8 (2.8%), 20 (21%) and 35 (37%) respectively using the three cortisol cut-offs. Factors predicting AI were diastolic hypotension, sedative medication, diabetes insipidus, skull base fracture and intra-parenchymal haematoma. Mortality was highest in patients with acute cortisol <276nmol/L (44.6% with OR for death 1.64, 95% CI 0.92-3.0, p=0.12). During the recovery phase, AI was present in 3/3, 12/24, 4/16 and 20/66 patients with week 1 cortisol <83, 83-276, 277-414 and >414nmol/L.

Conclusion

Hydrocortisone replacement is advised in TBI patients with morning cortisol <276 nmol/L or those <414 nmol/L with additional risk factors for AI. Since acute and subsequent AI are poorly correlated patients with moderate/severe TBI require adrenal re-evaluation during the recovery phase.

This article is protected by copyright. All rights reserved.

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The Free Androgen Index is inaccurate in women when the SHBG concentration is low

Abstract

Objective/Context

The free androgen index (FAI) is known to give erroneous results in men but it is still a commonly used test for the investigation of hyperandrogenism in women. This study aimed to compare the results of the FAI with the gold standard equilibrium dialysis method for free testosterone in women.

Design/Patients

Free serum testosterone T (ED-T) and total serum T (T) were measured by equilibrium dialysis and LC-MS/MS in patients with polycystic ovarian syndrome (n=130), normal female controls (n=53) and normal males (n=120). Calculated free T (cFT) and free androgen index (FAI) were also measured in these patients. In addition cFT was retrospectively calculated in 4223 female patients with a normal T (<1.6 nmol/L) routinely investigated for hyperandrogenism.

Results

The cFT showed good agreement with measured ED-T and the ratio cFT/ED-T was stable across all SHBG concentrations. In contrast the FAI/ED-T ratio and the FAI/cFT ratio increased when the concentration of SHBG fell below 30 nmol/L.

Conclusions

The FAI is not a reliable indicator of free T when the SHBG concentration is low and would give misleading information in a large number of women being investigated for hyperandrogenism.

This article is protected by copyright. All rights reserved.

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Title page / Editorial Board

Publication date: February 2018
Source:Cancer Epidemiology, Volume 52





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Table of contents

Publication date: February 2018
Source:Cancer Epidemiology, Volume 52





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Metastatic melanoma with dedifferentiation and extensive rhabdomyosarcomatous heterologous component

Melanoma may undergo dedifferentiation and sarcomatous transformation with loss of melanocytic markers. Dedifferentiated melanoma rarely forms true rhabdomyoblasts with skeletal muscle immunophenotype (rhabdomyosarcomatous heterologous component). A 52 year-old woman was diagnosed with invasive melanoma (Breslow depth 0.83 mm) of the upper back in 2012, treated by wide local excision only. In 2013, an axillary mass was excised to show metastatic melanoma with two morphologies: an epithelioid morphology expressing S100 and MART-1 and a spindled morphology with loss of melanocytic markers but strong expression of desmin. This metastasis was found to have BRAF V600E mutation. In 2015, a thoracic epidural mass biopsy showed atypical spindle cells with focal HMB-45 but essentially no S100 expression. Numerous rhabdomyoblasts, some with striations that were strongly positive for desmin and myogenin, were present. In 2016, a right nephrectomy was performed for metastasis to the kidney, and showed sheets of spindle cells and rhabdomyoblasts expressing desmin and myogenin but not S100. Only focal areas demonstrated expression of HMB-45 and SOX-10, supporting the melanocytic origin of the tumor. The numerous rhabdomyoblasts and the loss of S100 expression in the metastatic lesions in this case could have easily led to misdiagnosis if the clinical history was not known.

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Surface texture keeps katydids on the hop

Publication date: Available online 5 February 2018
Source:Materials Today
Author(s): Cordelia Sealy




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Tools, techniques, and technologies for pollution prevention, control, and resource recovery

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MiR-93-5p targeting PTEN regulates the NMDA-induced autophagy of retinal ganglion cells via AKT/mTOR pathway in glaucoma

Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Rui Li, Yiping Jin, Qian Li, Xinghuai Sun, Haohao Zhu, Hongping Cui
BackgroundGlaucoma is hallmarked with the death of retinal neurons in the ganglion cell layer, which results in irreversible vision loss. The abnormal levels of miRNA have been associated with glaucoma. Our study purposed to explore the underlying molecule mechanism of miR-93-5p in NMDA-induced glaucoma.MethodsThe Sprague-Dawley (SD) rats were used for the establishment of glaucoma model with the injection of NMDA. Vision behavior test were performed on the glaucoma rats. MiR-93-5p expression was determined by real-time PCR. The levels of autophagy-related protein and PTEN were assessed by Western blot assays. TUNEL assay and flow cytometry were performed to analyze cell apoptosis in vivo and in vitro, respectively. And cell viability was examined by CKK-8 assay. The relationship between miR-93-5p and PTEN was confirmed by Dual-Luciferase reporter gene system.ResultsNMDA-induced glaucoma rats exhibited less time in the dark box, suggesting the recession of their vision. Moreover, the retinal ganglion cell (RGC) viability was reduced not only in the glaucoma rat models but also in the glaucoma RGC models. The autophagy-related protein was obviously increased in the NMDA-treated rats or RGCs. PTEN regulated the autophagy of RGCs through AKT/mTOR pathway in NMDA-treated RGCs. MiR-93-5p could target regulate PTEN negatively, and exhibit the similar effect of 3-MA on the survival of RGCs.ConclusionUp-regulation of miR-93-5p binding with PTEN suppressed the autophagy of RGCs through AKT/mTOR pathway in NMDA-induced glaucoma.



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Effective long-term solution to therapeutic remission in Inflammatory Bowel Disease: Role of Azathioprine

Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Lyla Adam, Alisa Phulukdaree, Prashilla Soma
Azathioprine (AZA) is a well-known immunosuppressant used for many years for its ability to ensure long term disease remission in inflammatory bowel diseases (IBD) at an affordable cost to the public. However, the side effect profile has raised many concerns with numerous investigations into the risk, cause and prevention of these effects. Much of the side effect profile of AZA can be linked to a single nucleotide polymorphism (SNP) in the thiopurine methyltransferase (TPMT) gene which ensures the breakdown and efficacy of AZA. Mutated TPMT alleles result in low or deficient TPMT levels which directly correlate to cytotoxity. This is a review of the role of AZA in the treatment of IBD. Knowing a patient's TPMT status allows the prescribing doctor to make an informed decision about dosage and be more alert to the signs of cytotoxicity. It is essential to include "early warning" SNP testing into common practice to ensure therapeutic efficacy.



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In Vitro and In Vivo Characterization of a Preclinical Radiation-Adapted Model for Ewing Sarcoma

Publication date: Available online 5 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Mary Carroll Shapiro, Tien Tang, Atreyi Dasgupta, Lyazat Kurenbekova, Ryan Shuck, M. Waleed Gaber, Jason T. Yustein
PurposeRadiation therapy (RT) is a viable therapeutic option for Ewing sarcoma (ES) patients. However, little progress has been made to elucidate mechanisms of radioresistance. This study establishes a novel ES radiation-adapted model designed to assess molecular and fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) alterations secondary RT.Methods and MaterialsRadiation-adapted cell lines (RACL) were created in vitro by exposing ES human cell lines to fractionated doses of radiation. Assays to assess migration/invasion potential and RNA expression were performed on the RACL. Orthotopic intra-tibial in vivo investigations were performed with radiation-sensitive and radiation-adapted ES cells to generate tumors. Transplanted mice were imaged using ¹⁸F-FDG-PET followed by fractionated RT directed at the primary tumor. Mice were monitored for tumor regression and change in metabolic activity using ¹⁸F-FDG PET imaging. Protein expression analyses were performed on the RACL and orthotopic tumors.ResultsExposure to fractionated doses of radiation caused a significant increase in migratory and invasive properties in the RACL when compared to non-irradiated wild type ES cells. RACL transcriptomic and proteomic analysis suggests enhanced activation of the mTOR-AKT pathway when compared to wild type ES cells. Radiation-adapted tumors demonstrated significantly less tumor regression (p = 0.03) compared to wild type tumors. Wild type tumors also had decreased expression of lactate dehydrogenase A (LDHA) protein and significantly lower metabolic activity after RT compared to radiation-adapted tumors (p = 0.03).ConclusionsWe developed novel in vitro and in vivo radiation-adapted ES models. In vitro investigations revealed increased migratory and invasive phenotypes in the RACL. In vivo investigations demonstrated increased metabolic activity and significantly decreased sensitivity to RT in the radiation-adapted tumors as demonstrated by growth response curves and ¹⁸F-FDG PET activity. Investigations of the RACL identified possible radiosensitizing-dependent targets in LDHA and mTOR-AKT pathway.

Teaser

Ewing sarcoma (ES) is the second most common pediatric bone cancer, and patients with relapsed/resistant disease have a five-year overall survival rate of only 15-20%. Front-line standard of care treatment for patients with ES includes chemotherapy and local control with surgery and/or radiation. We have developed novel in vitro and in vivo radiation-adapted ES models that demonstrate a relationship between metabolism and radioresistance as well as identify several candidate biomarkers for radioresistant disease in ES.


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Does Prophylactic Radiotherapy to avoid Gynecomastia in Patients with Prostate Cancer increase the risk of Breast Cancer?

Publication date: Available online 5 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Bjørg Y. Aksnessæther, Arne Solberg, Olbjørn H. Klepp, Tor Åge Myklebust, Eva Skovlund, Solveig Roth Hoff, Lars J. Vatten, Jo-Åsmund Lund
PurposeProstate cancer (PC) patients treated with antiandrogen monotherapy are offered prophylactic radiotherapy to the breast buds (PRT) to avoid gynecomastia. The aim of this study was to evaluate whether the risk of breast cancer (BC) in men with PC as their first cancer diagnosis, was influenced by PRT.Methods and MaterialsFrom the Norwegian Cancer Registry we collected data on all patients with PC as their first cancer diagnosis diagnosed between 1997- 2014. We registered all radiotherapy given to the patients in the same period, and the occurrence of BC diagnosed 3 months or more following the PC diagnosis. The histopathological diagnoses of all BC cases were collected. Subdistribution hazard ratios (SHR) for the risk of BC in PRT and non-PRT treated patients were estimated. A standardized incidence ratio (SIR) for BC was calculated by comparing our cohort to the standard male population.ResultsWe analyzed 59 169 patients with PC, whom 7864 (13.3%) had received PRT. Median follow-up time was 4 years. Three of 12 men diagnosed with BC had received PRT, and two of three were phyllodes tumors. The risk of BC was not statistically significantly different in patients given RT as compared to the non-RT patients, SHR 1.62 95% CI 0.41-5.62, adjusted for age and time of diagnosis. SIR was 0.996 95 % CI 0.57-1.75.ConclusionsIn this registry based study, we did not find an increased risk of BC in PC patients treated with PRT. The number of BC cases in our study was low, and the risk of secondary breast cancer following PRT seems to be negligible. The incidence of BC may, however rise with additional follow-up. It is noteworthy that two patients who had been treated with PRT were diagnosed with malignant phyllodes tumor, an extremely rare type of BC associated with gynecomastia.

Teaser

Nordic patients with prostate cancer receive prophylactic radiotherapy to the breast buds to avoid gynecomastia when treated with antiandrogen monotherapy. In this study with data from the Norwegian Cancer Registry, we did not find increased risk of breast cancer (BC) in irradiated patients compared to non-irradiated patients. It is noteworthy that in the RT group, there were two cases of malignant phyllodes breast tumor, an extremely rare type of BC associated with gynecomastia.


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A daily single dose of a novel modafinil analogue CE-123 improves memory acquisition and memory retrieval

Publication date: 2 May 2018
Source:Behavioural Brain Research, Volume 343
Author(s): Martina Kristofova, Yogesh D. Aher, Marija Ilic, Bojana Radoman, Predrag Kalaba, Vladimir Dragacevic, Nilima Y. Aher, Johann Leban, Volker Korz, Lisa Zanon, Winfried Neuhaus, Marcus Wieder, Thierry Langer, Ernst Urban, Harald H. Sitte, Harald Hoeger, Gert Lubec, Jana Aradska
Dopamine reuptake inhibitors have been shown to improve cognitive parameters in various tasks and animal models. We recently reported a series of modafinil analogues, of which the most promising, 5-((benzhydrylsulfinyl)methyl) thiazole (CE-123), was selected for further development. The present study aims to characterize pharmacological properties of CE-123 and to investigate the potential to enhance memory performance in a rat model. In vitro transporter assays were performed in cells expressing human transporters. CE-123 blocked uptake of [3H] dopamine (IC50 = 4.606 μM) while effects on serotonin (SERT) and the norepinephrine transporter (NET) were negligible. Blood-brain barrier and pharmacokinetic studies showed that the compound reached the brain and lower elimination than R-modafinil. The Pro-cognitive effect was evaluated in a spatial hole-board task in male Sprague-Dawley rats and CE-123 enhances memory acquisition and memory retrieval, represented by significantly increased reference memory indices and shortened latency. Since DAT blockers can be considered as indirect dopamine receptor agonists, western blotting was used to quantify protein levels of dopamine receptors D1R, D2R and D5R and DAT in the synaptosomal fraction of hippocampal subregions CA1, CA3 and dentate gyrus (DG). CE-123 administration in rats increased total DAT levels and D1R protein levels were significantly increased in CA1 and CA3 in treated/trained groups. The increase of D5R was observed in DG only. Dopamine receptors, particularly D1R, seem to play a role in mediating CE-123-induced memory enhancement. Dopamine reuptake inhibition by CE-123 may represent a novel and improved stimulant therapeutic for impairments of cognitive functions.



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The effect of dietary selenium addition on the concentrations of heavy metals in the tissues of fallow deer ( Dama dama L.) in Croatia

Abstract

The aim of this research was to determine the concentrations of cadmium, lead, mercury, and arsenic and the essential elements iron and selenium in the tissues (muscle, kidney, liver, spleen, and fat) of fallow deer (Dama dama L.) without and with supplemental selenium addition. Another aim was to determine the effect of selenium addition on the indicators of oxidative stress, namely, the levels of superoxide dismutase, glutathione peroxidase, glutathione, and vitamin E. The research was carried out with 40 fallow deer during two research periods. Supplemental feed without selenium addition was provided during the first research period, and supplemental feed with added selenium (3 mg/kg) was provided for 60 days during the second research period. The concentration of selenium in tissues was higher in the second research period than in the first research period (in kidney tissue, 0.957 vs. 0.688 mg/kg, P < 0.05). The dietary addition of selenium decreased (P < 0.05) the concentrations of some heavy metals (lead in the spleen = 0.06 vs. 0.27 mg/kg and in the fatty tissue = 0.17 vs. 0.69 mg/kg; arsenic in the muscle tissue = 0.005 vs. 0.014 mg/kg, liver = 0.003 vs. 0.009 mg/kg, spleen = 0.004 vs. 0.013 mg/kg, and fat = 0.008 vs. 0.016 mg/kg). The activity of glutathione peroxidase was significantly higher (P < 0.05) in the second research period than in the first research period (1375.36 vs. 933.23 U/L).

http://ift.tt/2FRfVtX

In situ investigation of heavy metals at trace concentrations in greenhouse soils via portable X-ray fluorescence spectroscopy

Abstract

Soil pollution by heavy metals (HMs) has rapidly become a major threat to vegetable security. Nearly all cultivated soils are at risk of metal accumulation, and greenhouse soils are among the most heavily impacted soils. In this study, a rapid assessment of HMs at trace concentrations was conducted via portable X-ray fluorescence (PXRF) spectroscopy in Shouguang, China. Measurements were made via PXRF under in situ, ex situ and sieved conditions and by inductively coupled plasma mass spectrometry (ICP-MS) after acid digestion. The performance of each PXRF measure relative to the ICP-MS method was assessed by linear regression. Redundancy analysis was performed to quantify the proportion of explained variability between the PXRF and ICP-MS data. Evaluation of the possible sources of HMs and their potential risks was then conducted by multivariate analysis. The results showed that the PXRF data were closely correlated with ICP-MS quantification for Cu, Mn and Zn, whereas no significant correlations were found for As, Ni and Pb. The uncertainties of PXRF measurement derived from soil heterogeneity accounted for 20.02% of total variability and those from moisture and particle size accounted for 20.15%. The geo-accumulation index (I_geo) indicated that the greenhouse soils were potentially contaminated by Cu and Zn (I_geo > 0), which can be attributed to anthropogenic activities. Overall, PXRF spectroscopy is promising as a rapid and nondestructive in situ technique for assessing the potential risks of HMs at trace concentrations in greenhouse soils.

http://ift.tt/2E4bvDF

Slow-Wave Sleep: From the Cell to the Clinic

In recent decades, increasing evidence has positioned slow-wave sleep (SWS) as a major actor in neurophysiological phenomena such as glucose metabolism, hormone release, immunity and memory. This proposed role for SWS, coupled with observations of impaired SWS in several pathologies as well as in aging, has led some researchers to implement methods that could specifically enhance SWS.This review aims to gather the current knowledge extending from the cell to the clinic, in order to construct an overview of what is currently known about so-called SWS.

http://ift.tt/2BcT9xB

Mesenchymal stem cell (MSC)-mediated survival of insulin producing pancreatic β-cells during cellular stress involves signalling via Akt and ERK1/2

Publication date: Available online 5 February 2018
Source:Molecular and Cellular Endocrinology
Author(s): Chune Liu, Weiwei Zhang, Natia Peradze, Leonie Lang, Jan Straetener, Peter J. Feilen, Marcus Alt, Christina Jäger, Katharina Laubner, Nikolaos Perakakis, Jochen Seufert, Günter Päth
Mesenchymal stem cells (MSC) are of interest for cell therapy since their secreted factors mediate immunomodulation and support tissue regeneration. This study investigated the direct humoral interactions between MSC and pancreatic β-cells using human telomerase-immortalized MSC (hMSC-TERT) and rat insulinoma-derived INS-1E β-cells. hMSC-TERT supported survival of cocultured INS-1E β-cells during cellular stress by alloxan (ALX) and streptozotocin (STZ), but not in response to IL-1β. Accordingly, hMSC-TERT had no effect on inflammatory cytokine-related signalling via NF-kB and p-JNK but maintained p-Akt and upregulated p-ERK1/2. Inhibition of either p-Akt or p-ERK1/2 did not abolish protection by hMSC-TERT but activated the respective non-inhibited pathway. This suggests that one pathway compensates for the other. Main results were confirmed in mouse islets except hMSC-TERT-mediated upregulation of p-ERK1/2. Therefore, MSC promote β-cell survival by preservation of p-Akt signalling and further involve p-ERK1/2 activation in certain conditions such as loss of p-Akt or insulinoma background.



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Increasing Pulmonary Arterial Pressure at Low Level of Exercise in Asymptomatic, Organic Mitral Regurgitation

http://ift.tt/2EkYNQ0

JACC Instructions for Authors

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Compliance With Guideline-Directed Medical Therapy in Contemporary Coronary Revascularization Trials

AbstractBackground

Despite the well-established benefits of secondary cardiovascular prevention, the importance of concurrent medical therapy in clinical trials of coronary revascularization is often overlooked.

Objectives

The goal of this study was to assess compliance with guideline-directed medical therapy (GDMT) in clinical trials and its potential impact on the comparison between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG).

Methods

The Cochrane Central Register of Controlled Trials and MEDLINE were searched from 2005 to August 2017. Clinical trial registries and reference lists of relevant studies were also searched. Randomized controlled trials comparing PCI with drug-eluting stents versus CABG and reporting medical therapy after revascularization were included. The study outcome was compliance with GDMT, defined as the following: 1) any antiplatelet agent plus beta-blocker plus statin (GDMT1); and 2) any antiplatelet agent plus beta-blocker plus statin plus angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (GDMT2). Data collection and analysis were performed according to the methodological recommendations of The Cochrane Collaboration.

Results

From a total of 439 references, 5 trials were included based on our inclusion and exclusion criteria. Overall, compliance with GDMT1 was low and decreased over time from 67% at 1 year to 53% at 5 years. Compliance with GDMT2 was even lower and decreased from 40% at 1 year to 38% at 5 years. Compliance with both GDMT1 and GDMT2 was higher in PCI than in CABG at all time points. Meta-regression suggested an association between lower use of GDMT1 and adverse clinical outcomes in PCI versus CABG at 5 years.

Conclusions

Compliance with GDMT in contemporary clinical trials remains suboptimal and is significantly lower after CABG than after PCI, which may influence the comparison of clinical trial endpoints between those study groups.

http://ift.tt/2FPBaw8

Reply: LDL-Cholesterol and Atherosclerotic Cardiovascular Disease: Innocent Bystander or Essential Ingredient?

http://ift.tt/2Ena5U0

Suboptimal Medical Therapy After Coronary Revascularization: A Missed Opportunity

http://ift.tt/2Ejdvai

Environmental Noise and the Cardiovascular System

Abstract

Noise has been found associated with annoyance, stress, sleep disturbance, and impaired cognitive performance. Furthermore, epidemiological studies have found that environmental noise is associated with an increased incidence of arterial hypertension, myocardial infarction, heart failure, and stroke. Observational and translational studies indicate that especially nighttime noise increases levels of stress hormones and vascular oxidative stress, which may lead to endothelial dysfunction and arterial hypertension. Novel experimental studies found aircraft noise to be associated with oxidative stress–induced vascular damage, mediated by activation of the NADPH oxidase, uncoupling of endothelial nitric oxide synthase, and vascular infiltration with inflammatory cells. Transcriptome analysis of aortic tissues from animals exposed to aircraft noise revealed changes in the expression of genes responsible for the regulation of vascular function, vascular remodeling, and cell death. This review focuses on the mechanisms and the epidemiology of noise-induced cardiovascular diseases and provides novel insight into the mechanisms underlying noise-induced vascular damage.

http://ift.tt/2Ejd0wW

Performance of Coronary Risk Scores Among Patients With Chest Pain in the Emergency Department

AbstractBackground

Both the modified History, Electrocardiogram, Age, Risk factors and Troponin (HEART) score and the Emergency Department Assessment of Chest pain Score (EDACS) can identify patients with possible acute coronary syndrome (ACS) at low risk (<1%) for major adverse cardiac events (MACE).

Objectives

The authors sought to assess the comparative accuracy of the EDACS (original and simplified) and modified HEART risk scores when using cardiac troponin I (cTnI) cutoffs below the 99th percentile, and obtain precise MACE risk estimates.

Methods

The authors conducted a retrospective study of adult emergency department (ED) patients evaluated for possible ACS in an integrated health care system between 2013 and 2015. Negative predictive values for MACE (composite of myocardial infarction, cardiogenic shock, cardiac arrest, and all-cause mortality) were determined at 60 days. Reclassification analyses were used to assess the comparative accuracy of risk scores and lower cTnI cutoffs.

Results

A total of 118,822 patients with possible ACS were included. The 3 risk scores' accuracies were optimized using the lower limit of cTnI quantitation (<0.02 ng/ml) to define low risk for 60-day MACE, with reclassification yields ranging between 3.4% and 3.9%, while maintaining similar negative predictive values (range 99.49% to 99.55%; p = 0.27). The original EDACS identified the largest proportion of patients as low risk (60.6%; p < 0.0001).

Conclusions

Among ED patients with possible ACS, the modified HEART score, original EDACS, and simplified EDACS all predicted a low risk of 60-day MACE with improved accuracy using a cTnI cutoff below the 99th percentile. The original EDACS identified the most low-risk patients, and thus may be the preferred risk score.

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Left Ventricle Replacement Fibrosis Detected by CMR Associated With Cardiovascular Events in Systemic Sclerosis Patients

http://ift.tt/2EjaIOi

Evaluating Chest Pain in the Emergency Department: Searching for the Optimal Gatekeeper

http://ift.tt/2EjdjI6

Is Skipping Breakfast a Marker for Current Smoking?

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Lipids, Lipoproteins, and Metabolites and Risk of Myocardial Infarction and Stroke

AbstractBackground

Blood lipids are established risk factors for myocardial infarction (MI), but uncertainty persists about the relevance of lipids, lipoprotein particles, and circulating metabolites for MI and stroke subtypes.

Objectives

This study sought to investigate the associations of plasma metabolic markers with risks of incident MI, ischemic stroke (IS), and intracerebral hemorrhage (ICH).

Methods

In a nested case-control study (912 MI, 1,146 IS, and 1,138 ICH cases, and 1,466 common control subjects) 30 to 79 years of age in China Kadoorie Biobank, nuclear magnetic resonance spectroscopy measured 225 metabolic markers in baseline plasma samples. Logistic regression was used to estimate adjusted odds ratios (ORs) for a 1-SD higher metabolic marker.

Results

Very low-, intermediate-, and low-density lipoprotein particles were positively associated with MI and IS. High-density lipoprotein (HDL) particles were inversely associated with MI apart from small HDL. In contrast, no lipoprotein particles were associated with ICH. Cholesterol in large HDL was inversely associated with MI and IS (OR: 0.79 and 0.88, respectively), whereas cholesterol in small HDL was not (OR: 0.99 and 1.06, respectively). Triglycerides within all lipoproteins, including most HDL particles, were positively associated with MI, with a similar pattern for IS. Glycoprotein acetyls, ketone bodies, glucose, and docosahexaenoic acid were associated with all 3 diseases. The 225 metabolic markers showed concordant associations between MI and IS, but not with ICH.

Conclusions

Lipoproteins and lipids showed similar associations with MI and IS, but not with ICH. Within HDL particles, cholesterol concentrations were inversely associated, whereas triglyceride concentrations were positively associated with MI. Glycoprotein acetyls and several non–lipid-related metabolites associated with all 3 diseases.

http://ift.tt/2FRauLE

Metabolic Surgery: Weight Loss, Diabetes, and Beyond

Abstract

The alarming rise in the worldwide prevalence of obesity is paralleled by an increasing burden of type 2 diabetes mellitus. Metabolic surgery is the most effective means of obtaining substantial and durable weight loss in individuals with obesity. Randomized trials have recently shown the superiority of surgery over medical treatment alone in achieving improved glycemic control, as well as a reduction in cardiovascular risk factors. The mechanisms seem to extend beyond the magnitude of weight loss alone and include improvements in incretin profiles, insulin secretion, and insulin sensitivity. Moreover, observational data suggest that the reduction in cardiovascular risk factors translates to better patient outcomes. This review describes commonly used metabolic surgical procedures and their current indications and summarizes the evidence related to weight loss and glycemic outcomes. It further examines their potential effects on cardiovascular outcomes and mortality and discusses future perspectives.

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Cardiovascular Risk Beyond Low-Density Lipoprotein Cholesterol

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Tele-Cardiology in the Syrian War

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Long-Term Sirolimus for Primary Immunosuppression in Heart Transplant Recipients

AbstractBackground

Small studies have reported superiority of sirolimus (SRL) over calcineurin inhibitor (CNI) in mitigating cardiac allograft vasculopathy (CAV) after heart transplantation (HT). However, data on the long-term effect on CAV progression and clinical outcomes are lacking.

Objectives

The aim of this study was to test the long-term safety and efficacy of conversion from CNI to SRL as maintenance therapy on CAV progression and outcomes after HT.

Methods

A cohort of 402 patients who underwent HT and were either treated with CNI alone (n = 134) or converted from CNI to SRL (n = 268) as primary immunosuppression was analyzed. CAV progression was assessed using serial coronary intravascular ultrasound during treatment with CNI (n = 99) and after conversion to SRL (n = 235) in patients who underwent at least 2 intravascular ultrasound studies.

Results

The progression in plaque volume (2.8 ± 2.3 mm³/mm vs. 0.46 ± 1.8 mm³/mm; p < 0.0001) and plaque index (plaque volume–to–vessel volume ratio) (12.2 ± 9.6% vs. 1.1 ± 7.9%; p < 0.0001) were significantly attenuated when treated with SRL compared with CNI. Over a mean follow-up period of 8.9 years from time of HT, all-cause mortality occurred in 25.6% of the patients and was lower during treatment with SRL compared with CNI (adjusted hazard ratio: 0.47; 95% confidence interval: 0.31 to 0.70; p = 0.0002), and CAV-related events were also less frequent during treatment with SRL (adjusted hazard ratio: 0.35; 95% confidence interval: 0.21 to 0.59; p < 0.0001). Further analyses suggested more attenuation of CAV and more favorable clinical outcomes with earlier conversion to SRL (≤2 years) compared with late conversion (>2 years) after HT.

Conclusions

Early conversion to SRL is associated with attenuated CAV progression and with lower long-term mortality and fewer CAV-related events compared with continued CNI use.

http://ift.tt/2FMwK96

Impact of Sleep Duration and Race on Recurrent Cardiovascular Events Following Acute Coronary Syndrome

http://ift.tt/2FNRM7o

The Return of the mTOR Inhibitors: Getting it Right in Patients After Cardiac Transplantation

http://ift.tt/2Ekqj01

LDL-Cholesterol and Atherosclerotic Cardiovascular Disease: Innocent Bystander or Essential Ingredient

http://ift.tt/2FOrJ02

Activation of Serine One-Carbon Metabolism by Calcineurin A{beta}1 Reduces Myocardial Hypertrophy and Improves Ventricular Function

AbstractBackground

In response to pressure overload, the heart develops ventricular hypertrophy that progressively decompensates and leads to heart failure. This pathological hypertrophy is mediated, among others, by the phosphatase calcineurin and is characterized by metabolic changes that impair energy production by mitochondria.

Objectives

The authors aimed to determine the role of the calcineurin splicing variant CnAβ1 in the context of cardiac hypertrophy and its mechanism of action.

Methods

Transgenic mice overexpressing CnAβ1 specifically in cardiomyocytes and mice lacking the unique C-terminal domain in CnAβ1 (CnAβ1ⁱ¹² mice) were used. Pressure overload hypertrophy was induced by transaortic constriction. Cardiac function was measured by echocardiography. Mice were characterized using various molecular analyses.

Results

In contrast to other calcineurin isoforms, the authors show here that cardiac-specific overexpression of CnAβ1 in transgenic mice reduces cardiac hypertrophy and improves cardiac function. This effect is mediated by activation of serine and one-carbon metabolism, and the production of antioxidant mediators that prevent mitochondrial protein oxidation and preserve ATP production. The induction of enzymes involved in this metabolic pathway by CnAβ1 is dependent on mTOR activity. Inhibition of serine and one-carbon metabolism blocks the beneficial effects of CnAβ1. CnAβ1ⁱ¹² mice show increased cardiac hypertrophy and declined contractility.

Conclusions

The metabolic reprogramming induced by CnAβ1 redefines the role of calcineurin in the heart and shows for the first time that activation of the serine and one-carbon pathway has beneficial effects on cardiac hypertrophy and function, paving the way for new therapeutic approaches.

http://ift.tt/2FPATth

Mobility of 232Th and 210Po in red mud

Publication date: April 2018
Source:Journal of Environmental Radioactivity, Volumes 184–185
Author(s): Miklós Hegedűs, Edit Tóth-Bodrogi, Jácint Jónás, János Somlai, Tibor Kovács
The valorization of industrial by-products such as red mud became a tempting opportunity, but the understanding of the risks involved is required for the safe utilization of these products. One of the risks involved are the elevated levels of radionuclides (in the 100–1300 Bq/kg range for both the ²³⁸U and ²³² Th decay chains, but usually lower than 1000 Bq/kg, which is the recommended limit for excemption or clearance according to the EU BSS released in 2013) in red mud that can affect human health. There is no satisfactory answer for the utilization of red mud; the main current solution is still almost exclusively disposal into a landfill. For the safe utilization and deposition of red mud, it is important to be able to assess the leaching behaviour of radionuclides. Because there is no commonly accepted measurement protocol for testing the leaching of radionuclides in the EU a combined measurement protocol was made and tested based on heavy metal leaching methods. The leaching features of red mud were studied by methods compliant with the MSZ-21470-50 Hungarian standard, the CEN/TS 14429 standard and the Tessier sequential extraction method for ²³²Th and ²¹⁰Po. The leached solutions were taken to radiochemical separation followed by spontaneous deposition for Po and electrodeposition for Th. The 332 ± 33 Bq/kg ²³²Th content was minimally mobile, 1% became available for distilled water 1% and 6% for Lakanen-Erviö solution; the Tessier extraction showed minimal mobility in the first four steps, while more than 85% remained in the residue. The ²¹⁰Po measurements had a severe disturbing effect in many cases, probably due to large amounts of iron present in the red mud, from the 310 ± 12 Bq/kg by aqua regia digestion, distilled water mobilized 23%, while Lakanen-Erviö solution mobilized ∼13%. The proposed protocol is suitable for the analysis of Th and Po leaching behaviour.



http://ift.tt/2sdMPTD

Hybrid porous thin films: Opportunities and challenges for sensing applications

Publication date: 1 May 2018
Source:Biosensors and Bioelectronics, Volume 104
Author(s): Pawan Kumar, Ki-Hyun Kim, Kowsalya Vellingiri, Pallabi Samaddar, Parveen Kumar, Akash Deep, Naresh Kumar
In this paper, the scientific progress in the field of thin film materials and their associated sensing technologies are described comprehensively to address the directions for future research and developments as per the need of modern-day technologies. To begin with, we briefly discussed the fundamental synthesis approaches for advanced thin films with an emphasis on the properties necessary for controlled fabrication (e.g., the elemental ratio and spatial arrangement). Subsequently, we explored the control, characterization, and optimization of hybrid porous thin films with respect to diverse sensing applications. The application of hybrid porous thin film materials has also been discussed in relation to the mechanisms used for biological, optical, electrical, acoustic, and other advanced sensing techniques (e.g., surface-enhanced Raman scattering (SERS)). Finally, conclusions are drawn to highlight the current status of thin film-based sensing technology along with its opportunities and challenges.



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Editorial Board

Publication date: 15 May 2018
Source:Biosensors and Bioelectronics, Volume 105





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Editorial Board

Publication date: 1 May 2018
Source:Biosensors and Bioelectronics, Volume 104





http://ift.tt/2s9il53

Peptide nanoparticles (PNPs) modified disposable platform for sensitive electrochemical cytosensing of DLD-1 cancer cells

Publication date: 1 May 2018
Source:Biosensors and Bioelectronics, Volume 104
Author(s): Yesim Tugce Yaman, Öznur Akbal, Gulcin Bolat, Betul Bozdogan, Emir Baki Denkbas, Serdar Abaci
A novel diphenylalaninamid (FFA) based peptide nanoparticles (PNPs) modified pencil graphite electrodes (PGEs) for construction of electrochemical cytosensor was demonstrated for the first time in this study. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images revealed the spherical nanostructure of the synthesized FFA based PNPs while attenuated total reflectance-fourier transform infrared (ATR-FTIR) spectra provided information about the structure and conformation of proteins in their structure. Self-assembly of PNPs on PGE surface and adhesion of DLD-1 cancer cells on this surface was also characterized by electrochemical measurements. PNP/PGEs acted as a sensitive platform for simple and rapid quantification of low concentration of DLD-1 cancer cells in early diagnosis using the electrochemical impedance method (EIS). The offered cytosensor demonstrated outstanding performance for the detection of DLD-1 cells by the EIS method. The impedance of electronic transduction was associated with the amount of the immobilized cells ranging from 2 × 10² to 2.0 × 10⁵ cellsmL⁻¹ with a limit of detection of 100 cellsmL⁻¹. The efficient performance of the cytosensor was attributed to the well-defined nanostructure and biocompability of PNPs on the substrate.



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Editorial Board

Publication date: February 2018
Source:Journal of Autoimmunity, Volume 87





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Geochemistry of rare earth elements within waste rocks from the Montviel carbonatite deposit, Québec, Canada

Abstract

Several rare earth element (REE) mine projects around the world are currently at the feasibility stage. Unfortunately, few studies have evaluated the contamination potential of REE and their effects on the environment. In this project, the waste rocks from the carbonatites within the Montviel proterozoic alkaline intrusion (near Lebel-sur-Quévillon, Quebec, Canada) are assessed in this research. The mineralization is mainly constituted by light REE (LREE) fluorocarbonates (qaqarssukite-Ce, kukharenkoite-Ce), LREE carbonates (burbankite, Sr-Ba-Ca-REE, barytocalcite, strontianite, Ba-REE-carbonates), and phosphates (apatite, monazite). The gangue minerals are biotites, chlorite, albite, ankerite, siderite, and calcite. The SEM-EDS analyses show that (i) the majority of REE are associated with the fine fraction (< 106 μm), (ii) REE are mainly associated with carbonates, (iii) all analyzed minerals preferably contain LREE (La, Ce, Pr, Nd, Sm, Eu), (iv) the sum of LREE in each analyzed mineral varies between ~ 3 and 10 wt%, (v) the heavy REE (HREE) identified are Gd and Yb at < 0.4 wt%, and (vi) three groups of carbonate minerals were observed containing variable concentrations of Ca, Na, and F. Furthermore, the mineralogical composition of REE-bearing minerals, REE mobility, and REE speciation was investigated. The leachability and geochemical behavior of these REE-bearing mine wastes were tested using normalized kinetic testing (humidity cells). Leachate results displayed higher LREE concentrations, with decreasing shale-normalized patterns. Thermodynamical equilibrium calculations suggest that the precipitation of secondary REE minerals may control the REE mobility.

http://ift.tt/2E0gRvl

Integrated optoelectronic microprobes

Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50
Author(s): L Rudmann, MT Alt, D Ashouri Vajari, T Stieglitz
Optogenetics opened not only new exciting opportunities to interrogate the nervous system but also requires adequate probes to facilitate these wishes. Therefore, a multidisciplinary effort is essential to match these technical opportunities with biological needs in order to establish a stable and functional material-tissue interface. This in turn can address an optical intervention of the genetically modified, light sensitive cells in the nervous system and recording of electrical signals from single cells and neuronal networks that result in behavioral changes. In this review, we present the state of the art of optoelectronic probes and assess advantages and challenges of the different design approaches. At first, we discuss mechanisms and processes at the material-tissue interface that influence the performance of optoelectronic probes in acute and chronic implantations. We classify optoelectronic probes by their property of delivering light to the tissue: by waveguides or by integrated light sources at the sites of intervention. Both approaches are discussed with respect to size, spatial resolution, opportunity to integrate electrodes for electrical recording and potential interactions with the target tissue. At last, we assess translational aspects of the state of the art. Long-term stability of probes and the opportunity to integrate them into fully implantable, wireless systems are a prerequisite for chronic applications and a transfer from fundamental neuroscientific studies into treatment options for diseases and clinical trials.



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Relationships between compulsive exercise, quality of life, psychological distress and motivation to change in adults with anorexia nervosa

Abstract

Background

For people with anorexia nervosa (AN), compulsive exercise is characterized by extreme concerns about the perceived negative consequences of stopping/reducing exercise, dysregulation of affect, and inflexible exercise routines. It is associated with increased eating disorder psychopathology and poor clinical outcome. However, its relationships with two important clinical issues, quality of life (QoL) and motivation to change, are currently unknown. This study aimed to assess the cross-sectional relationships between compulsive exercise, QoL, psychological distress (anxiety and depressive symptoms, and obsessive-compulsive traits) and motivation to change in patients with AN.

Method

A total of 78 adults with AN participated in this study, which was nested within a randomized controlled trial of psychological treatments for AN. At baseline (pre-treatment), participants completed questionnaires assessing compulsive exercise, eating disorder (ED) psychopathology, QoL, psychological distress and motivation to change.

Results

Baseline correlational analyses demonstrated a moderate positive relationship between compulsive exercise and ED psychopathology, and a weak positive relationship between compulsive exercise and psychological distress. There was a moderate negative relationship between compulsive exercise and eating disorder QoL.

Conclusions

These results indicate compulsive exercise is moderately associated with poorer QoL and weakly associated with higher distress. Targeting compulsive exercise in the treatment of anorexia nervosa may help reduce the burden of illness and improve patients' engagement in treatment.

Trial registration

ACTRN12610000585022. Taking a LEAP forward in the treatment of anorexia nervosa: a randomized controlled trial. NHMRC grant: 634922.

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Causes and treatments for nasolabial folds

Nasolabial folds are the lines on either side of the mouth that extend from the edge of the nose to the mouth's outer corners. Learn more here.

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Aortoiliac Dissection After Blunt Abdominal Trauma

Publication date: Available online 4 February 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Dennis Hundersmarck, Raechel J. Toorop




http://ift.tt/2E3x4nJ

Kombination aus perkutaner Strahlentherapie, Brachytherapie und Androgendeprivation gleichwertige Alternative zur radikalen Prostatektomie beim Prostatakarzinom

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Direct dose correlation of MRI morphologic alterations of healthy liver tissue after robotic liver SBRT

Abstract

Purpose

For assessing healthy liver reactions after robotic SBRT (stereotactic body radiotherapy), we investigated early morphologic alterations on MRI (magnetic resonance imaging) with respect to patient and treatment plan parameters.

Patients and methods

MRI data at 6–17 weeks post-treatment from 22 patients with 42 liver metastases were analyzed retrospectively. Median prescription dose was 40 Gy delivered in 3–5 fractions. T2- and T1-weighted MRI were registered to the treatment plan. Absolute doses were converted to EQD2 (Equivalent dose in 2Gy fractions) with α/β-ratios of 2 and 3 Gy for healthy, and 8 Gy for modelling pre-damaged liver tissue.

Results

Sharply defined, centroid-shaped morphologic alterations were observed outside the high-dose volume surrounding the GTV. On T2-w MRI, hyperintensity at EQD2 isodoses of 113.3 ± 66.1 Gy₂, 97.5 ± 54.7 Gy₃, and 66.5 ± 32.0 Gy₈ significantly depended on PTV dimension (p = 0.02) and healthy liver EQD2 (p = 0.05). On T1-w non-contrast MRI, hypointensity at EQD2 isodoses of 113.3 ± 49.3 Gy₂, 97.4 ± 41.0 Gy₃, and 65.7 ± 24.2 Gy₈ significantly depended on prior chemotherapy (p = 0.01) and total liver volume (p = 0.05). On T1-w gadolinium-contrast delayed MRI, hypointensity at EQD2 isodoses of 90.6 ± 42.5 Gy₂, 79.3 ± 35.3 Gy₃, and 56.6 ± 20.9 Gy₈ significantly depended on total (p = 0.04) and healthy (p = 0.01) liver EQD2.

Conclusions

Early post-treatment changes in healthy liver tissue after robotic SBRT could spatially be correlated to respective isodoses. Median nominal doses of 10.1–11.3 Gy per fraction (EQD2 79–97 Gy₃) induce characteristic morphologic alterations surrounding the lesions, potentially allowing for dosimetric in-vivo accuracy assessments. Comparison to other techniques and investigations of the short- and long-term clinical impact require further research.

http://ift.tt/2EgdkN4

Do children with obesity have worse table manners? Associations between child table manners, weight status and weight gain

Publication date: 1 June 2018
Source:Appetite, Volume 125
Author(s): Naomi F. Briones, Robert J. Cesaro, Danielle P. Appugliese, Alison L. Miller, Katherine L. Rosenblum, Megan H. Pesch
BackgroundChildren with obesity experience stigma stemming from stereotypes, one such stereotype is that people with obesity are "sloppy" or have poor manners. Teaching children "proper table manners" has been proposed as an obesity prevention strategy. Little is known about the association between children's weight status and table manners.ObjectivesTo examine correlates of child table manners and to examine the association of child table manners with child obese weight status and prospective change in child body mass index z-score (BMIz).MethodsMother-child dyads (N = 228) participated in a videotaped laboratory eating task with cupcakes. Coding schemes to capture child table manners (making crumbs, chewing with mouth open, getting food on face, shoving food in mouth, slouching, and getting out of seat), and maternal attentiveness to child table manners, were reliably applied. Anthropometrics were measured at baseline and at follow-up two years later. Regression analyses examined the association of participant characteristics with child table manners, as well as the associations of child table manners with child obese weight status, and prospective change in BMIz/year.ResultsPredictors of poorer child table manners were younger child age, greater cupcake consumption, and greater maternal attentiveness to child table manners. Poorer child table manners were not associated with child obese (vs. not) weight status, but were associated with a prospective decrease in BMIz/year in children with overweight/obesity.ConclusionsObesity interventions to improve table manners may be perpetuating unfavorable stereotypes and stigma. Future work investigating these associations is warranted to inform childhood obesity guidelines around table manners.



http://ift.tt/2GNhPNo

Effect of dewatering and composting on helminth eggs removal from lagooning sludge under semi-arid climate

Abstract

In this work, we assessed the drying and composting effectiveness of helminth eggs removal from sewage sludge of a lagoon wastewater treatment plant located in Chichaoua city. The composting was run after mixing sludge with green waste in different proportions: M1 (½ sludge + ½ green waste), M2 ( \( \raisebox{1ex}{\(2\)}\!\left/ \!\raisebox{-1ex}{\(3\)}\right. \) sludge + \( \raisebox{1ex}{\(1\)}\!\left/ \!\raisebox{-1ex}{\(3\)}\right. \) green waste), and M3 ( \( \raisebox{1ex}{\(1\)}\!\left/ \!\raisebox{-1ex}{\(3\)}\right. \) sludge + \( \raisebox{1ex}{\(2\)}\!\left/ \!\raisebox{-1ex}{\(3\)}\right. \) green waste) for 105 days. The analysis of the dewatered sewage sludge showed a load of 8–24 helminth eggs/g of fresh matter identified as Ascaris spp. eggs (5–19 eggs/g) followed by Toxocara spp. (0.2 to 2.4 eggs/g); Hookworm spp. and Capillaria spp. (0.4–1 egg/g); Trichuris spp., Taenia spp., and Shistosoma spp. (< 1 egg/g) in the untreated sludge. After 105 days of treatment by composting, we noted a total reduction of helminth eggs in the order of 97.5, 97.83, and 98.37% for mixtures M1, M2, and M3, respectively. The Ascaris spp. eggs were reduced by 98% for M1 and M3 treatments and by 97% for M₂ Treatment. Toxocara spp., Hookworm spp., Trichuris spp., Capillaria spp., and Shistosoma spp. eggs were totally eliminated (100% decrease) and the Taenia spp. was absent from the first stage of composting. These results confirm the effectiveness of both dehydrating and composting processes on the removal of helminth eggs.

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Cutaneous meningeal heterotopia on the thigh

Abstract

Cutaneous aggregates of meningeal cells have been variously designated as cutaneous meningioma, meningeal heterotopia, and ectopic meningeal rest, with most cases occurring on the head and neck.^1,2 We present an unusual dermal collection of meningeal, adipose, and smooth muscle tissue arising on the thigh of an adult.

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Melanoma Mimicking Rosai-Dorfman Disease

Abstract

Despite advances in treatment and increased public awareness, the incidence of melanoma has dramatically increased over the last 50 years ^1,2. Primary and secondary prevention is critical for decreasing the incidence and improving outcomes in melanoma³. A proper clinical and histopathological diagnosis is necessary for definitive management.

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Agminated Spitz naevi or metastatic spitzoid melanoma?

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Short communication: Comparison of a palmitic acid-enriched triglyceride supplement and calcium salts of palm fatty acids supplement on production responses of dairy cows

Publication date: Available online 4 February 2018
Source:Journal of Dairy Science
Author(s): J. de Souza, A.L. Lock
The objective of our study was to evaluate the effects of feeding a palmitic acid-enriched triglyceride supplement or a calcium salts of palm fatty acid (FA) supplement on nutrient digestibility and production responses of mid-lactation dairy cows. Fifteen Holstein cows (139 ± 39 d in milk) were randomly assigned to treatment sequence in a 3 × 3 Latin square design. Treatments were a control diet (CON; no fat supplement) and 1.5% of FA added either as a palmitic acid-enriched triglyceride supplement (PA-TG) or as calcium salts of palm FA supplement (Ca-FA). Fat-supplemented treatments did not affect dry matter intake (DMI) compared with CON, but Ca-FA reduced DMI compared with PA-TG. Compared with CON, fat-supplemented treatments increased 18-carbon FA digestibility by 2.0 percentage units but did not affect digestibility of total FA or 16-carbon FA. Compared with Ca-FA, PA-TG reduced total FA digestibility by 8.7 percentage units due to a decrease in 16-carbon FA digestibility (21.7 percentage units). Both fat supplements increased neutral detergent fiber (NDF) digestibility compared with CON (3.90 percentage units), and PA-TG tended to increase NDF digestibility by 1.60 percentage units compared with Ca-FA. Compared with CON, fat-supplemented treatments increased milk yield (1.05 kg/d), 3.5% fat-corrected milk yield (2.20 kg/d), and energy-corrected milk yield (1.80 kg/d). Also, PA-TG increased milk fat yield (50 g/d) and milk energy output (1.0 Mcal/d) and tended to increase milk fat content (0.07 percentage units) and energy-corrected milk yield (1.0 kg/d) compared with Ca-FA. Fat-supplemented treatments reduced the yield of de novo milk FA (23 g/d) and increased the yields of mixed (43 g/d) and preformed (52 g/d) milk FA compared with CON. The PA-TG treatment increased the yield of 16-carbon (66 g/d) milk FA compared with Ca-FA, whereas Ca-FA increased the yield of preformed (60 g/d) milk FA. Fat-supplemented treatments increased intake of net energy for lactation by 1.80 Mcal/d, milk energy output by 1.30 Mcal/d, and energy in body reserves by 0.30 Mcal/d compared with CON. The Ca-FA treatment increased energy allocated to body reserves (0.60 Mcal/d), energy partitioning toward body reserves (1.20 percentage units), and body condition score change (0.06 units), and tended to increase body weight change (0.16 kg/d) and body condition score (0.08 units) compared with PA-TG. In conclusion, feeding a palmitic acid-enriched triglyceride supplement increased milk energy output due to increased yields of milk and milk fat, whereas feeding a calcium salts of palm FA supplement increased FA digestibility and energy partitioned to body reserves.



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Udder health in Canadian dairy heifers during early lactation

Publication date: Available online 4 February 2018
Source:Journal of Dairy Science
Author(s): S. Ali Naqvi, Jeroen De Buck, Simon Dufour, Herman W. Barkema
Mastitis is the most prevalent and costly disease in dairy cattle worldwide, with implications for animal health and welfare as well as production and economics. Nonlactating heifers are an often-neglected group of animals concerning mastitis management, as they are assumed to be free of mastitis. An observational field study was conducted between 2007 and 2008 on 91 dairy herds across Canada, representative of provincial averages of bulk milk somatic cell count (BMSCC) and barn type. The aims of that study were to (1) estimate in early-lactating heifers overall and pathogen-specific incidence rate of clinical mastitis (IRCM), prevalence of intramammary infection (IMI), and prevalence of subclinical mastitis (SCM; defined as SCC ≥200,000 cells/mL); (2) compare these udder health parameters between heifers and multiparous cows; and (3) determine regional patterns and variations in these udder health parameters across BMSCC categories. During the first day of lactation, IRCM was higher in heifers than in multiparous cows (99 vs. 48 cases per 10,000 quarter-days at risk, respectively). Clinical mastitis affected 4% of heifers (0.73 cases per 100 quarters) in the first 30 d after calving, with the most common pathogens isolated being Staphylococcus aureus and Escherichia coli, whereas S. aureus and non-aureus staphylococci were the most commonly isolated pathogens in multiparous cows. The IRCM in heifers was highest in Ontario heifers, but overall IRCM did not vary by BMSCC category and it was only higher in multiparous cows than heifers in high-BMSCC Ontario herds. Intramammary infections were present in 33% of heifer quarters, with non-aureus staphylococci the most commonly isolated group of bacteria in both heifers (26% of quarters) and multiparous cows (18% of quarters). Pathogen-specific prevalence of IMI did not differ between heifers and multiparous cows, but we noted regional differences and differences across BMSCC categories in pathogen-specific prevalence of IMI. Prevalence of SCM in heifers was 13.6% and was lowest in Alberta herds. In all regions, SCM prevalence was higher in multiparous cows than in heifers. In conclusion, udder health of Canadian dairy heifers was similar to that of other countries, demonstrating the importance of the issue. Differences between heifers and multiparous cows early in lactation highlighted the need for management practices to target the precalving period in heifers, when exposure to risk factors differs from that in lactating cows.



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Effect of delaying colostrum feeding on passive transfer and intestinal bacterial colonization in neonatal male Holstein calves

Publication date: Available online 4 February 2018
Source:Journal of Dairy Science
Author(s): A.J. Fischer, Y. Song, Z. He, D.M. Haines, L.L. Guan, M.A. Steele
The objective of this study was to investigate the effect of time of first colostrum feeding on the passive transfer of IgG and on bacterial colonization in the intestine of neonatal dairy calves. Twenty-seven male Holstein calves were randomly assigned to 1 of 3 treatments at birth: calves were fed colostrum at 45 min (0 h, n = 9), 6 h (n = 9), or 12 h after birth (n = 9). Calves were fed pooled, heat-treated colostrum (62 g of IgG/L) at their respective feeding times at 7.5% of birth body weight and fed milk replacer at 2.5% of birth body weight per meal every 6 h thereafter. Blood samples were taken every 3 h using a jugular catheter and were analyzed for determination of serum IgG by radial immunodiffusion. At 51 h after birth, calves were euthanized for collection of tissue and digesta of the distal jejunum, ileum, and colon. Quantitative real-time PCR was used to estimate the prevalence of Bifidobacterium spp., Lactobacillus spp., Fecalibacterium prausnitzii, Clostridium cluster XIVa, and total Escherichia coli. Delaying colostrum feeding by 6 h (35.6 ± 1.88%) and 12 h (35.1 ± 3.15%) decreased the maximum apparent efficiency of absorption of IgG compared with feeding colostrum immediately after birth (51.8 ± 4.18%) and delayed the time to maximum serum IgG concentration (24 h vs. 15 h, respectively). Moreover, 12-h calves tended to have a lower prevalence of Bifidobacterium spp. (0.12 ± 0.017%) and Lactobacillus spp. (0.07 ± 0.019%) associated with the colon mucosa compared with 0-h calves (1.24 ± 0.648% and 0.26 ± 0.075%, respectively). In addition, 6-h (0.26 ± 0.124%) and 12-h (0.49 ± 0.233%) calves had a lower prevalence of total E. coli associated with ileum mucosa compared with 0-h calves (1.20 ± 0.458%). These findings suggest that delaying colostrum feeding within 12 h of life decreases the passive transfer of IgG and may delay the colonization of bacteria in the intestine, possibly leaving the calf vulnerable to infections during the preweaning period.



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Invited review: Mineral absorption mechanisms, mineral interactions that affect acid–base and antioxidant status, and diet considerations to improve mineral status

Publication date: Available online 4 February 2018
Source:Journal of Dairy Science
Author(s): Jesse P. Goff
Several minerals are required for life to exist. In animals, 7 elements (Ca, P, Mg, Na, K, Cl, and S) are required to be present in the diet in fairly large amounts (grams to tens of grams each day for the dairy cow) and are termed macrominerals. Several other elements are termed microminerals or trace minerals because they are required in much smaller amounts (milligrams to micrograms each day). In most cases the mineral in the diet must be absorbed across the gastrointestinal mucosa and enter the blood if it is to be of value to the animal. The bulk of this review discusses the paracellular and transcellular mechanisms used by the gastrointestinal tract to absorb each of the various minerals needed. Unfortunately, particularly in ruminants, interactions between minerals and other substances within the diet can occur within the digestive tract that impair mineral absorption. The attributes of organic or chelated minerals that might permit diet minerals to circumvent factors that inhibit absorption of more traditional inorganic forms of these minerals are discussed. Once absorbed, minerals are used in many ways. One focus of this review is the effect macrominerals have on the acid–base status of the animal. Manipulation of dietary cation and anion content is commonly used as a tool in the dry period and during lactation to improve performance. A section on how the strong ion theory can be used to understand these effects is included. Many microminerals play a role in the body as cofactors of enzymes involved in controlling free radicals within the body and are vital to antioxidant capabilities. Those same minerals, when consumed in excess, can become pro-oxidants in the body, generating destructive free radicals. Complex interactions between minerals can compromise the effectiveness of a diet in promoting health and productivity of the cow. The objective of this review is to provide insight into some of these mechanisms.



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Symposium review: Oxylipids and the regulation of bovine mammary inflammatory responses

Publication date: Available online 4 February 2018
Source:Journal of Dairy Science
Author(s): Lorraine M. Sordillo
Inflammation is a critical aspect of the innate immune system that can determine the outcome of several economically important diseases of dairy cattle such as mastitis. The purpose of the inflammatory response is to eliminate the source of tissue injury and then return tissues to normal function. Aggressive or uncontrolled inflammatory responses, however, can damage host tissues and contribute significantly to the pathophysiology associated with mastitis. A precarious balance between pro-inflammatory and pro-resolving mechanisms is needed to ensure optimal pathogen clearance and a prompt return to immune homeostasis. Therefore, inflammatory responses must be tightly regulated to avoid bystander damage to the milk-synthesizing tissues of the mammary gland. Oxylipids are potent lipid mediators that can regulate all aspects of the inflammatory response. The biosynthetic profiles of oxylipids are dependent on both the availability of diverse polyunsaturated fatty acids substrates and their subsequent metabolism through various oxidizing pathways. Changes in lipid metabolism in dairy cows around parturition can profoundly change the composition and concentration of oxylipids in the mammary gland that may be responsible for dysfunctional inflammatory responses during this time. This review will provide a brief overview of the bovine inflammatory response and the role that oxylipids play in contributing to the onset and resolution of inflammation especially as it pertains to mastitis. Factors associated with periparturient cows that can contribute to dysfunctional regulation of inflammation as a function of altered oxylipid biosynthesis and metabolism also will be described. Understanding the role that oxylipids may play in the development of mastitis is key to developing novel prevention and control programs for the dairy industry.



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Frequency of extended-spectrum β-lactamase (ESBL)– and AmpC β-lactamase–producing Enterobacteriaceae in a cheese production process

Publication date: Available online 4 February 2018
Source:Journal of Dairy Science
Author(s): Seda Özdikmenli Tepeli, Nükhet N. Demirel Zorba
The aim of this study was to investigate the extended-spectrum β-lactamase (ESBL) and AmpC β-lactamase activities of Enterobacteriaceae isolated from raw milk and cheese production line and to determine the probability of transmitting these bacteria to consumers. One hundred seventy-three samples from raw milk and cheese production lines were analyzed; 64 isolates were confirmed as Enterobacteriaceae. Sixteen of 64 isolates (25%) were resistant to at least one cephalosporin according to European Committee on Antimicrobial Susceptibility Testing Standards (EUCAST) and Clinical and Laboratory Standards Institute criteria. Seven of the 16 resistant isolates (43.75%) had confirmed ESBL activity. Additionally, phenotypic AmpC β-lactamase activity was observed in 31 (48.44%) of 64 Enterobacteriaceae isolates and confirmed in 27 of the 31 strains (89.1%). Overall, 3 isolates showed both ESBL activity and AmpC resistance, 28 isolates were only AmpC resistant, and 5 isolates had ESBL activity alone. Of the 173 samples, the proportions of samples that contained ESBL- and AmpC-producing isolates were 4.64 and 15.6%, respectively. Five of the ESBL-positive isolates (62.5%) and 11 of the AmpC-positive isolates (40.7%) were obtained from bulk milk tanks; therefore, the bulk tank plays a very important role in the spread of antibiotic-resistant bacteria. Periodic cleaning and maintenance of bulk tanks should be performed and recorded. Effective food safety and hygiene practices should significantly reduce cross-contamination in dairy plants.



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Effect of isoflurane alone or in combination with meloxicam on the behavior and physiology of goat kids following cautery disbudding

Publication date: Available online 4 February 2018
Source:Journal of Dairy Science
Author(s): Melissa N. Hempstead, Joseph R. Waas, Mairi Stewart, Suzanne K. Dowling, Vanessa M. Cave, Gemma L. Lowe, Mhairi A. Sutherland
Cautery disbudding of goat kids is painful, but may be alleviated with pain mitigation. We therefore evaluated the effect of administering general anesthesia (isoflurane) or a nonsteroidal anti-inflammatory drug (meloxicam) on goat kid behavior and physiology following cautery disbudding. Trial 1 (n = 12/treatment) evaluated behavioral responses in 72 female Saanen dairy goat kids (mean ± standard error of the mean; 3.9 ± 0.15 d old) and trial 2 (n = 10/treatment) evaluated physiological responses in 60 female Saanen dairy goat kids (4.3 ± 0.14 d old). Goat kids were randomly assigned to 1 of 6 treatment groups that were either (1) sham-handled only (simulated disbudding; SHAM) or disbudded with (2) no pain relief (CAUT), (3) isoflurane gas (ISO), (4) isoflurane and s.c. meloxicam combined (ISO+MEL), (5) meloxicam s.c. (0.5 mg/kg of body weight; I-MEL), or (6) oral meloxicam (0.2 mg/kg of body weight; O-MEL). Head shaking, head scratching, self-grooming, feeding, and body shaking were continuously video recorded for 24 h pre- and post-treatment. Lying behavior was recorded continuously for 24 h pre- and post-treatment using accelerometers. Plasma cortisol, glucose, and lactate concentrations were measured from blood samples collected immediately before treatment (baseline) and at 15, 60, and 120 min post-treatment. Body temperature was measured immediately after blood sampling at all blood sampling time points. Head shaking and body shaking frequencies were 50% higher in CAUT than SHAM kids 5 min post-treatment; ISO+MEL and ISO kids performed 25% less body shakes than CAUT kids. Head scratching durations 1 h post-treatment were higher in CAUT than SHAM kids, whereas O-MEL were similar to SHAM kids from 2 h post-treatment. Self-grooming, feeding, and lying did not differ between groups. Cortisol concentrations were higher in CAUT than SHAM kids (156.4 ± 26.41 and 104.1 ± 26.41 nmol/L, respectively), whereas ISO+MEL and ISO kids (88.3 ± 26.41 and 113.2 ± 26.41 nmol/L, respectively) had lower cortisol concentrations than CAUT kids over the 2-h sampling period. Moreover, O-MEL and I-MEL kids (163.0 ± 26.41 and 130.9 ± 26.41 nmol/L, respectively) had similar cortisol concentrations to CAUT kids. We found no evidence that plasma glucose and lactate concentrations or body temperature were affected by treatment. The administration of isoflurane, with or without meloxicam, appeared to reduce pain associated with cautery disbudding.



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Incorporating white clover (Trifolium repens L.) into perennial ryegrass (Lolium perenne L.) swards receiving varying levels of nitrogen fertilizer: Effects on milk and herbage production

Publication date: Available online 4 February 2018
Source:Journal of Dairy Science
Author(s): M. Egan, N. Galvin, D. Hennessy
White clover (Trifolium repens L.; clover) can offer a superior nutritional feed compared with perennial ryegrass (Lolium perenne L.; PRG) and offers an additional or alternative source (or both) of N for herbage production. The objective of this study was to investigate the effect of including clover into PRG swards receiving 150 (Cl150) or 250 kg of N/ha (Cl250) compared with a PRG-only sward receiving 250 kg of N/ha (Gr250) on herbage production, milk production, and herbage dry matter intake (DMI) in an intensive grass-based spring calving milk production system over 2 full lactations. A farm systems experiment was established in February 2013, and conducted over 2 grazing seasons [2013 (yr 1) and 2014 (yr 2)]. In February 2013 (yr 1), 42 Holstein-Friesian spring-calving dairy cows, and in February 2014 (yr 2), 57 Holstein-Friesian spring-calving dairy cows were allocated to graze the Cl150, Cl250, and Gr250 swards (n = 14 in yr 1 and n = 19 in yr 2) from February to November, at a stocking rate of 2.74 cows/ha. Herbage DMI was estimated twice in yr 1 (May and September) and 3 times in yr 2 (May, July, and September). Treatment did not have a significant effect on annual herbage production. Sward clover content was greater on the Cl150 treatment than the Cl250 treatment. The cows grazing both clover treatments (Cl250 and Cl150) produced more milk than the cows grazing Gr250 from June until the end of the grazing season. A significant treatment by measurement period interaction was observed on total DMI. In May, the cows on the Cl250 treatment had the greatest DMI. In July, the cows on the clover treatments had greater DMI than those on the Gr250 treatment, whereas in September, the cows on the Cl150 treatment had the lowest DMI. In conclusion, including clover in a PRG sward grazed by spring-calving dairy cows can result in increased animal performance, particularly in the second half of lactation. Reducing N fertilizer application to 150 kg of N/ha on grass-clover swards did not reduce herbage production compared with grass-only swards receiving 250 kg of N/ha. White clover can play an integral role in intensive grazing systems in terms of animal performance and herbage production.



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Hot topic: Holder pasteurization of human milk affects some bioactive proteins

Publication date: Available online 4 February 2018
Source:Journal of Dairy Science
Author(s): André F. Guerra, Caroline Mellinger-Silva, Amauri Rosenthal, Rosa H. Luchese
The aim of this research was to investigate the effect of Holder pasteurization (HoP; 62.5°C, 30 min) on the protein profile and activities of glutathione peroxidase (GPx) and lysozyme (LZ) in human milk. Over 6 mo of lactation, human milk samples were analyzed before (raw) and after HoP for GPx and LZ activity and electrophoresis protein profile. Holder pasteurization reduced human milk lactoferrin, immunoglobulin fractions, and GPx activity. In addition, GPx activity, which is high in colostrum and transitional milk, was naturally reduced over the 6-mo lactation period. In contrast, HoP did not affect human milk LZ activity. Besides its critical cellular antioxidant role in protecting the organism from oxidative damage, GPx decreases the redox potential of milk, stimulating the growth of anaerobic microorganisms, such as the probiotic Bifidobacterium. Considering the role of lactoferrin in infant health, we conclude that an important part of its function has been inactivated by pasteurization. These compounds should be replaced by human milk banks after the HoP step to recover lost functionality. Otherwise, an alternative technology to HoP that better retains human milk properties should be used by milk banks to eliminate the risk of transmission of infectious agents.



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How benchmarking motivates farmers to improve dairy calf management

Publication date: Available online 4 February 2018
Source:Journal of Dairy Science
Author(s): Christine L. Sumner, Marina A.G. von Keyserlingk, Daniel M. Weary
Dairy calves often receive inadequate colostrum for successful transfer of passive immunity and inadequate milk to achieve their potential for growth and avoid hunger, but little is known about what motivates farmers to improve calf management around these concerns. Our aim was to assess if and how access to benchmarking reports, providing data on calf performance and peer comparison, would change the ways in which farmers think about calves and their management. During our study, 18 dairy farmers in the lower Fraser Valley (British Columbia, Canada) each received 2 benchmark reports that conveyed information on transfer of immunity and calf growth for their own calves and for other farms in the region. Farmers were interviewed before and after receiving their benchmarking reports to gain an understanding of how they perceived access to information in the reports. We conducted qualitative analysis to identify major themes. Respondents generally saw having access to these data and peer comparisons favorably, in part because the reports provided evidence of how their calves were performing. Benchmarking encouraged farmers to make changes in their calf management by identifying areas needing attention and promoting discussion about best practices. We conclude that some management problems can be addressed by providing farmers better access to data that they can use to judge their success and inform changes.



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Short communication: Test of the relationship between prepartum milk leakage and blood calcium concentration in Holstein cows—An observational study

Publication date: Available online 4 February 2018
Source:Journal of Dairy Science
Author(s): Ehsan Mahjoubi, Davood Zahmatkesh, Mehdi Hossein-Yazdi, Mohammad Hadi Khabbazan, Mohammad Reza Samadian
Prepartum milk leakage happens in some pregnant dairy cows close to calving. It has been hypothesized that low blood Ca is a cause of this event. To investigate the possible reason(s) of milk leakage, 137 multiparous pregnant Holstein cows were enrolled in the experiment and categorized by the presence (72 heads; leak group) or lack (65 heads; control group) of milk leakage before calving. The concentrations of Ca and P and the length of the teat were measured for all cows. Data showed that Ca concentration was not different between cows in the leak group (7.90 mg/dL) and those in the control group (7.99 mg/dL). Moreover, neither P concentration (4.62 vs. 4.54 mg/dL) nor teat length (4.28 vs 4.10 cm) differed between leak and control groups. Milk yield was greater for the leak group (53.6 kg/d) compared with the control group (50.1 kg/d) through 4 mo in milk. The leakage did not affect the odds of postpartum disorders such as retained placenta, metritis, mastitis, displaced abomasum, or lameness occurrence. The current results show that hypocalcemia is not a reason for observed prepartum leakage and that cows in the leak group produced more milk in the subsequent lactation period.



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Plasma glucose and nonesterified fatty acids response to epinephrine challenges in dairy cows during a 670-d lactation

Publication date: Available online 4 February 2018
Source:Journal of Dairy Science
Author(s): L.C. Marett, M.J. Auldist, W.J. Wales, K.L. Macmillan, F.R. Dunshea, B.J. Leury
This experiment investigated the metabolic response to a 2-dose epinephrine challenge of dairy cows undergoing an extended lactation. Twelve multiparous Holstein-Friesian cows that calved in late winter in a seasonally calving pasture-based dairying system were managed for a 670-d lactation by delaying rebreeding. In each of four 40-d experimental periods commencing at 73, 217, 422, and 520 (±9.1) d in milk (DIM), cows were offered a diet of perennial ryegrass (73 and 422 DIM) or pasture hay and silage (217 and 520 DIM), supplemented with 1 (CON; n = 6) or 6 kg of grain (GRN; n = 6) as a ration. Daily energy intake was approximately 160 and 215 MJ of metabolizable energy/cow for the CON and GRN treatments, respectively. At all other times, cows were managed as a single herd and grazed pasture supplemented with grain to an estimated daily total intake of 180 MJ of metabolizable energy/cow. Cows were fitted with a jugular catheter during the final week of each experimental period. Two doses of epinephrine (0.1 and 1.6 µg/kg of body weight) were infused via the catheter 2 h apart to each cow at approximately 100, 250, 460, and 560 DIM. Blood plasma concentrations of glucose and nonesterified fatty acids (NEFA) were measured before and after infusions. Cows in the GRN treatment had greater milk yield, milk fat and protein yields, and body weight than cows in the CON treatment. The maximum plasma glucose concentration was observed at 100 DIM for both the low and high doses of epinephrine. Thus, sensitivity and responsiveness to exogenous epinephrine were greater during early lactation, coinciding with increased priority of milk synthesis. Both the sensitivity and responsiveness to epinephrine decreased with decreasing milk yield, as measured by the acute appearance of NEFA in the plasma. Increased plasma glucose and NEFA clearance rates before 300 DIM indicated greater uptake of these substrates by the mammary gland for milk synthesis in early and mid lactation. These results support previous findings that major changes occur in terms of adipose tissue metabolism during extended lactations. Overall, sensitivity to epinephrine was not affected by diet, but responsiveness was greater in cows fed the GRN diet. The endocrine regulation of nutrient partitioning throughout traditional and extended lactations is complex, with many interactions between stage of lactation, diet, and milk yield potential.



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