Intensive Care to Facilitate Organ Donation: A Report on the Experience of 2 Spanish Centers with A Common Protocol\

Background The aim of this study is to report the experience with a program of Intensive Care to facilitate Organ Donation (ICOD) in 2 Spanish centers based on a common protocol. Methods Retrospective review of clinical charts of patients with a devastating brain injury whose families were approached to discuss the possibility of ICOD once further treatment was deemed futile by the treating team. Study period: 1/1/2011-12/31/2015. Results ICOD was discussed with families of 131 patients. Mean age of possible donors was 75 (SD=11) years. The main cause of brain injury was an intracranial hemorrhage (72%). Interviews with families were held after the decision had been made not to intubate/ventilate in 50% of cases, and after the decision not to continue with invasive ventilation in the remaining cases. Most interviews (66%) took place in the emergency department. The majority of families (95%) consented to ICOD. Of the 125 consented cases, 101 (81%) developed brain death (BD), most in ≤72 hours. Ninety-nine patients (98%) transitioned to actual donation after BD, with 1.2 organs transplanted per donor. Of patients who did not evolve to BD, 4 died following an unexpected cardiac arrest and 18 after the withdrawal of life-sustaining measures. ICOD contributed to 33% of actual donors registered at both centers. Conclusions ICOD is well accepted by families. Most patients evolve to BD within a short period of time. The practice substantially contributes to increasing organ donation and offers more patients the chance of donating their organs after death. CORRESPONDENCE INFORMATION: Beatriz Domínguez-Gil, MD, PhD. Director General, Organización Nacional de Trasplantes. C/Sinesio Delgado 6, pabellón 3, 28029 Madrid, Spain, Email: bdominguez@msssi.es AUTHORSHIP PAGE: FMS, JMPV and BDG conceived and designed the study. FMS, LMC and JMPV contributed with the data required for the study. EC and BDG coordinated the data collection and undertook the statistical analysis. JLM, AFC and PM participated in the performance of the research. FMS, JMPV and BDG drafted the first version of the paper, with contributions from the rest of the authors. The authors declare no conflict of interests. The study received no external funding. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Donor Derived Viral Infections in Liver Transplantation

Donor-derived infections are defined as any infection present in the donor that is transmitted to 1 or more recipients. Donor-derived infections can be categorized into 2 groups: 'expected' and 'unexpected' infections. Expected transmissions occur when the donor is known to have an infection, such as positive serology for CMV, EBV or hepatitis B core antibody, at the time of donation. Unexpected transmissions occur when a donor has no known infection prior to donation, but 1 or more transplant recipients develop an infection derived from the common donor. Unexpected infections are estimated to occur in far less than 1% of solid organ transplant recipients. We will review the epidemiology, risk factors and approaches to prevention and management of donor-derived viral infectious disease transmission in liver transplantation. *Co-First Authors Corresponding Author: Michael G. Ison, MD MS FIDSA FAST, Divisions of Infectious Diseases and Organ Transplantation, Northwestern University Feinberg School of Medicine, 645 N Michigan Avenue Suite 900, Chicago, Illinois 60611, 312-695-4186 (Office), 312-695-5088 (Fax). mgison@northwestern.edu Authorship Page Hannah Nam, MD and Kathy M Nilles, MD are co-first authors. Both have made substantial contributions in gathering information necessary in drafting the article, participated in writing the article, and revised it critically for important intellectual content. Josh Levitsky, MD MS and Michael G Ison, MD MS have revised the article critically for important intellectual content and gave final approval of the version to be submitted, as well as any revised versions. Disclosures: HN and KMN have nothing to disclose. JL is a paid speaker for Gilead and Novartis. MGI has received support for research, paid to Northwestern University from Beckman Coulter, Cephied, Chimerix, Emergent BioScience, Gilead, Janssen, and Shire; compensated consultation from Chimerix, Celltrion, Genentech/Roche, MediVector, Seqirus, Shionogi, and VirBio; and paid membership of DSMB from GlaxoSmithKlein, Shionogi. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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The First Kidney Transplant in Ireland

No abstract available

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Minimally invasive transplantation of primary human hepatocyte inserts that facilitate vascularization

No abstract available

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TACROLIMUS INDUCED CHOLESTATIC HEPATITIS IN A PATIENT WITH LIVER TRANSPLANT

No abstract available

https://ift.tt/2ISL9SA

SiChoose Kidney for Treatment Options: Updated Models for Shared Decision Aid

No abstract available

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Incidence, Risk Factors and Outcomes of Early Acute Kidney Injury After Heart Transplantation: An 18-year Experience

Background Little is known about the incidence of acute kidney injury (AKI), as defined using the Kidney Disease Improving Global Outcome (KDIGO) classification, after heart transplantation (HT). Objective. Our objective was to evaluate the impact of AKI in a cohort of HT recipients. (Setting: University Hospital.) Methods We studied 310 consecutive HT recipients from 1999 to 2017, with AKI being defined according to the KDIGO criteria. Risk factors were analyzed by multivariable analyses, and survival by Kaplan-Meier curves and a risk-adjusted Cox proportional hazards regression model. Results 125 patients (40.3%) developed AKI, with 73 (23.5%), 18 (5.8%) and 34 (11%) patients having AKI stage 1, 2 and 3, respectively. Cardiac tamponade (OR: 16.82; 95% CI: 1.06–138), acute right ventricular failure (OR: 3.54; 95% CI: 1.82–6.88), and major bleeding (OR: 2.46; 95% CI: 1.18–5.1) were the principal risk factors for AKI. Patients with AKI had a greater hospital mortality (3.8% vs. 16%, P

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The "Orbital Oval Balance Principle": a Morphometric Clinical Analysis

Background: The aim of this study was to test the validity of the "Orbital Oval Balance Principle", a system of analysis and guideline that is used among aestheticians, artist and make-up artist to create and design aesthetically pleasing eyebrows for optimal upper facial appearance. According to this principle, a face is optimally attractive when the eye is centered in an "oval" defined by the lid-cheek junction and the eyebrow. Methods: One hundred participants were asked to rank digital morphed images of four female models with four different peri-orbital proportions: higher or lower lid-cheek junction versus higher or lower eyebrow position. In addition, the participants were asked to quantify seven emotions on these morphed images. Results: A higher lid-cheek junction was rated as significantly more attractive with a lower eyebrow position, and a lower lid-cheek junction was regarded far more attractive in combination with a higher eyebrow position. Moreover a higher lid-cheek junction was rated as more attractive than a lower lid-cheek junction and elevation of the lid-cheek junction improved the perceived emotions such as tiredness and sadness. Conclusion: This study lends support to the Orbital Oval Balance Principle that can provide important insight into facial attractiveness to surgeons undertaking procedures intended to improve and rejuvenate facial appearance. Moreover, this study has also shown that a high(er) lid- cheek junction is not only regarded as more youthful and attractive, but that it also may reduce the appearance of tiredness and sadness. There has been no financial support and there are no financial interests. Corresponding author: Prof dr. B. van der lei, M.D., Ph.D., University and University medical School of Groningen, The Netherlands. PO box 30.001, 9700 RB Groningen. info@berendvanderlei.nl ; b.van.der.lei@umcg.nl ©2018American Society of Plastic Surgeons

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Pre-Operative Multimodal Analgesia Decreases Post-Anesthesia Care Unit Narcotic Use and Pain Scores in Outpatient Breast Surgery

Background: The opioid epidemic demands changes in perioperative pain management. Of the 33,000 deaths due to opioid overdose in 2015, half received prescription opioids. Multimodal analgesia (MMA) is a practice-altering evolution that reduces reliance on opioid medications. Ambulatory breast surgery is an ideal opportunity to implement these strategies. Methods: A retrospective review of 560 patients undergoing outpatient breast procedures was conducted. Patients received 1) no pre-operative analgesia (n=333), 2) intra-operative IV acetaminophen (n=78), 3) pre-operative oral acetaminophen and gabapentin (n=95), or 4) pre-operative oral acetaminophen, gabapentin and celecoxib (n=54). Outcomes included PACU narcotic use, pain scores, PACU length-of-stay, rescue anti-emetic use and 30-day complications. Results: Both oral MMA regimens significantly reduced PACU narcotic use (GA:14.3 +/- 1.7 and GAC:11.9 +/- 2.2 versus no drug:19.2 +/- 1.1 mg oral morphine equivalents, p=0.0006), initial pain scores (GA:3.9 +/- 0.4 and GAC:3.4 +/- 0.7 versus no drug:5.3 +/- 0.3 on a 1-10 scale, p=0.0002) and maximum pain scores (GA:4.3 +/- 0.4 and GAC:3.6 +/- 0.7 versus no drug:5.9 +/- 0.3, 1-10 scale, p

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The Influence of Physician Payments on the Method of Breast Reconstruction: a National Claims Analysis

Introduction: Flap-based breast reconstruction demands greater operative labor and offers superior patient reported outcomes compared to implants. However, implants continue to outpace flaps, with some suggesting inadequate remuneration as one barrier. This study aims to characterize market variation in the ratio of implants to flaps and assess correlation with physician payments. Methods: Using the Blue Health Intelligence database from 2009-2013, patients were identified who received tissue expander (i.e. implant) or free-flap breast reconstruction. The ratio of implants/flaps and physician payments was assessed using quadratic modeling. Matched bootstrapped samples from the early and late periods generated probability distributions, approximating the odds of surgeons switching reconstructive method. Results: 21,259 episodes of breast reconstruction occurred within 122 U.S. markets. The distribution of implant/flap ratio varied by market, ranging from 5th percentile at 1.63 to 95th percentile at 43.7 (median 6.19). Modeling the implant/flap ratio vs. implant payment showed a more elastic quadratic equation (f(x)=0.955x2 + 2.766x) compared to the function for flap/implant ratio vs. flap payment (f(x)=-0.061x2 + 0.734x). Probability modeling demonstrated that switching the reconstructive method from implants to flaps with 0.75 probability required a $1,610 payment increase, while switching from flaps to implants at the same certainty occurred at a loss of $960. Conclusion: There was a correlation between the ratio of flaps/implants and physician reimbursement by market. Switching from implants to flaps required large surgeon payment increases. Despite a revenue value unit schedule over twice as high for flaps, current flap reimbursements do not appear commensurate with physician effort. Financial Disclosure: None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript. Funding: This research was funded in part though the NIH/NCI Cancer Center Support Grant P30 CA008748 Acknowledgement: none Corresponding Author: Evan Matros, MD, MMSc, MPH, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, MRI 1036, New York, N.Y. 10065, matrose@mskcc.org ©2018American Society of Plastic Surgeons

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Use of Composite Arterial and Venous Grafts in Microsurgical Breast Reconstruction: Technical Challenges and Lessons Learned

Summary: The success of microvascular reconstruction depends on many factors. While many factors can't be dictated by a surgeon, the success of anastomosis can be maximized by honing the anastomotic skill. However, size discrepancy of vessels still remains a common challenge given the lack of an ideal technique. In our study, we introduce our experience in using composite deep inferior epigastric (DIE) arterial and venous grafts to overcome the vessel size and pedicle length discrepancy in lateral thigh flap (LTP) and superficial inferior epigastric artery (SIEA) flaps, which can lead to higher flap failures secondary to vessel thrombosis and size discrepancy. Of the 1095 flaps performed, we identified a total of 12 flaps (1 LTP, 11 SIEA) on 9 patients for breast reconstruction. We used DIE-vessels to act as an interposition grafts between internal mammary (IMA) and flap pedicle. For the SIEA flaps, we anastomosed SIEA system to the DIEA system, checked viability of flap, and then transferred to the IMA system in 3 patients. In the last 5 patients, we anastomosed the DIE-vessels to the IMA system first, and then transferred the SIEA flap. For the LTP flap, we anastomosed grafts to IMA system first as well. There were no flap losses or fat necrosis. While our outcomes are only limited to breast reconstruction, we believe this method could be expanded to different types of reconstruction, especially head and neck. Financial Disclosure and Products: The authors have no financial interest to declare in relation to the content of this article Institutional review board statement: IRB has approved this study Corresponding Author Contact Information: Address correspondence to: Sumeet S. Teotia M.D., Department of Plastic Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, TX 75390. Sumeet.Teotia@UTSouthwestern.edu ©2018American Society of Plastic Surgeons

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Abdominoplasty with circumferential liposuction: a review of 1000 consecutive cases

Background: Authors present the technique called 'abdominoplasty with concurrent circumferential liposuction' where the whole trunk is addressed as a single aesthetic unit. Materials and methods: Between January 2008 and June 2016, abdominoplasty with circumferential liposuction was performed in 1000 patients (984 female, 16 male) by the senior author. Patients had a mean body mass index of 27.5 (range: 18.1-34.5). Liposuction was performed circumferentially and the abdominal flap was detached up to the costal margins. Simultaneous fat grafting was also performed if required. Outcomes, and complications were documented. Results: Traditional abdominoplasty incisions were used in 359 patients (Fig. 1 A), whereas extended incisions were utilized in 641 patients(Fig. 1 B). The mean duration of follow-up was 27 months (12 days to 61 months) and the mean duration of surgery was 154 minutes (109-260 min). The mean amount of simultaneously aspired supernatant lipoaspirate was 1940 cc (1700-4580 cc ). Simultaneous gluteal fat grafting was performed in 34%. None of the patients had any skin necrosis. The most common complication was seroma. (19%). Conclusion: In abdominoplasty, the entire central body should be considered as a single unit. Circumferential widespread liposuction with standard undermining of the abdominal flap up to the costal margins is both safe and yields superior aesthetic outcomes. Financial Disclosure and Products: None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript. Author Contact Information: Sadri Ozan Sozer, Address: 651 S. Mesa Hills, El Paso, Texas 79912, El Paso Cosmetic Surgery, Phone: +1 915-351-1116 Mobile: +1 915-525-0176, E-mail: ozansozer@gmail.com ©2018American Society of Plastic Surgeons

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Insulin promotes ADSC differentiation after fat grafting

Background: Adipose-derived stem cells (ADSCs) are used to enhance fat graft survival. However, the mechanism of action of grafted ADSCs is controversial. The grafted ADSCs can be replaced by connective tissue or survive at the recipient site and differentiate. Insulin is a powerful agent used to induce the differentiation of ADSCs to adipocytes. To elucidate the fate of grafted ADSCs in nonvascularized fat grafts with or without insulin. Methods: Fat was harvested from a female human donor who underwent reduction mammoplasty. Also, we isolated and cultured ADSCs expressing green fluorescent protein (GFP) from transgenic Sprague-Dawley rats. The experiment was performed on the backs of thirty nude mice. The injection of free fat graft, the ADSCs, phosphate-buffered saline (PBS) and insulin was performed on the 4 para-vertebral points of the back of each mouse as follows: group A (control group) received adipose tissue and PBS; group B received adipose tissue and ADSCs (5×105 cells/100l); group C received adipose tissue, ADSCs, and PBS; and group D received adipose tissue, ADSCs, and insulin. GFP expression was evaluated using an in vivo imaging system. The volume of transplanted fat was evaluated at 8 weeks after graft with six histologic parameters. The fat graft was immunostained with GFP, DAPI and perilipin. Statistical analysis was performed using a one-way ANOVA test. Results: The fat graft volume was significantly higher in group D (P

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Augmentation Gluteoplasty: A Brazilian Perspective

According to recent data, augmentation gluteoplasty continues to gain popularity in the US and globally, especially in procedures involving fat grafts. However, serious concerns about its safety have been raised over the last two years. Will this trend continue or has it already reached its peak? The answer depends on how the technique is going to be performed hereafter. In this paper, the following seven learning objectives are covered to perform gluteal augmentation safely and effectively: 1. the concept of what is a beautiful buttock and how to select the patients who will have better outcomes; 2. diagram each patient's needs for liposuction and graft; 3. employ maneuvers for contouring and projection; 4. compare specific indications for fat graft and gluteal implants; 5. evaluate ptosis grade to indicate whether volume repositioning is sufficient; 6. formulate care protocols for risk management and 7. develop lasting and high satisfaction rate results. it is pivotal to recognize each patient's body characteristics and ability to achieve a good result, work on her expectations preoperatively and accordingly in order to perform the procedure in the safest manner possible. Meetings: Rosique, Rodrigo G.; Gluteoplasty with autologous fat tissue: A Brazilian Perspective, Instructional Course presented at Plastic Surgery - The Meeting 2015 (Annual Meeting of the American Society of Plastic Surgeons), in Boston, MA, 16th October, 2015. Rosique, Rodrigo G.; Gluteoplasty with autologous fat tissue: A Brazilian Perspective, Instructional Course presented at Plastic Surgery - The Meeting 2016 (Annual Meeting of the American Society of Plastic Surgeons), in Los Angeles, CA, 26th September, 2016. Financial Disclosures: None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript. Acknowledgements: The authors would like to give thanks to Ilson Rosique, MD, MsC, for teaching them the basics about the fat graft technique and for contributing to the casuistic analysis. Corresponding Author: Rodrigo Gouvea Rosique, Av. Antonio Diederichsen, 400, Conj. 1204, Ribeirão Preto, São Paulo, Brazil. ZIP Code 14020-250. Email: Rodrigo@rosique.com.br ©2018American Society of Plastic Surgeons

https://ift.tt/2lSoj4a

“Fate of free fat grafts with or without adipogenic adjuncts to enhance graft outcomes”

Background: Free fat grafting is popular but it is still unclear how it works. Although focusing on graft survival seems an obvious direction for improving clinical results, our research suggests that long term volume retention is in part due to new fat regeneration. Measures to facilitate adipogenesis may therefore be equally important. Methods: To investigate the relative roles of survival and regeneration of fat grafts, we measured the fate of human lipoaspirate implanted into the scalps of immunodeficient mice, with and without stromal vascular fraction (SVF) and a porcine extracellular matrix (Adipogel). Specifically, we were interested in volume retention, as well as composition of implanted or regenerated tissue at 6 and 12 weeks. Results: Free fat grafts exhibited poor volume retention and survival. Almost all the injected human adipocytes died but new mouse fat formed peripheral to the encapsulated fat graft. Adipogel and SVF improved proliferation of murine fat and human vasculature. Human CD34+ stromal cells were present but only in the periphery, and there was no evidence that these cells differentiated into adipocytes. Conclusions: In our model most of the implanted tissue died but un-resorbed dead fat accounted substantially for the long term, reduced volume. A layer of host-derived, regenerated adipose tissue was present at the periphery. This regeneration may be driven by the presence of dying fat, and it was enhanced by addition of our adipogenic adjuncts. Future research should perhaps focus not only on improving graft survival but also enhancing the adipogenic environment conducive to fat regeneration. Financial disclosure statement: Nothing to disclose Not presented at conferxences etc. Acknowledgments: This research was funded by a National Health and Medical Research Council of Australia Project Grant (# 1064786), the Australian Catholic University AORTEC agreement, the Wicking Foundation, and the Stafford Fox Foundation and the Victorian State Government. Valuable surgical and technical assistance was provided by of the staff of the Experimental Medical and Surgical Unit, St Vincent's Hospital, Melbourne (Sue McKay, Liliana Pepe, Anna Deftereos and Amanda Rixon). Corresponding author: Jason Palmer BSc (Hons), O'Brien Institute Department at St Vincent's Institute, 42 Fitzroy St, Fitzroy Victoria 3065, Australia. jpalmer@svi.edu.au, ©2018American Society of Plastic Surgeons

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Micro-RNA Regulated Pro-Angiogenic Signaling in Arteriovenous Loops in Patients with Combined Vascular and Soft Tissue Reconstructions – Reisiting the Nutrient Flap Concept

Background: The placement of arteriovenous (AV) loops can enable microvascular anastomoses of free flaps when recipient vessels are scarce. In animal models, elevated fluid shear stress in AV loops promotes neoangiogenesis. Anecdotal reports in patients indicate that vein grafts used in free flap reconstructions of ischemic lower extremities are able to induce capillary formation. However, flow-stimulated angiogenesis has never been systematically investigated in humans and it is unclear whether shear stress alters proangiogenic signaling pathways within the vascular wall of human AV loops. Methods: Eight patients with lower extremity soft tissue defects underwent two-stage reconstructions with AV loop placements, and free flap anastomoses to the loops 10-14 days later. MicroRNA and gene expression profiles were determined in tissue samples harvested from vein grafts of AV loops by microarray analysis and quantitative real time polymerase chain reaction. Samples from untreated veins served as controls. Results: A strong deregulation of microRNA and gene expression was detected in AV loops, showing an overexpression of angiopoetic cytokines, oxygenation associated genes, vascular growth factors, as well as connexin-43. We discovered inverse correlations and validated as well as bioinformatically predicted interactions between angiogenesis regulating genes and microRNAs in AV loops. Conclusion: Our findings demonstrate that elevated shear stress triggers pro-angiogenic signaling pathways in human venous tissue, indicating that AV loops may have the ability to induce neoangiogenesis in humans. Our data corroborate the nutrient flap hypothesis and provide a molecular background for AV loop based tissue engineering with potential clinical applications for soft tissue defect reconstruction. * These authors contributed equally to this work. Financial Disclosure Statement: The authors have no financial disclosures : The funding of this study was solely institutional. Acknowledgements: The authors thank Dr. Matthias Schulte for excellent technical support. Corresponding author: Dominic Henn, MD, Department of Hand, Plastic and Reconstructive Surgery, BG Trauma Center Ludwigshafen, Department of Plastic Surgery, University of Heidelberg, Ludwig-Guttmann-Str. 13, 67071 Ludwigshafen, Germany. tel: +49-621-6810-8953, email: dominic.henn@bgu-ludwigshafen.de ©2018American Society of Plastic Surgeons

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Abdominal Panniculectomy: Determining the Impact of Diabetes on Complications and Risk Factors for Adverse Events

Background: The prevalence of Obesity along with bariatric surgery and massive weight loss requiring panniculectomy is increasing in the United States. The effect of Diabetes Mellitus (DM) on outcomes following panniculectomy remains poorly defined despite its prevalence. Our study aims to evaluate the impact of DM on complications following panniculectomy and determine risk factors for adverse events. Methods: The American College of Surgeons National Surgical Quality Improvement (ACS NSQIP) database was used to identify patients undergoing panniculectomy between 2010 and 2015. Patients were stratified based on diabetic status. Multivariate regression was performed to control for confounders. Results: Review of the database identified 7,035 eligible patients who underwent panniculectomy, out of which 770 (10.9%) were diabetic. Multivariate regression showed that DM was a significant risk factor for wound dehiscence (OR = 1.92; 95% CI: 1.41-3.15; p=0.02). Obesity was a significant risk factor for superficial (OR = 2.78; 95% CI: 1.53 - 3.69; p

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Presence of gastric Helicobacter species in children suffering from gastric disorders in Southern Turkey

Helicobacter, EarlyView.


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Presence of gastric Helicobacter species in children suffering from gastric disorders in Southern Turkey

Helicobacter, EarlyView.


https://ift.tt/2lVOcQX

Targeting tumor-associated acidity in cancer immunotherapy

Abstract

Checkpoint inhibitors, such as cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) and programmed cell death-1 (PD-1) monoclonal antibodies have changed profoundly the treatment of melanoma, renal cell carcinoma, non-small cell lung cancer, Hodgkin lymphoma, and bladder cancer. Currently, they are tested in various tumor entities as monotherapy or in combination with chemotherapies or targeted therapies. However, only a subgroup of patients benefit from checkpoint blockade (combinations). This raises the question, which all mechanisms inhibit T cell function in the tumor environment, restricting the efficacy of these immunotherapeutic approaches. Serum activity of lactate dehydrogenase, likely reflecting the glycolytic activity of the tumor cells and thus acidity within the tumor microenvironment, turned out to be one of the strongest markers predicting response to checkpoint inhibition. In this review, we discuss the impact of tumor-associated acidity on the efficacy of T cell-mediated cancer immunotherapy and possible approaches to break this barrier.

https://ift.tt/2Nt4Vr9

Delayed high-frequency suppression after automated single-pulse electrical stimulation identifies the seizure onset zone in patients with refractory epilepsy

Publication date: Available online 4 July 2018
Source:Clinical Neurophysiology
Author(s): Tyler S. Davis, John D. Rolston, Robert J. Bollo, Paul A. House
ObjectiveSingle-pulse electrical stimulation (SPES) of intracranial electrodes evokes responses that may help identify the seizure onset zone (SOZ); however, lack of automation and response variability has limited clinical adoption of this technique. We evaluated whether automated delivery of low-current SPES could evoke delayed high-frequency suppression (DHFS) of ongoing electrocorticography (ECoG) signals that, when combined with objective analytic techniques, may provide a reliable marker of this zone.MethodsLow-current SPES (1-ms, 3.5-mA biphasic pulses) was delivered to 652 electrodes across 10 patients undergoing ECoG for seizure focus localization. DHFS was measured by calculating the normalized trial-averaged time-frequency power (70-250 Hz) 0.4-1 sec post-stimulation. Electrodes that evoked suppression when stimulated or recorded suppression when stimulation was nearby were used to estimate the SOZ.ResultsThe estimated SOZ significantly identified the clinical SOZ in 6 of 10 patients (5 of 7 temporal foci) with a false-positive rate of 0-0.06. Stimulation required <2 hours, was undetectable by patients, and did not induce seizures or after-discharges.ConclusionsWe show that DHFS provides accurate estimates of the clinical SOZ in patients with refractory epilepsy.SignificanceThis approach may increase the safety, speed, and reproducibility of SOZ identification while reducing cost, subjectivity, and patient discomfort.



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Behavioral and electrophysiological evidence for GABAergic modulation through transcutaneous vagus nerve stimulation

Publication date: September 2018
Source:Clinical Neurophysiology, Volume 129, Issue 9
Author(s): Marius Keute, Philipp Ruhnau, Hans-Jochen Heinze, Tino Zaehle
ObjectiveTranscutaneous vagus nerve stimulation (tVNS) has been hypothesized to modulate γ-aminobutyric (GABA) transmission in the human brain. GABA in the motor cortex is highly correlated to measures of automatic motor inhibition that can be obtained in simple response priming paradigms. To test the effects of tVNS on GABA transmission, we measured tVNS-induced alterations in behavioral and electrophysiology during automatic motor inhibition.MethodsParticipants were 16 young, healthy adults (8 female). We combined a subliminal response priming paradigm with tVNS and EEG measurement. In this paradigm, automatic motor inhibition leads to a reversal of the priming effect, a phenomenon referred to as the negative compatibility effect (NCE). We compute the NCE separated by response hands, hypothesizing a modulation of the left-hand NCE. Using EEG we measured readiness potentials, an established electrophysiological index of cortical motor preparation.ResultsAs hypothesized, for the ipsilateral hand/contralateral hemisphere, compared to sham stimulation, tVNS increased the NCE and modulated the electrophysiological readiness potentials.ConclusionOur results indicate that tVNS is selectively affecting the GABAergic system in the motor system contralateral to the stimulated ear as reflected in a behavioral and electrophysiological modulation.SignificanceWe provide first combined behavioral and electrophysiological evidence for direct GABAergic neuromodulation through tVNS.



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Doing it the other way round – mapping motor function by intrinsic activity

Publication date: Available online 5 July 2018
Source:Clinical Neurophysiology
Author(s): Johannes Sarnthein, Richard Wennberg




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Electrophysiological Evidence of an Attentional Bias towards Appetitive and Aversive Words in Adults with Attention-Deficit/Hyperactivity Disorder

Publication date: Available online 4 July 2018
Source:Clinical Neurophysiology
Author(s): Shushakova A., Wiesner C. D., Ohrmann P., Pedersen A.
ObjectiveEmotional dysregulation has emerged as a core symptom domain in adults with Attention-Deficit/Hyperactivity Disorder (ADHD). However, the pathophysiological underpinnings remain poorly understood. This study investigated attentional biases to positive and negative emotional words as possible contributing mechanisms.MethodsEvent-related potentials (ERPSs) and behavioral attention bias indices were recorded from 39 adult patients with ADHD and 41 healthy controls during a verbal dot-probe task with positive-neutral, negative-neutral, and neutral-neutral word pairs.ResultsCue-locked N2pc amplitudes indicated a significant attentional bias towards emotional words in patients with ADHD and healthy controls. In healthy controls, the bias was only significant in positive trials. In patients, the bias was associated with ADHD severity and self-reported poor emotion regulation skills. ADHD patients also exhibited reduced target-locked P1 amplitudes and inferior behavioral performance compared with healthy controls.ConclusionsOur findings provide evidence of an attention bias to positive and negative emotional stimuli in adult patients with ADHD and adverse effects of emotional stimuli on task performance.SignificanceAn attentional bias to emotional stimuli might contribute to emotional reactivity and dysregulation in adult patients with ADHD.



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Diagnostic accuracy of quantitative EEG to detect delayed cerebral ischemia after subarachnoid hemorrhage: A preliminary study

Publication date: Available online 5 July 2018
Source:Clinical Neurophysiology
Author(s): B. Balança, F. Dailler, S. Boulogne, T. Ritzenthaler, F. Gobert, S. Rheims, N. Andre-Obadia
ObjectiveDelayed cerebral ischemia (DCI) is the most important and preventable morbidity cause after subarachnoid hemorrhage (SAH). Therefore, DCI early detection is a major challenge. Yet, neurological examination can be unreliable in poor grade SAH patients. EEG provides information from most superficial cortical area, with ischemia-related changes. This study aims at defining an alpha-theta/delta (AT/D) ratio decrease thresholds to detect DCI.MethodsWe used EEG with a montage matching vascular territories (right and left anterior central and posterior) and compared them to follow-up brain imaging.Results15 SAH patients (Fischer≥3, World Federation of Neurological Surgeons scale ≥4, 9 DCI) were monitored during 6.4 [4-8] days (min=2d, max=13d). AT/D changes could follow three different patterns: (1) prolonged or (2) transient decrease and (3) no decrease or progressive increase. A regional 30% decrease outlasting 3.7h reached 100% sensitivity and 88.9% specificity to detect DCI. Only 22.6% were in a zone of uncertain diagnosis (3.7-8.04h). These prolonged decreases, with a loss of transient changes, started in cortical areas evolving toward DCI, and preceded intracranial changes when available.ConclusionAlthough this study has a small sample size, prolonged AT/D decrease seems to be a reliable biomarker of DCI.SignificancecEEG changes are likely to precede cerebral infarction and could be useful at the bedside to detect DCI before irreversible damage.



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Cervical dystonia: Normal auditory mismatch negativity and abnormal somatosensory mismatch negativity

Publication date: Available online 4 July 2018
Source:Clinical Neurophysiology
Author(s): Jui-Cheng Chen, Antonella Macerollo, Anna Sadnicka, Min-Kuei Lu, Chon-Haw Tsai, Prasad Korlipara, Kailash Bhatia, John C. Rothwell, Mark J. Edwards
ObjectivePrevious electrophysiological and psychophysical tests have suggested that somatosensory integration is abnormal in dystonia. Here, we hypothesised that this abnormality could relate to a more general deficit in pre-attentive error/deviant detection in patients with dystonia. We therefore tested patients with dystonia and healthy subjects using a mismatch negativity paradigm (MMN), where evoked potentials generated in response to a standard repeated stimulus are subtracted from the responses to a rare "odd ball" stimulus.MethodsWe assessed MMN for somatosensory and auditory stimuli in patients with cervical dystonia and healthy age matched controls.ResultsWe found a significant group∗oddball type interaction effect (F (1, 34) = 4.5, p = 0.04, ρI = 0.63). A follow up independent t-test for sMMN data, showed a smaller sMMN amplitude in dystonic patients compared to controls (mean difference control-dystonia: -1.0 µV ± 0.3, p < 0.00, t = -3.1). However the amplitude of aMMN did not differ between groups (mean difference control-dystonia: -0.2 µV ± 0.2, p = 0.24, t = -1.2). We found a positive correlation between somatosensory MMN and somatosensory temporal discrimination threshold.ConclusionThese results suggest that pre-attentive error/deviant detection, specifically in the somatosensory domain, is abnormal in dystonia. This could underlie some previously reported electrophysiological and psychophysical abnormalities of somatosensory integration in dystonia.SignificanceOne could hypothesize a deficit in pre-conscious orientation towards potentially salient signals might lead to a more conservative threshold for decision-making in dystonia.



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Implicit reward associations impact face processing: Time-resolved evidence from event-related brain potentials and pupil dilations

Publication date: 1 October 2018
Source:NeuroImage, Volume 179
Author(s): Wiebke Hammerschmidt, Igor Kagan, Louisa Kulke, Annekathrin Schacht
The present study aimed at investigating whether associated motivational salience causes preferential processing of inherently neutral faces similar to emotional expressions by means of event-related brain potentials (ERPs) and changes of the pupil size. To this aim, neutral faces were implicitly associated with monetary outcome, while participants (N = 44) performed a face-matching task with masked primes that ensured performance around chance level and thus an equal proportion of gain, loss, and zero outcomes. During learning, motivational context strongly impacted the processing of the fixation, prime and mask stimuli prior to the target face, indicated by enhanced amplitudes of subsequent ERP components and increased pupil size. In a separate test session, previously associated faces as well as novel faces with emotional expressions were presented within the same task but without motivational context and performance feedback. Most importantly, previously gain-associated faces amplified the LPC, although the individually contingent face-outcome assignments were not made explicit during the learning session. Emotional expressions impacted the N170 and EPN components. Modulations of the pupil size were absent in both motivationally-associated and emotional conditions. Our findings demonstrate that neural representations of neutral stimuli can acquire increased salience via implicit learning, with an advantage for gain over loss associations.



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A generative model of whole-brain effective connectivity

Publication date: 1 October 2018
Source:NeuroImage, Volume 179
Author(s): Stefan Frässle, Ekaterina I. Lomakina, Lars Kasper, Zina M. Manjaly, Alex Leff, Klaas P. Pruessmann, Joachim M. Buhmann, Klaas E. Stephan
The development of whole-brain models that can infer effective (directed) connection strengths from fMRI data represents a central challenge for computational neuroimaging. A recently introduced generative model of fMRI data, regression dynamic causal modeling (rDCM), moves towards this goal as it scales gracefully to very large networks. However, large-scale networks with thousands of connections are difficult to interpret; additionally, one typically lacks information (data points per free parameter) for precise estimation of all model parameters.This paper introduces sparsity constraints to the variational Bayesian framework of rDCM as a solution to these problems in the domain of task-based fMRI. This sparse rDCM approach enables highly efficient effective connectivity analyses in whole-brain networks and does not require a priori assumptions about the network's connectivity structure but prunes fully (all-to-all) connected networks as part of model inversion. Following the derivation of the variational Bayesian update equations for sparse rDCM, we use both simulated and empirical data to assess the face validity of the model. In particular, we show that it is feasible to infer effective connection strengths from fMRI data using a network with more than 100 regions and 10,000 connections. This demonstrates the feasibility of whole-brain inference on effective connectivity from fMRI data – in single subjects and with a run-time below 1 min when using parallelized code. We anticipate that sparse rDCM may find useful application in connectomics and clinical neuromodeling – for example, for phenotyping individual patients in terms of whole-brain network structure.



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Effect sizes of BOLD CVR, resting-state signal fluctuations and time delay measures for the assessment of hemodynamic impairment in carotid occlusion patients

Publication date: 1 October 2018
Source:NeuroImage, Volume 179
Author(s): Jill B. De Vis, Alex A. Bhogal, Jeroen Hendrikse, Esben T. Petersen, Jeroen C.W. Siero
Background and purposeThe BOLD signal amplitude as a response to a hypercapnia stimulus is commonly used to assess cerebrovascular reserve. Despite recent advances, the implementation remains cumbersome and alternative ways to assess hemodynamic impairment are desirable. Resting-state BOLD signal fluctuations (rsBOLD) have been proposed however data on its sensitivity and dependence on baseline venous cerebral blood volume (vCBV) is limited. The primary aim of this study was to compare the effect sizes of resting-state and hypercapnia induced BOLD signal changes in the detection of hemodynamic impairment. The second aim of the study was to assess the dependence of BOLD signal variability on vCBV.Materials and methodsFifteen patients with internal carotid artery occlusive disease and 15 matched healthy controls were included in this study. The BOLD signal was derived from a dual-echo gradient-echo echo-planar sequence during hypercapnia (HC) and hyperoxia (HO) gas modulations. BOLD (fractional) amplitude of low frequency fluctuations ((f)ALFF) was compared to HC-BOLD, BOLD response delays derived from time delay analysis and ΔBOLD in response to progressively increasing HC. Effect sizes (i.e. the standard mean difference between patients and controls) were calculated. HO-BOLD was used to estimate vCBV, and its contribution to the variability in rsBOLD signal was evaluated.ResultsThe effect sizes of ALFF and fALFF (0.61 and 0.72) were lower than the effect sizes related to hypercapnia-based hemodynamic assessment analysis; 1.62, 1.56 and 0.90 for HC-BOLD, BOLD response delays and ΔBOLD in response to progressively increasing HC. A moderate relation was found between (f)ALFF and HC-BOLD in controls (R² of 0.61 and 0.42), but this relation decreased in patients (R² of 0.33 and 0.15). (f)ALFF did not differ between patients and controls whereas HC-BOLD did (p < 0.005). The ΔBOLD response to progressively increasing HC was significantly different in between patients and controls for ΔEtCO2 values ≥ 2 mmHg (at +2  mmHg F(1, 18) = 5.85, p = 0.026). Up to 31% and 53% of the variance in the ALFF and HC-BOLD spatial distribution could be explained by HO-BOLD.ConclusionALFF and fALFF demonstrated a moderate effect size to detect hemodynamic impairment whereas the effect size was large for methods employing a hypercapnia-based vascular stress stimulus. Based on our analysis of BOLD signal change as a response to a progressively increasing hypercapnia stimulus we can argue that a hypercapnia stimulus of at least 2 mmHg above baseline EtCO2 is necessary to evaluate hemodynamic impairment. We also demonstrated that a substantial amount of information imbedded in the rsBOLD and HC-BOLD was explained by HO-BOLD. HO-BOLD can serve as a proxy for vCBV and this thus indicates that one should be careful when adopting these techniques in disease cases with compromised CBV.



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Unsupervised machine learning of radiomic features for predicting treatment response and overall survival of early stage non-small cell lung cancer patients treated with stereotactic body radiation therapy

Publication date: Available online 4 July 2018
Source:Radiotherapy and Oncology
Author(s): Hongming Li, Maya Galperin-Aizenberg, Daniel Pryma, Charles B. Simone, Yong Fan
Background and purposeTo predict treatment response and survival of NSCLC patients receiving stereotactic body radiation therapy (SBRT), we develop an unsupervised machine learning method for stratifying patients and extracting meta-features simultaneously based on imaging data.Material and methodsThis study was performed based on an ¹⁸F-FDG-PET dataset of 100 consecutive patients who were treated with SBRT for early stage NSCLC. Each patient's tumor was characterized by 722 radiomic features. An unsupervised two-way clustering method was used to identify groups of patients and radiomic features simultaneously. The groups of patients were compared in terms of survival and freedom from nodal failure. Meta-features were computed for building survival models to predict survival and free of nodal failure.ResultsDifferences were found between 2 groups of patients when the patients were clustered into 3 groups in terms of both survival (p = 0.003) and freedom from nodal failure (p = 0.038). Average concordance measures for predicting survival and nodal failure were 0.640±0.029 and 0.664±0.063 respectively, better than those obtained by prediction models built upon clinical variables (p < 0.04).ConclusionsThe evaluation results demonstrate that our method allows us to stratify patients and predict survival and freedom from nodal failure with better performance than current alternative methods.



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Early nonreactivity in the conjunctival provocation test predicts beneficial outcome of sublingual immunotherapy

Clinical practice needs a common parameter that can provide an early, reliable estimation of the outcome of sublingual immunotherapy (SLIT) in an upcoming pollen season. We investigated whether the conjunctiva...

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Randomized prospective trials to study effects of reduced antibiotic usage in abdominal surgery in cows

Publication date: Available online 4 July 2018
Source:Journal of Dairy Science
Author(s): R. Jorritsma, I.M. van Geijlswijk, M. Nielen
Societal concerns about antibiotic resistance prompted us to evaluate the use of prophylactic and postoperative antibiotic treatments following cesarean section (CS) and exploratory laparotomy (EL) in a surgery theater within the Farm Animal Health clinic. All procedures were performed by supervised veterinary students for training purposes. Cows undergoing CS (n = 100) received either a prophylaxis with a single 5-g injection of ampicillin-sodium i.v. only (CSL), or in combination with postoperative i.m. injections of ampicillin-trihydrate 20% for 3 d (10 mg/kg, twice a day; CSH). Cows undergoing EL (n = 110) received either no antibiotic prophylaxis (ELN) or were given a single 5-g injection of ampicillin-sodium i.v. (ELL). The primary outcome measure was healthy recovery after surgery, which we assessed according to the need to treat surgery-related complications within a 10-d follow-up period based on daily clinical observations. Cows in all groups had a normal temperature and feed intake, and a satisfying clinical appearance at the end of the follow-up period. The clinical need to treat cows with antibiotics to deal with postoperative complications was higher for the CS groups than the EL groups. Within both CS and EL groups, the number of complications for each protocol was the same. However, in terms of the secondary outcomes, we observed that CSL cows required, for example, more treatments for mastitis and other diseases unrelated to the surgery than CSH cows (odds ratio 2.8; confidence interval 1.2–7.2). The percentage of infected sutures was higher for ELN cows compared with ELL cows (odds ratio 2.6; confidence interval 1.5–4.9). We estimated that 29 CSH treatments were needed to prevent 1 CS cow with serious surgery-related complications in the CSL group. Likewise, 53 ELL treatments would prevent 1 EL cow with surgery-related complications in the ELN group. We therefore concluded that it is possible to reduce antibiotic prophylaxis in CS and EL cows. The low number cows of clinically detected complications were effectively treated with a postoperative antibiotic intervention at the moment of detection.



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Investigation of ammonium lactate supplementation on fermentation end products and bacterial assimilation of nitrogen in dual-flow continuous culture

Publication date: Available online 4 July 2018
Source:Journal of Dairy Science
Author(s): B.K. Wagner, B.A. Wenner, J.E. Plank, G.D. Poppy, J.L. Firkins
Supplements investigated throughout the present study are produced by fermenting lactose that is present in whey to lactate, yielding products differing in ammonium relative to lactate concentrations and in physical form (liquid or dry). Trials 1 and 2 investigated Lacto-Whey (LW; Fermented Nutrition Corp., Luxemburg, WI) and GlucoBoost (GB; Fermented Nutrition Corp.), respectively, using dual-flow continuous culture systems (n = 4), each with a 4 × 4 Latin square design. A greater proportion of nonprotein nitrogen was present in GB than in LW. In trial 1, the treatment with LW was isonitrogenously dosed against soybean meal (SBM) as a control (no LW) and factorialized with either a wheat- or corn-based concentrate (55% inclusion rate, dry matter basis). We hypothesized that LW would increase propionate production and that the combination of +LW with wheat would increase bacterial assimilation of NH3-N into cellular N. No differences were observed for total volatile fatty acid (VFA) production per day. However, treatment × time interactions revealed that +LW increased lactate concentration at 0, 0.5, and 1 h and tended to increase molar percentage of propionate at 1 and 1.5 h postfeeding, documenting the immediate availability of lactate converted to propionate in the +LW treatments. The main effect of corn increased the proportion of bacterial N derived from NH3-N. Trial 2 was designed to investigate GB; isonitrogenous treatments included an SBM control, crystal GB, liquid GB (LGB), and LGB with yeast culture, which were dosed twice daily. We hypothesized that GB would increase propionate production and bacterial assimilation of NH3-N; the combination of LGB and yeast culture was expected to have a positive additive effect, yielding the greatest VFA production and bacterial NH3-N assimilation. No differences were observed for total VFA production; however, LGB decreased molar percentage of acetate and increased propionate and butyrate molar percentages. There were no differences in non-NH3-N flow or microbial N flow. Under the conditions of our studies, lactate in LW and GB was fermented extensively to propionate, and microbial protein synthesis in these treatments was comparable with that in SBM controls.



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A national methodology to quantify the diet of grazing dairy cows

Publication date: Available online 4 July 2018
Source:Journal of Dairy Science
Author(s): D. O'Brien, B. Moran, L. Shalloo
The unique rumen of dairy cows allows them to digest fibrous forages and feedstuffs. Surprisingly, to date few attempts have been made to develop national methods to gain an understanding on the make-up of a dairy cow's diet, despite the importance of milk production. Consumer interest is growing in purchasing milk based on the composition of the cows' diet and the time they spend grazing. The goal of this research was to develop such a methodology using the national farm survey of Ireland as a data source. The analysis was completed for a 3-yr period from 2013 to 2015 on a nationally representative sample of 275 to 318 dairy farms. Trained auditors carried out economic surveys on farms 3 to 4 times per annum. The auditors collected important additional information necessary to estimate the diet of cows including the length of the grazing season, monthly concentrate feeding, type of forage(s) conserved, and milk production. Annual cow intakes were calculated to meet net energy requirements for production, maintenance, activity, pregnancy, growth, and live weight change using survey data and published literature. Our analysis showed that the average annual cow feed intake on a fresh matter basis ranged from 22.7 t in 2013 to 24.8 t in 2015 and from 4.8 to 5 t on a dry matter basis for the same period. Forage, particularly pasture, was the largest component of the Irish cow diet, typically accounting for 96% of the diet on a fresh matter basis and 82% of dry matter intake over the 3 yr. Within the cows' forage diet, grazed pasture was the dominant component and on average contributed 74 to 77% to the average annual cow fresh matter diet over the period. The proportion of pasture in the annual cow diet as fed was also identified as a good indicator of the time cows spend grazing (e.g., coefficient of determination = 0.85). Monthly, forage was typically the main component of the cow diet, but the average contribution of concentrate was substantial for the early spring months of January and February (30 to 35% of dry matter intake). Grazed pasture was the dominant source of forage from March to October and usually contributed 95 to 97% of the diet as fed in the summer period. Overall, the national farm survey from 2013 to 2015 shows that Irish dairy farms are very reliant on forage, particularly pasture, regardless of whether it is reported on a dry matter basis or as fed. There is potential to replicate this methodology in any regions or nations where representative farm surveys are conducted.



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A survey of United States dairy hoof care professionals on costs associated with treatment of foot disorders

Publication date: Available online 4 July 2018
Source:Journal of Dairy Science
Author(s): K.A. Dolecheck, R.M. Dwyer, M.W. Overton, J.M. Bewley
The objective of this study was to collect information regarding hoof care professionals' billing practices and to gather their opinions about foot disorders and the value of their prevention. Responses were gathered from veterinarians (n = 18) and hoof trimmers (n = 116) through both online and paper survey platforms. Because of the limited number of respondents, veterinarian responses were not further analyzed. Of the 6 foot disorders included in the survey, the treatment cost per case was greatest for toe ulcers (mean ± standard deviation; $20.2 ± 8.5), sole ulcers ($19.7 ± 8.6), white line disease ($19.5 ± 8.1), and thin soles ($18.1 ± 8.1), and least for infectious disorders (foot rot and digital dermatitis; $8.0 ± 7.6 and $7.5 ± 9.6, respectively). Of the disorders, digital dermatitis represented most of the foot disorder cases treated by respondents over the past year (43.9 ± 20.4%), whereas toe ulcers and thin soles represented the least (5.3 ± 4.1 and 5.3 ± 5.7%, respectively). Respondents that served mostly large herds (>500 lactating cows) reported a lower prevalence of digital dermatitis (31.6 ± 4.2 vs. 44.4 ± 3.4 and 46.7 ± 3.2% in small and medium herds, respectively) and a higher prevalence of sole ulcers (23.1 ± 3.0 vs. 13.4 ± 2.4 and 13.3 ± 2.3% in small and medium herds, respectively). Region of the United States (Northeast, Midwest, or other) also influenced foot disorder prevalence; respondents from the Northeast reported more sole ulcers than respondents from other regions (22.1 ± 2.3 vs. 12.4 ± 3.3%). When respondents were asked which disorder was associated with the greatest total cost per case to the producer (treatment and labor costs plus the reduction in milk yield, reduced reproductive performance, and so on), hoof trimmers ranked digital dermatitis as having the greatest total cost per case and thin soles as having the least total cost per case. Finally, respondents indicated that the most important benefits of reducing foot disorders were enhanced animal welfare and increased milk production, whereas the least important benefit was reduced veterinary and hoof trimmer fees. Results from this survey can be used to improve the accuracy of foot disorder cost estimates and contribute to better decision-making regarding both foot disorder treatment and prevention.



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Multidrug residues and antimicrobial resistance patterns in waste milk from dairy farms in Central California

Publication date: Available online 4 July 2018
Source:Journal of Dairy Science
Author(s): P.N. Tempini, S.S. Aly, B.M. Karle, R.V. Pereira
Waste milk (WM) is a common source of feed for preweaned calves in US dairy farms. However, limited information is available about characteristics of this product, including concentration of drug residues and potential hazards from antibiotic-resistant bacteria present in the milk. The aims of this cross-sectional study were to (1) identify and measure the concentration of antimicrobial residues in raw WM samples on dairy farms in the Central Valley of California, (2) survey farm management practices for factors associated with the occurrence of specific antimicrobial residues in raw WM, (3) characterize the antimicrobial resistance patterns of E. coli cultured from raw WM samples, and (4) evaluate the potential association between WM quality parameter and risk of identifying drug residues in milk. A single raw bulk tank WM sample was collected from dairy farms located in California's Central Valley (n = 25). A questionnaire was used to collect information about farm management practices. Waste milk samples were analyzed for a multidrug residue panel using liquid chromatography–tandem mass spectrometry. Bacteria were cultured and antimicrobial resistance was tested using standard techniques; milk quality parameters (fat, protein, lactose, solids-not-fat, somatic cell count, coliform count, and standard plate count) were also measured. Of the 25 samples collected, 15 (60%) contained detectable concentrations of at least 1 antimicrobial. Of the drug residue–positive samples, 44% (11/25) and 16% (4/25) had detectable concentrations of β-lactams and tetracycline, respectively. The most prevalent drug residues were ceftiofur (n = 7, 28%), oxytetracycline (n = 4, 16%), and cephapirin (n = 3, 12%). No significant associations were identified between farm characteristics or management practices and presence of drug residues in WM. In this study, 20% of farms did not pasteurize WM before feeding to calves. Two of the 10 Escherichia coli isolated from WM samples were multidrug resistant. Streptococcus spp. (n = 21, 84%) was the most common genus cultured from WM samples, followed by Staphylococcus spp. (n = 20, 80%) and E. coli (n = 10, 40%). Mycoplasma spp. was cultured from 2 WM samples (n = 2, 8%). The presence of drug residues in WM at concentrations that increase selection of resistant bacteria indicates the need for additional studies targeting on-farm milk treatments to degrade drug residues before feeding to calves. The presence of multidrug-resistant E. coli in WM urges the need for on-farm practices that reduce calf exposure to resistant bacteria, such as pasteurization.



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Use of a breeding bull and absence of a calving pen as risk factors for the presence of Mycoplasma bovis in dairy herds

Publication date: Available online 4 July 2018
Source:Journal of Dairy Science
Author(s): Linde Gille, J. Callens, K. Supré, F. Boyen, F. Haesebrouck, L. Van Driessche, K. van Leenen, P. Deprez, B. Pardon
Mycoplasma bovis is an important cause of pneumonia and mastitis in cattle throughout the world, often reported as emerging. In absence of an effective vaccine for M. bovis, current prevention and control strategies rely on the identification of risk factors for within- and between-herd spread. The objective of this study was to determine the prevalence of M. bovis in Belgian dairy herds and to identify risk factors associated with a positive PCR or antibody ELISA bulk tank milk (BTM) test. A cross-sectional study was performed in 2016 on 100 dairy farms, analyzing BTM using PCR and antibody ELISA. Information on herd-level risk factors focusing on biosecurity and management were collected through a questionnaire and sourced from the national herd identification system (SANITRACE, Animal Health Service Flanders). Multivariable logistic regression was used to identify herd-level risk factors for the presence of M. bovis DNA and antibodies in BTM. The apparent prevalence on BTM was 7 and 17% for PCR and antibody ELISA, respectively. The true prevalence was 7.1% [95% confidence interval (CI) = 2.1–11.5%] and 24.8% (95% CI = 16.4–33.2%). There was no overlap between ELISA- and PCR-positive farms, resulting in a combined true prevalence of 31.8% of the Belgian farms being in recent contact with M. bovis. Risk factor analysis showed that herds with a breeding bull [M. bovis-positive results for 45.5 and 13.6% of herds with and without a bull, respectively, odds ratio = 4.7 (95% CI = 1.1–19.8)] and without a calving pen [M. bovis-positive result in 52.4 and 20.6% of the herds without and with a calving pen, respectively, odds ratio = 3.7 (95% CI = 1.06–12.5)] had higher odds to harbor M. bovis antigen or antibodies in BTM. In conclusion, the present study points to a several fold increase in the prevalence of M. bovis in Belgian dairy herds. The importance of the breeding bull and calving pen in the between- and within-herd spread of M. bovis might have been underestimated in the past. Focusing on these factors might contribute to more effective control programs in the future.



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Effect of ammonia fiber expansion on the available energy content of wheat straw fed to lactating cattle and buffalo in India

Publication date: Available online 4 July 2018
Source:Journal of Dairy Science
Author(s): Preeti Mor, Bryan Bals, Amrish Kumar Tyagi, Farzaneh Teymouri, Nitin Tyagi, Sachin Kumar, Venkataraman Bringi, Michael VandeHaar
The seasonal lack of availability of lush green forages can force dairy farmers in developing nations to rely on crop residues such as wheat and rice straw as the major feed source. We tested whether ammonia fiber expansion (AFEX) treatment of wheat straw would increase the energy available to Murrah buffalo and Karan-Fries cattle consuming 70% of their diet as wheat straw in India. Forty lactating animals of each species were blocked by parity and days in milk and randomly assigned to 1 of 4 treatment diets (n = 10). Treatments were a nutrient-rich diet with 0 to 20% straw (positive control; PC) and 3 high-straw diets with various levels of AFEX-treatment: (1) 70% untreated straw (no AFEX), (2) 40 to 45% untreated straw with 25 to 30% AFEX-treated straw (low AFEX), and (3) 20% untreated straw with 50% AFEX-treated straw (high AFEX). The AFEX-treated straw was pelleted. Urea was added to the no and low AFEX diets so they were isonitrogenous with the high AFEX diet. Animals were individually fed the PC diet for 14 d followed by 7 d of adaptation to treatments, full treatments for 28 to 35 d, and finally PC diets for 21 d. Compared with buffalo fed the PC diet, those fed high-straw diets consumed 29% less feed dry matter, put out 16% less milk energy, and lost 0.8 kg/d more body weight; the AFEX treatment of straw did not alter intake or milk production but greatly ameliorated the body weight loss (−1.0 kg/d for no AFEX and −0.07 kg/d for high AFEX). In Karan-Fries cattle, high-straw diets decreased dry matter intake by 39% and milk energy by 24%, and the high AFEX diet increased intake by 42% and milk energy by 18%. The AFEX treatment increased digestibilities of organic matter, dry matter, neutral detergent fiber, acid detergent fiber, and crude protein by 6 to 13 percentage points in buffalo and 5 to 10 points in cattle. In conclusion, AFEX treatment increased the digestibility and energy availability of wheat straw for lactating buffalo and cattle and has commercial potential to improve milk production and feed efficiency when high-quality forages or grains are not available.



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A randomized clinical trial of topical treatments for mild and severe udder cleft dermatitis in Dutch dairy cows

Publication date: Available online 4 July 2018
Source:Journal of Dairy Science
Author(s): T. van Werven, J. Wilmink, S. Sietsma, J. van den Broek, M. Nielen
Udder cleft dermatitis (UCD) is a skin lesion in dairy cows affecting the anterior parts of the udder, with the lesions often needing a long time to heal. The lesions can be characterized as mild or severe. The etiology of UCD is not fully understood and studies on the effectiveness of topical treatments have not been published. The objective of this study, therefore, was to conduct a randomized clinical trial to investigate the effectiveness of 2 different topical treatments, one for mild and one for severe UCD lesions, compared with untreated control groups. The treatment and control groups were randomized within herd for mild and severe UCD. The treatments were applied for a maximum period of 12 wk on 8 Dutch dairy farms. Mild UCD lesions were treated once a d 3 times a week on fixed days with a non-sting barrier film. Severe UCD lesions were first stratified into class A (lesion length <5 cm) or class B (lesion length ≥5 cm) and then randomly allocated to treatment or control groups within herd. Both severe lesion classes were treated once per day every day with an enzyme alginogel. Every week, the lesions of affected animals were inspected and photographed by the investigator. These photographs were reviewed weekly by an external wound expert who classified the lesions as mild, severe class A, severe class B, or healed. Based on this classification, the investigator judged weekly whether the lesions had improved compared with their classification of the previous week. For mild UCD lesions, improvement was defined as occurring when lesions were healed. For severe UCD lesions, improvement was defined as a transition from class B to class A, transition from any severe UCD lesion (class A or B) to a mild UCD lesion, or when the lesion was defined as healed. Data were analyzed using a discrete time survival analysis with time to first improvement as dependent variable. In total, data from 214 animals were analyzed to estimate the effectiveness of treatment. Results showed that treatment of mild UCD lesions had no influence on improvement compared with untreated lesions. Treated severe lesions, however, showed 3.4 times more improvement compared with the untreated controls. Improvement varied between herds, and cows with a parity of 5 or higher showed significantly less improvement than first parity animals. Early identification of severe UCD lesions followed by prompt treatment with an enzyme alginogel supports the healing process.



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Environmental sample characteristics and herd size associated with decreased herd-level prevalence of Mycobacterium avium subspecies paratuberculosis

Publication date: Available online 4 July 2018
Source:Journal of Dairy Science
Author(s): Caroline S. Corbett, S. Ali Naqvi, Jeroen De Buck, Uliana Kanevets, John P. Kastelic, Herman W. Barkema
Environmental sampling is an effective method for estimating regional dairy herd-level prevalence of infection with Mycobacterium avium ssp. paratuberculosis (MAP). However, factors affecting prevalence estimates based on environmental samples are not known. The objective was to determine whether odds of environmental samples collected on farm changed culture status over 2 sampling times and if changes were specific for location and type of housing (freestall, tiestall, or loose housing), the sample collected (i.e., manure of lactating, dry, or sick cows; namely, cow group), and effects of herd size. In 2012–2013 [sampling 1 (S1)] and 2015–2017 [sampling 2 (S2)], 6 environmental samples were collected and cultured for MAP from all 167 (99%) and 160 (95%) farms, respectively, in the province of Saskatchewan, Canada. Only the 148 dairy farms sampled at both sampling periods were included in the analysis. A mixed effects logistic regression was used to determine whether differences between sampling periods were associated with herd size and sample characteristics (cow group contributing to environmental sample, type of housing, and location). In S1 and S2, 55 and 34%, respectively, of farms had at least 1 MAP-positive environmental sample. Correcting for sensitivity of environmental sampling, estimated true prevalence in S1 and S2 was 79 and 48%, respectively. Herds with >200 cows were more often MAP-positive than herds with <51 cows in both S1 and S2. The percentage of positive samples was lower in S2 compared with S1 for all sampled areas, cow groups contributing to samples, types of housing where samples were collected, and herd size categories. However, samples collected from dry cow areas had the largest decrease in MAP-positive samples in S2 compared with all other cow group samples. Herds that were MAP-negative in S1 with a herd size 51 to 100 or 101 to 150 were more likely to stay MAP-negative, whereas MAP-positive herds with >200 cows more frequently stayed MAP-positive. No difference was observed in the odds of a sample being MAP-positive among housing types or location of sample collection in both sample periods. Of all farms sampled, 104 (70%) did not change status from S1 to S2. In conclusion, when herd-level MAP prevalence decreased over the 3-yr interval, the change in prevalence differed among herd size categories and was larger in samples from dry cow areas. It was, however, not specific to other characteristics of environmental samples collected.



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Cheese yield, cheesemaking efficiency, and daily production of 6 breeds of goats

Publication date: Available online 4 July 2018
Source:Journal of Dairy Science
Author(s): Giuseppe M. Vacca, Giorgia Stocco, Maria L. Dettori, Andrea Summer, Claudio Cipolat-Gotet, Giovanni Bittante, Michele Pazzola
Little is known about the complex process of cheesemaking at the individual level of dairy goats because of the difficulties of producing a high number of model cheeses. The objectives of this work were (1) to study the cheesemaking ability of goat milk; (2) to investigate the variability of cheesemaking-related traits among different farms; (3) to assess the effects of stage of lactation and parity; and (4) to compare 6 breeds of goat (Saanen and Camosciata delle Alpi for the Alpine type; Murciano-Granadina, Maltese, Sarda and Sarda Primitiva for the Mediterranean type) for their cheesemaking ability. For each goat (n = 560) we studied (1) 8 milk quality traits (fat, protein, total solids, casein, lactose, pH, somatic cell score, and bacterial count); (2) 4 milk nutrient recovery traits (fat, protein, total solids, and energy) in curd; (3) 3 actual cheese yield traits (fresh cheese, cheese solids, and cheese water); (4) 2 theoretical cheese yield values (fresh cheese and cheese solids) and the related cheesemaking efficiencies; and (5) daily milk yield and 3 daily cheese yield traits (fresh cheese, cheese solids, and water retained in the curd). With respect to individual animal factors, farm was not particularly important for recovery traits or actual and theoretical cheese yield and estimates of efficiency, whereas it highly influenced daily productions. Parity of goats influenced daily cheese production, whereas DIM slightly affected recovery as well as percent and daily cheese yield traits. Breed was the most important source of variation for almost all cheesemaking traits. Compared with those of Alpine type, the 4 Mediterranean breeds had, on average, lower daily milk and cheese productions, greater actual and theoretical cheese yield, and higher recovery of nutrients in the curd. Among Alpine type, Camosciata delle Alpi was characterized by greater nutrients recovery than Saanen. Within the 4 Mediterranean types, the 3 Italians produced much less milk per day, with much more fat and protein and greater recovery traits than the Murciano-Granadina, resulting in greater actual cheese yield. Within the Italian breeds, milk from Sarda and Sarda Primitiva was characterized by lower daily yields, higher protein and fat content, and greater recoveries of nutrients than Maltese goats. These results confirmed the potential of goat milk for cheese production and could be useful to give new possibilities and direction in breeding programs.



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A retrospective comparative study of endoscopic and microscopic Tympanoplasty

This study compares endoscopic and microscopic tympanoplasty for the treatment of chronic otitis media (COM) without cholesteatoma.

https://ift.tt/2tSJlV4

Safety and efficacy of Nab-paclitaxel plus gemcitabine in patients with advanced pancreatic cancer suffering from cholestatic hyperbilirubinaemia—A retrospective analysis

Publication date: September 2018
Source:European Journal of Cancer, Volume 100
Author(s): Uwe Pelzer, Lilianna Wislocka, Anja Jühling, Jana Striefler, Fritz Klein, Josefine Roemmler-Zehrer, Marianne Sinn, Tim Denecke, Marcus Bahra, Hanno Riess
IntroductionTreatment of patients with advanced pancreatic carcinoma (APC) and hyperbilirubinaemia is problematic because these patients were regularly excluded from clinical studies. Nanoparticle albumin–bound paclitaxel and gemcitabine (nab-P/G) is an evidence-based treatment for patients with APC. This retrospective study investigated the safety and efficacy of nab-P/G in patients with APC and cholestatic hyperbilirubinaemia.MethodsWe screened our prospective database for patients with APC treated with nab-P/G at total bilirubin levels of ≥1.2 mg/dl. Patients were assigned into three groups according to their bilirubin level (A: 1.2–3 mg/dl, B: >3–5 mg/dl, C: >5 mg/dl). Analyses with regard to safety and survival were performed.ResultsTwenty-nine of 168 patients screened between Dec 2013 and Dec 2015 fulfilled the inclusion criteria. Most patients (83%) were male; median age was 63 [41–79] years. Nab-P/G administrations in patients with an elevated bilirubin level (median, range) did not result in unexpected toxicities assessed by predefined (non-)haematological parameters. Median overall survival (mOS) for the whole group was 11.7 (95% confidence interval [CI]: 6.8–14.0) months; for A: 11.8 (95% CI: 6.5–16.5), B: 9.2 (95% CI: 1.1 – NA) months and C 11.8 (95% CI: 5.9–20.0] months (p = 0.843). Again, mOS from the first application of nab-P/G did not differ between the groups (p = 0.13).ConclusionNab-P/G administrations in our pts with cholestatic hyperbilirubinaemia suffering from APC were feasible and safe with respect to individualised dose administrations. A multicenter phase 1 trial in pts with hyperbilirubinaemia is started (AIO-PAK-0117) to confirm these findings in a prospective setting.



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Mapping the European cancer research landscape: An evidence base for national and Pan-European research and funding

Publication date: September 2018
Source:European Journal of Cancer, Volume 100
Author(s): Mursheda Begum, Grant Lewison, Mark Lawler, Richard Sullivan
BackgroundCancer research is among the most active biomedical research domains for the European Union (EU). However, little quantitative empirical evidence is available to guide the decisions on the choice of disease site to study, specific research domain focus or allocation of research resources. To inform national/supranational cancer research policy, high-resolution intelligence is needed.MethodsWe performed a bibliometric analysis of European cancer research papers in the Web of Science from 2002 to 2013 to quantify research activity in each of the 28 EU Member States, along with Iceland, Norway and Switzerland (EUR31), which cancer sites/research domains they addressed, and their sources of financial support (2009–2013).FindingsCancer research papers from EUR31 correlated well with national Gross Domestic Products (r² = 0.94). However, certain cancer sites (lung, oesophagus and pancreas) were under-researched relative to their disease burden, whereas central nervous system and blood cancers were more generously supported than their burden would warrant. An analysis of research domains indicated a paucity of research on radiotherapy (5%), palliative care (1.2%) and quality of life (0.5%). European cancer research funding in 2012–2013 amounted to ∼€7.6 billion and came from diverse sources, especially in western Europe/Scandinavia, where in nine countries the charitable sector outspent the government but not in Eastern Europe where charitable research funding barely exists.InterpretationSeveral countries need to increase their cancer research outputs substantially, and/or alter their research portfolios to better match their growing (and changing) cancer burden. More co-ordination among funding agencies is required, so that resources can be attuned to align activities to research gaps and perceived clinical needs. In Eastern Europe, the charitable funding sector needs to be developed, so that both public and patient advocacy can have an active role in research.



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Clinicopathologic findings of CARS2 mutation

Publication date: Available online 4 July 2018
Source:Pediatric Neurology
Author(s): Debopam Samanta, Murat Gokden, Erin Willis
OBJECTIVESWe report a 13-year-old girl with a past medical history of epilepsy, intellectual impairment, dysphagia with gastric tube dependence, and autism spectrum disorder who presented with focal status epilepticus.METHODSVideo electroencephalogram showed left occipital pseudoperiodic epileptiform discharges and frequent seizures originating from the left hemisphere. The seizure was refractory to anti-epileptic medications and pharmacologic coma. Subsequently, left occipital lobectomy was done. Extensive workup including whole exome sequencing, histopathologic examination of brain and muscle samples, mitochondrial DNA content analysis of tissue sample was completed to detect the etiology.RESULTSSkeletal muscle mitochondrial DNA content (qPCR) analysis showed approximately 37% of the mean value of age and tissue matched controls consistent with a mitochondrial depletion syndrome. Microscopic examination of the brain showed cortical abnormalities that largely consisted of infarct-like pathology in a laminar manner, abnormalities of neuronal distribution, and white matter changes. Compound heterozygous mutations of the CARS2 gene were identified by whole exome sequencing; V52G variant [p.Val52Gly (GTG>GGG):c.155 T>G in exon 1] was inherited from the mother and T188M variant[p.Thr188Met (ACG>ATG): c.563 C>T in exon 5] was inherited from the father.CONCLUSIONThis is the first detailed clinicopathologic description of Alpers-Huttenlocher syndrome (AHS) phenotype from CARS mutations.



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Bizarre beading in a child with stroke

Publication date: Available online 4 July 2018
Source:Pediatric Neurology
Author(s): Nupur Parakh, Vinit Baliyan, Puneet Jain, Suvasini Sharma, Atin Kumar
None



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Occurrence and distribution of antibiotic resistance genes in the sediments of drinking water sources, urban rivers, and coastal areas in Zhuhai, China

Abstract

Antibiotic resistance genes (ARGs) are regarded as emerging contaminants related with human activities. Aquatic environments of an urban city are apt for the persistence and prevalence of ARGs. In this study, we investigated the occurrence and distribution of ARGs and integrase genes in the sediment samples collected from drinking water sources, urban rivers, and coastal areas of Zhuhai, China, in the dry and wet seasons of 2016. The results show that sulfonamide resistance gene of sulII was present at the highest detection frequency (85.71%); and its average concentrations were also the highest in both dry and wet seasons (3.78 × 10⁷ and 9.04 × 10⁷ copies/g sediment, respectively), followed by tetC, tetO, tetA, ermB, dfrA1, and bla_PSE-1. Temporally, the concentrations of total ARGs in the wet season were likely higher than those in the dry season; and spatially, the concentrations of total ARGs in the drinking water sources were substantially lower than those in the urban rivers and nearby coastal areas, indicating the different degrees of anthropogenic impact and consequent health risks. Positive correlations were found between intI1 and each quantitative ARG in all wet season samples rather than dry season samples, which suggested higher temperature and more rain in summer might have positive influences on ARG dissemination, especially that mediated by intI1 gene and class I integrons.

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αβ T Cell Receptor Mechanosensing Forces out Serial Engagement

Publication date: Available online 4 July 2018
Source:Trends in Immunology
Author(s): Yinnian Feng, Ellis L. Reinherz, Matthew J. Lang
T lymphocytes use αβ T cell receptors (TCRs) to recognize sparse antigenic peptides bound to MHC molecules (pMHCs) arrayed on antigen-presenting cells (APCs). Contrary to conventional receptor–ligand associations exemplified by antigen–antibody interactions, forces play a crucial role in nonequilibrium mechanosensor-based T cell activation. Both T cell motility and local cytoskeleton machinery exert forces (i.e., generate loads) on TCR–pMHC bonds. We review biological features of the load-dependent activation process as revealed by optical tweezers single molecule/single cell and other biophysical measurements. The findings link pMHC-triggered TCRs to single cytoskeletal motors; define the importance of energized anisotropic (i.e., force direction dependent) activation; and characterize immunological synapse formation as digital, revealing no serial requirement. The emerging picture suggests new approaches for the monitoring and design of cytotoxic T lymphocyte (CTL)-based immunotherapy.



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The brain metabolic signature of visual hallucinations in Dementia with Lewy Bodies

Publication date: Available online 4 July 2018
Source:Cortex
Author(s): Leonardo Iaccarino, Arianna Sala, Silvia Paola Caminiti, Roberto Santangelo, Sandro Iannaccone, Giuseppe Magnani, Daniela Perani
Visual hallucinations (VH) are a core clinical feature of dementia with Lewy bodies (DLB), but their specific neural substrate remains elusive. We used ¹⁸F-FDG-PET to study the neural dysfunctional signature of VH in a group of 38 DLB patients (mean age±sd 72.9±7.5) with available anamnestic records, cognitive and neurological examination and NeuroPsychiatric Inventory assessing VH. We tested the voxel-wise correlation between ¹⁸F-FDG-PET hypometabolism and VH NPI scores at the whole-group level, then adopting inter-regional correlation analysis to explore the resting-state networks (RSNs) metabolic connectivity in DLB patients with and without visual hallucinations, as compared to N=38 age-matched healthy controls (HCs) (mean age±sd 71.5±6.9). At the whole-group level, we found a negative correlation between VH NPI scores and ¹⁸F-FDG-PET hypometabolism in the right occipito-temporal cortex (p<0.001 uncorrected, p<0.05 Family-Wise Error cluster-corrected). Then, splitting the group according to VH presence, we found that DLB non-hallucinators presented a pattern of connectivity seeding from this occipito-temporal cluster and extending to the ventral visual stream. At difference, the DLB hallucinators showed a metabolic connectivity pattern limited to the occipital-dorsal parietal regions. As for RSNs, both the DLB subgroups showed a markedly reduced extent of attentional and visual networks compared to HCs, with a variable alteration in the topography. DLB-VH patients showed a more pronounced shrinkage of the primary visual network, which was disconnected from the higher visual hubs, at difference with both HC and DLB non-hallucinators. These findings suggest that an altered brain metabolic connectivity within and beyond visual systems may promote VH in DLB. These results support the most recent neurocognitive models interpreting VH as the result of an inefficient recruitment of the ventral visual stream and of a large-scale multi-network derangement.



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Discriminating scene categories from brain activity within 100 ms

Publication date: Available online 4 July 2018
Source:Cortex
Author(s): Matthew X. Lowe, Jason Rajsic, Susanne Ferber, Dirk B. Walther
Humans have the ability to make sense of the world around them in only a single glance. This astonishing feat requires the visual system to extract information from our environment with remarkable speed. How quickly does this process unfold across time, and what visual information contributes to our understanding of the visual world? We address these questions by directly measuring the temporal dynamics of the perception of colour photographs and line drawings of scenes with electroencephalography (EEG) during a scene-memorization task. Within a fraction of a second, event-related potentials (ERPs) show dissociable response patterns for global scene properties of content (natural versus manmade) and layout (open versus closed). Subsequent detailed analyses of within-category versus between-category discriminations found significant dissociations of basic-level scene categories (e.g., forest; city) within the first 100ms of perception. The similarity of this neural activity with feature-based discriminations suggests low-level image statistics may be foundational for this rapid categorization. Interestingly, our results also suggest that the structure preserved in line drawings may form a primary and necessary basis for visual processing, whereas surface information may further enhance category selectivity in later-stage processing. Critically, these findings provide evidence that the distinction of both basic-level categories and global properties of scenes from neural signals occurs within 100ms.



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Dual-Tasking and Multitasking

Publication date: Available online 4 July 2018
Source:Cortex
Author(s): Sarah E. MacPherson




https://ift.tt/2u2ohdS

Multivariate single-subject analysis of short-term reorganization in the language network

Publication date: Available online 4 July 2018
Source:Cortex
Author(s): Gesa Hartwigsen, Danilo Bzdok




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Enhanced postsynaptic inhibitory strength in hippocampal principal cells in high-performing aged rats

Publication date: October 2018
Source:Neurobiology of Aging, Volume 70
Author(s): Trinh Tran, Michela Gallagher, Alfredo Kirkwood
Hyperactivity within the hippocampal formation, frequently observed in aged individuals, is thought to be a potential contributing mechanism to the memory decline often associated with aging. Consequently, we evaluated the postsynaptic strength of excitatory and inhibitory synapses in the granule cells of the dentate gyrus and CA1 pyramidal cells of a rat model of aging, in which each individual was behaviorally characterized as aged impaired (AI) or aged unimpaired (AU, with performance comparable to young (Y) individuals). In hippocampal slices of these 3 aged groups (Y, AI, AU), we found that compared to the young, the miniature excitatory and inhibitory currents (mEPSCs and mIPSCs) were larger in amplitude in the granule cells of the AU group and smaller in the AI group. In contrast, in CA1 cells, neither the mEPSCs nor the mIPSCs were affected by age, whereas the extrasynaptic conductance responsible for tonic inhibition was selectively enhanced in CA1 cells of AU individuals. Tonic inhibition conductance was not affected by age in the granule cells. These results support the notion that upregulation of synaptic inhibition could be a necessary condition for the maintenance of performance during aging. These findings also underscore the notions that successful aging requires adaptive upregulation, not merely the preservation of youthful functionality, and that age effects are not homogeneous across hippocampal subfields.



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An isoform-selective p38α mitogen-activated protein kinase inhibitor rescues early entorhinal cortex dysfunctions in a mouse model of Alzheimer's disease

Publication date: October 2018
Source:Neurobiology of Aging, Volume 70
Author(s): Grazia Rutigliano, Martina Stazi, Ottavio Arancio, D. Martin Watterson, Nicola Origlia
Neuroinflammation is a fundamental mechanism in Alzheimer's disease (AD) progression. The stress-induced activation of the p38α mitogen-activated protein kinase (MAPK) leads to increased production of proinflammatory cytokines and neurodegeneration. We investigated the effects of an isoform selective p38α MAPK inhibitor, MW01-18-150SRM (MW150), administered at 2.5 mg/kg/d (i.p.; 14 days) on early entorhinal cortex (EC) alterations in an AD mouse model carrying human mutations of the amyloid precursor protein (mhAPP). We used electrophysiological analyses with long-term potentiation induction in EC-containing brain slices and EC-relevant associative memory tasks. We found that MW150 was capable of rescuing long-term potentiation in 2-month old mhAPP mice. Acute delivery of MW150 to brain slices was similarly effective in rescuing long-term potentiation, with a comparable efficacy to that of the widely used multikinase inhibitor SB203580. MW150-treated mhAPP mice demonstrated improved ability to discriminate novel associations between objects and their position/context. Our findings suggest that the selective inhibition of the stress-activated p38α MAPK with MW150 can attenuate the EC dysfunctions associated with neuroinflammation in an early stage of AD progression.



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Evaluation of Vascular Remodeling in Carotid Atherosclerosis Among Type 2 Diabetes Mellitus Patients Using High-Frequency Ultrasonography Combined with Serum Resistin

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0577-7658

Diabetes remains a long standing public health issue among the Chinese population, with an incidence of up to 11.6%, of which type 2 diabetes mellitus (T2DM) accounts for 85%–95%. During this study, we aimed to elucidate the value of high-frequency ultrasonography (HFUS) combined with serum resistin on vascular remodeling (VR) in carotid atherosclerosis (CA) among patients suffering from T2DM. A total of 432 T2DM were recruited and assigned into the short T2DM duration group (<5 years), middle T2DM duration group (5~10 years) and long T2DM duration group (>10 years), while another 172 healthy cases were recruited as the control group. The intima-media thickness (IMT) as well as plaque score, detection rate and type were detected by the HFUS. The respective blood pressure readings were measured and pulse pressure was calculated accordingly. The serum resistin level, remodeling incidence and type, levels of total cholesterol (TC), fasting blood glucose (FBG), low-density lipoprotein cholesterol (LDL-C), high-density liproprotein cholesterol (HDL-C), and triglyceride (TG) were measured. The correlation between IMT, the plaque detection rate and blood pressure were analyzed. A receiver operating characteristic (ROC) curve was constructed in order to evaluate the impact of VR in CA on T2DM patients who were solely using HFUS and serum resistin respectively, as well as a combination of HFUS with serum resistin. As In comparison with the control group, the short, middle and long T2DM duration groups all displayed increased IMT, plaque score and detection rate, serum resistin level and VR incidence, especially for the long T2DM duration group. Levels of TC, TG, FBG and LDL-C were much higher while HDL-C was lower among patients with T2DM than those in the control group. A positive correlation was detected between the disease course and IMT. The detection rate of plaque with thickening IMT exhibited upregulated levels when compared to those with normal IMT. The HFUS, serum resistin and HFUS combined with serum resistin respective areas under the ROC curve were 0.873, 0.867 and 0.923, respectively, suggesting that the combination of HFUS and serum resistin was superior to that of individual HFUS or individual serum resistin in regard to the impact of VR in CA on T2DM patients. The results of this study revealed that the combination of HFUS and serum resistin was superior to individual HFUS or individual serum resistin in relation to its ability to evaluate the impact of VR in CA in patients with T2DM.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Correction: Amiodarone-Induced Thyroid Dysfunction: A Clinical Update

Exp Clin Endocrinol Diabetes 2018; 126: e1-e1
DOI: 10.1055/a-0650-8694

[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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The polyherbal drug GGEx18 from Laminaria japonica, Rheum palmatum, and Ephedra sinica inhibits hepatic steatosis and fibroinflammtion in high-fat diet-induced obese mice

Publication date: 28 October 2018
Source:Journal of Ethnopharmacology, Volume 225
Author(s): Jonghoon Lim, Haerim Lee, Jiwon Ahn, Jeongjun Kim, Joonseong Jang, Yonghyun Park, Birang Jeong, Heejung Yang, Soon Shik Shin, Michung Yoon
Ethnopharmacological relevanceThe herbal composition Gyeongshingangjeehwan 18 (GGEx18), composed of Rheum palmatum L. (Polygonaceae), Laminaria japonica Aresch (Laminariaceae), and Ephedra sinica Stapf (Ephedraceae), is used as an antiobesity drug in Korean clinics. The constituents of GGEx18 have traditionally been reported to inhibit obesity and related metabolic diseases such as insulin resistance and dyslipidemia.ObjectiveThis study investigated the effects of GGEx18 on nonalcoholic fatty liver disease (NAFLD) in mice fed a high-fat diet (HFD) and the underlying cellular and molecular mechanisms involved.MethodsC57BL/6 J mice were fed either a low-fat diet (LFD), an HFD, or an HFD supplemented with GGEx18 (125, 250, or 500 mg/kg of body weight/day). After 13 weeks, blood analyses, histology, immunohistochemistry, and real-time PCR were performed to assess NAFLD development in these mice.ResultsMice fed an HFD had increases in body weight, epididymal adipose tissue mass, adipocyte size, and adipose expression of inflammation-related genes compared with those fed an LFD. These increases were ameliorated in mice treated with 500 mg/kg/day GGEx18 without affecting food consumption profiles. GGEx18 not only decreased serum levels of triglycerides, free fatty acids, and alanine aminotransferase, but also decreased hepatic lipid accumulation, numbers of mast cells and α-smooth muscle actin-positive cells, and collagen levels induced by an HFD. Consistent with the histological data, the hepatic expression of lipogenesis-, inflammation-, and fibrosis-related genes was lower, while hepatic fatty acid β-oxidation-related gene expression was higher, in mice receiving GGEx18 compared to mice fed only the HFD.Discussion and conclusionThese results indicate that GGEx18 attenuates visceral obesity and NAFLD, in part by altering the expression of genes involved in hepatic steatosis and fibroinflammation in HFD-induced obese mice. These findings suggest that GGEx18 may be effective for preventing and treating NAFLD associated with visceral obesity.

Graphical abstract

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Production from both wild harvest and cultivation: The cross-border Swertia chirayita (Gentianaceae) trade

Publication date: 28 October 2018
Source:Journal of Ethnopharmacology, Volume 225
Author(s): A.B. Cunningham, J.A. Brinckmann, U. Schippmann, D. Pyakurel
Ethnopharmacological relevanceSwertia chirayita is the most widely traded species in a genus of 150 species, many of which are used in traditional medicine. S. chirayita is used mainly in Ayurvedic and Tibetan systems of medicine and the homoeopathic system of medicine as well as in regional folk medicine. Primarily wild collected, with some cultivation. S. chirayita is traded as a medicinal substance and exported in the forms of dried whole plant or extract of whole plant individually and/or as active ingredients of Ayurvedic medicines. S. chirayita export valuations continue to make S. chirayita one of Nepal's highest foreign exchange earning medicinal plant species.Aims of the reviewThe aims of this review were first, to assess the scale of the global trade in S. chirayita, second, to review evidence from plant population biology and from studies on the impacts of wild harvest on S. chirayita populations and cultivation as an alternative source of supply.MethodsThe taxonomy and trade names for S. chirayita were reviewed, followed by a synthesis of published information on Swertia population biology and studies on impacts of wild S. chirayita harvest from across the geographic range of this species. Data on the prices paid for S. chirayita were then compiled for the period 2001–2017, followed by an analysis of global trade data for S. chirayita.Results and conclusionsBased on India import data and assuming an estimate in an earlier study that 60% of Nepal's S. chirayita production goes to India and 35% to Tibet, then Nepal's 2013 annual production was about 711 metric tonnes (MT) of which about 675.6 MT would be exported (India + Tibet). Nepal's 2014 annual production would be an estimated 503.25 MT of which about 478 MT would be exported. Declines in S. chirayita populations have been widely noted across its range. In India, since 2004, a ban was placed on the export of wild harvested S. chirayita by the Government of India, where the Director General of Foreign Trade prohibited export of S. chirayita plants, plant portions and their derivatives and extracts obtained from the wild with the exception of 'formulations'. Cultivation of S. chirayita to meet commercial demand has been an important part of a solution to over-exploitation of wild stocks in eastern Nepal for 25 years, producing significant quantities that enter the export trade to India and Tibet. In Sankhuwasabha district, for example, 53.1 MT of S. chirayita were produced in 2013/014, just over half of which (27 MT) were exported to India, with the remainder exported to Tibet. Based on value-chain analysis and cost-benefit assessments, S. chirayita cultivation has been shown to be profitable in Nepal. However, since the first cost-benefit assessment was done (2013), prices dropped from NRs750/kg in April 2013 to a low of 250 NRs/kg in December 2017). Taking inflation into account further highlights the steep decline in the profitability for local farmers, who have limited options for value-adding. Consequently, farmers prefer to grow more profitable alternative crops, such as Nepal cardamom (Amomum subulatum Roxb.).

Graphical abstract

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