Publication date: Available online 12 December 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): S. Mourad, M. Abd Al-Ghaffar, Mohamed Al-Amir Bassiony, G. Fawzi
ObjectiveTo evaluate the perception of complex ABR (C-ABR) in aphasic patients and to compare it before and 3 months after management of stroke.MethodologyA prospective study was conducted on 30 aphasic patients using C-ABR. The results were compared within 2 weeks post-stroke and 3 months after management. The results of aphasic patients were compared with normal subjects.ResultsThe seven C-ABR waves regarding the onset (wave V and A), offset (peak O), transition (peak C) and frequency following responses (peak D, E and F) were identified in all participants. There was a statistically significant difference in C-ABR latencies between control and study group in the waves D, E, F and O, this means that aphasic patients exhibited abnormal neural synchrony affecting the source elements (fundamental frequency) (waves D, E, F and O) however there was no effect on the filter elements (transients).ConclusionAphasic patients exhibited abnormal neural synchrony affecting the source elements (waves D, E, F and O) however there was no effect on the filter elements (transients).
http://ift.tt/2AyNq5Y
Τρίτη 12 Δεκεμβρίου 2017
Value of complex evoked auditory brainstem response in patients with post-stroke aphasia (prospective study)
The GDNF Family: a Role in Cancer?
Publication date: January 2018
Source:Neoplasia, Volume 20, Issue 1
Author(s): Graeme C. Fielder, Teresa Wen-Shan Yang, Mahalakshmi Razdan, Yan Li, Jun Lu, Jo K. Perry, Peter E. Lobie, Dong-Xu Liu
The glial cell line–derived neurotrophic factor (GDNF) family of ligands (GFLs) comprising of GDNF, neurturin, artemin, and persephin plays an important role in the development and maintenance of the central and peripheral nervous system, renal morphogenesis, and spermatogenesis. Here we review our current understanding of GFL biology, and supported by recent progress in the area, we examine their emerging role in endocrine-related and other non–hormone-dependent solid neoplasms. The ability of GFLs to elicit actions that resemble those perturbed in an oncogenic phenotype, alongside mounting evidence of GFL involvement in tumor progression, presents novel opportunities for therapeutic intervention.
http://ift.tt/2C9TU8H
Synchronous Premaxillary Osteotomy with Primary Cheiloplasty for BCLP Patients with Protrusion of the Premaxillae
Background: In bilateral cleft lip and palate (BCLP) patients with protrusion and/or torsion of the premaxillae, it is difficult to achieve a good outcome. We have developed a series of procedures of premaxillary osteotomy with primary cheiloplasty for BCLP patients who did not respond well to presurgical orthodontics (PSO). Methods: A total of 27 BCLP patients with protrusion and/or torsion of the premaxillae underwent PSO. For 3 BCLP patients in whom the protruded premaxillae could not be returned to a good position, a primary premaxillary osteotomy and gingivoperiosteoplasty (GPP) with cheiloplasty were performed simultaneously. Subsequently, Furlow palatoplasty was performed by one and a half years of age. Maxillary growth was evaluated by dental occlusion at 4 years of age. Results: A premaxillary osteotomy and GPP with cheiloplasty were performed at 6 months. The patients' facial structures improved, their premaxillae were positioned more superiorly, and normal inclination of the incisors was achieved. They had edge-to-edge occlusions or cross bites at 4 years of age. Conclusions: As advantages, the patients' facial structures improved, and the alveolar bones were formed by GPP. As a disadvantage, premaxillary necrosis might occur because of poor blood circulation. It is important to secure the following 2 blood supplies: from the periosteum and soft-tissue of the anterior premaxillae and from the periosteum and mucosa of the nasal septum. Synchronous premaxillary osteotomy and GPP with primary cheiloplasty are appropriate when the premaxillae cannot be properly repositioned by PSO or PSO cannot be done.http://ift.tt/2j17aYj
Craniofacial Reconstruction by a Cost-Efficient Template-Based Process Using 3D Printing
Summary: Craniofacial defects often result in aesthetic and functional deficits, which affect the patient's psyche and wellbeing. Patient-specific implants remain the optimal solution, but their use is limited or impractical due to their high costs. This article describes a fast and cost-efficient workflow of in-house manufactured patient-specific implants for craniofacial reconstruction and cranioplasty. As a proof of concept, we present a case of reconstruction of a craniofacial defect with involvement of the supraorbital rim. The following hybrid manufacturing process combines additive manufacturing with silicone molding and an intraoperative, manual fabrication process. A computer-aided design template is 3D printed from thermoplastics by a fused deposition modeling 3D printer and then silicone molded manually. After sterilization of the patient-specific mold, it is used intraoperatively to produce an implant from polymethylmethacrylate. Due to the combination of these 2 straightforward processes, the procedure can be kept very simple, and no advanced equipment is needed, resulting in minimal financial expenses. The whole fabrication of the mold is performed within approximately 2 hours depending on the template's size and volume. This reliable technique is easy to adopt and suitable for every health facility, especially those with limited financial resources in less privileged countries, enabling many more patients to profit from patient-specific treatment.http://ift.tt/2iXquSB
Acral melanoma foot lesions. Part 2: clinical presentation, diagnosis, and management
Summary
Acral melanoma (AM) is a rare subtype of cutaneous malignant melanoma found on acral skin, primarily on the soles of the feet. Although rare, it is the most common subtype of melanoma found in patients of African or Asian ethnicity and has a poor prognosis, often because of the more advanced stage of presentation at diagnosis. In the second of this two-part series, we review the clinical presentation, histopathology, diagnosis and management of AM. Clinically, AM presents as a variegated lesion with blue–black pigment and irregular borders on acral skin. A parallel-ridge pattern is a very specific dermoscopic finding for AM. The differential diagnoses of AM include acral naevus, pyoderma gangrenosum, pyogenic granuloma, verrucous carcinoma and peripheral neuropathy-induced foot ulcers. If there is a clinical suspicion of AM, an excisional biopsy should be taken. Once diagnosis is confirmed by histology, surgical excision is the standard treatment. Overall, dermoscopy and histopathology are key tools in the diagnosis of AM. A greater emphasis on melanoma screening and awareness is essential in minority populations to improve survival outcomes in AM.
http://ift.tt/2o0AGiT
Fenestrated Thoracic Endovascular Aortic Repair Using Physician Modified Stent Grafts for Acute Type B Aortic Dissection with Unfavourable Landing Zone
Publication date: Available online 12 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Jiechang Zhu, Lujing Zhao, Xiangchen Dai, Yudong Luo, Hailun Fan, Zhou Feng, Yiwei Zhang, Fanguo Hu
ObjectivesThe aim was to evaluate the early results of fenestrated thoracic endovascular aortic repair (fTEVAR) using physician modified stent grafts (PMSGs) to revascularise aortic branches for acute type B aortic dissection (ABAD) with unfavourable proximal landing zone.MethodsTwenty consecutive patients who underwent fenestrated TEVAR using PMSGs between November 2015 and December 2016 were retrospectively reviewed. Pre-, intra-, and post-operative clinical data were recorded.ResultsThe median patient age was 53 years (range, 18–83 years), and 16 of the 20 (80%) patients were men. Indications were complicated ABAD with unfavourable proximal landing zones, including inadequate proximal landing zone (n = 4), retrograde dissection extending to the left subclavian artery (LSA) (n = 13), and retrograde haematoma involving the LSA (n = 3). Twenty PMSGs (Medtronic Valiant stent grafts, n = 4; Relay thoracic stent grafts, n = 10; Ankura thoracic stent grafts, n = 6) were deployed. One LSA fenestration was created in 19 patients, and one LSA fenestration combined with a left common carotid artery (LCCA) scallop was created in one patient. Branch stents consist of a covered stent for the LSA (n = 7), an uncovered stent for the LSA (n = 14), and an uncovered stent for the LCCA (n = 1). The median duration for stent graft modifications was 40 min (range 30–60 min). The mean interval between symptom onset and treatment was 5 ± 3 days (range, 1–10 days). The initial technical success rate was 90% (18 of 20). Partial coverage of the LCCA in one patient resolved after uncovered chimney stent implantation in the LCCA. Type III endoleak between the LSA covered stent and the PMSG occurred in this patient 1 week post fTEVAR and resolved after re-intervention with deployment of an Amplatzer occluder device across the site of the leak. A chimney stent was deployed to solve the misalignment of the LSA in another patient. The mean operation time was 101 ± 48 min, and fluoroscopy time was 24 ± 16 min. There were no in hospital deaths and no peri-operative neurological complications. The median length of stay was 9 ± 6 days (range, 5–26 days). One patient had a left brachial artery (LBA) pseudoaneurysm at the puncture site that required open repair. One patient presented renal deterioration post-operatively and recovered uneventfully after conservative therapy. All patients survived at a mean follow-up of 6.95 months (range, 2–14 months). During follow-up, no post-operative complications occurred and all target vessels remained patent. No fenestration related Type I or III endoleaks were observed.ConclusionsfTEVAR using PMSGs may be a viable alternative for patients who present with ABAD without healthy proximal landing zones and who are unable to wait for a custom made fenestrated device.
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Endovascular Repair of Acute Thoraco-abdominal Aortic Aneurysms
Publication date: Available online 12 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Chiara Mascoli, Massimo Vezzosi, Andreas Koutsoumpelis, Mauro Iafrancesco, Aaron Ranasinghe, Paul Clift, Jorge Mascaro, Martin Claridge, Donald J. Adam
ObjectivesThe outcome of endovascular repair (EVAR) for acute TAAA is reported and the applicability of the t-Branch off the shelf (OTS) device is determined.MethodsInterrogation of a prospectively maintained database identified all patients who underwent EVAR for acute TAAA between September 2012 (when the first non-elective t-Branch case was performed) and November 2015. Early and medium-term outcomes were analysed. Survival and re-intervention-free survival were calculated by Kaplan–Meier analysis.ResultsA total of 39 patients (27 men; mean ± SD age, 72 ± 8 years) were treated for acute symptomatic (n = 29) or ruptured (n = 10) TAAA (20 anatomical extent I–III, 19 extent IV). Fourteen patients had mycotic aneurysms. The mean aneurysm diameter was 80 ± 20 mm. The mean ± SD follow-up was 21.4 ± 15.4 months. Surgeon modified fenestrated EVAR was used in 24 patients, chimney/periscope EVAR in two, and t-Branch in 13 (33%) patients. Aortic coverage was greater than 40 mm above the coeliac axis in all patients. A total of 127 target vessels (TVs) were preserved (mean 3.3 per patient) and two occluded within 30 days. The 30 day mortality was 26%. Four (10%) patients developed spinal cord ischaemia (SCI): two with paraplegia died within 30 days, and two with paraparesis recovered completely with blood pressure manipulation and cerebrospinal fluid drainage. Estimated overall survival (±SD) at 12 and 24 months was 71.8 ± 7.2% and 63.2 ± 7.9%, respectively. Estimated freedom from re-intervention at 12 and 24 months was 93 ± 4.8% and 85.3 ± 6.8%, respectively.ConclusionsEVAR for acute TAAA is associated with acceptable early and mid-term results in patients who have no other treatment options. Only one third of these patients were suitable for the t-Branch device, indicating that further advances in device design are required to treat the majority of acute TAAA patients with commercially available OTS technology.
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Re: “Catheter Foam Sclerotherapy of the Great Saphenous Vein, with Peri-saphenous Tumescence Infiltration and Saphenous Irrigation”—Is Modified Catheter Foam Sclerotherapy a Step Back in the Evolution of Endovenous Ablation for Varicose Veins?
Publication date: Available online 12 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Alok Tiwari, Tze Tec Chong, Tjun Y. Tang
http://ift.tt/2ykls8f
Aortofemoral Reconstruction for an Infected Graft Using Thrombosed Femoral Veins
Publication date: Available online 12 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Grigol Keshelava, Davit Kovziridze, Alexander Mkervalishvili
IntroductionTreatment of an infected aortic prosthesis is difficult and the ideal graft material is subject to debate.ReportA case of infected aortic prosthesis treated using bilateral thrombosed superficial femoral veins (SFVs) is presented. Bilateral reversed SFVs were cut longitudinally at both proximal ends about 3–4 cm and were sutured side by side. The operating time was 5 h. No sign of recurrent infection was observed when the patient suffered a myocardial infarction and died 6 months post-operatively.DiscussionThrombosed SFVs may be considered as a therapeutic option for infected aortic graft replacement.
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Promoting Student Integrity: Ethical Issues in the Digital Age
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Tony Peregrin
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Confirmation of the immunoreactivity of monoclonal anti-human C-terminal EGFR antibodies in bronze Corydoras Corydoras aeneus (Callichthyidae Teleostei) by Western Blot method
Source:Acta Histochemica
Author(s): Jennifer Mytych, Leszek Satora, Katarzyna Kozioł
Bronze corydoras (Corydoras aeneus) uses the distal part of the intestine as accessory respiratory organ. Our previous study showed the presence of epidermal growth factor receptor (EGFR) cytoplasmic domain in the digestive tract of the bronze corydoras. In this study, using Western Blot method, we validated the results presented in the previous research. In detail, results of Western Blot analysis on digestive and respiratory part of bronze corydoras intestine homogenates confirmed the immunoreactivity of anti-cytoplasmic domain (C-terminal) human EGFR antibodies with protein band of approximately 180kDa (EGFR molecular weight). This indicates a high homology of EGFR domain between these species and the possibility of such antibody use in bronze corydoras. Statistically significantly higher EGFR expression was observed in the respiratory part of intestine when compared to the digestive part. This implies higher proliferation activity and angiogenesis of epithelium in this part of intestine, creating conditions for air respiration. Therefore, Corydoras aeneus may be considered as a model organism for the molecular studies of the mechanisms of epithelial proliferation initiation and inhibition depending on hypoxia and normoxia.
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Polyploidy and nuclear phenotype characteristics of cardiomyocytes from diabetic adult and normoglycemic aged mice
Source:Acta Histochemica
Author(s): Isabela S. Silva, Flávia G. Ghiraldini, Giovana M.B. Veronezi, Maria Luiza S. Mello
The frequency of polyploid nuclei in the aging human heart is in sharp contrast with that in the human liver. An inverse pattern exists between the mouse heart and liver cells. Ploidy degrees in mouse hepatocytes under hyperglycemic conditions are elevated to higher levels than those in aged hepatocytes. In this study, image analysis cytometry was used to investigate the effect of diabetes and aging on Feulgen-DNA quantities, ploidy degrees, nuclear shapes and chromatin texture in mouse cardiomyocytes compared to previously reported data for mouse hepatocytes. Adult, non-obese diabetic (NOD) hyperglycemic and normoglycemic females and 56-week-old normoglycemic BALB/c females were used. A small percentage (∼7%) of the cardiomyocyte nuclei in severely hyperglycemic NOD adult mice possessed higher ploidy values than those in the 8-week-old normoglycemic mice. Surprisingly, the Feulgen-DNA values and the frequency of nuclei belonging to the 4C and 8C ploidy classes were even higher (∼6%) in normoglycemic NOD specimens than in age-matched hyperglycemic NOD specimens. Additionally, a pronounced elongated nuclear shape was observed especially in adult normoglycemic NOD mice. In conclusion, NOD mice, irrespective of their glycemic level, exhibit a moderate increase in ploidy degrees within cardiomyocyte nuclei during the adult lifetime. As expected, aging did not affect the Feulgen-DNA values and the ploidy degrees of cardiomyocytes in BALB/c mice. The differences in ploidy degrees and chromatin textures such as absorbance variability and entropy, between adult NOD and aged BALB/c mice are consistent with other reports, indicating dissimilarities in chromatin functions between diabetes and aging.
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Analysis of NRAS gain in 657 patients with melanoma and evaluation of its sensitivity to a MEK inhibitor
Source:European Journal of Cancer, Volume 89
Author(s): Junya Yan, Xiaowen Wu, Jiayi Yu, Huan Yu, Tianxiao Xu, Kevin M. Brown, Xue Bai, Jie Dai, Meng Ma, Huan Tang, Lu Si, Zhihong Chi, Xinan Sheng, Chuanliang Cui, Yan Kong, Jun Guo
BackgroundNeuroblastoma rat-sarcoma (NRAS) mutations have been described in Chinese patients with melanoma. However, the status and the clinical significance of NRAS gain have not been investigated on a large scale.MethodsA total of 657 melanoma samples were included in the study. NRAS copy number was examined using the QuantiGene Plex DNA assay. The sensitivities of cell lines and patient-derived xenograft (PDX) models containing NRAS gain to a MAP/ERK kinase (MEK) inhibitor (binimetinib) were also evaluated.ResultsThe overall incidence of NRAS gain was 14.0% (92 of 657). Incidence of NRAS gain in acral, mucosal, chronic sun-induced damage (CSD) and non-CSD melanomas was 12.2%, 15.8%, 9.5% and 19.4%, respectively. NRAS gain was mutually exclusive to NRAS mutations (P = 0.036). The median survival time for melanoma patients with NRAS gain was significantly shorter than that for patients with normal NRAS copy number (P = 0.006). For patients containing NRAS gain, the median survival time for higher copy number (>4 copies) was significantly shorter than those with lower copy number (2–4 copies; P = 0.002). The MEK inhibitor (binimetinib) inhibited the proliferation of melanoma cells and the tumour growth of PDX models with NRAS gain.ConclusionsNRAS gain is frequent in patients with melanoma and may predict a poor prognosis of melanoma. The melanoma cells and PDX models containing NRAS gain are sensitive to MEK inhibitor (binimetinib), indicating that NRAS gain might be a new therapeutic target for melanoma.
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No overdiagnosis in the Norwegian Breast Cancer Screening Program estimated by combining record linkage and questionnaire information in the Norwegian Women and Cancer study
Publication date: January 2018
Source:European Journal of Cancer, Volume 89
Author(s): Eiliv Lund, Aurelie Nakamura, Jean-Christophe Thalabard
BackgroundThe Norwegian Breast Cancer Screening Program (NBCSP) was implemented across the country in 2005 and has been criticised for potential 'overdiagnosis', i.e. a breast cancer diagnosis that otherwise would not have been detected or treated in a woman's lifetime. We aimed to estimate overdiagnosis in the NBCSP based on the Norwegian Women and Cancer (NOWAC) study using both questionnaire information and record linkage information from NBCSP.MethodFor 124,978 women aged 49–79 years from the NOWAC study, information on screened women could be cross-validated from the NBCSP database. Based on information from the NOWAC questionnaire, unscreened women were further divided into those who had mammograms taken only outside the NBCSP and those who had never had taken a mammogram. Breast cancers diagnosed in 2005–2013 were identified through linkage to the Cancer Registry of Norway; in situ or DCIS 417; invasive 2845; combined 3262. Cumulative incidence rates (CIRs) for ages 49–79 years of breast cancer were compared using the log-rank test.ResultsAfter exclusion of women with a family history of breast cancer, screened women had a CIR of 9.7% for combined breast cancer, non-significantly lower compared with unscreened women. Screened women had a 1.1% increased CIR or 13.0% increased relative risk of breast cancer diagnosis (significant) compared with women who had never had a mammogram, but for invasive breast cancer alone the difference was reduced to −0.2% (95% CI: −9.1; 8.8). Invasive breast cancers were significantly smaller (<2.5 cm) in screened versus unscreened women. There was a borderline significant decrease in lymph node positive cancer among screened (p = 0.06).ConclusionThe findings of no significant overdiagnosis combined with smaller tumours and less lymph node metastases suggest that the prevailing view of overdiagnosis in the NBCSP should be challenged.
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Detection of Changes in Cervical Softness Using Shear Wave Speed in Early versus Late Pregnancy: An in Vivo Cross-Sectional Study
Source:Ultrasound in Medicine & Biology
Author(s): Lindsey C. Carlson, Timothy J. Hall, Ivan M. Rosado-Mendez, Mark L. Palmeri, Helen Feltovich
The aim of this study was to assess the ability of shear wave elasticity imaging (SWEI) to detect changes in cervical softness between early and late pregnancy. Using a cross-sectional study design, shear wave speed (SWS) measurements were obtained from women in the first trimester (5–14 wk of gestation) and compared with estimates from a previous study of women at term (37–41 wk). Two sets of five SWS measurements were made using commercial SWEI applications on an ultrasound system equipped with a prototype catheter transducer (128 elements, 3-mm diameter, 14-mm aperture). Average SWS estimates were 4.42 ± 0.32 m/s (n = 12) for the first trimester and 2.13 ± 0.66 m/s (n = 18) for the third trimester (p < 0.0001). The area under the curve was 0.95 (95% confidence interval: 0.82–0.99) with a sensitivity and specificity of 83%. SWS estimates indicated that the third-trimester cervix is significantly softer than the first-trimester cervix. SWEI methods may be promising for assessing changes in cervical softness.
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Editorial Board/Aims and Scope
Source:Vaccine, Volume 36, Issue 3
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Enhancing global vaccine pharmacovigilance: Proof-of-concept study on aseptic meningitis and immune thrombocytopenic purpura following measles-mumps containing vaccination
Source:Vaccine, Volume 36, Issue 3
Author(s): Silvia Perez-Vilar, Daniel Weibel, Miriam Sturkenboom, Steven Black, Christine Maure, Jose Luis Castro, Pamela Bravo-Alcántara, Caitlin N. Dodd, Silvana A. Romio, Maria de Ridder, Swabra Nakato, Helvert Felipe Molina-León, Varalakshmi Elango, Patrick L.F. Zuber
New vaccines designed to prevent diseases endemic in low and middle-income countries (LMICs) are now being introduced without prior record of utilization in countries with robust pharmacovigilance systems. To address this deficit, our objective was to demonstrate feasibility of an international hospital-based network for the assessment of potential epidemiological associations between serious and rare adverse events and vaccines in any setting. This was done through a proof-of-concept evaluation of the risk of immune thrombocytopenic purpura (ITP) and aseptic meningitis (AM) following administration of the first dose of measles-mumps-containing vaccines using the self-controlled risk interval method in the primary analysis. The World Health Organization (WHO) selected 26 sentinel sites (49 hospitals) distributed in 16 countries of the six WHO regions. Incidence rate ratios (IRR) of 5.0 (95% CI: 2.5–9.7) for ITP following first dose of measles-containing vaccinations, and of 10.9 (95% CI: 4.2–27.8) for AM following mumps-containing vaccinations were found. The strain-specific analyses showed significantly elevated ITP risk for measles vaccines containing Schwarz (IRR: 20.7; 95% CI: 2.7–157.6), Edmonston-Zagreb (IRR: 11.1; 95% CI: 1.4–90.3), and Enders'Edmonston (IRR: 8.5; 95% CI: 1.9–38.1) strains. A significantly elevated AM risk for vaccines containing the Leningrad-Zagreb mumps strain (IRR: 10.8; 95% CI: 1.3–87.4) was also found. This proof-of-concept study has shown, for the first time, that an international hospital-based network for the investigation of rare vaccine adverse events, using common standardized procedures and with high participation of LMICs, is feasible, can produce reliable results, and has the potential to characterize differences in risk between vaccine strains. The completion of this network by adding large reference hospitals, particularly from tropical countries, and the systematic WHO-led implementation of this approach, should permit the rapid post-marketing evaluation of safety signals for serious and rare adverse events for new and existing vaccines in all settings, including LMICs.
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Preventive effect of anti-VacA egg yolk immunoglobulin (IgY) on Helicobacter pylori-infected mice
Source:Vaccine, Volume 36, Issue 3
Author(s): Kyung Sook Hong, Mi-Ran Ki, H.M. Arif Ullah, Eun-Joo Lee, Yong Deuk Kim, Myung-Jin Chung, Ahmed K. Elfadl, Jin-Kyu Park, Kyu-Shik Jeong
BackgroundHelicobacter pylori, a gram-negative bacterium, is the causative agent of gastric disorders and gastric cancer in the human stomach. Vacuolating cytotoxin A (VacA) is among the multi-effect protein toxins released by H. pylori that enables its persistence in the human stomach.MethodsTo evaluate the effect of anti-VacA egg yolk immunoglobulin (anti-VacA IgY) on H. pylori infection, a highly specific anti-VacA IgY was produced from egg yolks of hens immunized with a mixture of two purified recombinant VacAs. Female C57BL/6 mice were supplemented anti-VacA IgY daily with drinking water for 2 weeks before and 4 weeks after H. pylori ATCC 43504 inoculation. Anti-VacA IgY recognized both native and denatured structures of VacA by enzyme-linked immunosorbent assay and immunoblotting analyses, respectively.ResultsOral administration of anti-VacA IgYs significantly (p < .05) reduced the serum levels of anti-H. pylori antibodies compared to those in the H. pylori-infected, untreated group. The reduction in the immune response was accompanied by a significant (p < .05) decrease in eosinophilic infiltration of the stomach in anti-VacA IgY treated group compared to other groups. Concomitantly, H. pylori–induced histological changes and H. pylori antigen-positivity in gastric tissues were decreased significantly (p < .05) in anti-VacA IgY treated group similar to the control group.ConclusionsOral administration of anti-VacA IgY is correlated with a protective effect against H. pylori colonization and induced histological changes in gastric tissues. Our experimental study has proved that it is expected to be a new drug candidate of Hp infection by further study.
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One or two doses of live varicella virus-containing vaccines: Efficacy, persistence of immune responses, and safety six years after administration in healthy children during their second year of life
Source:Vaccine, Volume 36, Issue 3
Author(s): Ouzama Henry, Jerzy Brzostek, Hanna Czajka, Giedra Leviniene, Olga Reshetko, Roberto Gasparini, Petr Pazdiora, Doina Plesca, Maria Giuseppina Desole, Rimantas Kevalas, Giovanni Gabutti, Michael Povey, Bruce Innis
BackgroundThis phase III B follow-up of an initial multicenter study (NCT00226499) will evaluate the ten-year efficacy of two doses of the combined measles-mumps-rubella-varicella vaccine (MMRV) and one dose of the live attenuated varicella vaccine (V) versus a measles-mumps-rubella control group (MMR) for the prevention of clinical varicella disease. Here we present efficacy results for six years post-vaccination.MethodsIn phase A of the study, healthy children aged 12–22 months from ten European countries were randomized (3:3:1) and received either two doses of MMRV, or one dose of combined MMR and one dose of monovalent varicella vaccine (MMR+V), or two doses of the MMR vaccine (control), 42 days apart. Vaccine efficacy against all and against moderate or severe varicella (confirmed by detection of viral DNA or epidemiological link) was assessed from six weeks up to six years post-dose 2 for the MMRV and MMR+V groups, and was calculated with 95% confidence intervals (CI). The severity of varicella was calculated using the modified Vázquez scale (mild ≤ 7; moderately severe = 8–15; severe ≥ 16). Herpes zoster cases were also recorded.Results5289 children (MMRV = 2279, mean age = 14.2, standard deviation [SD] = 2.5; MMR+V = 2266, mean age = 14.2, SD = 2.4; MMR = 744, mean age = 14.2, SD = 2.5 months) were included in the efficacy cohort. 815 varicella cases were confirmed. Efficacy of two doses of MMRV against all and against moderate or severe varicella was 95.0% (95% CI: 93.6–96.2) and 99.0% (95% CI: 97.7–99.6), respectively. Efficacy of one dose of varicella vaccine against all and against moderate or severe varicella was 67.0% (95% CI: 61.8–71.4) and 90.3% (95% CI: 86.9–92.8), respectively. There were four confirmed herpes zoster cases (MMR+V = 2, MMR = 2), all were mild and three tested positive for the wild-type virus.ConclusionsTwo doses of the MMRV vaccine and one dose of the varicella vaccine remain efficacious through six years post-vaccination.
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Oral administration of PLGA-encapsulated CpG ODN and Campylobacter jejuni lysate reduces cecal colonization by Campylobacter jejuni in chickens
Source:Vaccine, Volume 36, Issue 3
Author(s): Khaled Taha-Abdelaziz, Douglas C. Hodgins, Tamiru Negash Alkie, Wanderely Quinteiro-Filho, Alexander Yitbarek, Jake Astill, Shayan Sharif
Campylobacter jejuni (C. jejuni) is a major cause of bacterial food-borne illness in humans. It is considered a commensal organism of the chicken gut and infected chickens serve as a reservoir and shed bacteria throughout their lifespan. Contaminated poultry products are considered the major source of infection in humans. Therefore, to reduce the risk of human campylobacteriosis, it is essential to reduce the bacterial load in poultry products. The present study aimed to evaluate the protective effects of soluble and PLGA-encapsulated oligodeoxynucleotides (ODN) containing unmethylated CpG motifs (E-CpG ODN) as well as C. jejuni lysate as a multi-antigen vaccine against colonization with C. jejuni. The results revealed that oral administration of a low (5 µg) or high (50 µg) dose of CpG resulted in a significant reduction in cecal C. jejuni colonization by 1.23 and 1.32 log10 (P < .05) in layer chickens, respectively, whereas E-CpG significantly reduced cecal C. jejuni colonization by 1.89 and 1.46 log10 in layer and broiler chickens at day 22 post-infection (slaughter age in broilers), respectively. Similar patterns were observed for C. jejuni lysate; oral administration of C. jejuni lysate reduced the intestinal burden of C. jejuni in layer and broiler chickens by 2.24 and 2.14 log10 at day 22 post-infection, respectively. Moreover, the combination of E-CpG and C. jejuni lysate reduced bacterial counts in cecal contents by 2.42 log10 at day 22 post-infection in broiler chickens. Anti-C. jejuni IgG antibody (Ab) titers were significantly higher for broiler chickens receiving a low or high dose of E-CpG or a low dose of C. jejuni lysate than for chickens receiving the placebo. Furthermore, a positive correlation was observed between serum IgG Ab titers and cecal counts of C. jejuni in these groups. These findings suggest that PLGA-encapsulated CpG or C. jejuni lysate could be a promising strategy for control of C. jejuni in chickens.
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Implementing a province-wide mandatory vaccinate-or-mask policy at healthcare facilities in British Columbia, Canada
Source:Vaccine, Volume 36, Issue 3
Author(s): Alexandra Nunn, Audrey C. Campbell, Monika Naus, Jeffrey C. Kwong, David Puddicombe, Susan Quach, Bonnie Henry
ObjectivesIn 2012, British Columbia (BC) became the first Canadian province to implement an influenza prevention policy requiring healthcare workers (HCW) to either be vaccinated annually against influenza or wear a mask in patient care areas during the influenza season. This study describes an evaluation of influenza policy implementation processes and identifies supports and challenges related to successful policy implementation at the level of healthcare facilities, during the second policy year (2013/14).MethodsImplementation leaders from 262 long-term care (LTC) and acute care facilities, mostly in three of BC's five regional Health Authorities, were invited to participate in an online survey following the 2013/14 influenza season. Descriptive quantitative and qualitative analyses identified common and effective strategies for improving vaccination coverage and policy compliance.ResultsA total of 127 respondents completed the survey on behalf of 33 acute care and 99 LTC facilities, representing 36% of acute care and 27% of LTC facilities in BC. Respondents agreed that the policy was successfully implemented at 89% of facilities, and implementation was reported to be easy at 52% of facilities. The findings elaborate on communication and leadership strategies, campaign logistics and enforcement approaches involved in policy implementation.ConclusionImplementation of a vaccinate-or-mask influenza policy is complex. This study provides insight for other jurisdictions considering implementing such a policy and offers practical recommendations for facilities and health authorities.
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Efficacy of an inactivated Mycoplasma hyorhinis vaccine in pigs
Publication date: 8 January 2018
Source:Vaccine, Volume 36, Issue 3
Author(s): Brian Martinson, Whitney Zoghby, Kenneth Barrett, Lawrence Bryson, Rodney Christmas, F.C. Minion, Jeremy Kroll
Lameness and polyserositis in pigs caused by Mycoplasma hyorhinis are generally treated with antibiotics and may require multiple doses. The costs of these antibiotics combined with economic losses from culling and reduced feed conversion due to lameness are hardships to the swine producer. In this study we have demonstrated efficacy of an inactivated M. hyorhinis vaccine administered to three-week old caesarian-derived colostrum-deprived piglets. Three doses of vaccine (high, medium, and low) were evaluated and compared to a placebo control. Mycoplasma hyorhinis challenge occurred three weeks after vaccination. Pigs were observed for lameness and respiratory distress for three weeks following challenge. Pigs were then euthanized and a gross pathological evaluation for polyserositis and arthritis was performed. A minimum immunizing dose of vaccine was defined as containing at least 7.41 × 107 CCU of M. hyorhinis per 2.0 mL dose as represented by the medium dose vaccine. This vaccine provided significant reductions in lameness and pericarditis with preventive fractions of 0.76 (95% CI [0.26, 0.92]) and 0.58 (95% CI [0.31, 0.74]), respectively, compared to the placebo control group. A significant increase in post-challenge weight gain (P < .0001) was also achieved with this vaccine, with an average daily gain (ADG) of 0.92 lbs/day compared to 0.57 lbs/day in the placebo group.
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Cost-effectiveness of dengue vaccination in ten endemic countries
Publication date: 8 January 2018
Source:Vaccine, Volume 36, Issue 3
Author(s): Wu Zeng, Yara A. Halasa-Rappel, Nicolas Baurin, Laurent Coudeville, Donald S. Shepard
Following publication of results from two phase-3 clinical trials in 10 countries or territories, endemic countries began licensing the first dengue vaccine in 2015. Using a published mathematical model, we evaluated the cost-effectiveness of dengue vaccination in populations similar to those at the trial sites in those same Latin American and Asian countries. Our main scenarios (30-year horizon, 80% coverage) entailed 3-dose routine vaccinations costing US$20/dose beginning at age 9, potentially supplemented by catch-up programs of 4- or 8-year cohorts. We obtained illness costs per case, dengue mortality, vaccine wastage, and vaccine administration costs from the literature. We estimated that routine vaccination would reduce yearly direct and indirect illness cost per capita by 22% (from US$10.51 to US$8.17) in the Latin American countries and by 23% (from US$5.78 to US$4.44) in the Asian countries. Using a health system perspective, the incremental cost-effectiveness ratio (ICER) averaged US$4,216/disability-adjusted life year (DALY) averted in the five Latin American countries (range: US$666/DALY in Puerto Rico to US$5,865/DALY in Mexico). In the five Asian countries, the ICER averaged US$3,751/DALY (range: US$1,935/DALY in Malaysia to US$5,101/DALY in the Philippines). From a health system perspective, the vaccine proved to be highly cost effective (ICER under one times the per capita GDP) in seven countries and cost effective (ICER 1–3 times the per capita GDP) in the remaining three countries. From a societal perspective, routine vaccination proved cost-saving in three countries. Including catch-up campaigns gave similar ICERs. Thus, this vaccine could have a favorable economic value in sites similar to those in the trials.
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Incidence of invasive pneumococcal disease before and during an era of use of three different pneumococcal conjugate vaccines in Quebec
Source:Vaccine, Volume 36, Issue 3
Author(s): Philippe De Wals, Brigitte Lefebvre, Geneviève Deceuninck, Jean Longtin
BackgroundIn Quebec, 7-valent (PCV7), 10-valent (PCV10) and 13-valent (PCV13) pneumococcal conjugate vaccines were successively used for the immunization of children according to a 2+1 doses schedule.ObjectiveOur aim was to assess the impact of this program on the epidemiology of invasive pneumococcal disease (IPD) in children and adults.MethodsNotification and laboratory surveillance data were analyzed and the immunization status of IPD cases in children was checked.ResultsIn children < 5 years, the IPD rate decreased from 69/100,000 in 2003 to 12/100,000 in 2016 (83% reduction). Following PCV7 introduction in 2004, there has been a rapid decline in PCV7-type IPD cases and 6A. 7F and 19A serotypes emerged but their incidence decreased following PCV10 introduction in 2009 and PCV13 in 2011, whereas decrease in serotype 3 IPD was modest. Non-PCV13 types increased and represented 79% of cases in 2016. The same pattern was seen in adults but replacement was complete and there was no decrease in overall IPD rate. In those 65 years and over, PCV13 serotypes represented 28% of cases in 2016 and 62% were serotypes included in the 23-valent polysaccharide vaccine. Out of 10 IPD cases caused by serotype 3 in children vaccinated with PCV13 in 2011–2016, 6 occurred more than one year following the booster dose, which suggests short-term protection. Out of 31 breakthrough 19A cases, 19 occurred in children aged between 8 and 14 months who had received the 2 primary PCV13 doses but not the toddler booster dose, which suggests a window of susceptibility in a 2+1 schedule.ConclusionPCVs had a major impact on the IPD rate in children but not in adults. Among elderly adults, the proportion of cases caused by serotypes included in PCV13 is diminishing year after year but a majority of cases remains covered by the 23-valent polysaccharide vaccine.
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Immune response profiling of primary monocytes and oral keratinocytes to different Tannerella forsythia strains and their cell surface mutants
Summary
The oral pathogen Tannerella forsythia possesses a unique surface (S-) layer with a complex O-glycan containing a bacterial sialic acid mimic in the form of either pseudaminic acid or legionaminic acid at its terminal position. We hypothesize that different T. forsythia strains employ these stereoisomeric sugar acids for interacting with the immune system and resident host tissues in the periodontium. Here, we show how T. forsythia strains ATCC 43037 and UB4, displaying pseudaminic acid and legionaminic acid, respectively, and selected cell surface mutants of these strains, modulate the immune response in monocytes and human oral keratinocytes (HOK) using a multiplex immunoassay. When challenged with T. forsythia, monocytes secrete pro-inflammatory cytokines, chemokines and VEGF with the release of IL-1β and IL-7 being differentially regulated by the two T. forsythia wild-type strains. Truncation of the bacteria's O-glycan leads to significant reduction of IL-1β and regulates MIP-1. HOK infected with T. forsythia produce IL-1Ra, chemokines and VEGF. While the two wild-type strains elicit preferential immune responses for IL-8, both truncation of the O-glycan and deletion of the S-layer results in significantly increased release of IL-8, GM-CSF and MCP-1. Through immunofluorescence and confocal laser scanning microscopy of infected HOK we additionally show that T. forsythia is highly invasive and tends to localize to the perinuclear region. This indicates, that the T. forsythia S-layer and attached sugars, particularly pseudaminic acid in ATCC 43037, contribute to dampening the response of epithelial tissues to initial infection and, therefore, play a pivotal role in orchestrating the bacterium's virulence.
This article is protected by copyright. All rights reserved.
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A spatio-temporal reference model of the aging brain
Source:NeuroImage, Volume 169
Author(s): W. Huizinga, D.H.J. Poot, M.W. Vernooij, G.V. Roshchupkin, E.E. Bron, M.A. Ikram, D. Rueckert, W.J. Niessen, S. Klein
Both normal aging and neurodegenerative disorders such as Alzheimer's disease (AD) cause morphological changes of the brain. It is generally difficult to distinguish these two causes of morphological change by visual inspection of magnetic resonance (MR) images. To facilitate making this distinction and thus aid the diagnosis of neurodegenerative disorders, we propose a method for developing a spatio-temporal model of morphological differences in the brain due to normal aging. The method utilizes groupwise image registration to characterize morphological variation across brain scans of people with different ages. To extract the deformations that are due to normal aging we use partial least squares regression, which yields modes of deformations highly correlated with age, and corresponding scores for each input subject. Subsequently, we determine a distribution of morphologies as a function of age by fitting smooth percentile curves to these scores. This distribution is used as a reference to which a person's morphology score can be compared. We validate our method on two different datasets, using images from both cognitively normal subjects and patients with Alzheimer disease (AD). Results show that the proposed framework extracts the expected atrophy patterns. Moreover, the morphology scores of cognitively normal subjects are on average lower than the scores of AD subjects, indicating that morphology differences between AD subjects and healthy subjects can be partly explained by accelerated aging. With our methods we are able to assess accelerated brain aging on both population and individual level. A spatio-temporal aging brain model derived from 988 T1-weighted MR brain scans from a large population imaging study (age range 45.9–91.7y, mean age 68.3y) is made publicly available at www.agingbrain.nl.
http://ift.tt/2C0qWqC
Interocular interaction of contrast and luminance signals in human primary visual cortex
Source:NeuroImage, Volume 167
Author(s): E. Chadnova, A. Reynaud, S. Clavagnier, D.H. Baker, S. Baillet, R.F. Hess
Interocular interaction in the visual system occurs under dichoptic conditions when contrast and luminance are imbalanced between the eyes. Human psychophysical investigations suggest that interocular interaction can be explained by a contrast normalization model. However, the neural processes that underlie such interactions are still unresolved. We set out to assess, for the first time, the proposed normalization model of interocular contrast interactions using magnetoencephalography (MEG) and to extend this model to incorporate interactions based on interocular luminance differences. We used MEG to record steady-state visual evoked responses (SSVER), and functional magnetic resonance imaging (fMRI) to obtain individual retinotopic maps that we used in combination with MEG source imaging in healthy participants. Binary noise stimuli were presented in monocular or dichoptic viewing and were frequency-tagged at 4 and 6 Hz. The contrast of the stimuli was modulated in a range between 0 and 32%. Monocularly, we reduced the luminance by placing a 1.5 ND filter over one eye in the maximal contrast condition. This ND filter reduces the mean light level by a factor of 30 without any alteration to the physical contrast.We observed in visual area V1 a monotonic increase in the magnitude of SSVERs with changes in contrast from 0 to 32%. For both eyes, dichoptic masking induced a decrease in SSVER signal power. This power decrease was well explained by the normalization model. Reducing mean luminance delayed monocular processing by approximately 38 ms in V1. The reduced luminance also decreased the masking ability of the eye under the filter. Predictions based on a temporal filtering model for the interocular luminance difference prior to the model's binocular combination stage were incorporated to update the normalization model. Our results demonstrate that the signals resulting from different contrast or luminance stimulation of the two eyes are combined in a way that can be explained by an interocular normalization model.
http://ift.tt/2BXy1si
The z-spectrum from human blood at 7T
Source:NeuroImage, Volume 167
Author(s): Simon M. Shah, Olivier E. Mougin, Andrew J. Carradus, Nicolas Geades, Richard Dury, William Morley, Penny A. Gowland
Chemical Exchange Saturation Transfer (CEST) has been used to assess healthy and pathological tissue in both animals and humans. However, the CEST signal from blood has not been fully assessed. This paper presents the CEST and nuclear Overhauser enhancement (NOE) signals detected in human blood measured via z-spectrum analysis. We assessed the effects of blood oxygenation levels, haematocrit, cell structure and pH upon the z-spectrum in ex vivo human blood for different saturation powers at 7T. The data were analysed using Lorentzian difference (LD) model fitting and AREX (to compensate for changes in T1), which have been successfully used to study CEST effects in vivo. Full Bloch-McConnell fitting was also performed to provide an initial estimate of exchange rates and transverse relaxation rates of the various pools. CEST and NOE signals were observed at 3.5 ppm, −1.7 ppm and −3.5 ppm and were found to originate primarily from the red blood cells (RBCs), although the amide proton transfer (APT) CEST effect, and NOEs showed no dependence upon oxygenation levels. Upon lysing, the APT and NOE signals fell significantly. Different pH levels in blood resulted in changes in both the APT and NOE (at −3.5 ppm), which suggests that this NOE signal is in part an exchange relayed process. These results will be important for assessing in vivo z-spectra.
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Diffusion MRI and MR spectroscopy reveal microstructural and metabolic brain alterations in chronic mild stress exposed rats: A CMS recovery study
Source:NeuroImage, Volume 167
Author(s): Ahmad Raza Khan, Brian Hansen, Ove Wiborg, Christopher D. Kroenke, Sune Nørhøj Jespersen
Chronic mild stress (CMS) induced depression elicits several debilitating symptoms and causes a significant economic burden on society. High variability in the symptomatology of depression poses substantial impediment to accurate diagnosis and therapy outcome. CMS exposure induces significant metabolic and microstructural alterations in the hippocampus (HP), prefrontal cortex (PFC), caudate-putamen (CP) and amygdala (AM), however, recovery from these maladaptive changes are limited and this may provide negative effects on the therapeutic treatment and management of depression. The present study utilized anhedonic rats from the unpredictable CMS model of depression to study metabolic recovery in the ventral hippocampus (vHP) and microstructural recovery in the HP, AM, CP, and PFC. The study employed 1H MR spectroscopy (1H MRS) and in-vivo diffusion MRI (d-MRI) at the age of week 18 (week 1 post CMS exposure) week 20 (week 3 post CMS) and week 25 (week 8 post CMS exposure) in the anhedonic group, and at the age of week 18 and week 22 in the control group. The d-MRI data have provided an array of diffusion tensor metrics (FA, MD, AD, and RD), and fast kurtosis metrics (MKT, WL and WT). CMS exposure induced a significant metabolic alteration in vHP, and significant microstructural alterations were observed in the HP, AM, and PFC in comparison to the age match control and within the anhedonic group. A significantly high level of N-acetylaspartate (NAA) was observed in vHP at the age of week 18 in comparison to age match control and week 20 and week 25 of the anhedonic group. HP and AM showed significant microstructural alterations up to the age of week 22 in the anhedonic group. PFC showed significant microstructural alterations only at the age of week 18, however, most of the metrics showed significantly higher value at the age of week 20 in the anhedonic group. The significantly increased NAA concentration may indicate impaired catabolism due to astrogliosis or oxidative stress. The significantly increased WL in the AM and HP may indicate hypertrophy of AM and reduced volume of HP. Such metabolic and microstructural alterations could be useful in disease diagnosis and follow-up treatment intervention in depression and similar disorders.
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Dynamic phase alignment of ongoing auditory cortex oscillations
Source:NeuroImage, Volume 167
Author(s): Anna-Katharina R. Bauer, Martin G. Bleichner, Manuela Jaeger, Jeremy D. Thorne, Stefan Debener
Neural oscillations can synchronize to external rhythmic stimuli, as for example in speech and music. While previous studies have mainly focused on elucidating the fundamental concept of neural entrainment, less is known about the time course of entrainment. In this human electroencephalography (EEG) study, we unravel the temporal evolution of neural entrainment by contrasting short and long periods of rhythmic stimulation. Listeners had to detect short silent gaps that were systematically distributed with respect to the phase of a 3 Hz frequency-modulated tone. We found that gap detection performance was modulated by the stimulus stream with a consistent stimulus phase across participants for short and long stimulation. Electrophysiological analysis confirmed neural entrainment effects at 3 Hz and the 6 Hz harmonic for both short and long stimulation lengths. 3 Hz source level analysis revealed that longer stimulation resulted in a phase shift of a participant's neural phase relative to the stimulus phase. Phase coupling increased over the first second of stimulation, but no effects for phase coupling strength were observed over time. The dynamic evolution of phase alignment suggests that the brain attunes to external rhythmic stimulation by adapting the brain's internal representation of incoming environmental stimuli.
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A common neural network differentially mediates direct and social fear learning
Source:NeuroImage, Volume 167
Author(s): Björn Lindström, Jan Haaker, Andreas Olsson
Across species, fears often spread between individuals through social learning. Yet, little is known about the neural and computational mechanisms underlying social learning. Addressing this question, we compared social and direct (Pavlovian) fear learning showing that they showed indistinguishable behavioral effects, and involved the same cross-modal (self/other) aversive learning network, centered on the amygdala, the anterior insula (AI), and the anterior cingulate cortex (ACC). Crucially, the information flow within this network differed between social and direct fear learning. Dynamic causal modeling combined with reinforcement learning modeling revealed that the amygdala and AI provided input to this network during direct and social learning, respectively. Furthermore, the AI gated learning signals based on surprise (associability), which were conveyed to the ACC, in both learning modalities. Our findings provide insights into the mechanisms underlying social fear learning, with implications for understanding common psychological dysfunctions, such as phobias and other anxiety disorders.
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Loss of consciousness is related to hyper-correlated gamma-band activity in anesthetized macaques and sleeping humans
Source:NeuroImage, Volume 167
Author(s): Michał Bola, Adam B. Barrett, Andrea Pigorini, Lino Nobili, Anil K. Seth, Artur Marchewka
Loss of consciousness can result from a wide range of causes, including natural sleep and pharmacologically induced anesthesia. Important insights might thus come from identifying neuronal mechanisms of loss and re-emergence of consciousness independent of a specific manipulation. Therefore, to seek neuronal signatures of loss of consciousness common to sleep and anesthesia we analyzed spontaneous electrophysiological activity recorded in two experiments. First, electrocorticography (ECoG) acquired from 4 macaque monkeys anesthetized with different anesthetic agents (ketamine, medetomidine, propofol) and, second, stereo-electroencephalography (sEEG) from 10 epilepsy patients in different wake-sleep stages (wakefulness, NREM, REM). Specifically, we investigated co-activation patterns among brain areas, defined as correlations between local amplitudes of gamma-band activity. We found that resting wakefulness was associated with intermediate levels of gamma-band coupling, indicating neither complete dependence, nor full independence among brain regions. In contrast, loss of consciousness during NREM sleep and propofol anesthesia was associated with excessively correlated brain activity, as indicated by a robust increase of number and strength of positive correlations. However, such excessively correlated brain signals were not observed during REM sleep, and were present only to a limited extent during ketamine anesthesia. This might be related to the fact that, despite suppression of behavioral responsiveness, REM sleep and ketamine anesthesia often involve presence of dream-like conscious experiences. We conclude that hyper-correlated gamma-band activity might be a signature of loss of consciousness common across various manipulations and independent of behavioral responsiveness.
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Sensory and semantic activations evoked by action attributes of manipulable objects: Evidence from ERPs
Source:NeuroImage, Volume 167
Author(s): Chia-lin Lee, Hsu-Wen Huang, Kara D. Federmeier, Laurel J. Buxbaum
"Two route" theories of object-related action processing posit different temporal activation profiles of grasp-to-move actions (rapidly evoked based on object structure) versus skilled use actions (more slowly activated based on semantic knowledge). We capitalized on the exquisite temporal resolution and multidimensionality of Event-Related Potentials (ERPs) to directly test this hypothesis. Participants viewed manipulable objects (e.g., calculator) preceded by objects sharing either "grasp", "use", or no action attributes (e.g., bar of soap, keyboard, earring, respectively), as well as by action-unrelated but taxonomically-related objects (e.g., abacus); participants judged whether the two objects were related. The results showed more positive responses to "grasp-to-move" primed objects than "skilled use" primed objects or unprimed objects starting in the P1 (0–150 ms) time window and continuing onto the subsequent N1 and P2 components (150–300 ms), suggesting that only "grasp-to-move", but not "skilled use", actions may facilitate visual attention to object attributes. Furthermore, reliably reduced N400s (300–500 ms), an index of semantic processing, were observed to taxonomically primed and "skilled use" primed objects relative to unprimed objects, suggesting that "skilled use" action attributes are a component of distributed, multimodal semantic representations of objects. Together, our findings provide evidence supporting two-route theories by demonstrating that "grasp-to-move" and "skilled use" actions impact different aspects of object processing and highlight the relationship of "skilled use" information to other aspects of semantic memory.
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Resting-state functional connectivity remains unaffected by preceding exposure to aversive visual stimuli
Source:NeuroImage, Volume 167
Author(s): Léonie Geissmann, Leo Gschwind, Nathalie Schicktanz, Gunnar Deuring, Timm Rosburg, Kyrill Schwegler, Christiane Gerhards, Annette Milnik, Marlon O. Pflueger, Ralph Mager, Dominique J.F. de Quervain, David Coynel
While much is known about immediate brain activity changes induced by the confrontation with emotional stimuli, the subsequent temporal unfolding of emotions has yet to be explored. To investigate whether exposure to emotionally aversive pictures affects subsequent resting-state networks differently from exposure to neutral pictures, a resting-state fMRI study implementing a two-group repeated-measures design in healthy young adults (N = 34) was conducted. We focused on investigating (i) patterns of amygdala whole-brain and hippocampus connectivity in both a seed-to-voxel and seed-to-seed approach, (ii) whole-brain resting-state networks with an independent component analysis coupled with dual regression, and (iii) the amygdala's fractional amplitude of low frequency fluctuations, all while EEG recording potential fluctuations in vigilance. In spite of the successful emotion induction, as demonstrated by stimuli rating and a memory-facilitating effect of negative emotionality, none of the resting-state measures was differentially affected by picture valence. In conclusion, resting-state networks connectivity as well as the amygdala's low frequency oscillations appear to be unaffected by preceding exposure to widely used emotionally aversive visual stimuli in healthy young adults.
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Repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex modulates value-based learning during sequential decision-making
Source:NeuroImage, Volume 167
Author(s): Lennart Wittkuhn, Ben Eppinger, Lea M. Bartsch, Franka Thurm, Franziska M. Korb, Shu-Chen Li
Adaptive behavior in daily life often requires the ability to acquire and represent sequential contingencies between actions and the associated outcomes. Although accumulating evidence implicates the role of dorsolateral prefrontal cortex (dlPFC) in complex value-based learning and decision-making, direct evidence for involvements of this region in integrating information across sequential decision states is still scarce. Using a 3-stage deterministic Markov decision task, here we applied offline, inhibitory low-frequency 1-Hz repetitive transcranial magnetic stimulation (rTMS) over the left dlPFC in young male adults (n = 31, mean age = 23.8 years, SD = 2.5 years) in a within-subject cross-over design to study the roles of this region in influencing value-based sequential decision-making. In two separate sessions, each participant received 1-Hz rTMS stimulation either over the left dlPFC or over the vertex. The results showed that transiently inhibiting the left dlPFC impaired choice accuracy, particularly in situations in which the acquisition of sequential transitions between decision states and temporally lagged action-outcome contingencies played a greater role. Estimating parameters of a diffusion model from behavioral choices, we found that the diffusion drift rate, which reflects the efficiency of information integration, was attenuated by the stimulation. Moreover, the effects of rTMS interacted with session: individuals who could not efficiently integrate information across sequential states in the first session due to disrupted dlPFC function also could not catch up in performance during the second session with those individuals who could learn sequential transitions with intact dlPFC function in the first session. Taken together, our findings suggest that the left dlPFC is crucially involved in the acquisition of complex sequential relations and in the potential of such learning.
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Quantitative EEG power and synchronization correlate with Alzheimer's disease CSF biomarkers
Source:Neurobiology of Aging, Volume 63
Author(s): Una Smailovic, Thomas Koenig, Ingemar Kåreholt, Thomas Andersson, Milica Gregoric Kramberger, Bengt Winblad, Vesna Jelic
Synaptic dysfunction is the best anatomical correlate of early cognitive impairment in Alzheimer's disease (AD). Electroencephalography (EEG) directly reflects brain electrical activity at the level of synapses. The aim of the present study was to investigate correlations of quantitative EEG measures, global field power (GFP) and global field synchronization (GFS), with conventional cerebrospinal fluid (CSF) biomarkers of neurodegeneration in patients diagnosed with subjective cognitive decline (n = 210), mild cognitive impairment (n = 230), and AD (n = 197). Decreased CSF amyloid β42 significantly correlated with increased theta and delta GFP, whereas increased p- and t-tau with decreased alpha and beta GFP. Decreased CSF amyloid β42 and increased p- and t-tau were significantly associated with decreased GFS alpha and beta. Subanalysis of the separate diagnostic groups demonstrated significant correlations between CSF biomarkers and generalized power and synchronization already in the subjective cognitive decline and MCI group. These results provide evidence that quantitative EEG measures are associated and possibly sensitive to distinct AD-like CSF biomarker profiles in cognitively impaired patients and are therefore promising early noninvasive markers of AD.
http://ift.tt/2BYcjEB
Similar effect of CRF1 and CRF2 receptor in the basolateral or central nuclei of the amygdala on tonic immobility behavior.
Source:Brain Research Bulletin
Author(s): Richard Leandro Spinieli, Christie Ramos Andrade Leite-Panissi
Studies have used paradigms based on animal models to understand human emotional behavior because they appear to be correlated with fear- and anxiety-related defensive patterns in non-human mammals. In this context, tonic immobility (TI) behavior is an innate response associated with extreme threat situations, such as predator attack. Some reports have demonstrated the involvement of corticotropin-releasing factor (CRF) in regulation of the endocrine system, defensive behaviors and behavioral responses to stress. Particularly, a previous study showed that the activation of CRF receptors in the basolateral (BLA) or central (CeA) nuclei of the amygdala increased TI responses, whereas treatment with a non-selective CRF antagonist, alpha-helical-CRF9-41, decreased this innate fear response. However, while CRF1 receptors have pronounced effects in stress-induced anxiety, CRF2 receptors appear be involved in the expression of both stress-induced anxiety and spontaneous anxiety behavior. In this study, we investigated the effects of specific CRF receptors, CRF1 and CRF2, in the BLA and CeA on the duration of TI in guinea pigs. The results show that blockade of CRF1 and CRF2 receptors in the BLA and CeA produces a decrease in fear and/or anxiety, as suggested by a decrease in TI duration in the guinea pigs. Additionally, the specific antagonists for CRF1 and CRF2 receptors were able to prevent the increase in TI duration induced by CRF administration at the same sites. These results suggest that the modulation of fear and anxiety by the CRF system in the BLA and CeA occurs through concomitant effects on CRF1 and CRF2 receptors.
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Chronic adolescent morphine exposure alters the responses of lateral paragigantocellular neurons to acute morphine administration in adulthood
Source:Brain Research Bulletin
Author(s): Hamed Salmanzadeh, Hossein Azizi, S. Mohammad Ahmadi Soleimani, Narges Pachenari, Saeed Semnanian
Accumulating evidence support the growing non-medical use of morphine during adolescence. Despite this concern which has recently been addressed in some studies, cellular mechanisms underlying the long-term neurobiological and behavioral effects of opiate exposure during this critical period are still remained largely unexplored. Several reports have proposed that subtle long-lasting neurobiological alterations might be triggered by exposure to opiate derivatives or drugs of abuse particularly when this occurs during a critical phase of brain maturation such as adolescence. The present study was designed to investigate how chronic adolescent morphine exposure could affect the responsiveness of lateral paragigantocellular (LPGi) neurons to acute morphine administration in adult rats. Male Wistar rats received chronic escalating morphine or saline during adolescence (30-39d) for 10 days. During adulthood (65d), the extracellular unit activities of LPGi neurons were recorded in urethane-anesthetized animals. Results indicated that adolescent morphine treatment enhances the baseline activity of LPGi neurons. In addition, morphine-induced inhibition of spontaneous discharge rate was potentiated in adult rats received morphine during adolescence. However, this pretreatment did not affect the extent of morphine excitatory effect, onset or peak of cellular response and regularity of unit discharge in LPGi neurons. Our study supports the hypothesis that adolescent morphine exposure induces long-lasting neurophysiological alterations in brain regions known to play a role in mediating opiate effects. This finding sheds light on the possible effect of opiate pre-exposure on addiction susceptibility in future.
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Influence of the anteromedial thalamus on social defeat-associated contextual fear memory
Source:Behavioural Brain Research, Volume 339
Author(s): Miguel J. Rangel, Marcus Vinicius C. Baldo, Newton Sabino Canteras
The ventral part of the anteromedial thalamic nucleus (AMv) is heavily targeted by the dorsal premammillary nucleus (PMd), which is the main hypothalamic site that is responsive to both predator and conspecific aggressor threats. This PMd-AMv pathway is likely involved in modulating memory processing, and previous findings from our group have shown that cytotoxic lesions or pharmacological inactivation of the AMv drastically reduced contextual fear responses to predator-associated environments. In the present study, we investigated the role of the AMv in both unconditioned (i.e., fear responses during social defeat) and contextual fear responses (i.e., during exposure to a social defeat-associated context). We addressed this question by placing N-methyl-d-aspartate (NMDA) lesions in the AMv and testing unconditioned fear responses during social defeat and contextual fear responses during exposure to a social defeat-associated context. Accordingly, bilateral AMv lesions did not change unconditioned responses, but decreased contextual conditioning related to social defeat. Notably, our bilateral AMv lesions also included, to a certain degree, the nucleus reuniens (RE), but single RE lesions did not affect innate or contextual fear responses. Overall, our results support the idea that the AMv works as a critical hub, receiving massive inputs from a hypothalamic site that is largely responsive to social threats and transferring social threat information to circuits involved in the processing of contextual fear memories.
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Diabetes mellitus and Alzheimer’s disease: GSK-3β as a potential link
Source:Behavioural Brain Research, Volume 339
Author(s): Ying Zhang, Nan-qu Huang, Fei Yan, Hai Jin, Shao-yu Zhou, Jing-shan Shi, Feng Jin
It is well known that Alzheimer's disease (AD) is closely related to diabetes mellitus (DM), and AD is also regarded as Type 3 diabetes (T3D). However, the exact link between AD and DM is still unclear. Recently, more and more evidence has shown that glycogen synthase kinase-3β (GSK-3β) may be the potential link between DM and AD. In DM, GSK-3β is the crucial enzyme of glycogen synthesis, which plays a key role in regulating blood glucose. More importantly, GSK-3β is one of the key factors leading to insulin deficiency and insulin resistance, and insulin resistance is an important hallmark of the occurrence and development of DM. In AD, GSK-3β plays an important role in hyperphosphorylation of microtubule-associated protein tau (tau), which is one of the pathological features in AD. GSK-3β is one of the important kinases of tau phosphorylation and is involved in the insulin/phosphoinositide 3-kinase/protein kinase B (insulin/PI3K/Akt) signaling pathway. Dysfunction of the insulin/PI3K/Akt signaling pathway, which regulates glucose metabolism in the brain, can lead to tau hyperphosphorylation in the brain of AD patents. Additionally, insulin resistance in DM may cause β-amyloid (Aβ) deposition, which will be cleared by tau, but excessive phosphorylation of tau will further aggravate the neurotoxicity; then damage the brain and affect the cognitive function. GSK-3β is considered as a common kinase in insulin signaling transduction and tau protein phosphorylation, so we have reasons to believe that GSK-3β is a potential link between DM and AD.
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REM sleep deprivation and dopaminergic D2 receptors modulation increase recognition memory in an animal model of Parkinson’s disease
Source:Behavioural Brain Research, Volume 339
Author(s): Adriano D.S. Targa, Ana Carolina D. Noseda, Lais S. Rodrigues, Mariana F. Aurich, Marcelo M.S. Lima
Cognitive impairment is an important non-motor symptom of Parkinson's disease (PD). The neuronal death in nigrostriatal pathway is the main factor for motor symptoms and recent studies indicate a possible influence in non-motor symptoms as well. The pedunculopontine tegmental nucleus (PPT) and basal ganglia are closely related anatomically and functionally and, since they are affected by neurodegeneration in PD, they might be involved in recognition memory. To investigate this, we promoted an ibotenic acid lesion within the PPT or a rotenone lesion within substantia nigra pars compacta (SNpc) of Wistar rats, followed by 24h of REM sleep deprivation (REMSD). Then, we administered a dopaminergic D2 receptor agonist (piribedil, 3μg/μl), antagonist (raclopride, 10μg/μl) or vehicle (dimethylsulfoxide) directly in the striatum and the animals were submitted to the object recognition test (ORT). We observed that raclopride administration impaired object recognition memory as well as rotenone and ibotenic acid lesion. Interestingly, REMSD reversed the deleterious effects induced by these drugs. Also, raclopride administration after rotenone lesion allowed the animal to explore the new object for a longer time compared to the familiar object, suggesting that raclopride has a dual effect, dependent of the treatments. These findings suggest a role for PPT, SNpc and striatum in recognition memory and points the D2 receptors modulation and REMSD as possible targets for cognitive deficits in Parkinson's disease.
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Corrigendum to “Novel images and novel locations of familiar images as sensitive translational cognitive tests in humans” [Behav. Brain Res. 285 (2015) 53–59]
Publication date: 26 February 2018
Source:Behavioural Brain Research, Volume 339
Author(s): Jacob Raber
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Editorial Board
Source:Behavioural Brain Research, Volume 339
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Neuroanatomical correlates of time perspective: A voxel-based morphometry study
Source:Behavioural Brain Research, Volume 339
Author(s): Zhiyi Chen, Yiqun Guo, Tingyong Feng
Previous studies indicated that time perspective can affect many behaviors, such as decisions, risk taking, substance abuse and health behaviors. However, very little is known about the neural substrates of time perspective (TP). To address this question, we characterized different dimensions of TP (including the Past, Present, and Future TP) using standardized Zimbardo Time Perspective Inventory (ZTPI), and quantified the gray matter volume using voxel-based morphometry (VBM) method across two independent samples. Our whole-brain analysis (sample 1, N=150) revealed Past-Negative TP was positively correlated with the GMV of a cluster in LPFC whereas Past-Positive was negatively correlated with the GMV in OFC, and Future TP was negatively correlated with GMV in mPFC. Moreover, two present scales (Present-Hedonistic and Present-Fatalistic TPs) were positively correlated with the GMV of regions in MTG and precuneus, respectively. We further examined the reliability of these correlations between multidimensional TPs and neuroanatomical structures in another independent sample (sample 2, N=58). Results verified our findings that GMV in LPFC could predict Past-Negative TP while GMV in OFC could predict Past-Positive TP, and the GMV in MTG could predict Present-Hedonistic while the GMV in presuneus could predict Present-Fatalistic, as well as the GMV in mPFC could predict Future TP. Thus, our findings suggest that the existence of selective neural basis underlying TPs, and further provide the stable biomarkers for multidimensional TPs.
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Negative transfer effects between reference memory and working memory training in the water maze in C57BL/6 mice
Source:Behavioural Brain Research, Volume 339
Author(s): Lucas Ezequiel Serrano Sponton, Gonzalo Jose Soria, Sylvain Dubroqua, Philipp Singer, Joram Feldon, Pascual A. Gargiulo, Benjamin K. Yee
The water maze is one of the most widely employed spatial learning paradigms in the cognitive profiling of genetically modified mice. Oftentimes, tests of reference memory (RM) and working memory (WM) in the water maze are sequentially evaluated in the same animals. However, critical difference in the rules governing efficient escape from the water between WM and RM tests is expected to promote the adoption of incompatible mnemonic or navigational strategies. Hence, performance in a given test is likely poorer if it follows the other test instead of being conducted first. Yet, the presence of such negative transfer effects (or proactive interference) between WM and RM training in the water maze is often overlooked in the literature. To gauge whether this constitutes a serious concern, the present study determined empirically the magnitude, persistence, and directionality of the transfer effect in wild-type C57BL/6 mice. We contrasted the order of tests between two cohorts of mice. Performance between the two cohorts in the WM and RM tests were then separately compared. We showed that prior training of either test significantly reduced performance in the subsequent one. The statistical effect sizes in both directions were moderate to large. Although extended training could overcome the deficit, it could re-emerge later albeit in a more transient fashion. Whenever RM and WM water maze tests are conducted sequentially in the same animals – regardless of the test order, extra caution is necessary when interpreting the outcomes in the second test. Counterbalancing test orders between animals is recommended.
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Sleep disorder and altered locomotor activity as biomarkers of the Parkinson’s disease cholinopathy in rat
Publication date: 26 February 2018
Source:Behavioural Brain Research, Volume 339
Author(s): Jelena Ciric, Katarina Lazic, Slobodan Kapor, Milka Perovic, Jelena Petrovic, Vesna Pesic, Selma Kanazir, Jasna Saponjic
In order to find out the possible earliest biomarkers of Parkinson's disease (PD) cholinopathy, we followed the impact of bilateral pedunculopontine tegmental nucleus (PPT) lesion in rat on: the cortical and hippocampal sleep/wake states architectures, all sleep states related EEG microstructures, sleep spindles, the basal and stimulated locomotor activity.Sleep and basal locomotor activity in adult Wistar rats were followed during their inactive circadian phase, and throughout the same aging period. The bilateral PPT lesions were done by 0.1M ibotenic acid (IBO) during the surgical procedure for implantation of the electroencephalographic (EEG) and electromyographic (EMG) electrodes for chronic sleep recording. The cholinergic neuronal loss was identified by NADPH – diaphorase histochemistry. After all sleep and behavioral recording sessions, the locomotor activity was stimulated by d-amphetamine (d-AMPH) and the neuronal activity of striatum was followed by c-Fos immunolabeling.Impaired cholinergic innervation from the PPT was expressed earlier as sleep disorder then as movement disorder, and it was the earliest and long-lasting at hippocampal and thalamo-cortical level, and followed by a delayed "hypokinesia". This severe impact of a tonically impaired PPT cholinergic innervation was evidenced as the cholinergic interneuronal loss of the caudate putamen and as a suppressed c-Fos expression after stimulation by d-AMPH.In order how they occurred, the hippocampal non rapid eye movement (NREM) sleep disorder, altered high voltage sleep spindle (HVS) dynamics during rapid eye movement (REM) sleep in the hippocampus and motor cortex, and "hypokinesia" may serve as the biomarkers of PD cholinopathy onset and progression.
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The effect of intravitreal cholinergic drugs on motor control
Source:Behavioural Brain Research, Volume 339
Author(s): Gregory L. Willis, Christopher B. Freelance
The retina bears embryological, neurochemical and functional similarities to the circadian and dopamine systems of the brain. Recent studies have shown that the intravitreal injection of minute quantities of L-dopa and of the melatonin receptor antagonist ML-23 have anti-Parkinsonian potential. Furthermore, it has been suggested that light therapy may be potentially useful in treating some aspects of Parkinson's disease (PD) and it is hypothesized that this treatment works via the circadian system. Given that little is known about the mechanism by which such treatments work the present study was designed to examine the role of the acetyl cholinergic system of the retina in gross bodily movement. While IVIT atropine was shown to improve movement in intact rats Cogentin treated rats showed impairment of motor function compared to control rats or to rats treated with any other cholinergic drug. Furthermore, a link between the phase of the light/dark cycle and the efficacy of these drugs in altering movement was demonstrated. These results show that anticholinergic systems in the retina can exert control over movement which has been solely attributed to the function of deep brain structures.
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White matter integrity mediates decline in age-related inhibitory control
Source:Behavioural Brain Research, Volume 339
Author(s): Peipei Li, Angeliki Tsapanou, Razlighi R. Qolamreza, Yunglin Gazes
Previous DTI studies have reported associations between white matter integrity and performance on the Stroop interference task. The current study aimed to add to these studies of inhibitory control by investigating how the differences in age and in white matter integrity relate to Stroop performance, and to examine whether the effect of age on Stroop performance is mediated by white matter integrity. 179 healthy adults from 20 to 80 years old were recruited in the study. DTI data were processed through TRACULA and the mean fractional anisotropy (FA) of 18 major white matter tracts were extracted and used for statistical analysis. Correlation analysis showed a strong negative relationship between age and the Stroop interference score (IG). Higher IG indicated better inhibitory control. Simple linear regression analyses indicated that most of the tracts showed negative relationships with age, and positive relationships with IG. Moderation effect of age on the relationship between FA and IG was tested on tracts that significantly predicted IG after multiple comparison corrections, but none of these moderations were significant. Then we tested if these tracts mediated the effect of age on IG and found significant indirect effects of age on IG through the FA of the left corticospinal tract and through the right inferior longitudinal fasciculus. Our results highlight the role of a number of major white matter tracts in the processes supporting the Stroop inhibitory performance and further pinpointed the lower white matter integrity of specific tracts as contributors to the decrease in inhibitory control ability associated with the Stroop test in older age.
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Phytochemical allylguaiacol exerts a neuroprotective effect on hippocampal cells and ameliorates scopolamine-induced memory impairment in mice
Source:Behavioural Brain Research, Volume 339
Author(s): Hye-Sun Lim, Bu-Yeo Kim, Yu Jin Kim, Soo-Jin Jeong
Allylguaiacol is a phytochemical occurring in various plants such as cloves, cinnamon, basil, and nutmeg. Pharmacological effects of allylguaiacol include antimicrobial, anti-inflammatory, anticancer, antioxidant, and neuroprotective activity. Although allylguaiacol is considered to have neuroprotective effects, there is no report on its regulatory mechanisms at the molecular level. In the present study, we investigated the mechanisms of allylguaiacol as an antioxidant and neuroprotective agent using hydrogen peroxide (H2O2)-treated HT22 hippocampal cells. Allylguaiacol increased the scavenging activities of free radicals 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH), and enhanced the expression of antioxidant enzymes manganese superoxide dismutase (MnSOD) and catalase. In addition, allylguaiacol inhibited H2O2-induced damage of HT22 with increasing production of brain-derived neurotrophic factor (BDNF), phosphorylation of phosphoinositide 3-kinase (PI3K), and cyclic AMP response element-binding protein (CREB). Furthermore, antibody microarray data revealed that phospho-regulation of nuclear factor kappa B (NF-κB) p65 and death domain-associated protein (DAXX) is involved in protection against neuronal cell damage. In a mouse model of short-term memory impairment, allylguaiacol (2.5 or 5mg/kg) significantly ameliorated scopolamine-mediated cognitive impairment in a passive avoidance task. In addition, allylguaiacol significantly increased the expression of TrkA and B in the hippocampus from scopolamine-treated mice. Taken together, our findings suggest that allylguaiacol exerts a neuroprotective effect through the antioxidant activation and protein regulation of NF-κB p65 and DAXX-related signaling. The ameliorating effect of allylguaiacol may be useful for treatment of memory impairment in Alzheimer's and its related diseases.
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Resveratrol promotes hUC-MSCs engraftment and neural repair in a mouse model of Alzheimer’s disease
Source:Behavioural Brain Research, Volume 339
Author(s): Xinxin Wang, Shanshan Ma, Bo Yang, Tuanjie Huang, Nan Meng, Ling Xu, Qu Xing, Yanting Zhang, Kun Zhang, Qinghua Li, Tao Zhang, Junwei Wu, Greta Luyuan Yang, Fangxia Guan, Jian Wang
Mesenchymal stem cell transplantation is a promising therapeutic approach for Alzheimer's disease (AD). However, poor engraftment and limited survival rates are major obstacles for its clinical application. Resveratrol, an activator of silent information regulator 2, homolog 1 (SIRT1), regulates cell destiny and is beneficial for neurodegenerative disorders. The present study is designed to explore whether resveratrol regulates the fate of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and whether hUC-MSCs combined with resveratrol would be efficacious in the treatment of neurodegeneration in a mouse model of AD through SIRT1 signaling. Herein, we report that resveratrol facilitates hUC-MSCs engraftment in the hippocampus of AD mice and resveratrol enhances the therapeutic effects of hUC-MSCs in this model as demonstrated by improved learning and memory in the Morris water maze, enhanced neurogenesis and alleviated neural apoptosis in the hippocampus of the AD mice. Moreover, hUC-MSCs and resveratrol jointly regulate expression of hippocampal SIRT1, PCNA, p53, ac-p53, p21, and p16. These data strongly suggests that hUC-MSCs transplantation combined with resveratrol may be an effective therapy for AD.
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Hex Maze: A new virtual maze able to track acquisition and usage of three navigation strategies
Source:Behavioural Brain Research, Volume 339
Author(s): Meg J. Spriggs, Ian J. Kirk, Ronald W. Skelton
Spatial navigation is a complex and multi-faceted skill that, in humans, is understood to encompass two distinct navigational strategies, namely allocentric and egocentric navigation. These differ in the frame of reference used and the brain networks activated. However, egocentric navigation can be further divided into two, equally distinct strategies depending on whether the navigator is using subject-to-object relations (egocentric-cue) or direction of body turns (egocentric-response) to navigate. To date, there are no experimental paradigms able to distinguish between participants' employment of allocentric, egocentric-cue and egocentric-response strategies, and to track their usage over time. The current study presents the Hex Maze: a novel virtual environment that can not only distinguish between the three navigational strategies, but can also be used to index aspects of strategy use such as preference, acquisition, stability and competence. To illustrate this, 32 male and 32 female participants were presented with the Hex Maze and sex differences in strategy usage were explored. While the results offer some support for previously identified sex differences in strategy preference, there were no significant sex differences in the novel measures of strategy acquisition, stability, or multi-strategy competence. Additionally, our results suggest that strategy preference does not preclude learning to competently navigate using other strategies. Importantly, the current study offers validation for the Hex Maze as an unbiased method of exploring spatial navigation, and it is anticipated that this easy-to-use tool will be valuable across research and clinical settings.
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Shati/Nat8l knockout mice show behavioral deficits ameliorated by atomoxetine and methylphenidate
Source:Behavioural Brain Research, Volume 339
Author(s): Kazuya Toriumi, Junko Tanaka, Takayoshi Mamiya, Tursun Alkam, Hyoung-Chun Kim, Atsumi Nitta, Toshitaka Nabeshima
We previously identified a novel molecule, SHATI/NAT8L, as having an inhibitory effect on methamphetamine dependence. We generated Shati/Nat8l knockout (KO) mice and found that they showed neurochemical changes and behavioral abnormalities related to attention deficit/hyperactivity disorder (AD/HD). In this study, we assessed validities of the Shati/Nat8l KO mice as a new animal model for AD/HD through a behavioral pharmacology approach. We conducted a locomotor activity test in a novel environment, a cliff avoidance test, and an object-based attention assay using Shati/Nat8l KO mice at the ages of 4 and 8 weeks. We found that at the ages of both 4 and 8 weeks, Shati/Nat8l KO mice showed hyperactivity in locomotor activity test, shortened jumping latency in cliff avoidance test, and lower recognition index in object-based recognition test. Moreover, we evaluated the effects of atomoxetine (ATX) and methylphenidate (MPH) on the behavioral deficits in Shati/Nat8l KO mice. As the result, almost all behavioral deficits were improved by the treatment of both ATX and MPH. Our findings suggest that Shati/Nat8l KO mice have an impaired neural system similar to AD/HD pathophysiology. Shati/Nat8l KO mice might serve as a novel and a useful animal model for the pathophysiology of AD/HD.
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Perinatal fluoxetine increases hippocampal neurogenesis and reverses the lasting effects of pre-gestational stress on serum corticosterone, but not on maternal behavior, in the rat dam
Source:Behavioural Brain Research, Volume 339
Author(s): Mary Gemmel, Danny Harmeyer, Eszter Bögi, Marianne Fillet, Lesley A. Hill, Geoffrey L. Hammond, Thierry D. Charlier, Jodi L. Pawluski
There is increasing evidence that mental health concerns, stress-related mental illnesses, and parental stress prior to conception have long-term effects on offspring outcomes. However, more work is needed to understand how pre-gestational stress might affect neurobehavioral outcomes in the mother. We investigated how chronic stress prior to gestation affects maternal behavior and related physiology, and aimed to determine the role that perinatal SSRIs have in altering these stress effects. To do this, female Sprague-Dawley rats were subject to chronic unpredictable stress (CUS) prior to breeding. During the perinatal period they were administered fluoxetine (10mg/kg/day). Four groups of dams were studied: Control+Vehicle, Pre-gestational Stress+Vehicle, Control+Fluoxetine and Pre-gestational Stress+Fluoxetine. Maternal weight, breeding success, and maternal caregiving behaviors were recorded. Measures of serum corticosterone and corticosteroid-binging globulin (CBG) and the number of immature neurons in the dorsal hippocampus were also assessed in the late postpartum. Main findings show pre-gestational stress resulted in poor reproductive success and maintenance of pregnancy. Pre-gestationally stressed dams also showed higher levels of nursing and fewer bouts of licking/grooming offspring in the first week postpartum – behaviors that were not reversed by perinatal fluoxetine treatment. In the dam, perinatal fluoxetine treatment reversed the effect of pre-gestational maternal stress on serum corticosterone levels and increased serum CBG levels as well as neurogenesis in the dorsal hippocampus. Maternal corticosterone levels significantly correlated with blanket and passive nursing. This work provides evidence for a long-term impact of stress prior to gestation in the mother, and shows that perinatal SSRI medications can prevent some of these effects.
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Response to Letter to the Editor
J reconstr Microsurg
DOI: 10.1055/s-0037-1609015
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Article in Thieme eJournals:
Table of contents | Full text
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Risk Factors for Postoperative Venous Thromboembolic Complications after Microsurgical Breast Reconstruction
J reconstr Microsurg
DOI: 10.1055/s-0037-1608629
Background Venous thromboembolism (VTE) is a significant cause of postoperative morbidity and a focus of patient safety initiatives. Despite giving appropriate prophylaxis in accordance with the Caprini risk assessment model, we observed a high incidence of VTE in patients undergoing microsurgical breast reconstruction at our institution. To explore factors contributing to these events, we compared patients undergoing microsurgical breast reconstruction who sustained postoperative VTEs to those who did not. Methods A retrospective review of all patients who underwent microsurgical free flap breast reconstruction at Montefiore Medical Center from January 2009 to January 2016 was conducted. Patients were divided into two cohorts; those sustaining postoperative VTE and those who did not. Patients were compared based on demographics, comorbidities, operative time, estimated intraoperative blood loss, need for transfusion, volume of transfusion, and discharge on postoperative aspirin. Results A total of 133 patients underwent microsurgical breast reconstruction during the study period. Nine patients (6.8%) had postoperative VTE and there was one (0.8%) death. Patients having VTE were more likely to be Hispanic (33.3%, n = 3) in the VTE group versus 8.1% (n = 6) in the control group (p = 0.011), more likely to have an increased mean transfusion volume (455.5 ± 367.8 vs. 139.51 ± 221.7 mL, p = 0.03), and were more likely to be discharged without aspirin (77.8%, n = 7 and 58.1%, n = 72; p = 0.003). Conclusion Patients sustaining postoperative VTE after microsurgical breast reconstruction are more likely to have an increased volume of blood transfusions and lack of discharge on postoperative aspirin.
[...]
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Article in Thieme eJournals:
Table of contents | Abstract | Full text
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Assessment of the health status and risk of genotoxic and cytotoxic damage in Argentinian adolescents living near horticultural crops
Abstract
In some rural areas in Argentina, adolescents may be considered as a group indirectly exposed to agrochemicals because their parents plant small crops near their homes. This could become a health risk to children and adolescents who may be more sensitive to exposure to chemicals than adults. The objective of this study was to evaluate the health status of two different groups of Argentinian adolescents using biochemical parameters, dietary information, and cytogenetic biomarkers of genotoxicity and cytotoxicity. The study groups included 32 adolescents from Montecarlo, who were indirectly exposed to agrochemicals, and 30 unexposed adolescents from Exaltación de la Cruz. The values of total cholesterol, LDL cholesterol, triglycerides, gamma glutamyltransferase, and butyrylcholinesterase (BuChE) were higher (p < 0.05) in males from Exaltación de la Cruz compared with those from Montecarlo. The BuChE activity was also higher (p < 0.05) in females from this region. Furthermore, the consumption of citrus, vegetable-like fruits, tubers, and red meat was more frequent (p < 0.05) in Montecarlo. On the other hand, differences in frequency of biomarkers of genetic damage in lymphocytes were not found (p > 0.05). However, the cytome assay in buccal cells showed that karyorrhectic and pyknotic cells were more frequent (p < 0.05) in the Montecarlo group; whereas, the frequencies of cells with nuclear buds, condensed chromatin and karyolysis were higher (p < 0.05) in the Exaltación de la Cruz group. Despite the differences between the parameters and biomarkers evaluated, the adolescents of Montecarlo did not present health impairment probably due to the type and level of exposure to agrochemicals.
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Combined efficacy of oseltamivir, isoprinosine and ellagic acid in influenza A(H3N2)-infected mice
Publication date: February 2018
Source:Biomedicine & Pharmacotherapy, Volume 98
Author(s): Elitsa L. Pavlova, Lora S. Simeonova, Galina A. Gegova
Influenza pathogenesis comprises a complex cascade of impaired cellular processes resulting from the viral replication and exaggerated immune response accompanied by reactive oxygen species (ROS) burst and oxidative stress, destructing membranous structures and tissues. By classical virological and biochemical methods we compared and evaluated the therapeutic effects of 2.5mg/kg/day of the antiviral drug – oseltamivir (OS), 500mg/kg/day of the immune modulator – isoprinosine (IP) and 500mg/kg/day of the antioxidant agent ellagic acid (EA) with a focus on their combined activities in influenza H3N2 virus-infected mice. The survival, lung pathology and titers, as well as the oxidative stress biomarker thiobarbituric acid reactive substances (TBARS) in the lungs, liver and blood plasma, correlated to the activities of the antioxidant enzymes superoxide dismutase (SOD) and glutathione reductase (GR) were assessed.We found that the viral inhibitor applied together with the immune modulator and the antioxidant exhibited strong therapeutic effects on the survival of the influenza-challenged mice. That effect was mostly pronounced for the triple combination – protection index (PI) of 75.2%, mean survival time (MST) extended by 5.8 days compared to the PBS control and significant reduction of the lung titers by 1.38 Δlg; 2.3 scores lower lung pathology and 8 times reduction of the accumulated TBARS in the lungs and liver on the 5−th day p.i. The enzymatic assays revealed that this combination demonstrated very good protection against the damaging superoxide radicals (83% efficiency of SOD, in comparison to healthy controls 100%). The double combinations of OS with IP and EA also showed protective effects according to the virological analysis – PI of 53.1% and 54.5%. Ten times higher GR activity was observed when the combination EA+OS and monotherapy of EA were applied (96% in comparison to healthy controls 100%). The best antioxidant effect in blood plasma was observed in the EA+IP group – 4 times reduction in the TBARS-content compared to infected controls but it did not have any efficacy on the survival and lung injury.
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Summary Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an un...
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