Advanced solid-state NMR spectroscopy of natural organic matter

Publication date: Available online 5 January 2017
Source:Progress in Nuclear Magnetic Resonance Spectroscopy
Author(s): Jingdong Mao, Xiaoyan Cao, Dan C. Olk, Wenying Chu, Klaus Schmidt-Rohr
Solid-state NMR is essential for the characterization of natural organic matter (NOM) and is gaining importance in geosciences and environmental sciences. This review is intended to highlight advanced solid-state NMR techniques, especially a systematic approach to NOM characterization, and their applications to the study of NOM. We discuss some basics of how to acquire high-quality and quantitative solid-state ¹³C NMR spectra, and address some common technical mistakes that lead to unreliable spectra of NOM. The identification of specific functional groups in NOM, primarily based on ¹³C spectral-editing techniques, is detailed and the theoretical background of some recently-developed spectral-editing techniques is provided. Applications of solid-state NMR to investigating nitrogen in NOM are described, focusing on limitations of the widely used ¹⁵N CP/MAS experiment and the potential of improved advanced NMR techniques for characterizing N forms in NOM. Then techniques used for identifying proximities, heterogeneities and domains are reviewed, and some examples provided. In addition, NMR techniques for studying segmental dynamics in NOM are reviewed. We also briefly discuss applications of solid-state NMR to NOM from various sources, including soil organic matter, aquatic organic matter, organic matter in atmospheric particulate matter, carbonaceous meteoritic organic matter, and fossil fuels. Finally, examples of NMR-based structural models and an outlook are provided.

Graphical abstract

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Nutrition Recommendations from the US Dietary Guidelines Critical to Teach Low-Income Adults: Expert Panel Opinion

Publication date: Available online 4 January 2017
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Erin K. Murray, Susan Baker, Garry Auld




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Vertebral Tortuosity Index in Patients with Non-Connective Tissue Disorder-Related Aneurysm Disease

Publication date: Available online 5 January 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): F. Virgilio, B. Maurel, M. Davis, G. Hamilton, T.M. Mastracci
ObjectiveThe vertebral tortuosity index (VTI) predicts increased risk of acute aortic events in patients with known genetic aortopathies. This study describes the VTI in a cohort of patients with non-connective tissue disorder-related large aneurysms.MethodsHospital imaging records from July 2012 to March 2016 were interrogated to identify patients with aneurysmal disease who had undergone computed tomographic angiography that included imaging of vertebral arteries. A control group of consecutive patients undergoing carotid and vertebral imaging was also assessed. VTI was calculated using the formula: [(centre-line distance) / (straight-line distance)-1] ×100 for all patients, and statistical analysis undertaken to determine whether measured VTI was statistically different in patients of younger age, with larger aneurysms, or an acute presentation. Comparison was made with patients who had no aneurysm disease.ResultsSixty-five patients were identified with adequate imaging to assess the entire aorta, including vertebral arteries. The majority of patients were male (71%, 46/65) and mean age at the time of the CT scan was 71 years (SD 11.1 years). There were 11 patients under the age of 60 years in this cohort. The mean VTI was 33.17 (SD 20.43). There was no statistically significant difference between different territories of presentation (proximal vs. distal aneurysm, p=.94), age of patient (>60 years vs. <60 years, p=.2), or size of aneurysm (>6 cm vs. <6 cm, p=.09). Acuity of presentation was not predicted by a higher VTI (p=.69). The VTI in patients with aneurysms was higher than in patients without aneurysm disease (VTI = 16.1, p<.005)ConclusionsAn elevated VTI is consistently present in patients with degenerative aneurysms and has potential as a universally available predictive measurement. However, the increased VTI in the older cohort without connective tissue disease may not carry the same predictive value for acute presentations as has been demonstrated in younger patients with a known genetic basis for their aortopathy.



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Monitoring of a micro-smart grid: Power consumption data of some machineries of an agro-industrial test site

Publication date: February 2017
Source:Data in Brief, Volume 10
Author(s): Enrico Fabrizio, Alessandro Biglia, Valeria Branciforti, Marco Filippi, Silvia Barbero, Giuseppe Tecco, Paolo Mollo, Andrea Molino
For the management of a (micro)-smart grid it is important to know the patters of the load profiles and of the generators. In this article the power consumption data obtained through a monitoring activity developed on a micro-smart grid in an agro-industrial test-site are presented. In particular, this reports the synthesis of the monitoring results of 5 loads (5 industrial machineries for crop micronization, corncob crashing and other similar processes). How these data were used within a monitoring and managing scheme of a micro-smart grid can be found in (E. Fabrizio, V. Branciforti, A. Costantino, M. Filippi, S. Barbero, G. Tecco, P. Mollo, A. Molino, 2017) [1]. The data can be useful for other researchers in order to create benchmarks of energy use input appropriate energy demand values in optimization tools for the industrial sector.



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HPLC fucoxanthin profiles of a microalga, a macroalga and a pure fucoxanthin standard

Publication date: February 2017
Source:Data in Brief, Volume 10
Author(s): Su Chern Foo, Fatimah Md. Yusoff, Maznah Ismail, Mahiran Basri, Sook Kun Yau, Nicholas M.H. Khong, Kim Wei Chan, Mahdi Ebrahimi
Data in this article illustrate representative fucoxanthin chromatograms of a microalga, Chaetoceros calcitrans; a macroalga, Saccharina japonica and; a pure fucoxanthin standard. High performance liquid chromatography (HPLC) eluted fucoxanthin at the 7.008±0.024thmin. This data article refers to the research article ''Antioxidant capacities of fucoxanthin-producing algae as influenced by their carotenoid and phenolic contents'' Foo et al. [1]; where a more comprehensive data interpretation and analysis is explained.



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Stock Market Index Data and indicators for Day Trading as a Binary Classification problem

Publication date: February 2017
Source:Data in Brief, Volume 10
Author(s): Renato Bruni
Classification is the attribution of labels to records according to a criterion automatically learned from a training set of labeled records. This task is needed in a huge number of practical applications, and consequently it has been studied intensively and several classification algorithms are available today. In finance, a stock market index is a measurement of value of a section of the stock market. It is often used to describe the aggregate trend of a market. One basic financial issue would be forecasting this trend. Clearly, such a stochastic value is very difficult to predict. However, technical analysis is a security analysis methodology developed to forecast the direction of prices through the study of past market data. Day trading consists in buying and selling financial instruments within the same trading day. In this case, one interesting problem is the automatic individuation of favorable days for trading. We model this problem as a binary classification problem, and we provide datasets containing daily index values, the corresponding values of a selection of technical indicators, and the class label, which is 1 if the subsequent time period is favorable for day trading and 0 otherwise. These datasets can be used to test the behavior of different approaches in solving the day trading problem.



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Priming theta burst stimulation enhances motor cortex plasticity in young but not old adults

Publication date: Available online 4 January 2017
Source:Brain Stimulation
Author(s): George M. Opie, Eleni Vosnakis, Michael C. Ridding, Ulf Ziemann, John G. Semmler
BackgroundPrimary motor cortex neuroplasticity is reduced in old adults, which may contribute to the motor deficits commonly observed in the elderly. Previous research in young subjects suggests that the neuroplastic response can be enhanced using non-invasive brain stimulation (NIBS), with a larger plastic response observed following priming with both long-term potentiation (LTP) and depression (LTD)-like protocols. However, it is not known if priming stimulation can also modulate plasticity in older adults.ObjectiveTo investigate if priming NIBS can be used to modulate motor cortical plasticity in old subjects.MethodsIn 16 young (22.3 ± 1.0 years) and 16 old (70.2 ± 1.7 years) subjects, we investigated the response to intermittent theta burst stimulation (iTBS; LTP-like) when applied 10 min after sham stimulation, continuous TBS (cTBS; LTD-like) or an identical block of iTBS. Corticospinal plasticity was assessed by recording changes in motor evoked potential (MEP) amplitude.ResultsIn young subjects, priming with cTBS (cTBS + iTBS) resulted in larger MEPs than priming with either iTBS (iTBS + iTBS; P = 0.001) or sham (sham + iTBS; P < 0.0001), while larger MEPs were seen following iTBS + iTBS than sham + iTBS (P < 0.0001). In old subjects, the response to iTBS + iTBS was not different to sham + iTBS (P > 0.9), whereas the response to cTBS + iTBS was reduced relative to iTBS + iTBS (P = 0.02) and sham + iTBS (P = 0.04).ConclusionsPriming TBS is ineffective for modifying M1 plasticity in older adults, which may limit the therapeutic use of priming stimulation in neurological conditions common in the elderly.



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Transcranial static magnetic field stimulation of M1 reduces corticospinal excitability without distorting sensorimotor integration in humans

Publication date: Available online 4 January 2017
Source:Brain Stimulation
Author(s): Pablo Arias, Lucía Adán-Arcay, Beatriz Puerta-Catoira, Antonio Madrid, Javier Cudeiro




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A single session of prefrontal cortex transcranial direct current stimulation does not modulate implicit task sequence learning and consolidation

Publication date: Available online 4 January 2017
Source:Brain Stimulation
Author(s): Branislav Savic, René Müri, Beat Meier
BackgroundTranscranial direct current stimulation (tDCS) is assumed to affect cortical excitability and dependent on the specific stimulation conditions either to increase or decrease learning.ObjectiveThe purpose of this study was to modulate implicit task sequence learning with tDCS.MethodsAs cortico-striatal loops are critically involved in implicit task sequence learning, tDCS was applied above the dorsolateral prefrontal cortex (DLPFC). In Experiment 1, anodal, cathodal, or sham tDCS was applied before the start of the sequence learning task. In Experiment 2, stimulation was applied during the sequence learning task. Consolidation of learning was assessed after 24 h.ResultsThe results of both experiments showed that implicit task sequence learning occurred consistently but it was not modulated by different tDCS conditions. Similarly, consolidation measured after a 24 h interval including sleep was also not affected by stimulation.ConclusionsThese results indicate that a single session of DLPFC tDCS is not sufficient to modulate implicit task sequence learning. This study adds to the accumulating evidence that tDCS may not be as effective as originally thought.



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Scabiose de l’appareil unguéal chez un nourrisson

Publication date: Available online 4 January 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): A. Finon, G. Desoubeaux, M. Nadal, G. Georgescou, R. Baran, A. Maruani
IntroductionLa prise en charge de la gale du nourrisson n'est pas codifiée et les récidives sont fréquentes à cet âge. Nous rapportons un cas exceptionnel d'atteinte sous-unguéale et d'onychopathie des pieds, séquellaires d'une gale commune chez un nourrisson.ObservationUn nourrisson de 7 mois, traité par esdépalléthrine pour une gale 6 semaines auparavant, était vu en consultation pour des modifications unguéales acquises des orteils. Il existait un épaississement unguéal de trois orteils avec hyperkératose sous-unguéale. Le reste de l'examen cutanéo-muqueux et des phanères était normal. L'analyse mycologique de prélèvements d'ongles était négative, mais l'examen direct en microscopie optique trouvait de nombreuses larves de Sarcoptes scabiei, ainsi que des débris d'œufs. Le traitement consistait en une avulsion chimique des ongles atteints (urée à 40 %) associée à des applications d'esdépalléthrine topique et à une prise orale d'ivermectine ; l'enfant a été perdu de vue.DiscussionL'atteinte unguéale a été rapportée dans la gale hyperkératosique et exceptionnellement dans la gale commune de l'adulte. La localisation sous-unguéale et unguéale de S. scabiei pourrait constituer une source de réinfestation de la gale chez les nourrissons. Son traitement reste à définir mais reposerait sur une avulsion chimique de l'ongle et l'application prolongée d'antiscabieux topiques sur le lit unguéal.BackgroundThere are no guidelines regarding the management of scabies in infants and recurrence is common at this age. We report the case of an infant with subungual hyperkeratosis and ungual lesions subsequent to classic scabies.Patients and methodsA 7-month-girl, treated 6 weeks earlier with esdepallethrin for scabies, consulted for acquired lesions on 3 toe nails. These nails were thickened and displayed subungual hyperkeratosis. Physical examination of the skin, the finger nails and mucous membranes was otherwise normal. Fungal analyses were negative, but direct microscopic examination revealed numerous larvae of Sarcoptes scabiei as well as ovular debris. The child was treated with urea 40% to obtain chemical avulsion of the nails, and with topical esdepallethrin and a quarter tablet of ivermectin orally; there was no follow-up of the child.DiscussionUngual scabies has already been reported in crusted scabies and very rarely in classic scabies. Subungual and ungual locations of S. scabiei may constitute a source of reinfestation with scabies in infants. Treatment is not well defined and currently involves chemical avulsion of the nails and the application of topical antiscabies treatment.



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Risques infectieux similaires entre anti-TNFα et thérapies systémiques classiques dans le psoriasis

Publication date: Available online 5 January 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): J.-L. Schmutz




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White matter lesions relate to tract-specific reductions in functional connectivity

Publication date: March 2017
Source:Neurobiology of Aging, Volume 51
Author(s): Carolyn D. Langen, Hazel I. Zonneveld, Tonya White, Wyke Huizinga, Lotte G.M. Cremers, Marius de Groot, Mohammad Arfan Ikram, Wiro J. Niessen, Meike W. Vernooij
White matter lesions play a role in cognitive decline and dementia. One presumed pathway is through disconnection of functional networks. Little is known about location-specific effects of lesions on functional connectivity. This study examined location-specific effects within anatomically-defined white matter tracts in 1584 participants of the Rotterdam Study, aged 50–95. Tracts were delineated from diffusion magnetic resonance images using probabilistic tractography. Lesions were segmented on fluid-attenuated inversion recovery images. Functional connectivity was defined across each tract on resting-state functional magnetic resonance images by using gray matter parcellations corresponding to the tract ends and calculating the correlation of the mean functional activity between the gray matter regions. A significant relationship between both local and brain-wide lesion load and tract-specific functional connectivity was found in several tracts using linear regressions, also after Bonferroni correction. Indirect connectivity analyses revealed that tract-specific functional connectivity is affected by lesions in several tracts simultaneously. These results suggest that local white matter lesions can decrease tract-specific functional connectivity, both in direct and indirect connections.



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Aging reduces the high-frequency and short-term adaptation of the vestibulo-ocular reflex in mice

Publication date: March 2017
Source:Neurobiology of Aging, Volume 51
Author(s): Serajul I. Khan, Patrick P. Hübner, Alan M. Brichta, Doug W. Smith, Americo A. Migliaccio
Prevailing evidence indicates a relatively late life decline in human vestibulo-ocular reflex (VOR) function. Although mice are commonly used in mechanistic studies of vestibular function, it remains unclear whether aging produces a corresponding decline in VOR function in mice. We sought to determine how the baseline VOR and its short-term adaptation were affected by aging. We tested 8 young (3-month old) and 8 aged (30-month old–equivalent to a ∼80-year old human) C57BL/6 mice. We measured their VOR response to whole-body static tilts and during 0.1–10 Hz whole-body sinusoidal and transient rotations before and after VOR adaptation training. Our data revealed minimal differences in static counter-tilt response between young and aged mice, but a significant deficit in baseline VOR gain in aged mice during transient rotations. Moreover, aged mice had a significant decrease in short-term VOR adaptation, particularly for training that sought to decrease the VOR response.



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Rod-shaped microglia morphology is associated with aging in two human autopsy series

Publication date: Available online 5 January 2017
Source:Neurobiology of Aging
Author(s): Adam D. Bachstetter, Eseosa T. Ighodaro, Yasmin Hassoun, Danah Aldeiri, Janna H. Neltner, Ela Patel, Erin L. Abner, Peter T. Nelson
A subtype of microglia is defined by the morphological appearance of the cells as rod-shaped. Little is known about this intriguing cell type, as there are only a few case reports describing rod-shaped microglia in the neuropathological literature. Rod-shaped microglia were shown recently to account for a substantial proportion of the microglia cells in the hippocampus of both demented and cognitively intact aged individuals. We hypothesized that aging could be a defining feature in the occurrence of rod-shaped microglia. To test this hypothesis, two independent series of autopsy cases (total n=168 cases), which covered the adult lifespan from 20 - 100+ years old, were included in the study. The presence or absence of rod-shaped microglia was scored on IBA1 immunohistochemically stained slides for the hippocampus and cortex. We found that age was one of the strongest determinants for the presence of rod-shaped microglia in the hippocampus and the cortex. We found no association with the presence of rod-shaped microglia and a self-reported history of a TBI. Alzheimer's disease related pathology was found to influence the presence of rod-shaped microglia, but only in the parietal cortex and not in the hippocampus or temporal cortex. Future studies are warranted to determine the functional relevance of rod-shaped microglia in supporting the health of neurons in the aged brain, and the signaling processes that regulate the formation of rod-shaped microglia.



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Selective Use of Whole-Brain Radiotherapy for Brain Metastases

This Viewpoint asserts that whole-brain radiation therapy is beneficial for the treatment of brain metastases.

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Diagnosis and Management of Waldenström Macroglobulinemia

This Special Communication provides consensus recommendations for a risk-adapted approach to treatment of Waldenström macroglobulinemia.

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Diminishing Role of Whole-Brain Radiation for Brain Metastases

This Viewpoint asserts that there is limited benefit for whole-brain radiation therapy in the treatment of brain metastases.

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A Silver Lining

Lessons learnt,yet chattering lips lie restless.Passion for painless pleasures,yet pain permeates proud,arrogantly bearing his teeth of incision.

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Delayed Adjuvant Chemotherapy After Lung Cancer Surgery

This study assesses differences in survival according to the time interval between non–small-cell lung cancer resection and the initiation of postoperative chemotherapy to determine the association between adjuvant treatment timing and efficacy.

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Adjuvant Chemotherapy for Lung Cancer and Real-world Practice

The data from a wide range of prospective, randomized phase 3 trials are clear: There is a significant survival benefit from adjuvant cisplatin-based chemotherapy for patients with resected higher-risk non–small-cell lung cancer (NSCLC), often defined as node-positive and/or with the primary tumor measuring 4 cm or greater in diameter. As in many clinical settings, however, patients in real-world practice are not well represented by those on the relevant clinical trials, as those in the pivotal adjuvant trials are approximately a decade younger and with a near uniformly good performance status. A clinical trial directly comparing preoperative with postoperative chemotherapy for early-stage NSCLC also demonstrated an attrition rate of 34% for postoperative chemotherapy within the protocol-defined window of 6 to 7 weeks owing to a wide range of complicating factors. In practice, this means that many patients who would otherwise be appropriate candidates for adjuvant chemotherapy do not present for consideration of treatment until later than best practices would recommend. Should an intervention with an established survival benefit be deferred in this setting? While we do not have prospective evidence to speak to this, absence of proof is not proof of absence.

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Primary Surgical Resection vs Chemoradiation for Patients With OPSCC

This study compared survival outcomes among patients with newly diagnosed cT1-2 N1-2b human papillomavirus-negative oropharyngeal squamous cell carcinoma when treated with primary surgical resection vs chemoradiation.

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Supplement 2 Added

In the Brief Report titled "Intrinsic Subtype Switching and Acquired ERBB2/HER2 Amplifications and Mutations in Breast Cancer Brain Metastases," published online December 7, 2016, Supplement 2 was omitted when the article was initially published. This article was corrected online.

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Writing scientific articles like a native English speaker: concise writing for Portuguese speakers

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Passive acquisition of anti-Staphylococcus aureus antibodies by newborns via transplacental transfer and breastfeeding, regardless of maternal colonization

OBJECTIVE: To investigate the transmission of anti-Staphylococcus aureus (Sa) IgG, IgG1 and IgG2 via placental transfer and the transfer of IgA via the colostrum according to maternal Sa carrier status at delivery. METHODS: We evaluated anti-Sa IgG, IgG1 and IgG2 in maternal and cord sera and IgA in colostrum from a case (n=49, Sa+) and a control group (n=98, Sa-). RESULTS: Of the 250 parturients analyzed for this study, 49 were nasally colonized with S. aureus (prevalence of 19.6%). Ninety-eight non-colonized subjects were selected for the control group. The anti-Sa IgG, IgG1 and IgG2 levels and the IgG avidity indexes in the maternal and cord sera did not differ between the groups, with a low transfer ratio of anti-Sa IgG to the newborns in both groups. The anti-Sa IgG2 titers were significantly higher than the IgG1 titers in the maternal and cord sera. Inversely, the transfer ratios were higher for anti-Sa IgG1 compared with IgG2; however, no differences between the groups were detected. The Sa-specific IgA levels and avidity indexes in the colostrum were equivalent between groups. CONCLUSIONS: Maternal Sa nasal colonization at delivery is not associated with higher antibody levels in the mother or newborns. The high titers of anti-Sa IgG2 found in the cord serum indicate a greater reactivity with non-protein antigens, which may further contribute to the susceptibility to staphylococcal infections at birth. The presence of IgA in the colostrum with avidity to S. aureus reinforces the importance of breastfeeding shortly after birth.

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Mutation analysis of NANOS3 in Brazilian women with primary ovarian failure

OBJECTIVES: Primary ovarian failure is a rare disorder, and approximately 90% of cases are of unknown etiology. The aim of this study was to search for mutations in NANOS3, a gene that was recently related to the etiology of primary ovarian failure, in a group of Brazilian women. METHODS: We screened for NANOS3 DNA variants in 30 consecutive women who were previously diagnosed with primary ovarian failure, of unknown etiology and compared the results with those from 185 women with normal fertility. The NANOS3 gene was amplified by polymerase chain reaction using pairs of specific primers and then sequenced. The resulting sequences were compared with control sequences available in the National Center for Biotechnology and Information database. RESULTS: No mutations in NANOS3 were found in primary ovarian failure patients, but four previously described polymorphisms were identified at a similar frequency in the control and primary ovarian failure groups. CONCLUSIONS: Mutations in NANOS3 were not associated with primary ovarian failure in the present cohort.

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Serum concentration of vascular endothelial growth factor and depth of trophoblastic invasion in ampullary ectopic pregnancy

OBJECTIVE: To evaluate the association between the depth of trophoblastic infiltration and serum vascular endothelial growth factorconcentration in patients with an ampullary pregnancy. METHODS: This prospective cross-sectionalstudy involved 34 patients with an ampullary ectopic pregnancy who underwent salpingectomy between 2012 and 2013. Maternal serum vascular endothelial growth factor concentrations were measured using Luminex technology. Trophoblastic invasion was classified histologically as follows: stage I, limited to the tubal mucosa; stage II, reaching the muscle layer; and stage III,involving the full thickness. The qualitative data were compared using Fisher's exact test. The nonparametric Kruskal-Wallis and Mann-Whitney tests were used to evaluate differences in serum vascular endothelial growth factor among the degrees of trophoblastic invasion. ROC curves were constructed to determine vascular endothelial growth factor cut-off values that predict the degree of tubal invasion based on the best sensitivity and specificity. RESULTS: Eight patients had stage I trophoblastic invasion, seven had stage II, and 19 had stage III. The median serum vascular endothelial growth factorconcentration was 69.88 pg/mL for stage I, 14.53 pg/mL for stage II and 9.08 pg/mL for stage III, with a significant difference between stages I and III. Based on the ROC curve, a serum vascular endothelial growth factor concentration of 25.9 pg/mL best differentiated stage I from stages II and III with asensitivity of 75.0%, specificity of 76.9%, and area under the curve of 0.798. CONCLUSIONS: The depth of trophoblastic penetration into the tubal wall isassociated with serum vascular endothelial growth factor concentration in ampullary pregnancies.

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Evaluation of embolization for periuterine varices involving chronic pelvic pain secondary to pelvic congestion syndrome

OBJECTIVES: To evaluate the clinical response and success rate after periuterine varices embolization in patients with chronic pelvic pain secondary to pelvic congestion syndrome and to report the safety of endovascular treatment and its rate of complications. METHODS: Retrospective cohort of patients undergoing endovascular treatment of pelvic congestion syndrome in our department from January 2012 to November 2015. Data were analyzed based on patient background, imaging findings, embolized veins, rate of complications, and clinical response as indicated by the visual analog pain scale. RESULTS: We performed periuterine varices embolization in 22 patients during the study, four of which required a second embolization. Seventeen patients reported a reduction in pelvic pain after the first embolization and three patients reported a reduction in pelvic pain after the second embolization. Minor complications were observed in our patients, such as postural hypotension, postoperative pain, and venous perforation during the procedure, without clinical repercussion. CONCLUSION: Periuterine varices embolization in patients with chronic pelvic pain secondary to pelvic congestion syndrome appears to be an effective and safe technique.

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Serum adipocytokine profile and metabolic syndrome in young adult female dermatomyositis patients

OBJECTIVES: To analyse the frequency of metabolic syndrome in young adult female dermatomyositis patients and its possible association with clinical and laboratory dermatomyositis-related features and serum adipocytokines. METHOD: This cross-sectional study included 35 dermatomyositis patients and 48 healthy controls. Metabolic syndrome was defined according to the 2009 Joint Interim Statement. RESULTS: Patient age was comparable in the dermatomyositis and control groups, and the median disease duration was 1.0 year. An increased prevalence of metabolic syndrome was detected in the dermatomyositis group (34.3% vs. 6.3%; p=0.001). In addition, increased serum adiponectin and resistin levels were noted in contrast to lower leptin levels. In dermatomyositis patients, adipocytokine levels were correlated with the levels of total cholesterol, low-density cholesterol, triglycerides and muscle enzymes. A comparison of dermatomyositis patients with (n=12) and without (n=23) syndrome metabolic revealed that adipocytokine levels were also correlated with age, and that dermatomyositis patients with metabolic syndrome tended to have more disease activity despite similar adipocytokine levels. CONCLUSIONS: Metabolic syndrome is highly prevalent in young adult female dermatomyositis patients and is related to age and disease activity. Moreover, increased serum adiponectin and resistin levels were detected in dermatomyositis patients, but lower serum leptin levels were observed.

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Septic arthritis of the knee: clinical and laboratory comparison of groups with different etiologies

OBJECTIVES: To clinically and epidemiologically characterize a population diagnosed with and treated for septic arthritis of the knee, to evaluate the treatment results and to analyze the differences between patients with positive and negative culture results, patients with Gram-positive and Gram-negative bacterial isolates and patients with S. aureus- and non-S. aureus-related infections. METHODS: One hundred and five patients with septic knee arthritis were included in this study. The clinical and epidemiological data were evaluated. Statistical analysis was performed to compare patients with and without an isolated causative agent, patients with Gram-positive and Gram-negative pathogens and patients with S. aureus-related and non S. aureus-related infections. RESULTS: Causative agents were isolated in 81 patients. Gram-positive bacteria were isolated in 65 patients and Gram-negative bacteria were isolated in 16 patients. The most commonly isolated bacterium was S. aureus. Comparing cases with an isolated pathogen to cases without an isolated pathogen, no differences between the studied variables were found except for the longer hospital stays of patients in whom an etiological agent was identified. When comparing Gram-positive bacteria with Gram-negative bacteria, patients with Gram-positive-related infections exhibited higher leukocyte counts. Patients with S. aureus-related infections were more frequently associated with healthcare-related environmental encounters. CONCLUSION: S. aureus is the most common pathogen of septic knee arthritis. Major differences were not observed between infections with isolated and non-isolated pathogens and between infections with Gram-positive and Gram-negative bacteria. S. aureus infections were more likely to be associated with a prior healthcare environment exposure.

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Standardization of the face-hand test in a Brazilian multicultural population: prevalence of sensory extinction and implications for neurological diagnosis

OBJECTIVE: The face-hand test is a simple, practical, and rapid test to detect neurological syndromes. However, it has not previously been assessed in a Brazilian sample; therefore, the objective of the present study was to standardize the face-hand test for use in the multi-cultural population of Brazil and identify the sociodemographic factors affecting the results. METHODS: This was a cross sectional study of 150 individuals. The sociodemographic variables that were collected included age, gender, race, body mass index and years of education. Standardization of the face-hand test occurred in 2 rounds of 10 sensory stimuli, with the participant seated to support the trunk and their vision obstructed in a sound-controlled environment. The face-hand test was conducted by applying 2 rounds of 10 sensory stimuli that were applied to the face and hand simultaneously. The associations between the face-hand test and sociodemographic variables were analyzed using Mann-Whitney tests and Spearman correlations. Binomial models were adjusted for the number of face-hand test variations, and ROC curves evaluated sensitivity and specificity of sensory extinction. RESULTS: There was no significant relationship between the sociodemographic variables and the number of stimuli perceived for the face-hand test. There was a high relative frequency of detection, 8 out of 10 stimuli, in this population. Sensory extinction was 25.3%, which increased with increasing age (OR=1.4[1:01–1:07]; p=0.006) and decreased significantly with increasing education (OR=0.82[0.71-0.94]; p=0.005). CONCLUSION: In the Brazilian population, a normal face-hand test score ranges between 8–10 stimuli, and the results indicate that sensory extinction is associated with increased age and lower levels of education.

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Serum Klotho (but not haplotypes) associate with the post-myocardial infarction status of older adults

OBJECTIVES: The number of deaths from vascular diseases is incredibly high worldwide, and reliable markers for major events are still needed. The current cross-sectional study investigated the association of Klotho haplotypes and Klotho serum levels with classic risk factors and a clinical history of vascular events. METHODS: Clinical, anthropometric, biochemical and nutritional assessments were conducted with 168 older adults, complemented by genotyping (rs9536314 and rs9527025) and the detection of serum Klotho (ELISA). RESULTS: Klotho levels and haplotypes did not associate with most classic risk factors for vascular events, including markers such as C-reactive protein and homocysteine. A positive association was only found between Klotho levels and the previous occurrence of a myocardial infarction by both correlational (p=0.006) and variance analyses (p<0.001), and these associations were independent of the context. CONCLUSION: Our results suggest that serum Klotho is higher in individuals with a clinical history of myocardial infarction but not with a history of coronary artery disease or stroke. None of the Klotho haplotypes were associated with the variables investigated herein.

http://ift.tt/2hWAZ9c

Detection value of free cancer cells in peritoneal washing in gastric cancer: a systematic review and meta-analysis

Intraperitoneal free cancer cells in gastric adenocarcinoma are associated with a poor outcome. However, the true prognostic value of intraperitoneal free cancer cells is still unclear, leading to a lack of consensus in the management of gastric cancer. The aim of the present study is to perform a systematic review and meta-analysis to analyze intraperitoneal free cancer cells-positive patients with regard to tumor oncologic stage, recurrence, grade of cellular differentiation, and survival rates and to analyze the clinical significance of intraperitoneal free cancer cells with regard to prognosis. Databases were searched up to January 2016 for prognostic factors associated with intraperitoneal free cancer cells, including oncologic stage, depth of neoplasm invasion, lymph nodal spread, differentiation grade of the tumor, and recurrence and survival rates. A total of 100 studies were identified. Meta-analysis revealed a clear association between intraperitoneal free cancer cells and a poor prognosis. intraperitoneal free cancer cells -positive patients had higher rates of nodal spread (risk difference: 0.29; p<0.01), serosal invasion (risk difference: 0.43; p<0.01), recurrence (after 60 months of follow-up, risk difference: 0.44; p<0.01), and mortality (after 60 months of follow-up, risk difference: 0.34; p<0.01). Intraperitoneal free cancer cells are associated with a poor outcome in gastric cancer. This surrogate biomarker should be used to guide therapy both prior to and after surgery.

http://ift.tt/2iUazU9

Young pigs exhibit differential exploratory behavior during novelty preference tasks in response to age, sex, and delay

Publication date: 15 March 2017
Source:Behavioural Brain Research, Volume 321
Author(s): Stephen A. Fleming, Ryan N. Dilger
Novelty preference paradigms have been widely used to study recognition memory and its neural substrates. The piglet model continues to advance the study of neurodevelopment, and as such, tasks that use novelty preference will serve especially useful due to their translatable nature to humans. However, there has been little use of this behavioral paradigm in the pig, and previous studies using the novel object recognition paradigm in piglets have yielded inconsistent results. The current study was conducted to determine if piglets were capable of displaying a novelty preference. Herein a series of experiments were conducted using novel object recognition or location in 3- and 4-week-old piglets. In the novel object recognition task, piglets were able to discriminate between novel and sample objects after delays of 2min, 1h, 1 day, and 2 days (all P<0.039) at both ages. Performance was sex-dependent, as females could perform both 1- and 2-day delays (P<0.036) and males could perform the 2-day delay (P=0.008) but not the 1-day delay (P=0.347). Furthermore, 4-week-old piglets and females tended to exhibit greater exploratory behavior compared with males. Such performance did not extend to novel location recognition tasks, as piglets were only able to discriminate between novel and sample locations after a short delay (P>0.046). In conclusion, this study determined that piglets are able to perform the novel object and location recognition tasks at 3-to-4 weeks of age, however performance was dependent on sex, age, and delay.



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Assessment of mouse cognitive and anxiety-like behaviors and hippocampal inflammation following a repeated and intermittent paradoxical sleep deprivation procedure

Publication date: 15 March 2017
Source:Behavioural Brain Research, Volume 321
Author(s): Mengmei Yin, Yali Chen, Hui Zheng, Tinglin Pu, Charles Marshall, Ting Wu, Ming Xiao
It has been reported that more than one fourth of the world's population suffers from sleep problems. However, there is not a stable and reliable animal model to mimic the persistent and periodic features of sleep disorders, and correspondingly, the feasibility and effectiveness of repeated behavioral tests remains to be determined. In the present study, we repetitively, and intermittently, treated mice with 3days and 7days of paradoxical sleep deprivation (SD), using the modified multiple small-platforms-over-water method for 3 months. The behavioral results suggested that repeated open field and Y-maze tests are able to successfully detect anxiety-like behaviors and working memory dysfunction of the model mice. The Morris water maze test is not suitable for evaluating spatial learning ability following SD because the long-term utilization of the flower-pot method increases the familiarity of mice with the water environment. Moreover, neuroinflammation, microglial activation and neuronal apoptosis were observed in the hippocampus of model mice even recovery for 3 weeks later. This animal model and corresponding behavioral evaluation method will help to explore the pathogenesis and therapeutic strategies of chronic sleep disorders.



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Epigallocatechin-3-gallate promotes angiogenesis via up-regulation of Nfr2 signaling pathway in a mouse model of ischemic stroke

Publication date: 15 March 2017
Source:Behavioural Brain Research, Volume 321
Author(s): Qian Bai, Zhipai Lyu, Zhenjie Pan, Jiyu Lou, Tieli Dong
Epigallocatechin-3-gallate (EGCG) is the major effective component of green tea and has been known as a potential anticancer drug because of its antioxidant and anti-angiogenic properties. EGCG has also been reported to have preventive effects against ischemic stroke via nuclear factor erythroid 2-related factor 2 (Nfr2) signaling pathway, but how EGCG affect angiogenesis after stroke remains unclear. In this study, we investigated whether EGCG treatment in the acute phase of ischemic stroke can promote angiogenesis in a mouse model of transient middle cerebral artery occlusion (MCAO). We assessed neurological function with modified neurologic severity score (mNSS) test, infarct volume by Nessl staining, angiogenesis and oxidative stress by immunofluorescence analysis, intravital lectin perfusion analysis, western blot analysis and enzyme-linked immunosorbent assay (ELISA). In order to explore the role of Nrf2 in the angiogenesis of MCAO+EGCG-treated mice, we used MAPK/ERK inhibitor PD98059 to block the activation of Nrf2. We found MCAO+EGCG-treated mice had better neurologic outcome, less infarct volume, more number of Ki67/CD31-positive vessels, higher vascular density, unregulated VEGF-VEGFR2 signaling pathway, increased Nrf2 expression and decreased oxidative stress than did MCAO+vehicle-treated mice. Blocking Nrf2 with PD98059 significantly reduced the expression of Nrf2, increased oxidative stress and abolished the angiogenic and neuroprotective effects of EGCG on MCAO mice. We conclude that EGCG treatment in the early stage of ischemic stroke can promote angiogenesis in MCAO mice, possibly via upregulation of Nrf2 signaling pathway.



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Effects of acute caffeine on anxiety-related behavior in rats chronically exposed to the drug, with some evidence of possible withdrawal-reversal

Publication date: 15 March 2017
Source:Behavioural Brain Research, Volume 321
Author(s): Robert N. Hughes, Nicola J. Hancock
For 20days male and female PVG/c hooded rats were provided with caffeinated (approximately 50mg/kg/day) or unadulterated drinking water, and then their anxiety-related behavior was observed in an open field and elevated plus maze. Their choices of a brightness change were also observed in a Y maze to assess any caffeine effects on spatial memory. 24h later, all rats were tested again following an intraperitoneal injection of 50mg/kg acute caffeine, or vehicle. Earlier chronic caffeine decreased ambulation, walking, rearing, center occupancy and increased immobility in the open field thereby suggesting increased anxiety. However, occupancy of the plus-maze open arms and the Y-maze novel arm were increased by caffeine for male rats, but decreased for females probably because of sex differences in control levels of the response rather than to drug effects on anxiety and memory respectively. Following caffeine withdrawal, acute caffeine had the opposite effect to chronic treatment namely, increased open-field ambulation, walking, center occupancy and decreased immobility and defecation for caffeine-naïve rats that were suggestive of decreased anxiety. Similar but more consistent effects (plus decreased emergence latencies from a darkened start box into the open field) also typified the caffeine-experienced rats which in this case may have been accentuated by caffeine withdrawal-reversal. There was no evidence of either chronic or acute caffeine affecting spatial memory measured in the Y maze. There were also examples of lower overall activity and higher anxiety in male rats, than in females, and some sex-dependent caffeine effects.



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Why Good Is More Alike Than Bad: Processing Implications

Publication date: Available online 4 January 2017
Source:Trends in Cognitive Sciences
Author(s): Hans Alves, Alex Koch, Christian Unkelbach
Humans process positive information and negative information differently. These valence asymmetries in processing are often summarized under the observation that 'bad is stronger than good', meaning that negative information has stronger psychological impact (e.g., in feedback, learning, or social interactions). This stronger impact is usually attributed to people's affective or motivational reactions to evaluative information. We present an alternative interpretation of valence asymmetries based on the observation that positive information is more similar than negative information. We explain this higher similarity based on the non-extremity of positive attributes, discuss how it accounts for observable valence asymmetries in cognitive processing, and show how it predicts hitherto undiscovered phenomena.



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The Distributed Nature of Working Memory

Publication date: Available online 4 January 2017
Source:Trends in Cognitive Sciences
Author(s): Thomas B. Christophel, P. Christiaan Klink, Bernhard Spitzer, Pieter R. Roelfsema, John-Dylan Haynes
Studies in humans and non-human primates have provided evidence for storage of working memory contents in multiple regions ranging from sensory to parietal and prefrontal cortex. We discuss potential explanations for these distributed representations: (i) features in sensory regions versus prefrontal cortex differ in the level of abstractness and generalizability; and (ii) features in prefrontal cortex reflect representations that are transformed for guidance of upcoming behavioral actions. We propose that the propensity to produce persistent activity is a general feature of cortical networks. Future studies may have to shift focus from asking where working memory can be observed in the brain to how a range of specialized brain areas together transform sensory information into a delayed behavioral response.



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Brain Oscillations and the Importance of Waveform Shape

Publication date: Available online 4 January 2017
Source:Trends in Cognitive Sciences
Author(s): Scott R. Cole, Bradley Voytek
Oscillations are a prevalent feature of brain recordings. They are believed to play key roles in neural communication and computation. Current analysis methods for studying neural oscillations often implicitly assume that the oscillations are sinusoidal. While these approaches have proven fruitful, we show here that there are numerous instances in which neural oscillations are nonsinusoidal. We highlight approaches to characterize nonsinusoidal features and account for them in traditional spectral analysis. Instead of being a nuisance, we discuss how these nonsinusoidal features may provide crucial and so far overlooked physiological information related to neural communication, computation, and cognition.



http://ift.tt/2iM4jAu

Omission of Intact Parathyroid Hormone Testing During Surgery in Treating Patients With Primary Hyperparathyroidism

Conditions:   Parathyroid Gland Adenoma;   Primary Hyperparathyroidism
Interventions:   Other: Laboratory Biomarker Analysis;   Procedure: Parathyroidectomy
Sponsors:   Roswell Park Cancer Institute;   National Cancer Institute (NCI)
Recruiting - verified January 2017

http://ift.tt/2iHTgpC

Multicenter Phase II Study of Sentinel Node Detection in Squamous Cell Carcinoma T1-T2N0 of the Oropharynx Treated With Radiotherapy and Larynx Treated by Surgery, Laser or Robot

Condition:   Head and Neck Cancer
Intervention:   Procedure: Detection and resection of sentinel lymph node
Sponsor:   Gustave Roussy, Cancer Campus, Grand Paris
Recruiting - verified January 2017

http://ift.tt/2iLV6bt

Effect of Patient Information Leaflet on Working Pattern and Patient Satisfaction Level for Day Care Surgeries.

Condition:   Patient Compliance
Intervention:   Other: Information leaflet
Sponsor:   Tata Memorial Hospital
Not yet recruiting - verified January 2017

http://ift.tt/2iHQ0KS

Combination of Radiation Therapy and Peptide Specific CTL Therapy in Treating Patients With Esophageal Cancer

Conditions:   Esophageal Neoplasms;   Esophageal Diseases;   Digestive System Diseases
Intervention:   Biological: peptide specific CTL
Sponsor:   Shixiu Wu
Recruiting - verified January 2017

http://ift.tt/2iLXxuC

A Novel Robotic System for Single Port and Natural Orifice Transluminal Endoscopic Surgery

Conditions:   Colorectal Neoplasms;   Urologic Neoplasms;   Urologic Diseases;   Nasopharyngeal Neoplasms;   Oropharyngeal Neoplasms;   Oral Neoplasms;   Hypopharyngeal Neoplasms;   Laryngeal Neoplasms;   ENT Diseases
Intervention:   Procedure: Robotic single port surgery and NOTES
Sponsor:   Chinese University of Hong Kong
Recruiting - verified January 2017

http://ift.tt/2iHSclt

Separate effects of the ankylosing spondylitis associated ERAP1 and ERAP2 aminopeptidases determine the influence of their combined phenotype on the HLA-B*27 peptidome

Publication date: Available online 4 January 2017
Source:Journal of Autoimmunity
Author(s): Adrian Martín-Esteban, Alejandro Sanz-Bravo, Pablo Guasp, Eilon Barnea, Arie Admon, José A. López de Castro
Ankylosing spondylitis (AS) is an inflammatory disease strongly associated with the Major Histocompatibility Complex class I (MHC-I) allotype HLA-B*27. The endoplasmic reticulum aminopeptidases (ERAP)1 and 2, which trim peptides to their optimal length for MHC-I binding, are also susceptibility factors for this disease. Both highly active ERAP1 variants and ERAP2 expression favor AS, whereas loss-of-function ERAP1 and loss-of-expression ERAP2 variants are protective. Yet, only ERAP1 is in epistasis with HLA-B*27. We addressed two issues concerning the functional interaction of ERAP1 and ERAP2 with the HLA-B*27 peptidome in human cells: 1) distinguishing the effects of ERAP1 from those of ERAP2, and 2) determining the influence of ERAP2 in distinct ERAP1 contexts. Quantitative comparisons of the HLA-B*27:05 peptidomes from cells with various ERAP1/ERAP2 phenotypes were carried out. When cells expressing ERAP2 and either high or low activity ERAP1 variants were compared, increased amounts of nonamers, relative to longer ligands, and decreased amounts of peptides with Ala1, were observed in the more active ERAP1 context. When cells expressing ERAP2 in a low activity ERAP1 context or lacking ERAP2 but expressing a highly active ERAP1 variant were compared, the same effects on peptide length and Ala1, but also significantly lower amounts of peptides with N-terminal basic residues and lower affinity of the peptidome, were observed in the ERAP2-positive context. Thus, ERAP1 and ERAP2 have significant and distinct effects on the HLA-B*27 peptidome, suggesting that both enzymes largely act as separate entities in vivo. This may explain their different patterns of association with AS.



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The autoimmune risk gene ZMIZ1 is a vitamin D responsive marker of a molecular phenotype of multiple sclerosis

Publication date: Available online 4 January 2017
Source:Journal of Autoimmunity
Author(s): N.L. Fewings, P.N. Gatt, F.C. McKay, G.P. Parnell, S.D. Schibeci, J. Edwards, M.A. Basuki, A. Goldinger, M.J. Fabis-Pedrini, A.G. Kermode, C.P. Manrique, J.L. McCauley, D. Nickles, S.E. Baranzini, T. Burke, S. Vucic, G.J. Stewart, D.R. Booth
Multiple Sclerosis (MS) is a neurological condition driven in part by immune cells from the peripheral circulation, the targets for current successful therapies. The autoimmune and MS risk gene ZMIZ1 is underexpressed in blood in people with MS. We show that, from three independent sets of transcriptomic data, expression of ZMIZ1 is tightly correlated with that of hundreds of other genes. Further we show expression is partially heritable (heritability 0.26), relatively stable over time, predominantly in plasmacytoid dendritic cells and non-classical monocytes, and that levels of ZMIZ1 protein expression are reduced in MS. ZMIZ1 gene expression is increased in response to calcipotriol (1,25 Vitamin D3) (p < 0.0003) and associated with Epstein Barr Virus (EBV) EBNA-1 antibody titre (p < 0.004). MS therapies fingolimod and dimethyl fumarate altered blood ZMIZ1 gene expression compared to untreated MS. The phenotype indicates susceptibility to MS, and may correspond with clinical response and represent a novel clinical target.



http://ift.tt/2iLEfoW

Superoxide Dismutase 3 attenuates experimental Th2-driven allergic conjunctivitis

Publication date: Available online 4 January 2017
Source:Clinical Immunology
Author(s): Hyun Jung Lee, Bo-Mi Kim, Soojung Shin, Tae-Yoon Kim, So-Hyang Chung
Allergic conjunctivitis is an inflammatory eye disease mediated by Th2 type immune response. The role of extracellular superoxide dismutase 3 (SOD3) in immune response and allergic conjunctival inflammation was examined in a murine model for experimental allergic conjunctivitis (EAC). Allergic conjunctivitis was induced in mice by allergen challenge with ovalbumin in alum via the conjunctival sac. SOD3 was topically applied and allergy indicators were compared. Clinical signs associated with conjunctivitis, such as OVA-specific IgE production, IgG1/G2a ratio and eosinophil infiltration, were drastically reduced in mice treated with SOD3. They also had less dendritic cells and CD4⁺ T cells in conjunctiva than controls. Attenuated allergic inflammation was accredited to reduced Th2 type cytokine responses and increased Treg cytokine in draining lymph node. The characteristics of EAC were attributed to the absence of SOD3. Our findings suggest that SOD3 might be considered as a potential target for Th2 driven allergic conjunctival inflammation.



http://ift.tt/2ieJGJF

Alternative splicing at exon 2 results in the loss of the catalytic activity of mouse DNA polymerase iota in vitro

Publication date: Available online 4 January 2017
Source:DNA Repair
Author(s): Konstantin Y. Kazachenko, Nataliya A. Miropolskaya, Leonid V. Gening, Vyacheslav Z. Tarantul, Alena V. Makarova
Y-family DNA polymerase iota (Pol ι) possesses both DNA polymerase and dRP lyase activities and was suggested to be involved in DNA translesion synthesis and base excision repair in mammals. The 129 strain of mice and its derivatives have a natural nonsense codon mutation in the second exon of the Pol ι gene resulting in truncation of the Pol ι protein. These mice were widely used as a Pol ι-null model for in vivo studies of the Pol ι function. However whether 129-derived strains of mice are fully deficient in the Pol ι functions was a subject of discussion since Pol ι mRNA undergoes alternative splicing at exon 2. Here we report purification of mouse Pol ι lacking the region encoded by exon 2, which includes several conserved residues involved in catalysis. We show that the deletion abrogates both the DNA polymerase and dRP lyase activities of Pol ι in the presence of either Mg²⁺ or Mn²⁺ ions. Thus, 129-derived strains of mice express catalytically inactive alternatively spliced Pol ι variant, whose cellular functions, if any exist, remain to be established.



http://ift.tt/2iLFeFZ

Cell cycle-dependent positive and negative functions of Fun30 chromatin remodeler in DNA damage response

Publication date: Available online 5 January 2017
Source:DNA Repair
Author(s): Jasmine Siler, Bowen Xia, Carina Wong, Morgan Kath, Xin Bi
The evolutionally conserved Fun30 chromatin remodeler in Saccharomyces cerevisiae has been shown to contribute to cellular resistance to genotoxic stress inflicted by camptothecin (CPT), methyl methanesulfonate (MMS) and hydroxyurea (HU). Fun30 aids in extensive DNA resection of DNA double stranded break (DSB) ends, which is thought to underlie its role in CPT-resistance. How Fun30 promotes MMS- or HU-resistance has not been resolved. Interestingly, we have recently found Fun30 to also play a negative role in cellular tolerance to MMS and HU in the absence of the Rad5-dependent DNA damage tolerance pathway. In this report, we show that Fun30 acts to down regulate Rad9-dependent DNA damage checkpoint triggered by CPT or MMS, but does not affect Rad9-independent intra-S phase replication checkpoint induced by MMS or HU. These results support the notion that Fun30 contributes to cellular response to DSBs by preventing excessive DNA damage checkpoint activation in addition to its role in facilitating DNA end resection. On the other hand, we present evidence suggesting that Fun30's negative function in MMS- and HU-tolerance in the absence of Rad5 is not related to its regulation of checkpoint activity. Moreover, we find Fun30 to be cell cycle regulated with its abundance peaking in G2/M phase of the cell cycle. Importantly, we demonstrate that artificially restricting Fun30 expression to G2/M does not affect its positive or negative function in genotoxin-resistance, but confining Fun30 to S phase abolishes its functions. These results indicate that both positive and negative functions of Fun30 in DNA damage response occur mainly in G2/M phase.



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Post-WBRT cognitive impairment and hippocampal neuronal depletion measured by in vivo metabolic MR spectroscopy: Results of prospective investigational study

Publication date: Available online 4 January 2017
Source:Radiotherapy and Oncology
Author(s): Petr Pospisil, Tomas Kazda, Ludmila Hynkova, Martin Bulik, Marie Dobiaskova, Petr Burkon, Nadia N. Laack, Pavel Slampa, Radim Jancalek
Background and purposeThe aim of this prospective study is to evaluate post-whole brain radiotherapy (WBRT) changes in hippocampal concentration of N-acetylaspartate (h-tNAA) as a marker of neuronal loss and to correlate those changes to neurocognitive function.Material and methodsThirty-five patients with brain metastases underwent baseline single slice multi-voxel MR spectroscopy (MRS) examination for measurement of hippocampal h-tNAA together with baseline battery of neurocognitive tests focused on memory (Auditory Verbal Learning Test and Brief Visuospatial Memory Test – Revised) as well as quality of life questionnaires (EORTC QLQ-C30 a EORTC QLQ-BN20). Eighteen patients completed follow-up evaluation four months after standard WBRT (2 laterolateral fields, 10×3.0Gy, 6MV photons) and were included in this analysis. MRS and cognitive examinations were repeated and compared to baseline measurements.ResultsStatistically significant decreases in h-tNAA were observed in the right (8.52–7.42mM; −12.9%, 95%CI: −7.6 to −16.4%) as well as in the left hippocampus (8.64–7.60mM; −12%, 95%CI: −7.9 to −16.2%). Statistically significant decline was observed in all AVLT and BVMT-R subtests with exception of AVLT_Recognition. Quality of life declined after WBRT (mean Δ −14.1±20.3 points in transformed 0–100 point scale; p=0.018) with no correlation to changes in hippocampal metabolite concentrations. Moderate positive correlation was observed between left h-tNAA concentration decrease and AVLT_TR decline (r=+0.32; p=0.24) as well as with AVLT_DR (r=+0.33; p=0.22) decline. Changes in right h-tNAA/Cr negatively correlated with AVLT_DR (r=−0.48; p=0.061). No correlation between right hippocampus h-tNAA and memory decline (AVLT) was observed.ConclusionsOur results suggest hippocampal NAA concentrations decline after WBRT and MRS may be a useful biomarker for monitoring neuronal loss after radiotherapy.



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Ipsilateral axillary recurrence after breast conservative surgery: The protective effect of whole breast radiotherapy

Publication date: Available online 4 January 2017
Source:Radiotherapy and Oncology
Author(s): Oreste Gentilini, Edoardo Botteri, Maria Cristina Leonardi, Nicole Rotmensz, Jose Vila, Nickolas Peradze, Maria Virginia Thomazini, Barbara Alicja Jereczek, Viviana Galimberti, Alberto Luini, Paolo Veronesi, Roberto Orecchia
Background and purposeWhole breast radiotherapy (WBRT) is one of the possible reasons for the low rate of axillary recurrence after breast-conserving surgery (BCS).Patients and methodsWe retrospectively collected data from 4,129 consecutive patients with breast cancer ⩽2cm and negative sentinel lymph node who underwent BCS between 1997 and 2007. We compared the risk of axillary lymph node recurrence between patients treated by WBRT (n=2939) and patients who received partial breast irradiation (PBI; n=1,190) performed by a single dose of electron intraoperative radiotherapy.ResultsMedian tumour diameter was 1.1cm in both WBRT and PBI. Women who received WBRT were significantly younger and expressed significantly more multifocality, extensive in situ component, negative oestrogen receptor status and HER2 over-expression than women who received PBI. After a median follow-up of 8.3years, 37 and 28 axillary recurrences were observed in the WBRT and PBI arm, respectively, corresponding to a 10-year cumulative incidence of 1.3% and 4.0% (P<0.001). Multivariate analysis resulted in a hazard ratio of 0.30 (95% CI 0.17–0.51) in favour of WBRT.ConclusionsIn this large series of women with T1 breast cancer and negative sentinel lymph node treated by BCS, WBRT lowered the risk of axillary recurrence by two thirds as compared to PBI.



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Association of post-treatment positron emission tomography with locoregional control and survival after radiation therapy for squamous cell carcinoma of the vulva

Publication date: Available online 4 January 2017
Source:Radiotherapy and Oncology
Author(s): Yuan James Rao, Comron Hassanzadeh, Anupama Chundury, Caressa Hui, Barry A. Siegel, Farrokh Dehdashti, Todd DeWees, Daniel Mullen, Matthew A. Powell, David G. Mutch, Julie K. Schwarz, Perry W. Grigsby
Background/purposeThe aim of this study was to investigate the use of post-treatment F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for vulvar cancer and compare metabolic response to clinical outcomes.Materials/methodsThis retrospective study included 21 patients with vulvar squamous cell carcinoma treated with curative-intent radiation between 2007 and 2015. All patients received intensity-modulated radiation treatment (IMRT), a pre-treatment FDG/PET-CT, and a post-treatment FDG-PET/CT performed at a median time of 3months post-IMRT.ResultsMedian follow-up time was 28months. Post-treatment FDG-PET/CT demonstrated no evidence of disease (NED) in 12 patients and residual or progressive disease (PD) in 9. FDG-PET/CT response significantly correlated with biopsy-proven locoregional failure (p=0.02) and was the only significant factor associated with overall survival (OS) (p=0.049). Patients with NED on FDG-PET had a 2-year locoregional control (LRC) of 89% versus 25% for those with PD (p<0.01). Patients with NED on FDG-PET/CT had a 2-year OS of 100% versus 42% for those with PD (p=0.02). FDG-PET/CT evaluation had a sensitivity of 100% and a specificity of 71% for detecting pathologically proven residual disease in patients receiving neoadjuvant or definitive radiation.ConclusionIn this single-institution study of women with vulvar cancer, post-treatment response on FDG-PET/CT was associated with LRC and OS.



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LAT alleviates Th2/Treg imbalance in an OVA-induced allergic asthma mouse model through LAT-PLC-γ1 interaction

Publication date: March 2017
Source:International Immunopharmacology, Volume 44
Author(s): Xi Chen, Xiao-ming Li, Wen Gu, Di Wang, Yi Chen, Xue-jun Guo
IntroductionLow expression of linker for activation of T cells (LAT) is observed in asthma. LAT and its downstream regulator, phospholipase C-gamma 1 (PLC-γ1) play important roles in the T cell antigen receptor signaling pathway, and their interaction is associated with CD4⁺ cell polarization. Here, we investigated whether LAT can alleviate the imbalance among CD4⁺ cell subgroups and the possible mechanism.MethodsAn ovalbumin-induced allergic asthma mouse model was established and LAT plasmid was delivered. The pathological changes in lung were evaluated by hematoxylin and eosin and periodic acid-Schiff staining. The typical cytokines released by T helper 2 (Th2) and regulatory T (Treg) cells were measured using enzyme-linked immunosorbent assay and the number of Th1, Th2, and Treg cells were determined using flow cytometry. Lung CD4⁺ T cells were isolated by magnetic isolation. The mRNA expression of LAT and PLC-γ1 was determined by real-time PCR. Co-Immunoprecipitation was performed to confirm the interaction between LAT and PLC-γ1. The protein expression of LAT, PLC-γ1 and corresponding downstream signaling factors were determined by western blotting.ResultsThe delivery of LAT DNA to the lung could suppress an overactive Th2 response by decreasing allergic response and Th2 cytokine secretion, and by increasing Treg cytokine secretion. The Th2/Treg imbalance in lung and decreased phosphorylated PLC-γ1 expression in lung CD4⁺ T cells were rectified by LAT DNA delivery. Excessive activation of the Raf-MEK-ERK and PI3K-AKT-CREB pathways after asthma is attenuated by LAT.ConclusionThe site-specific delivery of LAT DNA to the lung could suppress an overactive Th2 response and rectify the Th2/Treg imbalance in asthmatic mouse model. LAT-PLC-γ1 interaction may contribute to LAT activity in vivo and LAT protects against asthma partly via Raf-MEK-ERK and PI3K-AKT-CREB pathways. The delivery of LAT DNA could offer a novel and safe strategy for asthma prevention.



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Does photobiomodulation therapy is better than cryotherapy in muscle recovery after a high-intensity exercise? A randomized, double-blind, placebo-controlled clinical trial

Abstract

This study aimed to determine the effectiveness of photobiomodulation therapy (PBMT) and cryotherapy, in isolated and combined forms, as muscle recovery techniques after muscle fatigue-inducing protocol. Forty volunteers were randomly divided into five groups: a placebo group (PG); a PBMT group (PBMT); a cryotherapy group (CG); a cryotherapy-PBMT group (CPG); and a PBMT-cryotherapy group (PCG). All subjects performed four sessions at 24-h intervals, during which they submitted to isometric assessment (MVC) and blood collection in the pre-exercise period, and 5 and 60 min post-exercise, while the muscle fatigue induction protocol occurred after the pre-exercise collections. In the remaining sessions performed 24, 48, and 72 h later, only blood collections and MVCs were performed. A single treatment with PBMT and/or cryotherapy was applied after only 2 min of completing the post-5-min MVC test at the first session. In the intragroup comparison, it was found that exercise led to a significant decrease (p < 0.05) in the production of MVC in all groups. Comparing the results of MVCs between groups, we observed significant increases in the MVC capacity of the PBMT, CPG, and PCG volunteers in comparison with both PG and CG (p < 0.05). We observed a significant decrease in the concentrations of the biochemical markers of oxidative damage (TBARS and PC) in all groups and muscle damage (creatine kinase—CK) in the PBMT, PCG, and CPG compared with the PG (p < 0.01). The clinical impact of these findings is clear because they demonstrate that the use of phototherapy is more effective than the use of cryotherapy for muscle recovery, additionally cryotherapy decreases PBMT efficacy.

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Circulating microRNAs as Potential Diagnostic, Prognostic and Therapeutic Targets in Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a very poor prognosis, and excessive resistance to chemotherapy. MicroRNAs have been shown to play important roles in PDAC oncogenesis as they can act as both oncogenes and tumor suppressor molecules. Altered expression of specific microRNAs in PDAC has diagnostic and prognostic implications. There is growing body of evidence showing the important role of miR-486-5p and miR-938 for discrimination of PDAC patients from healthy subjects and those with chronic pancreatitis. Additionally the diagnostic features of miR-486-5p were comparable with CA 19-9 for the detection of PDAC patients, suggesting its diagnostic value as a blood-based miRNA in PDAC, although further investigations are warranted for validation of this marker. In addition to these applications, several studies have suggested therapeutic potential of some miRNAs in PDAC. In particular, modulations of let-7, miR-29a, miR-17-5p, miR-365, miR-181b, miR-21, miR-221 and miR-96 are reported to be associated with tumor response. Moreover, enforced expression of miR-17-92 inhibits tumourigenicity and increased chemoresistance in PDAC cancer stem cells via TGF-β1 pathway, while overexpression of miR-96 suppresses cell proliferation, migration, and invasion in a manner associated with KRAS downregulation. In this review we attempt to give an overview about recent preclinical and clinical studies that have addressed the potential use of circulating microRNAs as diagnostic and prognostic biomarkers, their use as therapeutic targets and finally, we discuss the possible role of microRNAs in PDAC chemoresistance.

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SHARPIN Facilitates p53 Degradation in Breast Cancer Cells

Publication date: February 2017
Source:Neoplasia, Volume 19, Issue 2
Author(s): Huijie Yang, Sifan Yu, Weilong Wang, Xin Li, Yingxiang Hou, Zhenhua Liu, Yuanyuan Shi, Kun Mu, Gang Niu, Juntao Xu, Hui Wang, Jian Zhu, Ting Zhuang
The ubiquitin binding protein SHAPRIN is highly expressed in human breast cancer, one of the most frequent female malignancies worldwide. Here, we perform SHARPIN depletion in breast cancer cells together with RNA sequencing. The global expression profiling showed p53 signaling as a potential SHARPIN target. SHARPIN depletion decreased cell proliferation, which effect could be rescue by p53 knocking down. Depletion SHARPIN significantly increases p53 protein level and its target genes in multiple breast cancer cell lines. Further experiment revealed that SHARPIN could facilitate p53 poly-ubiquitination and degradation in MDM2 dependent manner. Immuno-precipitation assay showed that SHARPIN associated with MDM2 and prolonged MDM2 protein stability. Analysis of public available database showed SHARPIN correlated with poor prognosis specifically in p53 wild-type breast cancer patients. Together, our finding revealed a novel modifier for p53/MDM2 complex and suggested SHARPIN as a promising target to restore p53 function in breast cancer.



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Follicular lymphoma in situ in the spleen of a patient with autoimmune hemolytic anemia and carrying HCV was associated with more clonal B-cells than t(14;18) positive B-cells

Publication date: Available online 4 January 2017
Source:Pathology - Research and Practice
Author(s): Makoto Kashimura, Masaru Kojima, Naoki Matsuyama, Jirou Tadokoro
Certain autoimmune conditions are associated with an increased risk of lymphoid malignancy. We report a 65-year old patient with autoimmune hemolytic anemia (AIHA) complicated by a follicular lymphoma (FL) in situ and other B-cell clones in the spleen. This diagnosis was made by immunohistochemistry, flow cytometry, and Southern blot analysis of the B-cell receptor. Chromosomal analysis revealed 46,XX,t(14;18)(q32;q21) 2/20, 46,XX,del(7)(q?),del(11)(q?) 2/20, and 46,XX 16/20. It has been speculated that these preneoplastic conditions do not progress to overt FL and other lymphomas without a second lymphomagenic insult. However, AIHA confers a 27.4-fold higher risk of such an insult leading to lymphoma compared with the normal healthy population. Without any therapy after splenectomy, our current study patient remained healthy with no lymphoma development for 28 months. Based on this case, we discuss the pathophysiology of lymphomagenesis in a spleen with AIHA and the roles of a splenectomy for preventing further lymphomagenesis in AIHA patients.



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Nanomaterials-based sensitive electrochemiluminescence biosensing

Publication date: Available online 4 January 2017
Source:Nano Today
Author(s): Ying Chen, Shiwei Zhou, Lingling Li, Jun-jie Zhu
Nanomaterials with wonderful optical, electrical and chemical properties are widely studied in recent decades. In electrochemiluminescence (ECL) sensing area, nanomaterials have also gained crescent attention for their excellent performance based on different functions, such as innovative luminophores, molecule carriers, electrode modification materials and reaction catalysts. Deep insight into ECL biosensing strategies with multifunctional nanomaterials will benefit the design of advanced sensors. Based on this, nanomaterials-based ECL biosensors have shown more promising potentials than traditional ones in analytical applications. After a brief overview of basic ECL principles and sensing approaches, herein, a general description of nanomaterials-based ECL biosensing is presented, especially with emphasis on recently developed ECL resonance energy transfer (ECL-RET) strategy. Finally, future outlooks are considered in building sensitive ECL biosensors.

Graphical abstract

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USA300, A strain of community-associated methicillin-resistant Staphylococcus aureus, crossing Belgium's borders: outbreak of skin and soft tissue infections in a hospital in Belgium.

Related Articles

USA300, A strain of community-associated methicillin-resistant Staphylococcus aureus, crossing Belgium's borders: outbreak of skin and soft tissue infections in a hospital in Belgium.

Eur J Clin Microbiol Infect Dis. 2017 Jan 03;:

Authors: Kaïret K, Ho E, Van Kerkhoven D, Boes J, Van Calenbergh S, Pattyn L, Lemay P

Abstract
OBJECTIVE: to investigate an outbreak of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) USA300 in a hospital setting, and the effect of infection control measures.
DESIGN: outbreak investigation and retrospective chart review.
SETTING: local inpatient and outpatient clinic.
PATIENTS: all patients with a history of skin and soft tissue infections with culture-confirmed methicillin-resistant Staphylococcus aureus USA 300 infection from September, 2014, through June, 2015.
INTERVENTIONS: an outbreak investigation with a "search and destroy" policy was carried out. A review of infection control practices was conducted. Chart reviews were conducted to study the management and outcomes of the patients. Infection control measures included education and cultures of skin colonization sites (anterior nares, pharynx, perineum). Specific decontamination schemes for uncomplicated and complicated carriers were enforced. Separate decontamination schemes for neonates and children under 5 years of age were implemented.
RESULTS: between September 2014 and June 2015, 12 clinical cases and six carriers were identified. Of the twelve clinical presentations with positive cultures, eight were children. Of the four patients who had a relapse, three were children (75%). After outbreak investigation and infection control measures have been implemented, three persistent carriers remained. A policy of periodic screening, consultation, and watchful waiting for skin infections was instituted for these patients. No new cases linked to the CA-MRSA outbreak have since been reported.
CONCLUSION: we report the first Belgian outbreak of CA-MRSA USA300 in this article. A strict search and destroy strategy and continued surveillance are required in the management of CA-MRSA USA300.

PMID: 28050669 [PubMed - as supplied by publisher]

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A Letter to Program Directors: Global Surgery Rotations Are a Plus

Publication date: Available online 4 January 2017
Source:Journal of Surgical Education
Author(s): Shailvi Gupta, Clifton Ewbank, Adam L. Kushner




http://ift.tt/2hU1zwA

Validating proposed migration equation and parameters' values as a tool to reproduce and predict 137Cs vertical migration activity in Spanish soils

Publication date: April 2017
Source:Journal of Environmental Radioactivity, Volumes 169–170
Author(s): C. Olondo, F. Legarda, M. Herranz, R. Idoeta
This paper shows the procedure performed to validate the migration equation and the migration parameters' values presented in a previous paper (Legarda et al., 2011) regarding the migration of ¹³⁷Cs in Spanish mainland soils.In this paper, this model validation has been carried out checking experimentally obtained activity concentration values against those predicted by the model. This experimental data come from the measured vertical activity profiles of 8 new sampling points which are located in northern Spain. Before testing predicted values of the model, the uncertainty of those values has been assessed with the appropriate uncertainty analysis. Once establishing the uncertainty of the model, both activity concentration values, experimental versus model predicted ones, have been compared. Model validation has been performed analyzing its accuracy, studying it as a whole and also at different depth intervals. As a result, this model has been validated as a tool to predict ¹³⁷Cs behaviour in a Mediterranean environment.

Graphical abstract

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Reduced Hippocampal Functional Connectivity During Episodic Memory Retrieval in Autism

Increasing recent research has sought to understand the recollection impairments experienced by individuals with autism spectrum disorder (ASD). Here, we tested whether these memory deficits reflect a reduction in the probability of retrieval success or in the precision of memory representations. We also used functional magnetic resonance imaging (fMRI) to study the neural mechanisms underlying memory encoding and retrieval in ASD, focusing particularly on the functional connectivity of core episodic memory networks. Adults with ASD and typical control participants completed a memory task that involved studying visual displays and subsequently using a continuous dial to recreate their appearance. The ASD group exhibited reduced retrieval success, but there was no evidence of a difference in retrieval precision. fMRI data revealed similar patterns of brain activity and functional connectivity during memory encoding in the 2 groups, though encoding-related lateral frontal activity predicted subsequent retrieval success only in the control group. During memory retrieval, the ASD group exhibited attenuated lateral frontal activity and substantially reduced hippocampal connectivity, particularly between hippocampus and regions of the fronto-parietal control network. These findings demonstrate notable differences in brain function during episodic memory retrieval in ASD and highlight the importance of functional connectivity to understanding recollection-related retrieval deficits in this population.

http://ift.tt/2iL4Qml

The Neuro-Computational Architecture of Value-Based Selection in the Human Brain

Current neural models of value-based decision-making consider choices as a 2-stage process, proceeding from the "valuation" of each option under consideration to the "selection" of the best option on the basis of their subjective values. However, little is known about the computational mechanisms at play at the selection stage and its implementation in the human brain. Here, we used drift-diffusion models combined with model-based functional magnetic resonance imaging, effective connectivity, and multivariate pattern analysis to characterize the neuro-computational architecture of value-based decisions. We found that 2 key drift-diffusion computations at the selection stage, namely integration and choice readout, engage distinct brain regions, with the dorsolateral prefrontal cortex integrating a decision value signal computed in the ventromedial prefrontal cortex, and the posterior parietal cortex reading out choice outcomes. Our findings suggest that this prefronto-parietal network acts as a hub implementing behavioral selection through a distributed drift-diffusion process.

http://ift.tt/2iL8xbB

Preference for Cocaine is Represented in the Orbitofrontal Cortex by an Increased Proportion of Cocaine Use-Coding Neurons

Cocaine addiction is a harmful preference for drug use over and at the expense of other nondrug-related activities. Here we identify in the rat orbitofrontal cortex (OFC) a mechanism that explains individual preferences between cocaine use and an alternative, nondrug action. OFC neuronal activity was recorded while rats performed each of these 2 actions separately or while they chose between them. First, we found that these actions are encoded by 2 nonoverlapping neuronal populations and that the relative size of the cocaine population represented individual preferences. A larger relative size was only observed in cocaine-preferring individuals. Second, OFC neurons encoding a given individual's preferred action progressively fired more than other action-coding neurons few seconds before the preferred action was actually chosen, suggesting a prechoice neuronal competition for action selection. In cocaine-preferring rats, this manifested by a prechoice ramping-up activity in favor of the cocaine population. Finally, pharmacological manipulation of prechoice activity in favor of the cocaine population caused nondrug-preferring rats to shift their choice to cocaine. Overall, this study suggests that an individual preference for cocaine is represented in the OFC by a population size bias that systematically advantages cocaine use-coding neurons during prechoice competition for action selection.

http://ift.tt/2iGTKfy

In Vivo Evidence of Reduced Integrity of the Gray-White Matter Boundary in Autism Spectrum Disorder

Atypical cortical organization and reduced integrity of the gray–white matter boundary have been reported by postmortem studies in individuals with autism spectrum disorder (ASD). However, there are no in vivo studies that examine these particular features of cortical organization in ASD. Hence, we used structural magnetic resonance imaging to examine differences in tissue contrast between gray and white matter in 98 adults with ASD and 98 typically developing controls, to test the hypothesis that individuals with ASD have significantly reduced tissue contrast. More specifically, we examined contrast as a percentage between gray and white matter tissue signal intensities (GWPC) sampled at the gray–white matter boundary, and across different cortical layers. We found that individuals with ASD had significantly reduced GWPC in several clusters throughout the cortex (cluster, P < 0.05). As expected, these reductions were greatest when tissue intensities were sampled close to gray–white matter interface, which indicates a less distinct gray–white matter boundary in ASD. Our in vivo findings of reduced GWPC in ASD are therefore consistent with prior postmortem findings of a less well-defined gray–white matter boundary in ASD. Taken together, these results indicate that GWPC might be utilized as an in vivo proxy measure of atypical cortical microstructural organization in future studies.

http://ift.tt/2iH032D

Causal Evidence of Motion Signals in Macaque Middle Temporal Area Weighted-Pooled for Global Heading Perception

Accurate heading perception relies on visual information integrated across a wide field, that is, optic flow. Numerous computational studies have speculated how local visual information might be pooled by the brain to compute heading, but these hypotheses lack direct neurophysiological support. In the current study, we instructed human and monkey subjects to judge heading directions based on global optic flow. We showed that a local perturbation cue applied within only a small part of the visual field could bias the subjects' heading judgments, and shift the neuronal tuning in the macaque middle temporal (MT) area at the same time. Electrical microstimulation in MT significantly biased the animals' heading judgments predictable from the tuning of the stimulated neurons. Masking the visual stimuli within these neurons' receptive fields could not remove the stimulation effect, indicating a sufficient role of the MT signals pooled by downstream neurons for global heading estimation. Interestingly, this pooling is not homogeneous because stimulating neurons with excitatory surrounds produced relatively larger effects than stimulating neurons with inhibitory surrounds. Thus our data not only provide direct causal evidence, but also new insights into the neural mechanisms of pooling local motion information for global heading estimation.

http://ift.tt/2iL53ps

How the Brain Converts Negative Evaluation into Performance Facilitation

Surpassing negative evaluation is a recurrent theme of success stories. Yet, there is little evidence supporting the counterintuitive idea that negative evaluation might not only motivate people, but also enhance performance. To address this question, we designed a task that required participants to decide whether taking up a risky challenge after receiving positive or negative evaluations from independent judges. Participants believed that these evaluations were based on their prior performance on a related task. Results showed that negative evaluation caused a facilitation in performance. Concurrent functional magnetic resonance imaging revealed that the motivating effect of negative evaluation was represented in the insula and striatum, while the performance boost was associated with functional positive connectivity between the insula and a set of brain regions involved in goal-directed behavior and the orienting of attention. These findings provide new insight into the neural representation of negative evaluation-induced facilitation.

http://ift.tt/2iGSDN4

Enteric glial reactivity to systemic LPS administration: Changes in GFAP and S100B protein

Publication date: Available online 4 January 2017
Source:Neuroscience Research
Author(s): Raphaela da Cunha Franceschi, Patrícia Nardin, Clivia Valle Machado, Lucas Silva Tortorelli, Malcon Andrei Martinez-Pereira, Carolline Zanotto, Carlos Alberto Gonçalves, Denise Maria Zancan
Lipopolysaccharide (LPS) is used to induce inflammation and promotes nervous system activation. Different regions of the brain present heterogeneous glial responses; thus, in order to verify whether systemic LPS-induced inflammation affects the enteric glia differently across the intestinal segments, we evaluated the expressions of two glial activity markers, GFAP and S100B protein, in different intestine segments, at 1h, 24h and 7days after acute systemic LPS administration (0.25 or 2.5mg kg–1) in rats. Histological inflammatory analysis indicated that the cecum was most affected when compared to the duodenum and proximal colon at the highest doses of LPS. LPS induced an increased S100B content after 24h in all three regions, which decreased at 7days after the highest dose in all regions. Moreover, at 24h, this dose of LPS increased ex-vivo S100B secretion only in the cecum. The highest dose of LPS also increased GFAP in all regions at 24h, but earlier in the cecum, where LPS-induced enteric S100B and GFAP alterations were dependent on dose, time and intestine region. No associated changes in serum S100B were observed. Our results indicate heterogeneous enteric glial responses to inflammatory insult, as observed in distinct brain areas.



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Submicron particle dynamics for different surfaces under quiescent and turbulent conditions

Publication date: March 2017
Source:Atmospheric Environment, Volume 152
Author(s): Karn Vohra, Kunal Ghosh, S.N. Tripathi, I. Thangamani, P. Goyal, Anu Dutta, V. Verma
Experiments were conducted using CsI aerosols in a small scale test chamber to simulate behaviour of aerosols in the containment of a nuclear reactor. The primary focus of the study was on submicron particles (14.3 nm–697.8 nm) due to their hazardous effect on human health. Different wall surfaces, viz., plexiglass, concrete and sandpaper were chosen to study the effect of surface roughness on dry deposition velocity under both quiescent and turbulent conditions. An analytical approach to calculate dry deposition velocity of submicron particles for rough surfaces has been proposed with an improvement in the existing parameterization for shift in the velocity boundary layer. The predicted deposition velocity with the improved parameterization was found to have better agreement with published measured data of Lai and Nazaroff (2005) compared to the existing parameterizations (Wood, 1981; Zhao and Wu, 2006b). There was a significant reduction in root mean square error (RMSE) between predicted, using the improved parameterization and measured deposition velocity (upto 100%) compared to earlier ones. The new analytical deposition approach was coupled with volume conserving semi-implicit coagulation model. This aerosol dynamic model was evaluated against explicit particle size distribution for the first time for rough surfaces. Normalized RMSE between simulated and measured particle size distribution varied in the range of 2%–20% at different instances. The model seems to closely predict submicron particle behaviour in indoor environment.



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Multiphase reactivity of gaseous hydroperoxide oligomers produced from isoprene ozonolysis in the presence of acidified aerosols

Publication date: March 2017
Source:Atmospheric Environment, Volume 152
Author(s): Matthieu Riva, Sri Hapsari Budisulistiorini, Zhenfa Zhang, Avram Gold, Joel A. Thornton, Barbara J. Turpin, Jason D. Surratt
Ozonolysis of alkenes results in the formation of primary ozonides (POZs), which can subsequently decompose into carbonyl compounds and stabilized Criegee intermediates (sCIs). The sCIs generated from isoprene ozonolysis include the simplest congener, formaldehyde oxide (CH2OO), and isomers of C4-sCI. Although the bimolecular reaction with H2O is expected to be the main fate of sCIs, it was reported that sCIs can also react with carboxylic acids and/or organic hydroperoxides leading to gas-phase oligomeric compounds. While the impact of the gas-phase composition (H2O, sCI scavenger) on the formation of such products was recently studied, their fate remains unclear. In the present work, formation of oligomeric hydroperoxides from isoprene ozonolysis, proposed as reaction products composed of the sCI as a chain unit and formed from the insertion of sCI into a hydroperoxide or a carboxylic acid, was systematically examined in the presence of aerosol with varying compositions. The effect of hydroxyl (OH) radicals on the gas- and particle-phase compositions was investigated using diethyl ether as an OH radical scavenger. Thirty-four oligomeric compounds resulting from the insertion of sCIs into organic hydroperoxides or carboxylic acids were identified using iodide chemical ionization high-resolution mass spectrometry. Large reactive uptake onto acidified sulfate aerosol was observed for most of the characterized gaseous oligomeric species, whereas the presence of organic coatings and the lack of aerosol water significantly reduced or halted the reactive uptake of these species. These results indicate that highly oxidized molecules, such as hydroperoxides, could undergo multiphase reactions, which are significantly influenced by the chemical composition of seed aerosol. Furthermore, in addition to functionalization and accretion, decomposition and re-volatilization should be considered in SOA formation.



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H9N2 avian influenza virus enhances the immune responses of BMDCs by down-regulating miR29c

Publication date: Available online 4 January 2017
Source:Vaccine
Author(s): Jian Lin, Jing Xia, Ya T. Chen, Ke Y. Zhang, Yan Zeng, Qian Yang
Avian influenza virus (AIV) of the subtypes H9 and N2 is well recognised and caused outbreaks-due to its high genetic variability and high rate of recombination with other influenza virus subtypes. The pathogenicity of H9N2 AIV depends on the host immune response. Dendritic cells (DCs) are major antigen presenting cells that can significantly inhibit H9N2 AIV replication. MicroRNAs (miRNAs) influence the ability of DCs to present antigens, as well as the ability of AIVs to infect host cells and replicate. Here, we studied the molecular mechanism underlying the miRNA-mediated regulation of immune function of mouse DCs. We first screened for and verified the induction of miRNAs in DCs after H9N2 AIVstimulation. We also constructed miR29c, miR339 and miR222 over-expression vector and showed that only the induction of miR29c lead to a hugely increased expression of surface marker MHCII and CD40. Whilst the inhibition of miR29c, miR339 and miR222 in mouse DCs would repressed the expression of DCs surface markers. Moreover, we found that miR29c stimulation not only up-regulate MHCII and CD40, but also enhance the ability of DCs to activate lymphocytes and secrete cytokines IL-6 or TNF-a. Furthermore, we found that Tarbp1 and Rfx7 were targeted and repressed by miR29c. Finally, we revealed that the inhibition of miR29c marvelously accelerated virus replication. Together, our data shed new light on the roles and mechanisms of miR29c in regulating DC function and suggest new strategies for combating AIVs.



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Associations of trust and healthcare provider advice with HPV vaccine acceptance among African American parents

Publication date: Available online 4 January 2017
Source:Vaccine
Author(s): Linda Y. Fu, Gregory D. Zimet, Carl A. Latkin, Jill G. Joseph
ObjectiveHealthcare providers (HCPs) are advised to give all parents a strong recommendation for HPV vaccination. However, it is possible that strong recommendations could be less effective at promoting vaccination among African Americans who on average have greater mistrust in the healthcare system. This study examines the associations of parental trust in HCPs and strength of HCP vaccination recommendation on HPV vaccine acceptance among African American parents.MethodsParticipants were recruited from an urban, academic medical center between July 2012 and July 2014. We surveyed 400 African American parents of children ages 10–12years who were offered HPV vaccine by their HCPs to assess sociodemographic factors, vaccine beliefs, trust in HCPs, and the HPV vaccine recommendation received. Medical records were reviewed to determine vaccination receipt.ResultsIn multivariable analysis, children whose parents were "very strongly" recommended the HPV vaccine had over four times higher odds of vaccine receipt compared with those whose parents were "not very strongly" recommended the vaccine. Having a parent with "a lot of" versus "none" or only "some" trust in HCPs was associated with over twice the odds of receiving HPV vaccine. Very strong HCP recommendations were associated with higher odds of vaccination among all subgroups, including those with more negative baseline attitudes toward HPV vaccine and those with lower levels of trust. Adding the variables strength of HCP recommendation and parental trust in HCPs to a multivariable model already adjusted for sociodemographic factors and parental vaccine beliefs improved the pseudo R² from 0.52 to 0.55.ConclusionsAmong participants, receiving a strong vaccine recommendation and having a higher level of trust in HCPs were associated with higher odds of HPV vaccination, but did not add much to the predictive value of a model that already adjusted for baseline personal beliefs and sociodemographic factors.



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A novel vaccinological evaluation of intranasal vaccine and adjuvant safety for preclinical tests

Publication date: Available online 4 January 2017
Source:Vaccine
Author(s): Eita Sasaki, Madoka Kuramitsu, Haruka Momose, Kouji Kobiyama, Taiki Aoshi, Hiroshi Yamada, Ken J. Ishii, Takuo Mizukami, Isao Hamaguchi
Vaccines are administered to healthy humans, including infants, so the safety and efficacy must be very high. Therefore, evaluating vaccine safety in preclinical and clinical studies, according to World Health Organization guidelines, is crucial for vaccine development and clinical use. A change in the route of administration is considered to alter a vaccine's immunogenicity. Several adjuvants have also been developed and approved for use in vaccines. However, the addition of adjuvants to vaccines may cause unwanted immune responses, including facial nerve paralysis and narcolepsy. Therefore, a more accurate and comprehensive strategy must be used to develope next-generation vaccines for ensuring vaccine safety. Previously, we have developed a system with which to evaluate vaccine safety in rats using a systematic vaccinological approach and 20 marker genes. In this study, we developed a safety evaluation system for nasally administered influenza vaccines and adjuvanted influenza vaccines using these marker genes. Expression of these genes increased dose-dependent manner when mice were intranasally administered the toxicity reference vaccine. When the adjuvant CpG K3 or a CpG-K3-combined influenza vaccine was administered intranasally, marker gene expression increased in a CpG-K3-dose-dependent way. A histopathological analysis indicated that marker gene expression correlated with vaccine- or adjuvant-induced phenotypic changes in the lung and nasal mucosa. We believe that the marker genes expression analyses will be useful in preclinical testing, adjuvant development, and selecting the appropriate dose of adjuvant in nasal administration vaccines.



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Immunization with Salmonella Enteritidis secreting mucosal adjuvant labile toxin confers protection against wild type challenge via augmentation of CD3+CD4+ T-cell proliferation and enhancement of IFN-γ, IL-6 and IL-10 expressions in chicken

Publication date: Available online 4 January 2017
Source:Vaccine
Author(s): Jonathan Lalsiamthara, John Hwa Lee
The protective efficacy and immunological profiles of chickens immunized with an attenuated Salmonella Enteritidis (SE) constitutively secreting double mutant heat labile enterotoxin (dmLT) were investigated. The dmLT is a detoxified variant of Escherichia coli heat labile toxin and is a potent mucosal adjuvant capable of inducing both humoral and cell-mediated immunity. In this study, four-week-old chickens were inoculated with SE-dmLT strain JOL1641, parental SE strain JOL1087 or phosphate buffered saline control. Peripheral blood mononuclear cells of SE-dmLT inoculated birds showed significant proliferation upon stimulation with SE antigens as compared to the control and JOL1087 groups (P⩽0.05). One week post-challenge, the ratio of CD3⁺CD4⁺ to CD3⁺CD8⁺ T-cells showed a significant increase in the immunized groups. Significant increases in IFN-γ levels were observed in JOL1641 birds immunized via oral and intramuscular routes. While immunizations with the JOL1087 strain via the intramuscular route also induced significant increases in IFN-γ, immunization via the oral route did not trigger significant changes. Pro-inflammatory cytokine IL-6 was also elevated significantly in immunized birds; a significant elevation of IL-10 was observed only in oral immunization with JOL1641 (P⩽0.05). JOL1641 immunized birds showed significant reduction of challenge bacterial-organ recovery as compared to JOL1087 and non-immunized birds. Collectively, our results revealed that immunization with the adjuvant-secreting S. Enteritidis confers protection against wild type SE challenge via induction of strong cell proliferative response, augmentation of CD3⁺CD4⁺: CD3⁺CD8⁺ T-cells ratio and enhancement of IFN-γ, IL-6 and IL-10 cytokine secretion.



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Peroxisomal Dysfunction in Age-Related Diseases

Publication date: Available online 4 January 2017
Source:Trends in Endocrinology & Metabolism
Author(s): Cynthia M. Cipolla, Irfan J. Lodhi
Peroxisomes carry out many key functions related to lipid and reactive oxygen species (ROS) metabolism. The fundamental importance of peroxisomes for health in humans is underscored by the existence of devastating genetic disorders caused by impaired peroxisomal function or lack of peroxisomes. Emerging studies suggest that peroxisomal function may also be altered with aging and contribute to the pathogenesis of a variety of diseases, including diabetes and its related complications, neurodegenerative disorders, and cancer. With increasing evidence connecting peroxisomal dysfunction to the pathogenesis of these acquired diseases, the possibility of targeting peroxisomal function in disease prevention or treatment becomes intriguing. Here, we review recent developments in understanding the pathophysiological implications of peroxisomal dysfunctions outside the context of inherited peroxisomal disorders.



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Emerging Role for Mammalian Target of Rapamycin in Male Fertility

Publication date: Available online 5 January 2017
Source:Trends in Endocrinology & Metabolism
Author(s): Pedro F. Oliveira, C.Y. Cheng, Marco G. Alves
Male fertility is modulated by environmental, endocrine, paracrine, and metabolic cues. Mammalian target of rapamycin (mTOR) coordinates many cellular events in response to those signals. Here, we discuss how the mTOR pathway integrates and mediates signals throughout the male reproductive system, acting as a central player in the control of spermatogenesis.



http://ift.tt/2hVl0YT

Skincare Bootcamp: The Evolving Role of Skincare

Background: Although cosmetic procedures have a significant impact on certain aspects of aging, such as deep, wrinkling, sagging, and volume loss, they fail to address the overall quality of the skin. Methods: Daily skincare routines potentially can have a significant long-term impact on the overall quality of a person's complexion. Results: By expanding our product knowledge, we can help our patients individualize their at-home skincare routine using effective products and ingredients designed to address their specific skin concern and support the professional care we deliver. Conclusions: Here, we discuss the types of products and ingredients suitable for the most common dermatologic concerns, from wrinkling to skin sensitivity, acne to sun damage. Copyright (C) 2016 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

http://ift.tt/2hTHFBP