Κυριακή 23 Απριλίου 2017
Hair diameter evaluation in different regions of the safe donor area in Asian populations
Abstract
Background
There is little information about how hair diameter differences within the safe donor area. Thicker or thinner hair may be needed depending on the recipient area, hairline design, and surgical purpose.
Methods
Thirty-eight non-alopecic subjects (19 males and 19 females) were evaluated. The safe donor area was defined as the area contained within 28 cm from the horizontal plane of the upper border of the hair rim to the vertical line of the bilateral external acoustic meatus. Seven zones were defined starting 2 cm on each side (bilateral 4 cm) from the mid-occiput to the temporal side. The diameters of 10 randomly selected anagen hairs were measured from each of the seven zones.
Results
The results showed significant differences in hair diameter by zone between males and females (P < 0.0001). In general, hair diameter tended to decrease from zone 3 to 7.
Conclusion
Our results suggest that safe donor areas between zones 4 and 7 could be useful for specific hair transplantation surgeries requiring thinner hair, such as eyebrows, eyelashes, and female hairline correction surgery, whereas hair from zones 1–3 could be more useful for those requiring thicker hair, such as male and female pattern hair loss. Our data could be clinically valuable for planning hair transplant surgery and choosing the most optimal donor region.
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Early clinical presentations and progression of calciphylaxis
Abstract
Background
Untreated calciphylaxis is a fatal disease of intra- and extravascular calcification, most commonly presenting in end-stage renal disease (ESRD) patients. While early identification is critical for timely treatment, early-stage clinical and histopathological descriptions have not, to our knowledge, been elucidated. As early clinical recognition is essential to prompt definitive histopathological diagnosis, this study describes a range of clinical and histopathological manifestations of early-stage calciphylaxis.
Methods
Five patients with clinical photographs of lesions of early-phase calciphylaxis were chosen from a recent database of 101 patients. Their clinical histories were reviewed and correlated with their respective clinical and histopathological images of early-stage disease and progression of the disease.
Results
Two of the five patients were identified early to have calciphylaxis and were promptly initiated on aggressive, multimodal therapy, resulting in complete resolution and remission of calciphylaxis. The other three patients were also recognized in early stages, one without renal disease, although the disease had progressed to more advanced stages associated with greater morbidity and mortality.
Conclusions
These cases demonstrate that calciphylaxis may be clinically misdiagnosed due to ill-defined presentations, particularly in the early stages without the characteristic features of livedo racemosa and ulceration. However, recognition in the early stages is critical to implement timely treatment. As such, definitively diagnostic skin biopsy should be considered early in suspected cases to confirm the diagnosis of calciphylaxis and ensure prompt management of this lethal disease.
http://ift.tt/2pVBCVj
The use of topical minoxidil to accelerate nail growth: a pilot study
Abstract
Linear nail growth rate is affected by various conditions, one of which is the level of blood flow. Our supposition was that topical minoxidil, which has vasodilatory properties, can increase the rate of nail growth. The aim of this study was to determine the impact of topical minoxidil on nail growth. A 5% topical minoxidil solution was applied twice daily to the fingernails of 32 participants. Two groups of 16 participants were randomly chosen. In one group, the applications were made to the right index and left ring fingernails, and, in the other, the left index and right ring fingernails. During each visit (weekly during the first month and every 2 weeks during the second month), the nail length of six fingernails (index, middle, and ring of both hands) was measured using a digital caliper. Beginning in the first week, the mean nail length of the treated nails was greater than that of nails in the untreated group with statistical significance. There were no systemic or cutaneous side effects. During the first month, the mean growth of the treated nails was 4.27 mm/month compared with 3.91 mm/month in the untreated nails (P = 0.003). These findings suggest that a 5% concentration of topical minoxidil can stimulate nail growth with increased growth beginning in the first week of application. The results may have important implications for the treatment of nail disorders; however, a comparable study involving participants with nail disorders is highly recommended.
http://ift.tt/2pVz8WU
Burning mouth syndrome: results of screening tests for vitamin and mineral deficiencies, thyroid hormone, and glucose levels—experience at Mayo Clinic over a decade
Abstract
Background
Burning mouth syndrome (BMS) is a disorder characterized by chronic mouth pain in the absence of objective clinical abnormalities. Vitamin or mineral deficiencies may have a role in BMS, but data regarding the prevalence and relevance of hematinic deficiencies are conflicting. We aimed to determine the frequency of specific laboratory abnormalities in patients with BMS.
Methods
We retrospectively reviewed the results of screening blood tests in patients with BMS at our institution between January 2003 and December 2013.
Results
Among 659 patients with BMS, the most common decreased values or deficiencies were vitamin D3 (15%), vitamin B2 (15%), vitamin B6 (5.7%), zinc (5.7%), vitamin B1 (5.3%), thyrotropin (TSH) (3.2%), vitamin B12 (0.8%), and folic acid (0.7%). Laboratory values for fasting blood glucose and TSH were increased in 23.7% and 5.2%, respectively.
Conclusions
In patients with symptoms of BMS, our results suggest it is reasonable to screen for fasting blood glucose, vitamin D (D2 and D3), vitamin B6, zinc, vitamin B1, and TSH. Deficiencies of vitamin B12 and folic acid were rare (<1% abnormal).
http://ift.tt/2p8aIXA
QSAR modeling for predicting mutagenic toxicity of diverse chemicals for regulatory purposes
Abstract
The safety assessment process of chemicals requires information on their mutagenic potential. The experimental determination of mutagenicity of a large number of chemicals is tedious and time and cost intensive, thus compelling for alternative methods. We have established local and global QSAR models for discriminating low and high mutagenic compounds and predicting their mutagenic activity in a quantitative manner in Salmonella typhimurium (TA) bacterial strains (TA98 and TA100). The decision treeboost (DTB)-based classification QSAR models discriminated among two categories with accuracies of >96% and the regression QSAR models precisely predicted the mutagenic activity of diverse chemicals yielding high correlations (R 2) between the experimental and model-predicted values in the respective training (>0.96) and test (>0.94) sets. The test set root mean squared error (RMSE) and mean absolute error (MAE) values emphasized the usefulness of the developed models for predicting new compounds. Relevant structural features of diverse chemicals that were responsible and influence the mutagenic activity were identified. The applicability domains of the developed models were defined. The developed models can be used as tools for screening new chemicals for their mutagenicity assessment for regulatory purpose.
http://ift.tt/2prcbey
IgG4-related disease presenting as posterior scleritis and vitritis, progressing to multifocal orbital involvement
IgG4-related disease (IgG4-RD) is a rare, chronic inflammatory condition that may involve nearly every organ system. Originally identified as a cause of autoimmune pancreatitis, its characteristic histological and clinical features have been found in a wide variety of inflammatory presentations, including the eye and orbit. Here we describe an example of a case of IgG4-RD initially presenting as scleritis and vitritis, with further progression to multifocal bilateral orbital involvement. Tissue biopsy of an orbital mass was highly characteristic of IgG4-RD histology and a rapid clinical response to corticosteroids was observed. This case highlights IgG4-RD as a rare cause of intraocular inflammation that may progress to involve the orbit.
http://ift.tt/2okxhuL
Intradiaphragmatic hybrid lesion: surgical decision-making and value of minimal invasive surgery
Hybrid lesions (HLs) have elements of congenital pulmonary airway malformation and extrapulmonary sequestration (EPS) and belong to the congenital lung lesions. EPS usually arises in the thorax or the abdomen but rarely in the diaphragm. The preoperative diagnostic work-up based on chest radiograph, ultrasound (US) and CT often shows imprecise results. Therefore, the exact localisation of the lesion can only be ascertained intraoperatively. Here we present a patient, with an intradiaphragmatic HL, and demonstrate the difficulties of surgical decision making regarding the localisation of the lesion and discuss the value of minimal invasive surgery.
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An unusual cause for diffuse pulmonary nodules
Description
We present the case of a 67-year-old woman with a 3-week history of dysphagia in the absence of any respiratory or constitutional symptoms. A lifelong non-smoker with no significant medical comorbidities, it was thought unusual that a routine chest radiograph (figure 1) demonstrated diffuse, small, irregular nodules throughout her lung fields. The diagnosis of primary lung adenocarcinoma was made on the basis of a CT-guided biopsy (figure 2). It is likely that this atypical presentation and radiological appearance of primary malignancy is related to the erosion of tumour into one of the pulmonary arteries thus disseminating the neoplasm throughout the lungs. The cause for the patient's symptoms was attributed to malignant involvement of the central nervous system.
Figure 1
Chest X-ray.
Figure 2
CT scan of the chest.
To distinguish between...
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Complicated small bowel diverticular disease: a case series
Small bowel diverticulosis of the jejunum and ileum is an uncommon finding with a prevalence rate of 0.2% to 1.3% at autopsy and 0.3% to 1.9% on small bowel studies. Diagnosis can be difficult because there are no pathognomonic features or clinical symptoms that are specific for small bowel diverticulosis. Though rare, it is critical to keep the possibility of small bowel diverticulosis in mind when evaluating cases of malabsorption, chronic abdominal pain, haemorrhage, perforation and intestinal obstruction, especially in patients with connective tissue disorders, a family history of diverticula and a personal history of colonic diverticulosis. Guidelines for the treatment of complicated small bowel diverticulosis are not clearly defined. However, the consensus in treatment is to do a small bowel resection with primary anastomosis. We report three interesting cases of jejunoileal diverticula that presented in an occult manner and later progressed to more emergent manifestations.
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Respiratory difficulty with palatal, laryngeal and respiratory muscle tremor in adult-onset Alexanders disease
Sleep apnoea and respiratory difficulties are reported in adult-onset Alexander's disease (AOAD), an autosomal-dominant leukodystrophy that presents mainly with progressive ataxia. We demonstrate for the first time that the respiratory symptoms can result from association of palatal tremor with a similar tremor of laryngeal and respiratory muscles that interrupts normal inspiration and expiration.
A 60-year-old woman presented with progressive ataxia, palatal tremor and breathlessness. MRI revealed medullary atrophy, bilateral T2 hyperintensities in the dentate nuclei and hypertrophic olivary degeneration (HOD). AOAD was confirmed genetically with a positive glial fibrillary acidic protein (GFAP) mutation. Electrophysiological study revealed 1.5 Hz rhythmic laryngeal and respiratory muscle activity. Her respiratory symptoms were significantly improved at night with variable positive pressure ventilation.
This case illustrates that palatal tremor in AOAD, and potentially in other conditions, may be associated with treatable breathlessness due to a similar tremor of respiratory muscles.
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Efficiency of Ustekinumab in Crohn's Disease with Severe Psoriasiform Rash Induced by Biotherapies in an Adolescent
Abstract
Ustekinumab is approved for the treatment of psoriasis in adolescents and for the treatment of moderate to severe Crohn's disease (CD) in adults, but data are lacking in pediatric CD. We report a case of severe psoriasis induced by biotherapies in an adolescent with CD that improved after switching to ustekinumab (90 mg at weeks 0, 2, and 4 and then every 8 weeks). The patient had not experienced CD relapse after 1 year of follow-up. Ustekinumab can be an alternative therapy for psoriasis induced by biotherapies when conventional treatment fails and can maintain remission of CD.
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Cigarette dependence and depressive symptoms as predictors of smoking status at five-year follow-up after a workplace smoking cessation program
Source:Addictive Behaviors, Volume 73
Author(s): Gemma Nieva, Marina Comín, Sergi Valero, Eugeni Bruguera
Workplace smoking cessation interventions increase quit rates compared to no treatment or minimal interventions. However, most studies report data up to one year. This study aims to evaluate long-term effects of a worksite smoking cessation intervention based on cognitive behavioral cessation groups combined with first-line medications, and determine to what extent cigarette dependence (FTCD) and depressive symptoms may influence results at five-year follow-up. Participants were invited to answer a short survey five years after starting the program. A total of 90.4% (n=227) of those who had attended at least one treatment session and were alive, completed the survey. At the five-year follow-up, 29.5% participants reported continuous abstinence. Low scores in the FTCD and low depressive symptoms at baseline predicted continuous abstinence. Three out of four continuous abstainers at twelve months remained abstinent at the five-year follow-up. The study shows that workplace smoking cessation interventions have long-term effects and supports the traditional one-year follow-up period to assess smoking cessation.
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Trait mindfulness and protective strategies for alcohol use: Implications for college student drinking
Source:Addictive Behaviors, Volume 73
Author(s): Emma I. Brett, Thad R. Leffingwell, Eleanor L. Leavens
IntroductionThe use of Protective Behavioral Strategies (PBS) has been strongly linked with decreased experience of alcohol-related consequences, making them a potential target for intervention. Additionally, mindfulness is associated with decreased experience of alcohol-related consequences. The purpose of the current study was to evaluate a model of PBS as a mediator of the effect of mindfulness on alcohol-related consequences. Additionally, mindfulness as a moderator of the relationship between PBS and alcohol use and consequences was examined.MethodsCollege students (N=239) at a large South Central university completed self-report measures of demographics, alcohol use and consequences, use of PBS, and trait mindfulness.ResultsResults indicated that both higher levels of mindfulness and using more PBS predicted decreased alcohol-related consequences and consumption, with PBS mediating both relationships (p<0.01). Those with higher levels of mindfulness were more likely to use PBS, with individuals using more PBS experiencing fewer alcohol-related consequences and consuming fewer drinks per week. Mindfulness moderated the relationship between PBS and consequences, with a significantly stronger negative relationship for those with lower levels of mindfulness.ConclusionsIndividuals who are higher in trait mindfulness are more likely to use PBS, which leads to a decrease in the experience of alcohol-related consequences. Furthermore, for individuals lower in mindfulness, low PBS use may lead to increased experience of alcohol consequences. Interventions that incorporate PBS may be most beneficial for students who are low in mindfulness and unlikely to engage in drinking control strategies.
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The role of negative affect and message credibility in perceived effectiveness of smokeless tobacco health warning labels in Navi Mumbai, India and Dhaka, Bangladesh: A moderated-mediation analysis
Source:Addictive Behaviors, Volume 73
Author(s): Seema Mutti-Packer, Jessica L. Reid, James F. Thrasher, Daniel Romer, Geoffrey T. Fong, Prakash C. Gupta, Mangesh S. Pednekar, Nigar Nargis, David Hammond
ObjectiveThere is strong evidence showing that pictorial health warnings are more effective than text-only warnings. However, much of this evidence comes from high-income countries and is limited to cigarette packaging. Moreover, few studies have identified mechanisms that might explain the impact of warnings.MethodsThe current study examined the potential mediating role of negative affect and the moderating influence of message credibility in perceived effectiveness of smokeless tobacco warnings in two low- and middle-income countries (LMICs). Field interviews were conducted in India and Bangladesh, with adult (19+ years) smokeless tobacco users (n=1053), and youth (16–18years) users (n=304) and non-users (n=687). Respondents were randomly assigned to view warnings in one of four conditions: (1) Text-only, (2) pictorial with symbolic imagery, (3) pictorial with graphic images of health effects, or (4) pictorial with personalized graphic images plus a personal testimonial.ResultsThe findings provide support for the mediating influence of negative affect in perceived effectiveness, for adult and youth smokeless tobacco users who viewed pictorial warnings (vs. text-only), and graphic health warnings (vs. personal testimonials). Among adults, message credibility moderated the indirect effect; the association was stronger when credibility was high and weaker when it was low. Among youth users and non-users, message credibility did not moderate the indirect effect.ConclusionsConsistent with research from high-income countries, these findings highlight the importance of selecting imagery that will elicit negative emotional reactions and be perceived as credible. Differential effects among adults and youth highlight the importance of pre-testing images.
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Cannabis and cue-induced craving in cocaine-dependent individuals: A pilot study
Source:Addictive Behaviors, Volume 73
Author(s): K. Giasson-Gariépy, S. Potvin, M. Ghabrash, J. Bruneau, D. Jutras-Aswad
BackgroundCannabis consumption is common among cocaine users; however, little is known about its effect on cocaine craving. The objective of this study was to assess whether cannabis co-use is associated with lower cue-induced cocaine craving in non-treatment-seeking cocaine-dependent individuals.MethodsData from twenty-eight cocaine-dependent men were analyzed in this pilot study. Cocaine-dependent subjects (n=12) were compared with cocaine-dependent subjects who also abused or were dependent on cannabis (n=16). After at least 72h of cocaine abstinence, verified using the Timeline Followback and a drug screening test, subjects participated in a functional magnetic resonance imaging session during which neutral and drug cue video sequences were presented. Each sequence comprised four video blocks alternating with resting blocks. We report here subjective craving measures that were collected using the Visual Analog Scale, administered before and after each video block as per standard craving measurement paradigms.ResultsCocaine craving was successfully induced, with no significant difference in cue-induced craving between the two groups. However, post-hoc analyses revealed a significant increase in pre-video cocaine craving scores over time among individuals with cannabis use disorders.ConclusionWe could not highlight significant differences in cocaine craving induction between groups, but we observed a possible deficit in craving decay in the cocaine and cannabis group. In light of this finding, methodology of craving assessment in non-treatment-seeking users, particularly when different substances are combined, should possibly include outcomes linked to craving decay. Studies examining the association between cocaine craving decay and other outcome measures, such as relapse, are also warranted.
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In vitro PGPR properties and osmotic tolerance of different Azospirillum native strains and their effects on growth of maize under drought stress
Source:Microbiological Research
Author(s): Julia E. García, Guillermo Maroniche, Cecilia Creus, Ramón Suárez-Rodríguez, José Augusto Ramirez-Trujillo, María D. Groppa
Osmotic variations in the soil can affect bacterial growth diminishing the number of inoculated bacteria. In a scenario of water deficit having tolerant bacteria would be beneficial to achieve a better response of the plant to stress. Thus, selection of more resistant bacteria could be useful to design new inoculants to be used in arid zones. In this sense, a group of Azospirillum isolates deposited in INTA collection was characterized in order to select strains tolerant to osmotic stress. The results obtained demonstrated that Az19 strain has similar in vitro PGPR characteristics to Az39, the most used strain in Argentina for inoculants industries, with the advantage of a better tolerance to osmotic and salt stress. Inoculation of maize plants with this strain resulted in a better response against water deficit compared to Az39 strain, encouraging us to further study the behavior of this strain in greenhouse and field trials in view of developing new inoculants suitable for areas with water deficit.
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Progesterone Receptors (PR) Mediate STAT Actions: PR and Prolactin Receptor Signaling Crosstalk in Breast Cancer Models
Publication date: Available online 23 April 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Katherine A. Leehy, Thu H. Truong, Laura J. Mauro, Carol A. Lange
Estrogen is the major mitogenic stimulus of mammary gland development during puberty wherein ER signaling acts to induce abundant PR expression. PR signaling, in contrast, is the primary driver of mammary epithelial cell proliferation in adulthood. The high circulating levels of progesterone during pregnancy signal through PR, inducing expression of the prolactin receptor (PRLR). Cooperation between PR and prolactin (PRL) signaling, via regulation of downstream components in the PRL signaling pathway including JAKs and STATs, facilitates the alveolar morphogenesis observed during pregnancy. Indeed, these pathways are fully integrated via activation of shared signaling pathways (i.e. JAKs, MAPKs) as well as by the convergence of PRs and STATs at target genes relevant to both mammary gland biology and breast cancer progression (i.e. proliferation, stem cell outgrowth, tissue cell type heterogeneity). Thus, rather than a single mediator such as ER, transcription factor cascades (ER > PR > STATs) are responsible for rapid proliferative and developmental programming in the normal mammary gland. It is not surprising that these same mediators typify uncontrolled proliferation in a majority of breast cancers, where ER and PR are most often co-expressed and may cooperate to drive malignant tumor progression. This review will primarily focus on the integration of PR and PRL signaling in breast cancer models and the importance of this cross-talk in cancer progression in the context of mammographic density. Components of these PR/PRL signaling pathways could offer alternative drug targets and logical complements to anti-ER or anti-estrogen-based endocrine therapies.
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4′-Chlorodiazepam is neuroprotective against amyloid-beta in organotypic hippocampal cultures
Publication date: Available online 23 April 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): B.D. Arbo, J.B. Hoppe, K. Rodrigues, L.M. Garcia-Segura, C.G. Salbego, M.F. Ribeiro
The translocator protein (TSPO) is an outer mitochondrial membrane protein involved in the transport of cholesterol into the mitochondria, which is the first step for the synthesis of steroid hormones, as well as in the regulation of mitochondrial permeability transition pore opening and apoptosis. Studies have shown that the activation of TSPO may promote neuroprotective actions in experimental models of neurodegeneration and brain injury. In a previous study, our group showed that 4′-chlorodiazepam (4′-CD), a TSPO ligand, was neuroprotective against amyloid-beta (Aβ) in SHSY-5Y neuroblastoma cells. The aim of this study was to evaluate if 4′-CD was also neuroprotective against Aβ in organotypic hippocampal cultures and to identify its mechanisms of action. Aβ decreased the cell viability of organotypic hippocampal cultures, while 4′-CD had a neuroprotective effect when administered at 100nM and 1000nM. The neuroprotective effects of 4′-CD against Aβ were associated with an increased expression of superoxide dismutase (SOD). No differences were found in the expression of catalase, glial fibrillary acidic protein, Akt and procaspase-3. In summary, our results show that 4′-CD is neuroprotective against Aβ by a mechanism involving the modulation of SOD protein expression.
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Duplicated internal auditory canal with inner ear malformation: Case report and literature review
Source:Auris Nasus Larynx
Author(s): Yoshitaka Takanashi, Tetsuaki Kawase, Yasuko Tatewaki, Jun Suzuki, Izumi Yahata, Yuuri Nomura, Kazuha Oda, Hiromitsu Miyazaki, Yukio Katori
Internal auditory canal anomalies are rare. Narrow internal auditory canal is believed to occur as a result of aplasia or hypoplasia of the vestibulocochlear nerve. Narrow duplication of the internal auditory canal is considered to be very rare. Narrow duplication of the internal auditory canal with inner ear malformation has been reported in only 3 cases. We present 2 cases of narrow duplication of the internal auditory canal with inner ear malformation. The first case had inner ear malformation on only one side and the second case had inner ear malformation on both sides. The embryogenesis may be different between internal auditory canal and inner ear.
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Challenges in developing drugs for neurological and psychiatric disorders
Publication date: May 2017
Source:Progress in Neurobiology, Volume 152
Author(s): Neal G. Simon, Michael J. Brownstein
http://ift.tt/2ojnOEb
CO2: Editorial Board/Subscription info.
Publication date: May 2017
Source:Progress in Neurobiology, Volume 152
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Deregulation of α-synuclein in Parkinson’s disease: Insight from epigenetic structure and transcriptional regulation of SNCA
Source:Progress in Neurobiology
Author(s): Subhrangshu Guhathakurta, Eugene Bok, Baggio A. Evangelista, Yoon-Seong Kim
Understanding regulation of α-synuclein has long been a central focus for Parkinson's disease (PD) researchers. Accumulation of this protein in the Lewy body or neurites, mutations in the coding region of the gene and strong association of α-synuclein encoding gene multiplication (duplication/triplication) with familial form of PD have indicated the importance of this molecule in pathogenesis of the disease. Several years of research identified many potential faulty pathways associated with accumulation of α-synuclein inside dopaminergic neurons and its transmission to neighboring ones. Concurrently, an appreciable body of research is growing to understand the epigenetic and genetic deregulation of α-synuclein that might contribute to the disease pathology. Completion of the ENCODE (Encyclopedia of DNA Elements) project and recent advancement made in the epigenetic and trans factor mediated regulation of each gene, has tremendously accelerated the need to carefully understand the epigenetic structure of the gene (SNCA) encoding α-synuclein protein in order to decipher the regulation and contribution of α-synuclein to the pathogenesis of PD. We have also analyzed the detailed epigenetic structure of this gene with knowledge from ENCODE database, which may open new avenues in α-synuclein research. Interestingly, we have found that the gene contains several transcriptionally activate histone modifications and associated potential transcription factor binding sites in the non-coding areas that strongly suggest alternative regulatory pathways. Altogether this review will provide interesting insight of α-synuclein gene regulation from epigenetic, genetic and post-transcriptional perspectives and their potential implication in the PD pathogenesis.
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A one-pot thermal decomposition of C4H4ZnO6 to ZnO@carbon composite for lithium storage
Publication date: 15 August 2017
Source:Journal of Alloys and Compounds, Volume 714
Author(s): Denghu Wei, Zhijun Xu, Jie Wang, Yuanwei Sun, Suyuan Zeng, Wenzhi Li, Xiaona Li
Zinc oxide nanoparticles embedded in carbon framework (ZnO@C) were synthesized through a one-pot thermal decomposition of C4H4ZnO6 served as the precursor for both ZnO and carbon. As an anode material for lithium-ion batteries, the ZnO@C composite delivers a reversible capacity of 680 mAh g−1 at a current density of 1 A g−1, and remains the capacity at 610 mAh g−1 even after 300 cycles. Such a good performance could be attributed to the existence of the carbon, which can act as a scaffold for ZnO nanoparticles not only enhancing conductivity, but also relieving volume changes of the electrode during lithiation and delithiation processes. The obtained ZnO@C composite may be found use in other applications in the fields of solar cells, gas sensors, optoelectronic devices, and Zn/Ni secondary batteries.
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Preoperative implant selection for unilateral breast reconstruction using 3D imaging with the Microsoft Kinect sensor
This study aimed to investigate whether breast volume measured preoperatively with a Kinect 3D sensor could be used to determine the most appropriate implant size for reconstruction.
http://ift.tt/2pqV648
Anti-amnesic effect of extract and alkaloid fraction from aerial parts of Peganum harmala on scopolamine-induced memory deficits in mice
Publication date: Available online 23 April 2017
Source:Journal of Ethnopharmacology
Author(s): Wei Liu, Yudan Zhu, Yongli Wang, Shenglan Qi, Yuwen Wang, Chao Ma, Shuping Li, Bo Jiang, Xuemei Cheng, Zhengtao Wang, Zhenyu Xuan, Changhong Wang
Ethnopharmacological relevanceAerial parts of Peganum harmala Linn (APP) is used as traditional medical herb for treatment of forgetfulness in Uighur medicine in China. But, the active ingredients and underlying mechanisms are unclear.Aim of the studyThe present study was undertaken to investigate the improvement effects of extract and alkaloid fraction from APP on scopolamine-induced cognitive dysfunction and to elucidate their underlying mechanisms of action, and to support its folk use with scientific evidence, and lay a foundation for its further researches.Materials and methodsThe acetylcholinesterase (AChE) inhibitory activities of extract (EXT), alkaloid fraction (ALK) and flavanoid fraction (FLA) from APP were evaluated in normal male C57BL/6 mice. The anti-amnesic effects of EXT and ALK from APP were measured in scopolamine-induced memory deficits mice by the Morris water maze (MWM) tasks. The levels of biomarkers, enzyme activity and protein expression of cholinergic system were determined in brain tissues.ResultsThe AChE activity was significantly decreased and the content of neurotransmitter acetylcholine (ACh) was significantly increased in normal mice cortex and hippocampus by treatment with donepezil at dosage of 8mg/kg, EXT at dosages of 183, 550, 1650 mg/kg and ALK at dosages of 10, 30, 90mg/kg (P < 0.05), and the AChE activity and the content of ACh were not significantly changed in cortex and hippocampus after treatment with FLA at dosages of 10, 30, 90mg/kg (P > 0.05). In the MWM task, scopolamine-induced a decrease in both the swimming time within the target zone and the number of crossings where the platform had been placed were significantly reversed by treatment with EXT at dosages of 550, 1650 mg/kg and ALK at dosages of 30, 90mg/kg (P < 0.05). Moreover, the activity and protein expression of AChE was significantly decreased and the content of neurotransmitter ACh was significantly increased in cerebral cortex of scopolamine-induced mice by treatment with EXT at dosages of 183, 550, 1650 mg/kg and ALK at dosages of 10, 30, 90mg/kg (P < 0.05), compared with scopolamine-treated group.ConclusionsEXT and ALK from APP exert beneficial effect on learning and memory processes in mice with scopolamine-induced memory impairment. APP is an effective traditional folk medicine and the ALK fraction is proved to be the main effective components for the treatment of forgetfulness. The ALK may be valuable source for lead compounds discovery and drug development for treatment of memory impairment such as in Alzheimer's disease.
Graphical abstract
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Mitochondrial ROS Control of Cancer
Source:Seminars in Cancer Biology
Author(s): María del Pilar Sosa Idelchik, Ulrike Begley, Thomas J. Begley, J. Andrés Melendez
Mitochondria serve a primary role in energy maintenance but also function to govern levels of mitochondria-derived reactive oxygen species (mROS). ROS have long been established to play a critical role in tumorigenesis and are now considered to be integral to the regulation of diverse signaling networks that drive proliferation, tumor cell survival and malignant progression. mROS can damage DNA, activate oncogenes, block the function of tumor suppressors and drive migratory signaling. The mitochondrion's oxidant scavenging systems including SOD2, Grx2, GPrx, Trx and TrxR are key of the cellular redox tone. These mitochondrial antioxidant systems serve to tightly control the levels of the primary ROS signaling species, H2O2. The coordinated control of mROS levels is also coupled to the activity of the primary H2O2 consuming enzymes of the mitochondria which are reliant on the epitranscriptomic control of selenocysteine incorporation. This review highlights the interplay between these many oncogenic signaling networks, mROS and the H2O2 emitting and consuming capacity of the mitochondria.
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How to study and overcome tumor heterogeneity with circulating biomarkers: The breast cancer case
Source:Seminars in Cancer Biology
Author(s): Valentina Appierto, Serena Di Cosimo, Carolina Reduzzi, Valentina Pala, Vera Cappelletti, Maria Grazia Daidone
Breast cancer ranks first among female cancer-related deaths in Western countries. As the primary tumor can often be controlled by surgical resection, the survival of women with breast cancer is closely linked to the incidence of distant metastases. Molecular screening by next generation sequencing highlighted the spatial and temporal heterogeneity of solid tumors as well as the clonal evolution of cancer cells during progression and under treatment pressure. Such findings question whether an optimal assessment of disease progression and a screening for druggable mutations should be based on molecular features of primary or recurrent/metastatic lesions and therefore represent a crucial element for failure or success of personalized medicine. In fact, new targeted therapies may induce only short-term benefit annulled by the emergence of resistant clones with new driver mutations which would need to be rapidly and reliably identified. Serial tissue sampling is therefore essential but, unfortunately, also represents a problem since biopsies from solid lesions, which are invasive and potentially painful and risky, cannot be easily repeatedly sampled, are inaccessible or may not fully reflect tumor heterogeneity. The need to early detect and strike this "moving target" is now directing the scientific community towards liquid biopsy-based biomarkers, which include circulating tumor cells (CTC) and cell-free circulating tumor DNA (ctDNA), can be repeatedly assessed through non-invasive and easy-to-perform procedures and may act as reliable read-outs of functional and molecular features of recurrent/metastatic lesions. In this review we summarize the outcome of CTCs and ctDNA in breast cancer, with special reference on their role on unveiling and overcoming tumor heterogeneity, on their potential relevance for tumor surveillance and monitoring, and for the selection of therapeutic options. Finally, we propose integration between blood-based molecular and clinical approaches for monitoring disease progression according to the specific pattern of recurrence of the most aggressive breast cancer molecular subtypes.
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Never let it go: stopping key mechanisms underlying metastasis to fight pancreatic cancer
Source:Seminars in Cancer Biology
Author(s): E. Giovannetti, C.L. van der Borden, A.E. Frampton, A. Ali, O. Firuzi, G.J. Peters
Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive neoplasm, predicted to become the second leading cause of cancer-related deaths before 2030. This dismal trend is mainly due to lack of effective treatments against its metastatic behavior. Therefore, a better understanding of the key mechanisms underlying metastasis should provide new opportunities for therapeutic purposes. Genomic analyses revealed that aberrations that fuel PDAC tumorigenesis and progression, such as SMAD4 loss, are also implicated in metastasis. Recently, microRNAs have been shown to play a regulatory role in the metastatic behavior of many tumors, including PDAC. In particular, miR-10 and miR-21 have appeared as master regulators of the metastatic program, while members of the miR-200 family are involved the epithelial-to-mesenchymal switch, favoring cell migration and invasiveness. Several studies have also found a close relationship between cancer stem cells (CSCs) and biological features of metastasis, and the CSC markers ALDH1, ABCG2 and c-Met are expressed at high levels in metastatic PDAC cells. Emerging evidence reveals that exosomes are involved in the modulation of the tumor microenvironment and can initiate PDAC pre-metastatic niche formation in the liver and lungs. In this review, we provide an overview of the role of all these pivotal factors in the metastatic behavior of PDAC, and discuss their potential exploitation in the clinic to improve current therapeutics and identify new drug targets.
http://ift.tt/2ojfpRc
Dietary proanthocyanidins prevent ultraviolet radiation-induced non-melanoma skin cancer through enhanced repair of damaged DNA-dependent activation of immune sensitivity
Source:Seminars in Cancer Biology
Author(s): Santosh K. Katiyar, Harish C. Pal, Ram Prasad
Numerous plant products have been used to prevent and manage a wide variety of diseases for centuries. These products are now considered as promising options for the development of more effective and less toxic alternatives to the systems of medicine developed primarily in developed countries in the modern era. Grape seed proanthocyanidins (GSPs) are of great interest due to their anti-carcinogenic effects that have been demonstrated using various tumor models including ultraviolet (UV) radiation-induced non-melanoma skin cancer. In a pre-clinical mouse model supplementation of a control diet (AIN76A) with GSPs at concentrations of 0.2% and 0.5% (w/w) significantly inhibits the growth and multiplicity of UVB radiation-induced skin tumors. In this review, we summarize the evidence that this inhibition of UVB-induced skin tumor development by dietary GSPs is mediated by a multiplicity of coordinated effects including: (i) Promotion of the repair of damaged DNA by nuclear excision repair mechanisms, and (ii) DNA repair-dependent stimulation of the immune system following the functional activation of dendritic cells and effector T cells. Dietary GSPs hold promise for the development of an effective alternative strategy for the prevention of excessive solar UVB radiation exposure-induced skin diseases including the risk of non-melanoma skin cancer in humans.
http://ift.tt/2p7lUni
Cellular determinants and microenvironmental regulation of prostate cancer metastasis
Source:Seminars in Cancer Biology
Author(s): Kiera Rycaj, Hangwen Li, Jianjun Zhou, Xin Chen, Dean G. Tang
Metastasis causes more than 90% of cancer-related deaths and most prostate cancer (PCa) patients also die from metastasis. The 'metastatic cascade' is a complex biological process that encompasses tumor cell dissociation (from the primary tumor), local invasion, intravasation, transport in circulation, extravasation, colonization, and overt growth in end organs. It has become clear that successful metastasis not only involves many tumor cell-intrinsic properties but also depends on productive interactions between cancer cells and the tumor microenvironment. In this Review, we begin with a general summary on cancer metastasis and a specific discussion on PCa metastasis. We then discuss recent advances in our knowledge of the cellular determinants of PCa metastasis and the importance of tumor microenvironment, especially an immunosuppressive tumor microenvironment, in shaping metastatic propensities. We conclude with a presentation of current and future therapeutic options for patients with PCa metastasis, emphasizing the development of novel, mechanism-based combinatorial strategies for treating metastatic and castration-resistant PCa.
http://ift.tt/2ojqPV5
Mitochondrial Ribosomes in Cancer
Source:Seminars in Cancer Biology
Author(s): Hyun-Jung Kim, Priyanka Maiti, Antoni Barrientos
Mitochondria play fundamental roles in the regulation of life and death of eukaryotic cells. They mediate aerobic energy conversion through the oxidative phosphorylation (OXPHOS) system, and harbor and control the intrinsic pathway of apoptosis. As a descendant of a bacterial endosymbiont, mitochondria retain a vestige of their original genome (mtDNA), and its corresponding full gene expression machinery. Proteins encoded in the mtDNA, all components of the multimeric OXPHOS enzymes, are synthesized in specialized mitochondrial ribosomes (mitoribosomes). Mitoribosomes are therefore essential in the regulation of cellular respiration. Additionally, an increasing body of literature has been reporting an alternative role for several mitochondrial ribosomal proteins as apoptosis-inducing factors. No surprisingly, the expression of genes encoding for mitoribosomal proteins, mitoribosome assembly factors and mitochondrial translation factors is modified in numerous cancers, a trait that has been linked to tumorigenesis and metastasis. In this article, we will review the current knowledge regarding the dual function of mitoribosome components in protein synthesis and apoptosis and their association with cancer susceptibility and development. We will also highlight recent developments in targeting mitochondrial ribosomes for the treatment of cancer.
http://ift.tt/2p77vr2
Transcriptomic and genomic features of invasive lobular breast cancer
Source:Seminars in Cancer Biology
Author(s): Christine Desmedt, Gabriele Zoppoli, Christos Sotiriou, Roberto Salgado
Accounting for 10–15% of all breast neoplasms, invasive lobular breast cancer (ILC) is the second most common histological subtype of breast cancer after invasive ductal breast cancer (IDC). Understanding ILC biology, which differs from IDC in terms of clinical presentation, treatment response, relapse timing and patterns, is essential in order to adopt novel, disease-specific management strategies. While the contribution of the histological subtypes to tumour biology has been poorly investigated and acknowledged in the past, recently several major, independent efforts have led to the assembly and molecular characterization of well-annotated ILC case sets. In this review, we provide a critical overview of the literature exploring ILC, through comprehensive and multiomic methods. The first part specifically focuses on ILC transcriptomic features by reviewing the intrinsic molecular subtypes, the application of gene expression scores for the prediction of recurrence, and the identification of gene expression subtypes. The second part describes the main research efforts that lead to the identification of the genomic landscape of ILC, with a special focus to findings that differentiate ILC from IDC and carry potential clinical relevance.
http://ift.tt/2ojfnZx
Anticancer and cancer preventive compounds from edible marine organisms
Source:Seminars in Cancer Biology
Author(s): Marta Correia-da-Silva, Emília Sousa, Madalena M.M. Pinto, Anake Kijjoa
A direct impact of food on health, which demonstrates that dietary habit is one of the most important determinants of chronic diseases such as cancers, has led to an increased interest of the consumers toward natural bioactive compounds as functional ingredients or nutraceuticals. Epidemiological studies revealed that the populations of many Asian countries with high consumption of fish and seafood have low prevalence of particular type of cancers such as lung, breast, colorectal and prostate cancers. This observation has led to extensive investigations of the benefits of compounds present in edible marine organisms such as fish, marine invertebrates (mollusks, echinoderms) and marine algae as cancer chemopreventive agents. Interestingly, many of these marine organisms not only constitute as seafood delicacy but also as ingredients used in folk medicine of some East and Southeast Asian countries. The results of the investigations on extracts and compounds from fish (cods, anchovy, eel and also fish protein hydrolysates), mollusks (mussel, oyster, clams and abalone), as well as from sea cucumbers on the in vivo/in vitro anticancer/antitumor activities can, in part, support the health benefits of these edible marine organisms.
http://ift.tt/2p7aYWG
Tea phytochemicals for breast cancer prevention and intervention: From bench to bedside and beyond
Source:Seminars in Cancer Biology
Author(s): Dona Sinha, Jaydip Biswas, Seyed Mohammad Nabavi, Anupam Bishayee
The National Cancer Institute of the United States had projected breast cancer as one of the topmost prevalent malignancies of 2016. It was estimated that in 2016, 246,660 new cases of invasive breast cancer were expected to be diagnosed in women in the US, along with 61,000 new cases of non-invasive (in situ) breast cancer. The heterogeneity of breast cancer accounts for its differential molecular subtyping. Recent incorporation of high throughput approaches helps early prognosis of breast cancer, but recurrence of the disease stands to be one of the most daunting fact behind non-availability of third line treatment. At this point of crisis, application of chemopreventive measures could possibly resolve the enigma of breast cancer. The world class beverage tea has proven its efficacy in ameliorating various genetic and epigenetic anomalies in breast cancer. Tea phytoconstituents are known to modulate myriad molecular events which include prominent regulators of intracellular signaling, such as phosphatidylinositide 3-kinase/protein kinase B/nuclear factor-κB, epidermal growth factor receptor, vascular endothelial growth factor, B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X protein in the development and progression of breast carcinoma. This review aims to encompass the detailed modulatory roles of tea phytochemicals, their analogs and nanoformulations against mammary carcinoma and the probability of using tea in therapeutic management of breast cancer. Finally, current limitations, challenges and future directions of tea and breast cancer research are also critically discussed.
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The functional genomic studies of curcumin
Source:Seminars in Cancer Biology
Author(s): Lukasz Huminiecki, Jarosław Horbańczuk, Atanas G. Atanasov
Curcumin is a natural plant-derived compound that has attracted a lot of attention for its anti-cancer activities. Curcumin can slow proliferation of and induce apoptosis in cancer cell lines, but the precise mechanisms of these effects are not fully understood. However, many lines of evidence suggested that curcumin has a potent impact on gene expression profiles; thus, functional genomics should be the key to understanding how curcumin exerts its anti-cancer activities. Here, we review the published functional genomic studies of curcumin focusing on cancer. Typically, a cancer cell line or a grafted tumor were exposed to curcumin and profiled with microarrays, methylation assays, or RNA-seq. Crucially, these studies are in agreement that curcumin has a powerful effect on gene expression. In the majority of the studies, among differentially expressed genes we found genes involved in cell signaling, apoptosis, and the control of cell cycle. Curcumin can also induce specific methylation changes, and is a powerful regulator of the expression of microRNAs which control oncogenesis. We also reflect on how the broader technological progress in transcriptomics has been reflected on the field of curcumin. We conclude by discussing the areas where more functional genomic studies are highly desirable. Integrated OMICS approaches will clearly be the key to understanding curcumin's anticancer and chemopreventive effects. Such strategies may become a template for elucidating the mode of action of other natural products; many natural products have pleiotropic effects that are well suited for a systems-level analysis.
http://ift.tt/2p76Aa2
Cancer stem cells with increased metastatic potential as a therapeutic target for esophageal cancer
Source:Seminars in Cancer Biology
Author(s): D. Wang, J.Th.M. Plukker, R.P. Coppes
Esophageal cancers (EC) are highly aggressive tumors, commonly presented in a locally advanced stage with a poor prognosis and survival. Up to 50% of the patients are eligible for treatment with curative intent and receive the standard treatment with neoadjuvant chemoradiotherapy (nCRT) and surgery. Currently, pathologic complete response to nCRT is 20–30%, with a partial or no response in about 50% and 20%, respectively. EC recurrences occur frequently even after successful anti-cancer treatment, suggesting high aggressiveness with increased metastatic potential. A tumor sub-population of so-called cancer stem cells (CSCs), is known to display a high metastatic potential and resistance to conventional anti-cancer therapy, hereby being responsible for the unbeneficial clinical features. In this review, a concise overview will be given of the current literature on esophageal CSCs and related metastases. Esophageal CSC markers will be discussed followed by the pathways that initiate and sustain these cells. In addition, the cellular processes, epithelial-mesenchymal transition (EMT), hypoxia and autophagy, known to contribute to cancer stemness and metastasis will be explained. Finally, potential options for treatment also related to cancer genome atlas (TCGA) data on EC will be discussed.
http://ift.tt/2oj7UJQ
Key biological processes driving metastatic spread of pancreatic cancer as identified by multi-omics studies
Source:Seminars in Cancer Biology
Author(s): T.Y.S. Le Large, M.F. Bijlsma, G. Kazemier, H.W.M. van Laarhoven, E. Giovannetti, C.R. Jimenez
Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy, characterized by a high metastatic burden, already at the time of diagnosis. The metastatic potential of PDAC is one of the main reasons for the poor outcome next to lack of significant improvement in effective treatments in the last decade. Key mutated driver genes, such as activating KRAS mutations, are concordantly expressed in primary and metastatic tumors. However, the biology behind the metastatic potential of PDAC is not fully understood. Recently, large-scale omic approaches have revealed new mechanisms by which PDAC cells gain their metastatic potency. In particular, genomic studies have shown that multiple heterogeneous subclones reside in the primary tumor with different metastatic potential. The development of metastases may be correlated to a more mesenchymal transcriptomic subtype. However, for cancer cells to survive in a distant organ, metastatic sites need to be modulated into pre-metastatic niches. Proteomic studies identified the influence of exosomes on the Kuppfer cells in the liver, which could function to prepare this tissue for metastatic colonization. Phosphoproteomics adds an extra layer to the established omic techniques by unravelling key functional signaling. Future studies integrating results from these large-scale omic approaches will hopefully improve PDAC prognosis through identification of new therapeutic targets and patient selection tools. In this article, we will review the current knowledge on the biology of PDAC metastasis unravelled by large scale multi-omic approaches.
http://ift.tt/2p7bjZp
microRNAs as players and signals in the metastatic cascade: Implications for the development of novel anti-metastatic therapies
Source:Seminars in Cancer Biology
Author(s): Paolo Gandellini, Valentina Doldi, Nadia Zaffaroni
microRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. Increasing evidence emerging from human tumor preclinical models clearly indicates that specific miRNAs, collectively termed "metastamirs," play a functional role in different steps of the metastatic cascade, by exerting either pro- or anti-metastatic functions, and behave as signaling mediators to enable tumor cell to colonize a specific organ. miRNAs also actively participate in the proficient interaction of cancer cells with tumor microenvironment, either at the primary or at the metastatic site. Circulating miRNAs, released by multiple cell types, following binding to proteins or encapsulation in extracellular vesicles, play a main role in this cross-talk by acting as transferrable messages. The documented involvement of specific miRNAs in the dissemination process has aroused interest in the development of miRNA-based strategies for the treatment of metastasis. Preclinical research carried out in tumor experimental models, using both miRNA replacement and miRNA inhibitory approaches, is encouraging towards translating miRNA-based strategies into human cancer therapy, based on the observed therapeutic activity in the absence of main toxicity. However, to accelerate their adoption in the clinic, further improvements in terms of efficacy and targeted delivery to the tumor are still necessary.
http://ift.tt/2p72Q8y
Mechanisms governing metastatic dormancy in breast cancer
Source:Seminars in Cancer Biology
Author(s): Jürgen Dittmer
Breast cancer is a systemic disease characterized by early dissemination of tumor cells to distant organs. In this foreign environment, tumor cells may stay in a dormant state as single cells or as micrometastases for many years before growing out into a macrometastatic lesion. As metastasis is the primary cause for breast cancer-related death, it is important to understand the mechanisms underlying the maintenance of dormancy and dormancy escape to find druggable targets to eradicate metastatic tumor cells. Metastatic dormancy is regulated by complex interactions between tumor cells and the local microenvironment. In addition, cancer-directed immunity and systemic instigation play a crucial role.
http://ift.tt/2oj7Utk
Metabolic reprogramming in cancer cells, consequences on pH and tumour progression: Integrated therapeutic perspectives with dietary lipids as adjuvant to anticancer treatment
Source:Seminars in Cancer Biology
Author(s): Jean-François Dumas, Lucie Brisson, Stéphan Chevalier, Karine Mahéo, Gaëlle Fromont, Driffa Moussata, Pierre Besson, Sébastien Roger
While tumours arise from acquired mutations in oncogenes or tumour-suppressor genes, it is clearly established that cancers are metabolic diseases characterized by metabolic alterations in tumour cells, and also non-tumour cells of the host organism resulting in tumour cachexia and patient weakness. In this review, we aimed at delineating details by which metabolic alterations in cancer cells, characterized by mitochondrial bioenergetics deregulations and the preference for aerobic glycolysis, are critical parameters controlling the aggressive progression of tumours. In particular, metabolic alteration in cancer cells are coupled to the modulation of intracellular and extracellular pH, epithelial-to-mesenchymal transition and associated increased invasiveness, autophagy, and the development of anticancer treatment resistance. Finally, based on mechanistic, pre-clinical and clinical studies, we proposed the adjuvant supplementation of dietary n-3 polyunsaturated fatty acids for a complementary holistic treatment of the cancer disease.
http://ift.tt/2p79Imu
The challenge of targeting cancer stem cells to halt metastasis
Publication date: Available online 18 March 2017
Source:Seminars in Cancer Biology
Author(s): Alice Agliano, Alfonso Calvo, Carol Box
Despite a continuing debate about the existence of cancer stem cells (CSCs), recent discoveries have provided further support for their existence and their roles in drug resistance, cancer recurrence and metastasis. CSC characteristics, such as self-renewal and tumour initiation, and supporting cellular processes, particularly the epithelial-to-mesenchymal transition, are attracting a great deal of attention from cancer researchers as they offer opportunities for discovering novel therapeutic targets for future drug development. However, the identification of potential CSC targets presents clear obstacles due to a lack of truly specific CSC markers and the reality of CSC plasticity, making this task a significant challenge. Agents that target developmental signalling pathways, such as Notch, Wnt and Hedgehog, are now in clinical trials whilst alternative approaches including immune-based therapies and microRNA-mediated pathway inhibitors are producing promising pre-clinical results. Here, we discuss the contribution of CSCs to cancer metastasis and the scope of opportunities for therapeutic intervention. In particular, we consider CSC-targeting agents for which there is experimental evidence of anti-metastatic properties and which may have potential to eventually limit relapse and impede metastasis in patients.
http://ift.tt/2ojn4yG
Role of protein glycosylation in cancer metastasis
Source:Seminars in Cancer Biology
Author(s): Leticia Oliveira-Ferrer, Karen Legler, Karin Milde-Langosch
Although altered glycosylation has been detected in human cancer cells decades ago, only investigations in the last years have enormously increased our knowledge about the details of protein glycosylation and its role in tumour progression. Many proteins, which are heavily glycosylated, i.e. adhesion proteins or proteases, play an important role in cancer metastasis that represents the crucial and frequently life-threatening step in progression of most tumour types. Compared to normal tissue, tumour cells often show altered glycosylation patters with appearance of new tumour-specific antigens. In this review, we give an overview about the role of glycosylation in tumour metastasis, describing recent results about O-glycans, N-glycans and glycosaminoglycans. We show that glycan structures, glycosylated proteins and glycosylation enzymes have influence on different steps of the metastatic process, including epithelial-mesenchymal transition (EMT), migration, invasion/intravasation and extravasation of tumour cells. Regarding the important role of cancer metastasis for patients survival, further knowledge about the consequences of altered glycosylation patterns in tumour cells is needed which might eventually lead to the development of novel therapeutic approaches.
http://ift.tt/2p71mLF
Duplicated internal auditory canal with inner ear malformation: Case report and literature review
Internal auditory canal anomalies are rare. Narrow internal auditory canal is believed to occur as a result of aplasia or hypoplasia of the vestibulocochlear nerve. Narrow duplication of the internal auditory canal is considered to be very rare. Narrow duplication of the internal auditory canal with inner ear malformation has been reported in only 3 cases. We present 2 cases of narrow duplication of the internal auditory canal with inner ear malformation. The first case had inner ear malformation on only one side and the second case had inner ear malformation on both sides.
http://ift.tt/2ojlkFG
Duplicated internal auditory canal with inner ear malformation: Case report and literature review
Internal auditory canal anomalies are rare. Narrow internal auditory canal is believed to occur as a result of aplasia or hypoplasia of the vestibulocochlear nerve. Narrow duplication of the internal auditory canal is considered to be very rare. Narrow duplication of the internal auditory canal with inner ear malformation has been reported in only 3 cases. We present 2 cases of narrow duplication of the internal auditory canal with inner ear malformation. The first case had inner ear malformation on only one side and the second case had inner ear malformation on both sides.
http://ift.tt/2ojlkFG
The interactive role of CB1 receptors and L-type calcium channels in hippocampal long-term potentiation in rats
Source:Brain Research Bulletin
Author(s): Hamidreza Komaki, Fargol Saadat, Siamak Shahidi, Abdolrahman Sarihi, Parisa Hasanein, Alireza Komaki
'Long-term potentiation (LTP) of synaptic responses is a widely researched model of synaptic plasticity that occurs during learning and memory. The cannabinoid system is an endogenous system that modulate this kind of synaptic plasticity. In addition, voltage dependent calcium channels is essential for induction of LTP at some synapses in the hippocampus. However, there is currently debate over the interaction between L-type calcium channels and cannabinoid system on the synaptic plasticity. In this study, we examined the effects of an acute administration of the cannabinoid antagonist AM251 following a chronic administration of the Ca2+ channel blocker verapamil on LTP induction in the hippocampal dentate gyrus(DG) of rats. Male Wistar rats were administered verapamil(10,25,50mg/kg) or saline intraperitoneally(IP) daily for 13 days(n=10/group). After this treatment period, animals were anesthetized with an IP injection of urethane; the recording and stimulating electrodes were positioned in the DG and the perforant pathway. After obtaining a steady state baseline response, a single IP injection of saline or AM251(1 or 5mg/kg) was administered. LTP was induced by high-frequency stimulation(HFS). The population spike(PS) amplitude and the slope of excitatory postsynaptic potentials(EPSP) were compared between the experimental groups. The acute administration of the CB1 antagonist AM251 increased LTP induction. The EPSP slopes and PS amplitude in the verapamil and AM251 groups differed after HFS, such that AM251 increased LTP, whereas verapamil decreased LTP induction. These findings suggest that there are functional interactions between the L-type calcium channels and cannabinoid system in this model of synaptic plasticity in the hippocampus.
http://ift.tt/2pawCLG
The antimicrobial peptide hBD2 promotes itch through Toll-like receptor 4 signaling in mice
The psoriasis biomarker hBD2 produces a robust scratching response in a TLR4-dependent manner in mice. TRPV1 is a downstream mediator of hBD2-induced itch. These findings suggest that hBD2 might act as an endogenous pruritogen in psoriatic itch.
http://ift.tt/2paRVN5
Inhibition of Allogeneic Cytotoxic T Cell (CD8+) Proliferation Via Polymer-Induced Treg (CD4+) Cells
Publication date: Available online 23 April 2017
Source:Acta Biomaterialia
Author(s): Ning Kang, Wendy M. Toyofuku, Xining Yang, Mark D. Scott
T cell-mediated immune rejection remains a barrier to successful transplantation. Polymer-based bioengineering of cells may provide an effective means of preventing allorecognition and the proliferation of cytotoxic (CD8+) T lymphocytes (CTL). Using MHC-disparate murine splenocytes modified with succinimidyl valerate activated methoxypoly(ethylene glycol) [SVA-mPEG] polymers, the effects of leukocyte immunocamouflage on CD8+ and CD4+ alloproliferation and T regulatory (Treg) cell induction were assessed in a mixed lymphocyte reaction (MLR) model. Polymer-grafting effectively camouflaged multiple leukocyte markers (MHC class I and II, TCR and CD3) essential for effective allorecognition. Consequent to the polymer-induced immunocamouflage of the cell membrane, both CD8+ and CD4+ T cell alloproliferation were significantly inhibited in a polymer dose-dependent manner. The loss of alloproliferation correlated with the induction of Treg cells (CD4+CD25+Foxp3+). The Tregs, surprisingly, arose primarily via differentiation of naive, non-proliferating, CD4+ cells. Of biologic importance, the polymer-induced Treg were functional and exhibited potent immunosuppressive activity on allogeneic CTL proliferation. These results suggest that immunocamouflage-mediated attenuation of alloantigen-TCR recognition can prevent the tissue destructive allogeneic CD8+ T cell response, both directly and indirectly, through the generation/differentiation of functional Tregs. Immunocamouflage induced tolerance could be clinically valuable in attenuating T cell-mediated transplant rejection and in the treatment of autoimmune diseases.Statement of significanceWhile our previous studies have demonstrated that polymer-grafting to MHC disparate leukocytes inhibits CD4+ cell proliferation, the effects of PEGylation of on the alloproliferation of CD8+ cytotoxic T cells (CTL) was not examined. As shown here, PEGylation of allogeneic leukocytes prevents the generation of the CTL response responsible for acute rejection. The loss of CTL proliferation is consequent to the polymer-based attenuation of allorecognition and the induction of T regulatory cells (Tregs). Interestingly, the Tregs are primarily generated via the differentiation of non-proliferating naive T cells. Importantly, the Tregs are functional and effectively induce a tolerogenic environment when transferred to an alloresponsive environment. The use of polymer-modified leukocytes provides a unique approach to effectively maximize the biologic production of functional Tregs both in vitro and in vivo. By using this approach it may be possible to attenuate unwanted alloresponses (e.g., graft rejection) or to While our previous studies have demonstrated that polymer-grafting to MHC disparate leukocytes inhibits CD4+ cell proliferation, the effects of PEGylation of on the alloproliferation of CD8+ cytotoxic T cells (CTL) was not examined. As shown here, PEGylation of allogeneic leukocytes prevents the generation of the CTL response responsible for acute rejection. The loss of CTL proliferation is consequent to the polymer-based attenuation of allorecognition and the induction of T regulatory cells (Tregs). Interestingly, the Tregs are primarily generated via the differentiation of non-proliferating naive T cells. Importantly, the Tregs are functional and effectively induce a tolerogenic environment when transferred to an alloresponsive environment. The use of polymer-modified leukocytes provides a unique approach to effectively maximize the biologic production of functional Tregs both in vitro and in vivo. By using this approach it may be possible to attenuate unwanted alloresponses (e.g., graft rejection) or to
Graphical abstract
http://ift.tt/2oA46jp
Employment and choice-making for adults with intellectual disability, autism, and down syndrome
Source:Research in Developmental Disabilities, Volume 65
Author(s): Kelsey L. Bush, Marc J. Tassé
BackgroundAdults with disabilities are employed at a significantly lower rate than adults without disabilities. Of adults with disabilities in the workforce, more individuals work in a facility setting rather than a community setting, despite efforts to improve community inclusion. Choice-making has been proposed as a predictive factor for employment for individuals with disabilities.AimsThe purpose of this research was to examine the current state of employment for three groups of adults with intellectual disability (ID): individuals with autism spectrum disorder (ASD), individuals with Down syndrome (DS), and individuals with idiopathic ID. Choice-making and its relation to improved employment outcomes was explored.MethodsThis study used National Core Indicator's Adult Consumer Survey datasets from years 2011–2012 and 2012–2013. Factor analyses revealed latent variables from six choice-making questions in the Adult Consumer Survey. Ordinal logistic regression was used to identify factors related to employment status.ResultsAdults with DS had the highest rates of paid community jobs, but adults with ID had the highest rates of choice-making. ID severity level and short-term choice-making had the greatest effects on employment status in all three groups.ConclusionsEmployment rates remain low despite national efforts to find jobs for people with disabilities. Choice-making is a unique factor that was found to be associated with employment status and provides a target for interventions to increase employability.
http://ift.tt/2pUn6wY
A Pilot Study Examining a Computer-Based Intervention to Improve Recognition and Understanding of Emotions in Young Children with Communication and Social Deficits
Source:Research in Developmental Disabilities, Volume 65
Author(s): Neri L. Romero
BackgroundA common social impairment in individuals with ASD is difficulty interpreting and or predicting emotions of others. To date, several interventions targeting teaching emotion recognition and understanding have been utilized both by researchers and practitioners. The results suggest that teaching emotion recognition is possible, but that the results do not generalize to non-instructional contexts. This study sought to replicate earlier findings of a positive impact of teaching emotion recognition using a computer-based intervention and to extend it by testing for generalization on live models in the classroom setting.MethodTwo boys and one girl, four to eight years in age, educated in self-contained classrooms for students with communication and social skills deficits, participated in this study. A multiple probe across participants design was utilized. Measures of emotion recognition and understanding were assessed at baseline, intervention, and one month post-intervention to determine maintenance effects. Social validity was assessed through parent and teacher questionnaires.ResultsAll participants showed improvements in measures assessing their recognition of emotions in faces, generalized knowledge to live models, and maintained gains one month post intervention.ConclusionsThese preliminary results are encouraging and should be utilized to inform a group design, in order to test efficacy with a larger population.
http://ift.tt/2p6ZbYc
What does handedness reveal about ADHD? An analysis based on CPT performance
Source:Research in Developmental Disabilities, Volume 65
Author(s): Eunice N. Simões, Ana Lucia Novais Carvalho, Sergio L. Schmidt
BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a developmental disorder. Continuous performance Tests (CPTs) aid the diagnosis. Handedness is linked to disabilities.Objectives1-To study the association between handedness and ADHD; 2-To verify the usefulness of the CPT in school settings; 3-To exam the relationship between handedness and CPT performance.MethodEach child was classified as right-consistent, left-consistent, or non-consistent. From the sample, 171 controls and 68 ADHDs fulfilled the inclusion criteria. The effect of handedness on the CPT was studied using a paired-sample that matched handedness by age, grade, gender, and ADHD.ResultsLeft-handed students had a probability of suffering from ADHD 2.88 greater than right-handers. ANOVAs on standardized scores indicated that the ADHD students exhibited higher number of errors and higher variability of reaction times as compared to the controls. Discriminant analysis indicated that these CPT parameters could discriminate ADHD from controls. Repeated ANOVAs showed a significant effect of handedness on commission errors (CE) because left-handers made more CEs than right-handers.Conclusions1-The association between ADHD and handedness reflects that left-handers are less lateralized and have decreased interhemispheric connections; 2-The CPT can be used to measure different attention domains in school settings; 3- Left-handers have problems in the impulsive/hyperactivity domain.
http://ift.tt/2pUBLIK
Ipsilateral sagittal split ramus osteotomy to facilitate reconstruction of the temporomandibular joint after resection of condylar osteochondroma
We report the outcomes of 12 patients with osteochondroma of the mandibular condyle who were treated by condylectomy with sagittal split ramus osteotomy (SSRO) between January 2011 and October 2015. Variables assessed before and after operation were imaging, appearance, maximum mouth opening, maximum mandibular protrusion, lateral excursion, and function of the temporomandibular joint (TMJ). Patients were followed up for a mean (range) of 21 (13 - 30) months. Outcomes were satisfactory with no complications or recurrence.
http://ift.tt/2pUmFmB
External loading alters trunk kinematics and lower extremity muscle activity in a distribution-specific manner during sitting and rising from a chair
Publication date: Available online 23 April 2017
Source:Journal of Electromyography and Kinesiology
Author(s): Michelle C. Walaszek, Amanda L. Ransom, Steven Capehart, Michael B. Pohl, Robert Shapiro, Lance M. Bollinger
BackgroundExcess body mass alters gait biomechanics in a distribution-specific manner. The effects of adding mass centrally or peripherally on biomechanics during sitting and rising from a chair are unknown.MethodsMotion analysis and lower extremity EMG were measured for fifteen healthy, normal weight subjects during sit-to-stand (SitTS) and stand-to-sit (StandTS) from a chair under unloaded (UN), centrally loaded (CL), and peripherally loaded (PL) conditions.ResultsCompared to UN, PL significantly increased support width (SitTS and StandTS), increased peak trunk flexion velocity (SitTS), and trended to increase peak trunk flexion angle (SitTS). During StandTS, CL significantly reduced peak trunk flexion compared to UN and PL. EMG activity of the semitendinosus, vastus lateralis and/or medialis was significantly increased in CL compared to UN during SitTS and StandTS.ConclusionsAdding mass centrally or peripherally induces contrasting biomechanical strategies to successfully sit or rise from a chair. CL limits trunk flexion and increases knee extensor muscle activity whereas; PL increases support width and trunk flexion, thus preventing increased EMG activity.
http://ift.tt/2p6TwkX
18F-FDG PET/CT in aggressive angiomyxoma of the pelvis
Publication date: Available online 22 April 2017
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): L. Gilardi, M. Vadrucci, A. Pittaro, E. Pennacchioli, S. Rizzo
http://ift.tt/2oWaww3
Work first then play: Prior task difficulty increases motivation-related brain responses in a risk game
Source:Biological Psychology
Author(s): Barbara Schmidt, Patrick Mussel, Roman Osinsky, Björn Rasch, Stefan Debener, Johannes Hewig
Task motivation depends on what we did before. A recent theory differentiates between tasks that we want to do and tasks that we have to do. After a have-to task, motivation shifts towards a want-to task. We measured this shift of motivation via brain responses to monetary feedback in a risk game that was used as want-to task in our study. We tested 20 healthy participants that were about 28 years old in a within-subjects design. Participants worked on a Stroop task (have-to task) or an easier version of the Stroop task as a control condition and played a risk game afterwards (want-to task). After the Stroop task, brain responses to monetary feedback in the risk game were larger compared to the easier control task, especially for feedback indicating higher monetary rewards. We conclude that higher amplitudes of feedback-related brain responses in the risk game reflect the shift of motivation after a have-to task towards a want-to task.
http://ift.tt/2oW5ZJT
Neural correlates of evoked phantom limb sensations
Source:Biological Psychology
Author(s): J. Andoh, M. Diers, C. Milde, C. Köppe, D. Kleinböhl, H. Flor
Previous work showed the existence of changes in the topographic organization within the somatosensory cortex (SI) in amputees with phantom limb pain, however, the link between nonpainful phantom sensations such as cramping or tingling or the percept of the limb and cortical changes is less clear.We used functional magnetic resonance imaging (fMRI) in a highly selective group of limb amputees who experienced inducible and reproducible nonpainful phantom sensations. A standardized procedure was used to locate body sites eliciting phantom sensations in each amputee. Selected body sites that could systematically evoke phantom sensations were stimulated using electrical pulses in order to induce phasic phantom sensations. Homologous body parts were also stimulated in a group of matched controls.Activations related to evoked phantom sensations were found bilaterally in SI and the intraparietal sulci (IPS), which significantly correlated with the intensity of evoked phantom sensations. In addition, we found differences in intra- and interhemispheric interaction between amputees and controls during evoked phantom sensations. We assume that phantom sensations might be associated with a functional decoupling between bilateral SI and IPS, possibly resulting from transcallosal reorganization mechanisms following amputation.
http://ift.tt/2oW3NC6
Systematic review and meta-analysis on the proportion of patients with breast cancer who develop bone metastases
Publication date: Available online 23 April 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Jean-Jacques Body, Geoffrey Quinn, Susan Talbot, Emma Booth, Gaston Demonty, Aliki Taylor, Justyna Amelio
A systematic literature review was conducted to quantify populations of patients with primary breast cancer in whom bone metastases were detected at study start or during follow-up. Searches were performed in PubMed and EMBASE using terms related to breast cancer and bone metastases. Articles had to have been published 01/01/99–31/12/13, and to report data on the proportion of patients with bone metastases among patients with breast cancer. In total, 156 articles were included in the meta-analysis. A median of 12% of patients with stage I–III breast cancer developed bone metastases during a median follow-up of 60 months. Of patients who developed metastatic disease during follow-up, 55% (median) had bone metastases. Of those with metastatic breast cancer at study start, 58% (median) had bone metastases. These data help to inform on the global burden of bone metastases by defining patient populations that are at risk of developing bone metastases.
http://ift.tt/2pafXbc
A curated dataset of complete Enterobacteriaceae plasmids compiled from the NCBI nucleotide database
Publication date: Available online 23 April 2017
Source:Data in Brief
Author(s): Alex Orlek, Hang Phan, Anna E. Sheppard, Michel Doumith, Matthew Ellington, Tim Peto, Derrick Crook, A. Sarah Walker, Neil Woodford, Muna F. Anjum, Nicole Stoesser
Thousands of plasmid sequences are now publicly available in the NCBI nucleotide database, but they are not reliably annotated to distinguish complete plasmids from plasmid fragments, such as gene or contig sequences; therefore, retrieving complete plasmids for downstream analyses is challenging. Here we present a curated dataset of complete bacterial plasmids from the clinically relevant Enterobacteriaceae family. The dataset was compiled from the NCBI nucleotide database using curation steps designed to exclude incomplete plasmid sequences, and chromosomal sequences misannotated as plasmids. Over 2000 complete plasmid sequences are included in the curated plasmid dataset. Protein sequences produced from translating each complete plasmid nucleotide sequence in all 6 frames are also provided. Further analysis and discussion of the dataset is presented in an accompanying research article: "Ordering the mob: Insights into replicon and MOB typing…" [1]. The curated plasmid sequences are publicly available in the Figshare repository.
http://ift.tt/2ozP25r
Data on water consumption in streptozotocin-induced diabetic mice by a novel peach gum-derived polysaccharide
Publication date: Available online 23 April 2017
Source:Data in Brief
Author(s): Yuting Wang, Dingbo Lin, Xiaoli Wang, Wei Zhu, Junli Ye, Guohuai Li, Zhaocheng Ma, Xiuxin Deng
The data presented in this article are related to the article entitled "The impact of a novel peach gum-derived polysaccharide on postprandial blood glucose control in streptozotocin-induced diabetic mice" (Y. Wang, D. Lin, X. Wang, W. Zhu, J. Ye, G. Li, Z. Ma, X. Deng, 2017) [1]. Polydipsia was one of the most important symptoms of diabetic mellitus (DM) mice, which showed more water consumption than normal ones. The water consumption of DM mice in different groups administrated with metformin hydrochloride or a novel polysaccharide (coded as PGPSD) were exhibited in this article (Fig. 1). The field data set is made publicly available to enable critical or extended analyzes.
http://ift.tt/2oiBbV5
MRI ductography of contrast agent distribution and leakage in normal mouse mammary ducts and ducts with in situ cancer
Source:Magnetic Resonance Imaging, Volume 40
Author(s): Erica Markiewicz, Xiaobing Fan, Devkumar Mustafi, Marta Zamora, Suzanne D. Conzen, Gregory S. Karczmar
High resolution 3D MRI was used to study contrast agent distribution and leakage in normal mouse mammary glands and glands containing in situ cancer after intra-ductal injection. Five female FVB/N mice (~19weeks old) with no detectable mammary cancer and eight C3(1) SV40 Tag virgin female mice (~15weeks old) with extensive in situ cancer were studied. A 34G, 45° tip Hamilton needle with a 25μL Hamilton syringe was inserted into the tip of the nipple and approximately 15μL of a Gadodiamide was injected slowly over 1min into the nipple and throughout the duct on one side of the inguinal gland. Following injection, the mouse was placed in a 9.4T MRI scanner, and a series of high resolution 3D T1-weighted images was acquired with a temporal resolution of 9.1min to follow contrast agent leakage from the ducts. The first image was acquired at about 12min after injection. Ductal enhancement regions detected in images acquired between 12 and 21min after contrast agent injection was five times smaller in SV40 mouse mammary ducts (p<0.001) than in non-cancerous FVB/N mouse mammary ducts, perhaps due to rapid washout of contrast agent from the SV40 ducts. The contrast agent washout rate measured between 12min and 90min after injection was ~20% faster (p<0.004) in SV40 mammary ducts than in FVB/N mammary ducts. These results may be due to higher permeability of the SV40 ducts, likely due to the presence of in situ cancers. Therefore, increased permeability of ducts may indicate early stage breast cancers.
http://ift.tt/2oBFMwM
“The world is upside down“ – The Innsbruck Goggle Experiments of Theodor Erismann (1883-1961) and Ivo Kohler (1915-1985)
Source:Cortex
Author(s): Pierre Sachse, Ursula Beermann, Markus Martini, Thomas Maran, Markus Domeier, Marco R. Furtner
The "Innsbruck Goggle Experiments" on long-term wearing of reversing mirrors, prismatic and half prismatic goggles, and colored half goggles represent a milestone in research on adaptation (adapting to the introduced "disturbance") and after-effects (after removal of the "disturbance"). By means of these goggles it is, for example, possible to invert or distort the visual field (such as flipping top and bottom or left and right), as well as to observe how individuals learn to change the image back to vertical or recognize left and right. The Innsbruck Experiments gave decisive momentum to further international research on the ontogenetic development of perception, special perception, color perception, perceptual constancy, sensorimotor coordination, as well as to the development of theories. In the current paper, aside from presenting the history and results of selected studies, we will give an introduction to the life and work of the protagonists of these studies in Innsbruck, namely Theodor Erismann (1883-1961) and Ivo Kohler (1915-1985). Furthermore, we will propose ideas for future research on cognition and neuroscience.
http://ift.tt/2pU6ju5
Mechanical characteristic and biological behaviour of implanted and restorative bioglasses used in medicine and dentistry: A systematic review
Source:Dental Materials
Author(s): F. Lizzi, C. Villat, N. Attik, P. Jackson, B. Grosgogeat, C. Goutaudier
ObjectiveNowadays bioactive glasses are finding increasing applications in medical practice due to their ability to stimulate re-mineralisation. However, they are intrinsically brittle materials and the study of new compositions will open up new scenarios enhancing their mechanical properties and maintaining the high bioactivity for a broader range of applications. This systematic review aims to identify the relationship between the composition of bioactive glasses used in medical applications and their influence on the mechanical and biological properties.MethodsVarious electronic databases (PubMed, Science Direct) were used for collecting articles on this subject. This research includes papers from January 2011 to March 2016. PRISMA guidelines for systematic review and meta-analysis have been used. 109 abstracts were collected and screened, 68 articles were read as relevant articles and a total of 22 papers were finally selected for this study.ResultsMost of the studies obtained enhanced mechanical properties and the conservation of bioactivity behaviours; although a lack of homogeneity in the characterization methods makes it difficult to compare data.SignificanceNew compositions of bioactive glasses incorporating specific ions and the addition in polymers will be the most important direction for future researches in developing new materials for medical applications and especially for dentistry.
http://ift.tt/2oVPj5a
An information theory framework for dynamic functional domain connectivity
Source:Journal of Neuroscience Methods
Author(s): Victor M. Vergara, Robyn Miller, Vince Calhoun
BackgroundDynamic functional network connectivity (dFNC) analyzes time evolution of coherent activity in the brain. In this technique dynamic changes are considered for the whole brain. This paper proposes an information theory framework to measure information flowing among subsets of functional networks call functional domains.New MethodOur method aims at estimating bits of information contained and shared among domains. The succession of dynamic functional states is estimated at the domain level. Information quantity is based on the probabilities of observing each dynamic state. Mutual information measurement is then obtained from probabilities across domains. Thus, we named this value the cross domain mutual information (CDMI).ResultsStrong CDMIs were observed in relation to the subcortical domain. Domains related to sensorial input, motor control and cerebellum form another CDMI cluster. Information flow among other domains was seldom found.Comparison with existing methodsOther methods of dynamic connectivity focus on whole brain dFNC matrices. In the current framework, information theory is applied to states estimated from pairs of multi-network functional domains. In this context, we apply information theory to measure information flow across functional domains.ConclusionIdentified CDMI clusters point to known information pathways in the basal ganglia and also among areas of sensorial input, patterns found in static functional connectivity. In contrast, CDMI across brain areas of higher level cognitive processing follow a different pattern that indicates scarce information sharing. These findings show that employing information theory to formally measured information flow through brain domains reveals additional features of functional connectivity.
http://ift.tt/2pa7hBv
The effects of repeated nitroglycerin administrations in rats; modeling migraine-related endpoints and chronification
Source:Journal of Neuroscience Methods
Author(s): Hannah M. Harris, Jessica M. Carpenter, Jonathan R. Black, Todd A. Smitherman, Kenneth J. Sufka
BackgroundRodent models typically use a single nitroglycerin injection to induce migraine, yet migraine in clinical populations presents as recurrent episodes. Further, these models quantify behavioral endpoints that do not align with the clinical features of episodic migraine or migraine chronification and therefore may limit translational relevance.New MethodRats received 5 nitroglycerin (10mg/kg/2ml), propylene glycol/ethanol vehicle, or saline injections every third day over 15 days. Behavioral endpoints were assessed 110minutes post nitroglycerin administration and included time spent light/dark chambers for photophobia as well as activity, facial pain expressions, and tactile allodynia.ResultsAnimals administered nitroglycerin displayed photophobia, decreased activity, and increased facial pain expression. Similar alterations in photophobia and activity were seen in the vehicle treated animals, but these tended to diminish by the 4th or 5th injection. The presentation of spontaneous tactile allodynia was observed in the nitroglycerin group by the 5th episode.Comparison with Existing MethodsMost NTG migraine models entail a single NTG administration and quantification of evoked allodynia. This paradigm employs recurring NTG episodes and clinically-relevant measures of photophobia, hypoactivity and facial grimace endpoints as well as introduces a novel arena apparatus to quantify spontaneous allodynia.ConclusionsThis repeated NTG procedure and endpoint measures aligns with the frequency and clinical presentation of episodic migraine and its chronification, respectively. Further, propylene glycol ethanol vehicle contributes to migraine endpoints.
http://ift.tt/2pSWfys
Flow cytometry analysis of inflammatory cells isolated from the sciatic nerve and DRG after chronic constriction injury in mice
Source:Journal of Neuroscience Methods
Author(s): Liping Liu, Yan Yin, Fei Li, Charvi Malhotra, Jianguo Cheng
BackgroundCellular responses to nerve injury play a central role in the pathogenesis of neuropathic pain. However, the analysis of site specific cellular responses to nerve injury and neuropathic pain is limited to immunohistochemistry staining with numerous limitations.New MethodsWe proposed to apply flow cytometry to overcome some of the limitations and developed two protocols for isolation of cells from small specimens of the sciatic nerve and dorsal root ganglion (DRG) in mice.Results and comparasion with existingmethods We found that both the non-enzymatic and enzymatic approaches were highly effective in harvesting a sufficient number of cells for flow cytometry analysis in normal and pathological conditions. The total number of cells in the injury site of the sciatic and its DRGs increased significantly 14days after chronic constriction injury (CCI) of the sciatic nerve, compared to sham surgery control or the contralateral control. The enzymatic approach yielded a significantly higher total number of cells and CD45 negative cells, suggesting that this approach allows for harvest of more resident cells, compared to the non-enzymatic method. The percentage of CD45+/CD11b+ cells was significantly increased in the sciatic nerve but not in the DRG. These results were consistent with both protocols.ConclusionsWe thus offer two simple and effective protocols that allow for application of flow cytometry to the investigation of cellular and molecular mechanisms of neuropathic pain.
http://ift.tt/2pT8T0n
Rewiring brain circuits to block cataplexy in murine models of narcolepsy
Source:Current Opinion in Neurobiology, Volume 44
Author(s): Meng Liu, Carlos Blanco-Centurion, Priyattam J Shiromani
Narcolepsy was first identified almost 130 years ago, but it was only 15 years ago that it was identified as a neurodegenerative disease linked to a loss of orexin neurons in the brain. It is unclear what causes the orexin neurons to die, but our strategy has been to place the gene for orexin into surrogate neurons in the validated mouse models of narcolepsy, and test whether it can block narcolepsy symptoms, such as cataplexy. In both the orexin knockout and the orexin–ataxin-3 mouse models of narcolepsy we have found that cataplexy can be blocked if the surrogate neurons are part of the circuit responsible for cataplexy. We have also determined that the orexin gene can be inserted into surrogate neurons in the amygdala to block emotion-induced cataplexy. Through the use of optogenetics we anticipate that it will be possible to preemptively block cataplexy.
http://ift.tt/2ozlsgd
Interpretation of physiological indicators of motivation: Caveats and recommendations
Source:International Journal of Psychophysiology
Author(s): Michael Richter, Kate Slade
Motivation scientists employing physiological measures to gather information about motivation-related states are at risk of committing two fundamental errors: overstating the inferences that can be drawn from their physiological measures and circular reasoning. We critically discuss two complementary approaches, Cacioppo and colleagues' model of psychophysiological relations and construct validation theory, to highlight the conditions under which these errors are committed and provide guidance on how to avoid them. In particular, we demonstrate that the direct inference from changes in a physiological measure to changes in a motivation-related state requires the demonstration that the measure is not related to other relevant psychological states. We also point out that circular reasoning can be avoided by separating the definition of the motivation-related state from the hypotheses that are empirically tested.
http://ift.tt/2pSL60K
Digital quantitative analysis of microRNA in single cell based on ligation-depended polymerase colony (Polony)
Source:Biosensors and Bioelectronics, Volume 95
Author(s): Hui Wang, Honghong Wang, Xinrui Duan, Chenghui Liu, Zhengping Li
The ability to dissect cell-to-cell variations of microRNA (miRNA) expression with single-cell resolution has become a powerful tool to investigate the regulatory function of miRNAs in biological processes and the pathogenesis of miRNA-related diseases. Herein, we have developed a novel scheme for digital detection of miRNA in single cell by using the ligation-depended DNA polymerase colony (polony). Firstly, two simply designed target-specific DNA probes were ligated by using individual miRNA as the template. Then the ligated DNA probe acted as polony template that was amplified by PCR process in the thin polyacrylamide hydrogel. Due to the covalent attachment of a PCR primer on polyacrylamide matrix and the retarding effect of the polyacrylamide hydrogel matrix itself, as the polony reaction proceeds, the PCR products diffused radially near individual template molecule to form a bacteria colony-like spots of DNA molecules. The spots can be counted after staining the polyacrylamide gel with SYBR Green I and imaging with a microarray scanner. Our polony-based method is sensitive enough to detect 60 copies of miRNA molecules. Meanwhile, the new strategy has the capability of distinguishing singe-base difference. Due to its high sensitivity and specificity, the proposed method has been successfully applied to analysis of the expression profiling of miRNA in single cell.
http://ift.tt/2oisTwk
Portable aptamer biosensor of platelet-derived growth factor-BB using a personal glucose meter with triply amplified
Source:Biosensors and Bioelectronics, Volume 95
Author(s): Lu Hong, Fu Zhou, Dongmin Shi, Xiaojun Zhang, Guangfeng Wang
Sensitive and rapid detection of platelet-derived growth factor BB (PDGF-BB), a cancer-related protein, could help early diagnosis, treatment, and prognosis of cancers. Although some methods have been developed to detect PDGF-BB, few can provide quantitative results using an affordable and portable device that is suitable for home use or field application. In this work, we report the first use of a portable kind of personal glucose meter (PGM) combining a catalytic and molecular beacon (CAMB) system with a cation exchange reaction (CX reaction) for ultrasensitive PDGF-BB assay. It realized the amplification of the detection in three ways, including greater aptamer payload on nanoparticles, CX reaction releasing thousands of Zn2+ and the cycle by the catalyzing cleavage of 8–17 DNAzyme. In the process, with the addition of PDGF-BB into the aptasensor, the specific recognition between aptamer and protein was initiated resulting in the combination of ZnS NNC for further CX reaction to release thousands of Zn2+, which could cleave the substrate DNA in the CAMB system realizing multiple cycle. The cleaved DNA fragment was designed with invertase-labeled could convert sucrose into glucose which could be detected and quantified by PGM accompanying with the change of color of the control window from yellow to green. The enhanced signal of the PGM has a relationship with the concentration of PDGF-BB in the range of 3.16×10–16M to 3.16×10–12M, and the detection limit is 0.11fM. Moreover, the catalytic and cleavage activities of 8–17 DNAzyme can be achieved in solution; thus, no enzyme immobilization is needed for detection. The triply amplified strategy showed high selectivity, stability, and applicability for detecting the desired protein.
http://ift.tt/2p6830o
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