The multi-target effects of CNI-1493: convergence of anti-amylodogenic and anti-inflammatory properties in animal models of Alzheimer's disease.

Related Articles

The multi-target effects of CNI-1493: convergence of anti-amylodogenic and anti-inflammatory properties in animal models of Alzheimer's disease.

Mol Med. 2016 Nov 15;22:

Authors: Sankowski R, Herring A, Keyvani K, Frenzel K, Wu J, Röskam S, Noelker C, Bacher M, Al-Abed Y

Abstract
After several decades of Alzheimer's disease (AD) research and failed clinical trials, one can speculate that targeting a single pathway is not sufficient. However, a cocktail of novel therapeutics will constitute a challenging clinical trial. A more plausible approach will capitalize on a drug that has relevant and synergistic multiple-target effects in AD. We have previously demonstrated the efficacy of CNI-1493 in the CRND8 transgenic AD mouse model. Similar to many anti-inflammatory drugs that were tested in preclinical model of AD, it was speculated that the significant effect of CNI-1493 is due to its established anti-inflammatory properties in rodents and humans. In the present study, we set out to elucidate the protective mechanism of CNI-1493 as a drug simultaneously targeting several aspects of AD pathology. Using C1213, a highly similar analogue of CNI-1493 that lacks anti-inflammatory properties, we show that both compounds directly interact with soluble and insoluble Amyloid β (Aβ) aggregates and attenuate Aβ cytotoxicity in vitro. Additionally, CNI-1493 and C1213 ameliorated Aβ-induced behavioral deficits in nematodes. Finally, C1213 reduced Aβ plaque burden and cognitive deficits in transgenic CRND8 mice to a similar extent as previously shown with CNI-1493. Taken together, our findings suggest anti-amyloidogenic activity as a relevant component for the in-vivo efficacy of CNI-1493 and its analogue C1213. Thus, CNI-1493, a drug with proven safety in humans, is a viable candidate for novel multi-target therapeutic approaches to AD.

PMID: 27847962 [PubMed - as supplied by publisher]

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Herb medicines against osteoporosis: Active compounds & relevant biological mechanisms.

Herb medicines against osteoporosis: Active compounds & relevant biological mechanisms.

Curr Top Med Chem. 2016 Nov 16;

Authors: Wu L, Ling Z, Feng X, Mao C, Xu Z

Abstract
Osteoporosis is one of common bone disorders, affecting millions of people worldwide. Treatments of osteoporosis consist of pharmacotherapy and non-pharmacological interventions, such as mineral supplementation, lifestyle changes, and exercise programs. Due to the minimum side effects and favorable cost-effective therapeutic effects, herbal medicine has been widely applied in clinical practices for more than 2,000 years in China. Of the many traditional formulas reported for treating bone diseases, 4 single herbs namely (1) Herba Epimedii, (2) Rhizoma Drynariae, (3) Fructus Psoraleae, and (4) Cortex Eucommiae, are considered as the featured "Kidney-Yang" tonics, and frequently and effectively applied for preventing and treating osteoporosis. With the accruing development of modern chemistry, hundreds of active compounds have been identified and isolated for their anti-osteoporotic effects. This review would first sketch the phytochemistry of these featured "Kidney-Yang" tonics and present the pharmacological characteristics of the most abundant and bioactive compounds derived from the herb Herba Epimedii and Rhizoma Drynariae, including icariin and naringin. Then, the cellular and molecular underpinnings under anti-osteoporotic effects of icariin and naringin are discussed. The concerned structure-function relationships of the featured active herbal compounds would also be reviewed so as to pave the way for future drug design in treating osteoporosis.

PMID: 27848901 [PubMed - as supplied by publisher]

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Antioxidative Effects of Rhodiola genus: Phytochemistry and Pharmacological Mechanisms against the Diseases.

Antioxidative Effects of Rhodiola genus: Phytochemistry and Pharmacological Mechanisms against the Diseases.

Curr Top Med Chem. 2016 Nov 16;

Authors: Li Y, Wu J, Shi R, Li N, Xu Z, Sun M

Abstract
Rhodiola as one of traditional medicines has been used for clinical treatments due to their strong antioxidant properties. Phytochemical analysis revealed the presence of flavonoids, phenylpropanoids, phenylethanol/benzyl alcohol derivatives, cyanogenic glycosides and terpenoids. The bioactive compounds had been demonstrated to be effective at scavenging reactive oxygen species (ROS). The structures contain phenolic hydroxyl groups and unsaturated bonds. This article reviews antioxidant capacities of the extracts and bioactive components derived from Rhodiola plants. As the major pharmacological ingredient, salidroside is rigorously investigated and used in scientific researches and clinical practices. Accumulated evidences indicated that extracts of Rhodiola plants or salidroside could be able to reverse DNA damage and alter expression of cytokines and antioxidative enzymes induced by ROS. The underlying mechanisms for the antioxidative effects of the herb have been investigated in the last two decades. We summarize the possible effects and acting pathways for the herb involved in several chronic diseases in cardiovascular, respiratory, and nervous systems, as well as potential epigenetic influences. The information generated from experimental and clinical studies offered valuable insights for further investigations of medical potentials of Rhodiola plants.

PMID: 27848900 [PubMed - as supplied by publisher]

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Computational modeling approach in probing effects of cytosine methylation on the transcription factor binding to DNA.

Computational modeling approach in probing effects of cytosine methylation on the transcription factor binding to DNA.

Curr Top Med Chem. 2016 Nov 16;

Authors: Tenayuca J, Cousins K, Yang S, Zhang L

Abstract
Cytosine methylation at CpG dinucleotides is a chief mechanism in epigenetic modification of gene expression patterns. Previous studies demonstrated that increased CpG methylation of Sp1 sites at -268 and -346 of protein kinase C  promoter repressed the gene expression. The present study investigated the impact of CpG methylation on the Sp1 binding via molecular modeling and electrophoretic mobility shift assay. Each of the Sp1 sites contain two CpGs. Methylation of either CpG lowered the binding affinity of Sp1, whereas methylation of both CpGs produced a greater decrease in the binding affinity. Computation of van der Waals (VDW) energy of Sp1 in complex with the Sp1 sites demonstrated increased VDW values from one to two sites of CpG methylation. Molecular modeling indicated that single CpG methylation caused underwinding of the DNA fragment, with the phosphate groups at C1, C4 and C5 reoriented from their original positions. Methylation of both CpGs pinched the minor groove and increased the helical twist concomitant with a shallow, hydrophobic major groove. Additionally, double methylation eliminated hydrogen bonds on recognition helix residues located at positions -1 and 1, which were essential for interaction with O6/N7 of G-bases. Bonding from linker residues Arg565, Lys595 and Lys596 were also reduced. Methylation of single or both CpGs significantly affected hydrogen bonding from all three Sp1 DNA binding domains, demonstrating that the consequences of cytosine modification extend beyond the neighboring nucleotides. The results indicate that cytosine methylation causes subtle structural alterations in Sp1 binding sites consequently resulting in inhibition of side chain interactions critical for specific base recognition and reduction of the binding affinity of Sp1.

PMID: 27848899 [PubMed - as supplied by publisher]

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Proteomic analysis of endothelin-1 targets in the regulation of cardiomyocyte proliferation.

Proteomic analysis of endothelin-1 targets in the regulation of cardiomyocyte proliferation.

Curr Top Med Chem. 2016 Nov 16;

Authors: Shin AN, Dasgupta C, Zhang L, Zhang G, Seal K

Abstract
Hypoxia is a fetal stressor that leads to the production of endothelin-1 (ET-1). Previous work has shown that ET-1 treatment leads to the premature terminal differentiation of fetal cardiomyocytes. However, the precise mechanism is unknown. We tested the hypothesis that the fetal cardiomyocyte proteome will be greatly altered due to ET-1-treatment, which reveals a potential molecular mechanism of ET-1-induced terminal differentiation. Over a thousand proteins were detected in the fetal cardiomyocytes and among them 75 proteins were significantly altered due to ET-1 treatment. Using IPA pathway analysis, the merged network depicted several key proteins that appeared to be involved in regulating proliferation, including: EED, UBC, ERK1/2, MAPK, Akt, and EGFR. EED protein, which is associated with regulating proliferation via epigenetic mechanisms, is of particular interest. Herein we propose a model of the molecular mechanism by which ET-1 induced cardiomyocyte terminal differentiation occurs.

PMID: 27848898 [PubMed - as supplied by publisher]

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Bioinformatics and Drug Discovery.

Bioinformatics and Drug Discovery.

Curr Top Med Chem. 2016 Nov 16;

Authors: Xia X

Abstract
Bioinformatic analysis can not only accelerate drug target identification and drug candidate screening and refinement, but also facilitate characterization of side effects and predict drug resistance. High-throughput data such as genomic, epigenetic, genome architecture, cistromic, transcriptomic, proteomic, and ribosome profiling data have all made significant contribution to mechanism-based drug discovery and drug repurposing. Accumulation of protein and RNA structures, as well as development of homology modeling and protein structure simulation, coupled with large structure databases of small molecules and metabolites, paved the way for more realistic protein-ligand docking experiments and more informative virtual screening. I present the conceptual framework that drives the collection of these high-throughput data, summarize the utility and potential of mining these data in drug discovery, outline a few inherent limitations in data and software mining these data, point out news ways to refine analysis of these diverse types of data, and highlight commonly used software and databases relevant to drug discovery.

PMID: 27848897 [PubMed - as supplied by publisher]

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Probes and targets of DNA methylation and demethylation in drug development.

Probes and targets of DNA methylation and demethylation in drug development.

Curr Top Med Chem. 2016 Nov 16;

Authors: Mirfattah B, Herring J, Tang H, Zhang K

Abstract
DNA methylation and demethylation is part of the essential biological processes regulating gene expression in normal cell development. Abnormal methylation status of specific genes and their irregularly translated proteins are normally associated with certain kinds of diseases or cancer. The rapid development of innovative DNA methylation mapping techniques provides a better understanding of DNA methylation pattern and its mechanisms in the human genome and its correlation with numerous diseases. These new techniques can lead us to develop new epigenetic medications, such as DNA methyltransferase inhibitors. As part of the approaches to probe DNA methylation and evaluate the effects of epigenetic therapy, mass spectrometry has been taking an important role in the identification, validation, and quantification of DNA methylation and demethylation. In this review, we will briefly summarize the current breadth of knowledge on the topic of DNA methylation and its occurrence in diseases, DNA methylation drugs, and mass spectrometry based approaches used to study DNA methylation.

PMID: 27848896 [PubMed - as supplied by publisher]

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Metabolomic approach in probing drug candidates.

Metabolomic approach in probing drug candidates.

Curr Top Med Chem. 2016 Nov 16;

Authors: Liu C, D Alessandro A, Xia Y

Abstract
Metabolomics is the comprehensive characterization of endogenous small molecules metabolites, xenometabolites and their metabolisms. The recent introduction of high-throughput metabolomics approaches has fostered strides related to the capacity to in silico elaborate metabolomics data by means of system biology. Recent progresses in bioanalytical technologies assisted with algorithms enabling large-scale data analysis potentiate application of metabolomics approaches in biomarker-based disease diagnosis, therapeutic target identification, personalized medicine, and the monitoring of clinical outcomes. In this review article we will focus on recent applications of metabolomics approaches in the identification of potential therapeutic candidates based on our and others' confirmed experience with this cutting-edge technology.

PMID: 27848895 [PubMed - as supplied by publisher]

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LncRNA as a Therapeutic Target for Angiogenesis.

LncRNA as a Therapeutic Target for Angiogenesis.

Curr Top Med Chem. 2016 Nov 16;

Authors: M MK, Goyal R

Abstract
Out of 3 billion base pairs in human genome only ~2% code for proteins; and out of 180,000 transcripts in human cells, about 20,000 code for protein, remaining 160,000 are non-coding transcripts. Most of these transcripts are more than 200 base pairs and constitute a group of long non-coding RNA (lncRNA). Many of the lncRNA have its own promoter, and are well conserved in mammals. Accumulating evidence indicates that lncRNAs act as molecular switches in cellular differentiation, movement, apoptosis, and in the reprogramming of cell states by altering gene expression patterns. However, the role of this important group of molecules in angiogenesis is not well understood. Angiogenesis is a complex process and depends on precise regulation of gene expression. Dysregulation of transcription during this process may lead to several diseases including various cancers. As angiogenesis is an important process in cancer pathogenesis and treatment, lncRNA may be playing an important role in angiogenesis. In support of this, lncRNA microvascular invasion in hepatocellular carcinoma (MVIH) has been shown to activate angiogenesis. Furthermore, lncRNA-Meg3-knockout mouse showed increased expression of vascular endothelial growth factor pathway genes and increased cortical microvessel density. Overall, there is strong evidence that lncRNA is an important class of regulatory molecule, and a number of studies have demonstrated that these can be targeted to change cellular physiology and functions. In this review, we have attempted to summarize these studies and elucidate the potential of this novel regulatory molecule as a therapeutic target.

PMID: 27848894 [PubMed - as supplied by publisher]

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The medicinal chemistry of nitrite as a source of nitric oxide signaling.

The medicinal chemistry of nitrite as a source of nitric oxide signaling.

Curr Top Med Chem. 2016 Nov 16;

Authors: Blood AB

Abstract
Conventional understanding of nitric oxide (NO) signaling in biology is commonly based on the premise that it simply diffuses randomly from its site of production by NO synthases to its site of action or inactivation. This notion has been challenged on a systemic cardiovascular scale with the realization that NO has endocrine effects despite being unable to exist in blood for more than a few milliseconds. Investigation of this phenomenon has led to the understanding that many of the chemical pathways that consume NO may not render it inactive as once thought. Instead, many of NO's metabolic products are still capable of carrying out NO signaling, or participate in NO-independent signaling in their own right. Nitrite and nitrate are two such products of NO metabolism that were once thought to be inert at physiological concentrations but are now known to contribute to NO bioactivity. The activity of nitrate is dependent upon its reduction to nitrite by bacterial nitrate reductase activity in the mouth. Nitrite can be reduced to NO by several metal-containing proteins under hypoxic conditions, or by non-enzymatic reactions under acidic conditions. Reduction and oxidation products of nitrite metabolism may also result in the production of NO adducts with a wide array of biological functions. The following review provides a general overview of the basic pathways underlying the physiological activity of nitrate and nitrite, as well as insight into the therapeutic potential of these pathways.

PMID: 27848893 [PubMed - as supplied by publisher]

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Single-cell sequencing for drug discovery and drug development.

Single-cell sequencing for drug discovery and drug development.

Curr Top Med Chem. 2016 Nov 16;

Authors: Wu H, Wang C, Wu S

Abstract
Next-generation sequencing (NGS), particularly single-cell sequencing, has revolutionized the scale and scope of genomic and biomedical research. Recent technological advances in NGS and single-cell studies have made the deep whole-genome (DNA-seq), whole epigenome and whole-transcriptome sequencing (RNA-seq) at single-cell level feasible. NGS at the single-cell level expands our view of genome, epigenome and transcriptome and allows the genome, epigenome and transcriptome of any organism to be explored without a priori assumptions and with unprecedented throughput. And it does so with single-nucleotide resolution. NGS is also a very powerful tool for drug discovery and drug development. In this review, we describe the current state of single-cell sequencing techniques, which can provide a new, more powerful and precise approach for analyzing effects of drugs on treated cells and tissues. Our review discusses single-cell whole genome/exome sequencing (scWGS/scWES), single-cell transcriptome sequencing (scRNA-seq), single-cell bisulfite sequencing (scBS), and multiple omics of single-cell sequencing. We also highlight the advantages and challenges of each of these approaches. Finally, we describe, elaborate and speculate the potential applications of single-cell sequencing for drug discovery and drug development.

PMID: 27848892 [PubMed - as supplied by publisher]

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Immediate effects of the semi-occluded vocal tract exercise with LaxVox® tube in singers.

Immediate effects of the semi-occluded vocal tract exercise with LaxVox® tube in singers.

Codas. 2016 9-10;28(5):618-624

Authors: Fadel CB, Dassie-Leite AP, Santos RS, Santos CG, Dias CA, Sartori DJ

Abstract
Purpose: The purpose of this study was to analyze the immediate effects of the semi-occluded vocal tract exercise (SOVTE) using the LaxVox® tube in singers.
Methods: Participants were 23 singers, classical singing students, aged 18 to 47 years (mean age = 27.2 years). First, data was collected through the application of a demographic questionnaire and the recording of sustained emission - vowel /ε/, counting 1-10, and a music section from the participants' current repertoire. After that, the participants were instructed and performed the SOVTE using the LaxVox® tube for three minutes. Finally, the same vocal samples were collected immediately after SOVTE performance and the singers responded to a questionnaire on their perception regarding vocal changes after the exercise. The vocal samples were analyzed by referees (speech-language pathologists and singing teachers) and by means of acoustic analysis.
Results: Most of the singers reported improved voice post-exercise in both tasks - speech and singing. Regarding the perceptual assessment (sustained vowel, speech, and singing), the referees found no difference between pre- and post-exercise emissions. The acoustic analysis of the sustained vowel showed increased Fundamental Frequency (F0) and reduction of the Glottal to Noise Excitation (GNE) ratio post-exercise.
Conclusion: The semi-occluded vocal tract exercise with LaxVox® tube promotes immediate positive effects on the self-assessment and acoustic analysis of voice in professional singers without vocal complains. No immediate significant changes were observed with respect to auditory-perceptual evaluation of speech and singing.

PMID: 27849247 [PubMed - in process]

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Qualitative Inquiry Explores Health-Related Quality of Life of Female Veterans With Post-Traumatic Stress Disorder.

Qualitative Inquiry Explores Health-Related Quality of Life of Female Veterans With Post-Traumatic Stress Disorder.

Mil Med. 2016 Nov;181(11):e1470-e1475

Authors: Haun JN, Duffy A, Lind JD, Kisala P, Luther SL

Abstract
As the number of female veterans increases, health care systems must be prepared to meet the individualized needs of this population. To date, published data on health-related quality of life (HRQOL) of veterans with post-traumatic stress disorder (PTSD) focus on quantitative data and primarily represent the male population. The purpose of this study was to qualitatively explore the impact of PTSD on female veterans' HRQOL. A descriptive qualitative study used focus groups and demographic surveys to achieve data collection in a sample of veterans with PTSD. This report focuses on the analysis of a sample of 12 females to explore PTSD HRQOL experiences unique to female veterans. Female veterans reported several areas in which their HRQOL was impacted adversely in social participation, physical, cognitive, and emotional aspects of their lives. Issues with self-medication and substance abuse were also reported by participants. Female participants' perceptions about Veterans Health Administration were also discussed, highlighting unmet needs when receiving care for PTSD. These data provide unique insights from the perspective of female veterans with PTSD about their HRQOL and receiving care within the Veterans Health Administration health care system. These data can inform future research to better address the needs of female veterans living with PTSD.

PMID: 27849478 [PubMed - in process]

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Risk factors for failure to enter vocational rehabilitation services among individuals with disabilities.

Risk factors for failure to enter vocational rehabilitation services among individuals with disabilities.

Disabil Rehabil. 2016 Nov 16;:1-8

Authors: Langi FL, Balcazar FE

Abstract
PURPOSE: To investigate the risk factors for failure of individuals with disabilities to enter the vocational rehabilitation (VR) programme, including the cases where they had been formally accepted but were yet to receive any service.
METHODS: We used prospective cohort data from a Midwestern US state, and analysed 126,251 and 94,517 individuals, respectively, for acceptance and admission into VR services. Statistical analysis was conducted using Poisson regression models with robust variance estimator.
RESULTS: Individuals with blind/visual disability, had prior history of employment, and who received public support tended to have lower risks of non-acceptance and non-admission. Being non-White, at higher education, ever/currently married, and with physical/orthopaedic disability appeared to increase the risks of both outcomes. The adjusted relative risk of non-acceptance was 0.58 (95% confidence interval: 0.52, 0.64) if the individuals had 4 or more functional limitations as compared with those with fewer limitations. This factor was not significant for VR admission.
CONCLUSION: Disability factors, demographic determinants, and certain miscellaneous characteristics were associated with the risks of non-acceptance and non-admission into VR. Implications for Rehabilitation Individuals with disabilities are more likely to be unemployed than the population without disabilities, and they are thus more prone to adverse health effects of unemployment. Vocational rehabilitation (VR) is a proven intervention to improve employment outcomes among individuals with disabilities. Our study indicates that the complexity of the selection process for entering VR and various factors beyond disability may prevent individuals to benefit from the VR programme. Rehabilitation programme authorities need to monitor and simplify the selection process into VR services and, together with rehabilitation practitioners, promote a selection process that pays careful attention on the factors that are related to individual risk of failure for entering VR.

PMID: 27848261 [PubMed - as supplied by publisher]

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Prognostic predictors for ambulation in children with cerebral palsy: a systematic review and meta-analysis of observational studies.

Prognostic predictors for ambulation in children with cerebral palsy: a systematic review and meta-analysis of observational studies.

Disabil Rehabil. 2016 Nov 16;:1-9

Authors: Keeratisiroj O, Thawinchai N, Siritaratiwat W, Buntragulpoontawee M, Pratoomsoot C

Abstract
PURPOSE: The purpose of this study is to investigate the prognostic predictors for ambulation in children with cerebral palsy using meta-analysis of observational studies.
METHOD: Electronic searches were conducted in PubMed, SCOPUS, CINAHL, ProQuest, Ovid, Wiley InterScience, and ScienceDirect databases from their start dates to December 2015.
RESULTS: Of the 1123 identified articles, 12 met the inclusion criteria for qualitative synthesis, eight of which were deemed appropriate for meta-analysis. Qualitative synthesis found that the type of cerebral palsy, early motor milestones, primitive reflexes and postural reactions, absence of visual impairment, absence of intellectual disability, absence of epilepsy or seizure, and ability to feed self were indicated as potential predictors for ambulation. Meta-analysis detected four significant prognostic predictors for ambulation: sitting independently at 2 years, absence of visual impairment, absence of intellectual disability, and absence of epilepsy or seizure.
CONCLUSION: These prognostic predictors should be taken into consideration in therapeutic plans and rehabilitation goals, especially sitting independently before the age of 2 years. Implications for rehabilitation The meta-analysis supports strong evidence that sitting independently at 2 years of age, absence of visual impairment, absence of intellectual disability, and absence of epilepsy or seizure are positive predictors for ambulation in children with cerebral palsy. The therapeutic plans and rehabilitation goals should be considered cautiously for these predictors, especially sitting independently before the age of two years.

PMID: 27848255 [PubMed - as supplied by publisher]

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Patient-centered evaluation of home-based rehabilitation developed using community-based participatory research approach for people with disabilities: a case series.

Patient-centered evaluation of home-based rehabilitation developed using community-based participatory research approach for people with disabilities: a case series.

Disabil Rehabil. 2016 Nov 16;:1-11

Authors: Lee M, Heo HH, Oh S, Kim E, Yoon B

Abstract
PURPOSE: The purpose of this study was to evaluate the effectiveness of the locally tailored and individualized home-based rehabilitation (HBR) program developed using the community-based participatory research (CBPR) approach, in terms of perceived health in patients with different levels of social engagement, and to explore the perceived facilitators and barriers to rehabilitation.
METHOD: A concurrent mixed-method design was employed. Four patients participated in the combined therapist- and self-delivered HBR program for 5 months. The perceived health outcomes were quantitatively assessed at baseline, after the therapist-delivered intervention period, and at 1 and 3 months after the self-delivered intervention period. Then, in-depth individual interviews were conducted to explore the facilitators and barriers to rehabilitation.
RESULTS: The perceived health of patients who were fully or partially engaged in society was increased during the therapist-delivered intervention period, and maintained the increased level during the self-delivered intervention period, whereas that of patients who were rarely or not engaged dropped again to lower than the baseline. These results were caused by differentiated facilitators and barriers to rehabilitation depending on the level of social engagement.
CONCLUSIONS: Applying tailored strategies to patients with differing levels of social engagement is recommended to further optimize the local relevance of the HBR program. Implications for rehabilitation A community-based participatory research approach can provide an opportunity to enhance local relevance through community-academic partnerships, in developing a home-based rehabilitation (HBR) program for the people with disabilities. For community therapists, enhancing the local relevance of the HBR program, applying tailored strategies to patients with differing levels of social engagement is recommended because the perceived health of the HBR program can be different owing to differing perceived facilitators and barriers to rehabilitation, depending on the level of social engagement. For patients with rare or no engagement in society, satisfying their need for interaction with the therapists and helping them cope with their wrong belief about the possibility of their recovery is important to encourage behavioral change and perceived physical improvements.

PMID: 27848248 [PubMed - as supplied by publisher]

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Hospital rehabilitation for patients with obesity: a scoping review.

Hospital rehabilitation for patients with obesity: a scoping review.

Disabil Rehabil. 2016 Nov 16;:1-10

Authors: Seida JC, Sharma AM, Johnson JA, Forhan M

Abstract
PURPOSE: To explore the evidence on rehabilitation for hospitalized patients with obesity.
METHODS: Medline, Embase, CENTRAL, CINAHL, and PubMed were searched from 1994 to May 2016. Grey literature was hand-searched. Two reviewers independently selected studies examining patients with obesity receiving hospital-based therapy for a physical impairment. One reviewer extracted the data and a second reviewer verified a random sample.
RESULTS: Thirty-nine studies (two trials, 37 observational) were included. Patients underwent rehabilitation following orthopaedic surgery (n = 25), neurological conditions (n = 7), acute medical illnesses (n = 3), or various procedures (n = 4). Three studies investigated the effectiveness of a specific rehabilitation program in patients with obesity; however, two lacked a control group, precluding inferences of causal associations. Most studies compared functional outcomes across patients in different BMI categories (n = 33). There was much variability in the rehabilitation components, intensity, and providers used across the studies. The most frequent components were gait training and mobility (n = 17) and training in assistive devices (n = 12). Across the 50 outcomes measured, length of hospital stay (n = 24) and Functional Independence Measure (n = 15) were assessed most frequently.
CONCLUSIONS: Evidence to guide rehabilitation for patients with obesity is sparse and weak. Rigorous comparative studies with clearly defined interventions and consensus outcome measures are needed. Implications for Rehabilitation Obesity rates have dramatically increased among patients requiring rehabilitation following joint arthroplasty, stroke, injury, or an acute medical event. There are currently no guidelines by which to define best practice for rehabilitating patients with obesity and comparative studies on rehabilitation programs are needed. Professional development focused on patient-centered rehabilitation and sensitivity training is known to promote quality care, reduce weight bias, and improve patient satisfaction. Access to and knowledge about equipment is necessary to promote patient and health care provider safety.

PMID: 27848247 [PubMed - as supplied by publisher]

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Creating an inclusive leisure space: strategies used to engage children with and without disabilities in the arts-mediated program Spiral Garden.

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Creating an inclusive leisure space: strategies used to engage children with and without disabilities in the arts-mediated program Spiral Garden.

Disabil Rehabil. 2016 Nov 16;:1-9

Authors: Smart E, Edwards B, Kingsnorth S, Sheffe S, Curran CJ, Pinto M, Crossman S, King G

Abstract
PURPOSE: This article describes how service providers use a set of practical strategies to create an inclusive leisure space in Spiral Garden, an arts-mediated outdoor summer day program for children with and without disabilities.
METHODS: This study was guided by an interpretive qualitative approach. Fourteen Spiral Garden service providers participated in semi-structured interviews. Nine had extensive experience with the program and had been present during key phases of program development spanning over a 26-year period and five were service providers during the summer of 2013. Transcript data were analyzed using inductive thematic analysis.
RESULTS: The analysis produced eight strategies organized under three larger categories that service providers perceived to be essential in creating an inclusive leisure space: (1) engaging children in collective experiences; (2) encouraging peer interactions and friendships; and (3) facilitating collaborative child-directed experiences.
CONCLUSIONS: Service providers working across different inclusive settings can use findings from this study to contribute to program design and implementation. Presented strategies enable children to experience opportunities for spontaneous free play, individualized structured support, and meaningful social participation. Overall, service providers are encouraged to enhance supportive child and service provider relationships and reciprocal child and environment relationships in group-based programs. Implications for Rehabilitation Exploring and facilitating reciprocal relationships between children and their environment is essential to creating inclusive leisure spaces. Transforming program intentions of meaningful social participation into practice requires learning about and affecting change in children's individual social contexts. Service providers can engage themselves as full participants in inclusive leisure spaces through playful negotiations, internal reflections, and artistic expressions.

PMID: 27846741 [PubMed - as supplied by publisher]

http://ift.tt/2gjSh0e

Degenerative lumbar spinal stenosis and physical functioning: an exploration of associations between self-reported measures and physical performance tests.

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Degenerative lumbar spinal stenosis and physical functioning: an exploration of associations between self-reported measures and physical performance tests.

Disabil Rehabil. 2016 Nov 16;:1-6

Authors: Thornes E, Robinson HS, Vøllestad NK

Abstract
BACKGROUND: Degenerative spinal stenosis is a common lumbar condition in the elderly population. Clinical decision-making in the physiotherapy settings is based on assessments of the patients physical status. The purpose of this study was to examine how self-reported measures on symptoms and physical function relate to responses on physical performance tests.
METHODS: A total of 103 patients with LSS completed a comprehensive questionnaire and physical performance tests (functional leg-strength and dynamic balance). Associations between the subscales Symptom Severity (SYMP) and Physical Function (FUNC) from the Spinal Stenosis Questionnaire, and the performance tests were examined. Univariate correlation and multivariable linear regression analyses were applied.
RESULTS: The associations between SYMP or FUNC and the performance tests were moderate (?0.3 < rho < 0.6). The multivariable analyses showed that One-leg-Stand, 30s sit-to-stand were significantly associated with SYMP (< 0.001 < p < 0.03), whereas Stairclimb, was significantly associated with FUNC (< 0.001 < p < 0.005). The explained variance was fair for both adjusted models (R(2) = 0.31 and R(2) = 0.38).
CONCLUSIONS: The present study indicates that both self-reported symptoms and walking limitation are associated with leg strength, while only symptoms are associated with balance. The results suggest that a combination of simple performance tests will add information needed to map the patients disability and guide interventions. Implications for Rehabilitation One-leg-standing, 30-s sit-to-stand and stair climb test are easy to use and applicable for examining physical function in patients with lumbar spinal stenosis (LSS). Simple performance tests add information needed to map the patients' disability and guide interventions. Leg strength is a key factor for both symptoms and walking ability. Also, balance is of importance for the symptoms in LSS patients.

PMID: 27846739 [PubMed - as supplied by publisher]

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Complete mental health in adult siblings of those with a chronic illness or disability.

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Complete mental health in adult siblings of those with a chronic illness or disability.

Disabil Rehabil. 2016 Nov 16;:1-6

Authors: Hallion M, Taylor A, Roberts R

Abstract
INTRODUCTION: Sibling relationships have lifelong significance and childhood chronic illness and disability can have considerable impacts on healthy siblings, influencing development into adulthood. Research has not yet assessed well-being in this population using measures of both mental health and mental illness. Thus, this study assessed well-being in a comprehensive manner using the complete mental health (CMH) model.
METHOD: Participants (N = 144) included both adult siblings of those with chronic illness or disability and adults with healthy siblings. Measures of positive social, psychological and emotional well-being were used to assess mental health and a measure of depression, anxiety, and stress was used to assess mental illness.
RESULTS: A high proportion of participants, both with and without siblings with a chronic illness or disability, were experiencing symptoms of mental illness, accompanied by high wellbeing. This indicates that many participants fit into the struggling category of the CMH model.
DISCUSSION: The present research highlights the need for early intervention services to ensure that siblings of those with a chronic illness or disability are well supported in developing strengths, as well as managing difficulties. Results also indicate that targeting students in mental health promotion is important to encourage participation in services. Implications for rehabilitation Siblings of those with a chronic illness or disability need to be included in assessments in order to understand the experience of the family unit. It is important for families and clinicians to be aware of the needs of healthy siblings and encourage them to interact with support services in order to maximise and maintain well-being. Skills-based support could be beneficial, particularly for providing caregivers with strategies to meet the needs of both their child with a chronic illness or disability and their healthy children.

PMID: 27846732 [PubMed - as supplied by publisher]

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February 2017 Editor in Chief Letter.

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February 2017 Editor in Chief Letter.

World Neurosurg. 2016 Nov 12;:

Authors: Benzel E

PMID: 27847270 [PubMed - as supplied by publisher]

http://ift.tt/2fYVYEm

Intrasylvian/Intracerebral Hematomas Associated with Ruptured MCA-Aneurysms: A Single-center Series and a review of literature.

Related Articles

Intrasylvian/Intracerebral Hematomas Associated with Ruptured MCA-Aneurysms: A Single-center Series and a review of literature.

World Neurosurg. 2016 Nov 12;:

Authors: Zhang Y, Hu Q, Xue H, Zhang M, Shen J, Deing L, Liu Q, Li G

Abstract
OBJECTIVE: Ruptured MCA aneurysms usually lead to SAH，and several cases will represent concomitant intrasylvian or intracerebral hematomas. The objective of this paper was to compare the clinical and radiographic characteristics with their different outcomes.
METHODS: The charts of 30 consecutive patients with ruptured MCA aneurysm related intracranial hematoma were retrospectively reviewed. These patients were dichotomized into ISH group and ICH group by the presence of intrahematomal contrast enhancing vessel (IHCEV), and for patients under open surgery, hematoma type was further confirmed by intraoperative observation. The characteristics were compared between this two groups, i.e. age, gender, history of HP, history of smoking, systolic pressure at admission, hematoma volume, size and side of aneurysms, the angle between the pointing direction of the aneurysm and the MCA trunk and is denoted as α, middle line shifting, treatment modality and outcome. All of the angles are measured in the anterior-posterior projection.
RESULTS: In our series, only hematoma volume, the angle αand the middle line shift showed statistical significance regarding prognosis among two hematoma groups. The angle αbetween 109.0°and 216.0°is associated with ISH，while aneurysm with an angle beyond this range would indicate ICH. In our series patients in the ICH group had a much larger hematoma volume compared with the ISH patient(33.3±17.6versus 11.5±10.5 p=0.002). But there exists no statistical difference regarding prognosis between these two groups, even though there is a trend towards worse recovery for patients in the ISH group(GOS 3.0±1.3versus3.8±1.9, P=0.07).
CONCLUSIONS: In our series, the prognosis of patients with ICH was much worse than those with ISH. Early discrimination of these two types of hematoma helps to predict future outcome, the angle (between the pointing direction of aneurysm and the MCA trunk) between 109.0°and 216.0° is associated with ISH, while aneurysm with an angle beyond this range might suggest ICH.

PMID: 27847269 [PubMed - as supplied by publisher]

http://ift.tt/2fYZj6y

Curative effects of microneedle fractional radiofrequency system on skin laxity in Asian patients: a prospective, double-blind, randomized, controlled face-split study.

Curative effects of microneedle fractional radiofrequency system on skin laxity in Asian patients: a prospective, double-blind, randomized, controlled face-split study.

J Cosmet Laser Ther. 2016 Nov 16;:1-19

Authors: Lu W, Wu P, Zhang Z, Chen J, Chen X, Ewelina B

Abstract
BACKGROUND: To date, no studies compared curative effects of thermal lesions in deep and superficial dermal layers in the same patient (face-split study).
OBJECTIVE: To evaluate skin laxity effects of microneedle fractional radiofrequency induced thermal lesions in different dermal layers.
METHODS AND MATERIALS: 13 patients underwent three sessions of a randomized face-split microneedle fractional radiofrequency system (MFRS) treatment of deep dermal and superficial dermal layer. Skin laxity changes were evaluated objectively (digital images, 2 independent experts) and subjectively (patients' satisfaction numerical rating).
RESULTS: 12 of 13 subjects completed a course of 3 treatments and a 1-year follow-up. Improvement of nasolabial grooves in deep dermal approach was significantly better than the superficial at 3 months (P=.0002) and 12 months (P=.0057) follow up. Effects on infraorbital rhytides were only slightly better (P=.3531).
CONCLUSION: Microneedle fractional radiofrequency system (MFRS) is an effective method to improve skin laxity. Thermal lesion approach seems to provide better outcomes when applied to deep dermal layers. It is necessary to consider the skin thickness of different facial region when choosing the treatment depth.

PMID: 27849406 [PubMed - as supplied by publisher]

http://ift.tt/2glF3B1

Erbium Yttrium Aluminium Garnet laser versus Q-switched Neodymium: Yttrium Aluminium Garnet laser for the treatment of xanthelesma palpebrarum.

Erbium Yttrium Aluminium Garnet laser versus Q-switched Neodymium: Yttrium Aluminium Garnet laser for the treatment of xanthelesma palpebrarum.

J Cosmet Laser Ther. 2016 Nov 16;:1-19

Authors: Balevi A, Ustuner P, Ozdemir M

Abstract
BACKGROUND: Several lasers have been used for the treatment of xanthelasma palpebrarum (XP), such as Q-switched Neodymium:Yttrium Aluminium Garnet (QSNd:YAG), Erbium:Yttrium Aluminium Garnet (Er:YAG) laser. However, there is no comparemental study among these laser options in the treatment of XP.
OBJECTIVE: The aim of this study was to compare the clinical efficacy and response rates of QSNd:YAG and Er:YAG in the treatment of XP.
METHODS: Sixty patients with a total of 102 XP lesions were randomly and equally divided into two groups. The first group was treated with QSNd:YAG at a fluence of 10 joule/cm(2), 10 Hz and 2 mm spot size and the second group with Er:YAG at 200-300 milijoule, 4 Hz, 2 mm spot size.
RESULTS: In the Er:YAG group, the percentage of patients that required 3 or 4 sessions and wound healing time was higher compared to the QSNd:YAG group. Furthermore, the percentage of patients that had an improvement score of 4 was higher in the Er:YAG than in the QSNd:YAG group.
CONCLUSION: Er:YAG is an efficient, successful and minimally invasive method without long-lasting adverse effects.

PMID: 27849400 [PubMed - as supplied by publisher]

http://ift.tt/2fYV3oE

Low-frequency cortical oscillations are modulated by temporal prediction and temporal error coding

Publication date: Available online 16 November 2016
Source:NeuroImage
Author(s): Louise Catheryne Barne, Peter Maurice Erna Claessens, Marcelo Bussotti Reyes, Marcelo Salvador Caetano, André Mascioli Cravo
Monitoring and updating temporal predictions are critical abilities for adaptive behavior. Here, we investigated whether neural oscillations are related to violation and updating of temporal predictions. Human participants performed an experiment in which they had to generate a target at an expected time point, by pressing a button while taking into account a variable delay between the act and the stimulus occurrence. Our behavioral results showed that participants quickly adapted their temporal predictions in face of an error. Concurrent electrophysiological (EEG) data showed that temporal errors elicited markers that are classically related to error coding. Furthermore, intertrial phase coherence of frontal theta oscillations was modulated by error magnitude, possibly indexing the degree of surprise. Finally, we found that delta phase at stimulus onset was correlated with future behavioral adjustments. Together, our findings suggest that low frequency oscillations play a key role in monitoring and in updating temporal predictions.



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Deriving reproducible biomarkers from multi-site resting-state data: An Autism-based example

Publication date: Available online 16 November 2016
Source:NeuroImage
Author(s): Alexandre Abraham, Michael Milham, Adriana Di Martino, R. Cameron Craddock, Dimitris Samaras, Bertrand Thirion, Gael Varoquaux
Resting-state functional Magnetic Resonance Imaging (R-fMRI) holds the promise to reveal functional biomarkers of neuropsychiatric disorders. However, extracting such biomarkers is challenging for complex multi-faceted neuropathologies, such as autism spectrum disorders. Large multi-site datasets increase sample sizes to compensate for this complexity, at the cost of uncontrolled heterogeneity. This heterogeneity raises new challenges, akin to those face in realistic diagnostic applications. Here, we demonstrate the feasibility of inter-site classification of neuropsychiatric status, with an application to the Autism Brain Imaging Data Exchange (ABIDE) database, a large (N=871) multi-site autism dataset. For this purpose, we investigate pipelines that extract the most predictive biomarkers from the data. These R-fMRI pipelines build participant-specific connectomes from functionally-defined brain areas. Connectomes are then compared across participants to learn patterns of connectivity that differentiate typical controls from individuals with autism. We predict this neuropsychiatric status for participants from the same acquisition sites or different, unseen, ones. Good choices of methods for the various steps of the pipeline lead to 67% prediction accuracy on the full ABIDE data, which is significantly better than previously reported results. We perform extensive validation on multiple subsets of the data defined by different inclusion criteria. These enables detailed analysis of the factors contributing to successful connectome-based prediction. First, prediction accuracy improves as we include more subjects, up to the maximum amount of subjects available. Second, the definition of functional brain areas is of paramount importance for biomarker discovery: brain areas extracted from large R-fMRI datasets outperform reference atlases in the classification tasks.

Graphical abstract

Highlights

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Temporally correlated fluctuations drive epileptiform dynamics

Publication date: Available online 16 November 2016
Source:NeuroImage
Author(s): Maciej Jedynak, Antonio J. Pons, Jordi Garcia-Ojalvo, Marc Goodfellow
Macroscopic models of brain networks typically incorporate assumptions regarding the characteristics of afferent noise, which is used to represent input from distal brain regions or ongoing fluctuations in non-modelled parts of the brain. Such inputs are often modelled by Gaussian white noise which has a flat power spectrum. In contrast, macroscopic fluctuations in the brain typically follow a 1/fb spectrum. It is therefore important to understand the effect on brain dynamics of deviations from the assumption of white noise. In particular, we wish to understand the role that noise might play in eliciting aberrant rhythms in the epileptic brain.To address this question we study the response of a neural mass model to driving by stochastic, temporally correlated input. We characterise the model in terms of whether it generates "healthy" or "epileptiform" dynamics and observe which of these dynamics predominate under different choices of temporal correlation and amplitude of an Ornstein-Uhlenbeck process. We find that certain temporal correlations are prone to eliciting epileptiform dynamics, and that these correlations produce noise with maximal power in the δ and θ bands. Crucially, these are rhythms that are found to be enhanced prior to seizures in humans and animal models of epilepsy. In order to understand why these rhythms can generate epileptiform dynamics, we analyse the response of the model to sinusoidal driving and explain how the bifurcation structure of the model gives rise to these findings. Our results provide insight into how ongoing fluctuations in brain dynamics can facilitate the onset and propagation of epileptiform rhythms in brain networks. Furthermore, we highlight the need to combine large-scale models with noise of a variety of different types in order to understand brain (dys-)function.



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(Neo)adjuvant treatment in localised soft tissue sarcoma: The unsolved affair

Publication date: January 2017
Source:European Journal of Cancer, Volume 70
Author(s): Maristella Saponara, Silvia Stacchiotti, Paolo G. Casali, Alessandro Gronchi
Soft tissue sarcomas (STS) are rare and heterogeneous tumours. A correct definition of STS is imperative from the very beginning of disease management, to guide the diagnostic and imaging work-up, and help to establish the prognosis on which the therapeutic strategy will be based. Over the last few years, many efforts have been made to identify characteristics that could predict disease behaviour and to enrich the therapeutic armamentarium against the advanced disease, that is still characterised by poor prognosis. Surgery remains the milestone of treatment for localised STS, whereas many uncertainties regarding the role of adjuvant and neoadjuvant treatment persist. Some controlled evidence is available, but often conflicting and insufficient to make chemotherapy (CT) a standard practice and, currently, a common and shared strategy does not exist. The biggest question concerns the prospective identification of the subgroup of patients who would benefit the most from (neo)adjuvant therapies. In light of the growing understanding of different biologies and sensitivities of the various sarcoma subtypes, the value of histology in the selection of peri-operative treatments is one of the most intriguing topics under discussion. In this perspective, a new generation of neoadjuvant trials have been planned and are currently ongoing.The aim of this review was to rekindle interest in the long-standing topic of (neo)adjuvant CT in localised STS, providing an update on its role in sarcomas' management and highlighting future directions and consequential factors needed to further improve outcomes in this disease.



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A targeted door-to-door strategy for sleeping sickness detection in low-prevalence settings in Côte d'Ivoire.

A targeted door-to-door strategy for sleeping sickness detection in low-prevalence settings in Côte d'Ivoire.

Parasite. 2016;23:51

Authors: Koffi M, N'Djetchi M, Ilboudo H, Kaba D, Coulibaly B, N'Gouan E, Kouakou L, Bucheton B, Solano P, Courtin F, Ehrhardt S, Jamonneau V

Abstract
Significant efforts to control human African trypanosomiasis (HAT) over the three past decades have resulted in drastic reductions of disease prevalence in Côte d'Ivoire. In this context, the costly and labor-intensive active mass screening strategy is no longer efficient. In addition to a more cost-effective passive surveillance system being implemented in this low-prevalence context, our aim was to develop an alternative targeted active screening strategy. In 2012, we carried out a targeted door-to-door (TDD) survey focused on the immediate vicinities of former HAT patients detected in the HAT focus of Bonon and compared the results to those obtained during classical active mass screening (AMS) surveys conducted from 2000 to 2012 in the same area. The TDD that provides a friendlier environment, inviting inhabitants to participate and gain awareness of the disease, detected significantly more HAT cases than the AMS. These results suggest that the TDD is an efficient and useful strategy in low-prevalence settings where very localized transmission cycles may persist and, in combination with passive surveillance, could help in eliminating HAT.

PMID: 27849517 [PubMed - in process]

http://ift.tt/2fYX3x8

Studies of Laboulbeniales on Myrmica ants (III): myrmecophilous arthropods as alternative hosts of Rickia wasmannii.

Studies of Laboulbeniales on Myrmica ants (III): myrmecophilous arthropods as alternative hosts of Rickia wasmannii.

Parasite. 2016;23:50

Authors: Pfliegler WP, Báthori F, Haelewaters D, Tartally A

Abstract
Myrmecophilous arthropods and their manifold relations to host ants are interesting from an evolutionary perspective. Rickia wasmannii is an ectoparasitic fungus belonging to the Laboulbeniales order. Here, we show that inquiline mites can become infected by R. wasmannii, which was thought to be restricted to the genus Myrmica (Hymenoptera: Formicidae). This is the first report of R. wasmannii from an alternative host in another subphylum (Chelicerata). We also found immature fruiting bodies on a larva of Microdon myrmicae (Diptera: Syrphidae), which represents the first report of any Rickia species on flies. This fungus is capable of infecting alternative, unrelated host species as they co-occur in the ant nest "microhabitat". These observations provide direct evidence for ecological specificity in Laboulbeniales. The presence of R. wasmannii on inquilines in Myrmica ant nests suggests that the parasite may have adapted to the ant nest environment and is less dependent on acquiring specific nutrients from the hosts. However, the alternative cannot be excluded; these infections might also represent chance events if the fungus is incapable of fulfilling its life cycle.

PMID: 27849516 [PubMed - in process]

http://ift.tt/2glzYsu

Review of West Nile virus circulation and outbreak risk in Madagascar: Entomological and ornithological perspectives.

Review of West Nile virus circulation and outbreak risk in Madagascar: Entomological and ornithological perspectives.

Parasite. 2016;23:49

Authors: Tantely ML, Goodman SM, Rakotondranaivo T, Boyer S

Abstract
West Nile fever (WNF) is a zoonotic disease, occurring nearly globally. In Madagascar, West Nile virus (WNV) was first detected in 1978 from wild birds and the virus is currently distributed across the island, but no epidemic or epizootic period has been recorded. One fatal human case of WNV infection was reported in 2011, suggesting a "tip of the iceberg" phenomenon of a possible WNF epidemic/epizootic on the island. The main objective of this literature-based survey is to review patterns of WNV circulation in Madagascar from the entomological and ornithological points of view. Among the 235 mosquito species described from Madagascar, 29 species are widely associated with WNV infection; 16 of them are found naturally infected with WNV on the island and categorized into major, candidate, and potential vectors of WNV according to their vector capacity. This study upholds the hypothesis that WNV enzooticity is independent of annual movements of migratory birds passing through Madagascar. Moreover, the lack of regular migratory bird flux between Africa and Madagascar would reduce the probability of transmission and the subsequent reintroduction of the virus into locally occurring mosquito species. Given that Palearctic migratory birds are strongly implicated in the transmission of WNV, we highlight notable differences in the movements and species diversity of these birds in Madagascar as compared to eastern and northern Africa. Risk factors from this two-pronged approach are presented for the emergence of WNF outbreak.

PMID: 27849515 [PubMed - in process]

http://ift.tt/2fYRK0Q

First record of Phlebotomus (Transphlebotomus) mascittii in Slovakia.

First record of Phlebotomus (Transphlebotomus) mascittii in Slovakia.

Parasite. 2016;23:48

Authors: Dvorak V, Hlavackova K, Kocisova A, Volf P

Abstract
A large-scale entomological survey was carried out in summer 2016 in the Czech Republic and Slovakia. It revealed, for the first time, the presence of the phlebotomine sand fly Phlebotomus (Transphlebotomus) mascittii Grassi, 1908 (Diptera: Phlebotominae) in south-western Slovakia. Species identification of a captured female was confirmed by both morphological and sequencing (COI) analyses.

PMID: 27849514 [PubMed - in process]

http://ift.tt/2glzZwF

Forebrain-specific transgene rescue of 11β-HSD1 associates with impaired spatial memory and reduced hippocampal BDNF mRNA levels in aged 11β-HSD1 deficient mice

Abstract

Mice lacking the intracellular glucocorticoid-regenerating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) are protected from age-related spatial memory deficits. 11β-HSD1 is expressed predominantly in brain, liver and adipose tissue. Reduced glucocorticoid levels in brain in the absence of 11β-HSD1 may underlie the improved memory in aged 11β-HSD1 deficient mice. However, the improved glucose tolerance, insulin sensitization and cardio-protective lipid profile associated with reduced peripheral glucocorticoid regeneration may potentially contribute to the cognitive phenotype of aged 11β-HSD1 deficient mice. In this study, transgenic mice with forebrain-specific overexpression of 11β-HSD1 (Tg) were inter-crossed with global 11β-HSD1 knockout mice (HSD1KO) to examine the influence of forebrain and peripheral 11β-HSD1 activity on spatial memory in aged mice. Transgene-mediated delivery of 11β-HSD1 to the hippocampus and cortex of aged HSD1KO mice reversed the improved spatial memory retention in the Y-maze but not spatial learning in the watermaze. Brain-derived neurotrophic factor (BDNF) mRNA levels in the hippocampus of aged HSD1KO mice were increased compared to aged wild type mice. Rescue of forebrain 11β-HSD1 reduced BDNF mRNA in aged HSD1KO mice to levels comparable to aged wild type mice. These findings indicate that 11β-HSD1 regenerated glucocorticoids in forebrain and decreased levels of BDNF mRNA in the hippocampus plays a role in spatial memory deficits in aged wild type mice but 11β-HSD1 activity in peripheral tissues may also contribute to spatial learning impairments in aged mice.

This article is protected by copyright. All rights reserved.

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Bilateral Nasoalveolar Cyst Causing Nasal Obstruction

Nasoalveolar cysts, which originate from epithelial remnants of nasolacrimal duct, are nonodontogenic soft tissue lesions of the upper jaw. These cysts are thought to be developmental and are presented with fullness in the upper lip and nose, swelling on the palate, and sometimes nasal obstruction. Because of cosmetic problems, they are often diagnosed at an early stage. These lesions are mostly revealed unilaterally but also can be seen on both sides. In this case report, a patient who complained of nasal obstruction and then diagnosed with bilateral nasoalveolar cysts and treated by sublabial excision is presented and clinical features and treatment approaches are discussed with the review of literature.

http://ift.tt/2fYU2vT

Neural correlates of successful orbitofrontal 1 Hz rTMS following unsuccessful dorsolateral and dorsomedial prefrontal rTMS in major depression: A case report

Publication date: Available online 16 November 2016
Source:Brain Stimulation
Author(s): Peter Fettes, Sarah Peters, Peter Giacobbe, Jonathan Downar




http://ift.tt/2eJnTfq

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

Publication date: Available online 17 November 2016
Source:Brain Stimulation
Author(s): George M. Opie, Eleni Vosnakis, Michael C. Ridding, Ulf Ziemann, John G. Semmler
BackgroundPrimary motor cortex (M1) neuroplasticity is reduced in old adults, which may contribute to the motor deficits commonly observed in the elderly. Previous research in young subjects suggests that the neuroplastic response can be enhanced using non-invasive brain stimulation (NIBS), with a larger plastic response observed following priming with both long-term potentiation (LTP) and depression (LTD)-like protocols. However, it is not known if priming stimulation can also modulate plasticity in older adults.ObjectiveTo investigate if priming NIBS can be used to modulate motor cortical plasticity in old subjects.MethodsIn 16 young (22.3 ± 1.0 years) and 16 old (70.2 ± 1.7 years) subjects, we investigated the response to intermittent theta burst stimulation (iTBS; LTP-like) when applied 10 min after sham stimulation, continuous TBS (cTBS; LTD-like) or an identical block of iTBS. Corticospinal plasticity was assessed by recording changes in motor evoked potential (MEP) amplitude.ResultsIn young subjects, priming with cTBS (cTBS + iTBS) resulted in larger MEPs than priming with either iTBS (iTBS + iTBS; P = 0.001) or sham (sham + iTBS; P < 0.0001), while larger MEPs were seen following iTBS + iTBS than sham + iTBS (P < 0.0001). In old subjects, the response to iTBS + iTBS was not different to sham + iTBS (P > 0.9), whereas the response to cTBS + iTBS was reduced relative to iTBS + iTBS (P = 0.02) and sham + iTBS (P = 0.04).ConclusionsPriming TBS is ineffective for modifying M1 plasticity in older adults, which may limit the therapeutic use of priming stimulation in neurological conditions common in the elderly.



http://ift.tt/2fk0Ns6

Bilateral Nasoalveolar Cyst Causing Nasal Obstruction

Nasoalveolar cysts, which originate from epithelial remnants of nasolacrimal duct, are nonodontogenic soft tissue lesions of the upper jaw. These cysts are thought to be developmental and are presented with fullness in the upper lip and nose, swelling on the palate, and sometimes nasal obstruction. Because of cosmetic problems, they are often diagnosed at an early stage. These lesions are mostly revealed unilaterally but also can be seen on both sides. In this case report, a patient who complained of nasal obstruction and then diagnosed with bilateral nasoalveolar cysts and treated by sublabial excision is presented and clinical features and treatment approaches are discussed with the review of literature.

http://ift.tt/2fYU2vT

Richard Charles Pfister, MD.

Related Articles

Richard Charles Pfister, MD.

Radiology. 2003 Dec;229(3):936

Authors: Newhouse JH

PMID: 27845846 [PubMed - in process]

http://ift.tt/2f3IMNU

Less Invasive Phenotype Found in Isocitrate Dehydrogenase-mutated Glioblastomas than in Isocitrate Dehydrogenase Wild-Type Glioblastomas: A Diffusion-Tensor Imaging Study.

Less Invasive Phenotype Found in Isocitrate Dehydrogenase-mutated Glioblastomas than in Isocitrate Dehydrogenase Wild-Type Glioblastomas: A Diffusion-Tensor Imaging Study.

Radiology. 2016 Nov 16;:152679

Authors: Price SJ, Allinson K, Liu H, Boonzaier NR, Yan JL, Lupson VC, Larkin TJ

Abstract
Purpose To explore the diffusion-tensor (DT) imaging-defined invasive phenotypes of both isocitrate dehydrogenase (IDH-1)-mutated and IDH-1 wild-type glioblastomas. Materials and Methods Seventy patients with glioblastoma were prospectively recruited and imaged preoperatively. All patients provided signed consent, and the local research ethics committee approved the study. Patients underwent surgical resection, and tumor samples underwent immunohistochemistry for IDH-1 R132H mutations. DT imaging data were coregistered to the anatomic magnetic resonance study and reconstructed to provide the anisotropic and isotropic components of the DT. The invasive phenotype was determined by using previously published criteria and correlated with IDH-1 mutation status by using the Freeman-Halton extension of the Fisher exact probability test. Results Nine patients had an IDH-1 mutation and 61 had IDH-1 wild type. All of the patients with IDH-1 mutation had a minimally invasive DT imaging phenotype. Among the IDH-1 wild-type tumors, 42 of 61 (69%) were diffusively invasive glioblastomas, 14 of 61 (23%) were locally invasive, and five of 61 (8%) were minimally invasive (P < .001). Conclusion IDH-mutated glioblastomas have a less invasive phenotype compared with IDH wild type. This finding may have implications for individualizing the extent of surgical resection and radiation therapy volumes.

PMID: 27849434 [PubMed - as supplied by publisher]

http://ift.tt/2f3zEZC

Inflammatory mediators and signalling pathways controlling intervertebral disc degeneration.

Related Articles

Inflammatory mediators and signalling pathways controlling intervertebral disc degeneration.

Histol Histopathol. 2016 Nov 16;:11846

Authors: Navone SE, Marfia G, Giannoni A, Beretta M, Guarnaccia L, Gualtierotti R, Nicoli D, Rampini P, Campanella R

Abstract
Intervertebral disc (IVD) degeneration (IDD) is one of the major causes of back pain, a condition that represents a serious socio-economic burden. Deeper knowledge of the complex and fine relationship between IVD degeneration, tissue inflammation and pain, appears to be critical to improve the current therapies, which have so far proven themselves ineffective. Upon degeneration, IVD tissues become inflamed, and this inflammatory microenvironment is associated with a cascade of degenerative events that may eventually cause discogenic pain. In particular, several studies have highlighted the major role of a number of proinflammatory mediators not only in the onset of the inflammatory condition, but also in the development of IDD in general. In this review, we will present the main pathological events that occur during disc degeneration, focusing on the relationship between the abnormal inflammatory milieu of the degenerating IVD, IDD and the generation of pain. Finally, we will present the current therapies for the treatment of IDD and low back pain, and the perspectives of future, more effective therapies.

PMID: 27848245 [PubMed - as supplied by publisher]

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Contribution of submandibular gland and swallowing structure sparing to post-radiation therapy PEG dependence in oropharynx cancer patients treated with split-neck IMRT technique.

Related Articles

Contribution of submandibular gland and swallowing structure sparing to post-radiation therapy PEG dependence in oropharynx cancer patients treated with split-neck IMRT technique.

Radiat Oncol. 2016 Nov 15;11(1):151

Authors: Gensheimer MF, Nyflot M, Laramore GE, Liao JJ, Parvathaneni U

Abstract
BACKGROUND: Radiation therapy-related dysphagia is worsened by xerostomia. The submandibular glands (SMG) produce saliva rich in lubricating mucins, and sparing the SMG has been shown to reduce xerostomia. The goal of this study was to determine whether SMG sparing IMRT is associated with reduced post-treatment PEG dependence in locally advanced oropharynx cancer patients.
METHODS: Patients treated with definitive radiation therapy for oropharynx cancer were included in this retrospective study. Those with disease recurrence were excluded. Salivary glands and swallowing-related organs at risk, including pharyngeal constrictors, were contoured. Primary endpoint was time from end of radiation treatment to freedom from gastrostomy (PEG) tube dependence. Cox proportional hazards regression and logistic regression were used to assess influence of normal tissue doses on swallowing related endpoints.
RESULTS: Sixty-nine patients were included. All had stage III/IV disease and 97% received concurrent systemic therapy. Fifty-seven percent had contralateral SMG (cSMG) mean dose <50 Gy, a level shown to predict for xerostomia. Eighty four percent of patients had a PEG tube placed electively. On univariate analysis, the strongest predictor of time to freedom from PEG tube dependence was cSMG dose (HR 0.97 per Gy (95% CI 0.95-0.98), p < 0.0001). This relationship persisted on multivariate analysis (p = 0.052). The dose to superior and middle pharyngeal constrictor muscles, and larynx were also significant on univariate analysis. Patients with cSMG dose less than median (42 Gy, n = 34) had a significantly shorter time to freedom from PEG dependence: median 1.9 vs. 3.5 months, p < 0.0001. At 6 months, 3% of patients with cSMG dose < 42 Gy were PEG dependent compared to 31% with cSMG dose > 42 Gy (p = 0.002).
CONCLUSIONS: Patients treated with cSMG sparing radiotherapy had significantly shorter time to PEG tube removal after treatment, suggesting a clinically meaningful reduction in subacute dysphagia compared to non-cSMG sparing treatment.

PMID: 27846899 [PubMed - in process]

http://ift.tt/2fjVt7W

Differential Regulation of Macrophage Glucose Metabolism by Macrophage Colony-stimulating Factor and Granulocyte-Macrophage Colony-stimulating Factor: Implications for (18)F FDG PET Imaging of Vessel Wall Inflammation.

Differential Regulation of Macrophage Glucose Metabolism by Macrophage Colony-stimulating Factor and Granulocyte-Macrophage Colony-stimulating Factor: Implications for (18)F FDG PET Imaging of Vessel Wall Inflammation.

Radiology. 2016 Nov 16;:160839

Authors: Tavakoli S, Short JD, Downs K, Nguyen HN, Lai Y, Zhang W, Jerabek P, Goins B, Sadeghi MM, Asmis R

Abstract
Purpose To determine the divergence of immunometabolic phenotypes of macrophages stimulated with macrophage colony-stimulating factor (M-CSF) and granulocyte-M-CSF (GM-CSF) and its implications for fluorine 18 ((18)F) fluorodeoxyglucose (FDG) imaging of atherosclerosis. Materials and Methods This study was approved by the animal care committee. Uptake of 2-deoxyglucose and various indexes of oxidative and glycolytic metabolism were evaluated in nonactivated murine peritoneal macrophages (MΦ0) and macrophages stimulated with M-CSF (MΦM-CSF) or GM-CSF (MΦGM-CSF). Intracellular glucose flux was measured by using stable isotope tracing of glycolytic and tricyclic acid intermediary metabolites. (18)F-FDG uptake was evaluated in murine atherosclerotic aortas after stimulation with M-CSF or GM-CSF by using quantitative autoradiography. Results Despite inducing distinct activation states, GM-CSF and M-CSF stimulated progressive but similar levels of increased 2-deoxyglucose uptake in macrophages that reached up to sixfold compared with MΦ0. The expression of glucose transporters, oxidative metabolism, and mitochondrial biogenesis were induced to similar levels in MΦM-CSF and MΦGM-CSF. Unexpectedly, there was a 1.7-fold increase in extracellular acidification rate, a 1.4-fold increase in lactate production, and overexpression of several critical glycolytic enzymes in MΦM-CSF compared with MΦGM-CSF with associated increased glucose flux through glycolytic pathway. Quantitative autoradiography demonstrated a 1.6-fold induction of (18)F-FDG uptake in murine atherosclerotic plaques by both M-CSF and GM-CSF. Conclusion The proinflammatory and inflammation-resolving activation states of macrophages induced by GM-CSF and M-CSF in either cell culture or atherosclerotic plaques may not be distinguishable by the assessment of glucose uptake. (©) RSNA, 2016 Online supplemental material is available for this article.

PMID: 27849433 [PubMed - as supplied by publisher]

http://ift.tt/2gjWEIU

Erratum.

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Erratum.

Radiology. 2004 Jan;230(1):303

Authors:

PMID: 27846367 [PubMed - in process]

http://ift.tt/2f3Fg6b

Jack Lawrence Westcott, MD.

Related Articles

Jack Lawrence Westcott, MD.

Radiology. 2003 Sep;228(3):906

Authors: Gamsu G

PMID: 27845843 [PubMed - in process]

http://ift.tt/2f3Iarl

Increased PD-L1 and T-cell infiltration in the presence of HLA class I expression in metastatic high-grade osteosarcoma: a rationale for T-cell-based immunotherapy

Abstract

Introduction

Immunotherapy may be an excellent choice for treating osteosarcoma given its exceptionally high genomic instability, potentially generating neoantigens. In this study, we aim to investigate the HLA class I expression, PD-L1 and tumour-infiltrating lymphocytes in primary osteosarcomas and relapses/metastases, as well as their changes during disease progression.

Materials and methods

Tumour samples from multiple stages of the disease (pretreatment biopsies, surgical resections of primary osteosarcomas, relapses and metastases) were collected and stained for HLA-A (HCA2), HLA-B/C (HC10), β2-microglobulin and PD-L1 using immunohistochemistry on whole sections. Density and type of T-cell infiltrate were characterised by a triple immunofluorescent staining CD3-CD8-FOXP3.

Results

Overall, 85 formalin-fixed, paraffin-embedded blocks from 25 osteosarcoma patients were included. HLA class I expression was detected in 94% of osteosarcomas (strongly positive in 56%, heterogeneous in 38%) and negative or weakly positive in 6%, without differences between the stages of the disease. HLA-A expression was more frequently negative than HLA-B/C. Tumour-infiltrating lymphocytes were highly heterogeneous and mainly observed in tumour areas with expression of HLA class I. Density of T cells was significantly higher in metastases than in primary tumours and local relapses (p = 0.0003). Positive PD-L1 expression was found in 13% of primary tumours, 25% of relapses and 48% of metastases and correlated with a high T-cell infiltrate (p = 0.002).

Conclusion

An increased number of tumour-infiltrating T cells and PD-L1 expression in metastases compared with primary tumours, suggesting accessibility for T cells, could imply that osteosarcoma patients with metastatic disease may benefit from T-cell-based immunotherapy.

http://ift.tt/2eJkzB8

Raymond Gramiak, MD.

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Raymond Gramiak, MD.

Radiology. 2003 Sep;228(3):906

Authors: Lerner RM

PMID: 27845842 [PubMed - in process]

http://ift.tt/2f3ANAj

Erratum.

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Erratum.

Radiology. 2003 Nov;229(2):610

Authors:

PMID: 27845841 [PubMed - in process]

http://ift.tt/2f3Hdzf

Clinician's Commentary 1.

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Clinician's Commentary 1.

Radiology. 2003 Nov;229(2):365

Authors: Ward JD

PMID: 27845840 [PubMed - in process]

http://ift.tt/2f3Han3

Joint arthropathy at the cranio-vertebral junction. Scintigraphic patterns on bone SPECT/CT.

Joint arthropathy at the cranio-vertebral junction. Scintigraphic patterns on bone SPECT/CT.

Br J Neurosurg. 2016 Nov 16;:1-5

Authors: Russo VM, Duits A, Dhawan RT, Casey AT

Abstract
Osteoarthritic degeneration at the cranio-vertebral junction (CVJ) is an underrecognized source of suboccipital and neck pain, limited range of motion and cervicogenic headaches. Correlation of radiographic findings with clinical symptoms is often difficult. Limited evidence currently exists to support the use of bone single-photon emission computed tomography/computed tomography (SPECT/CT) in this subgroup of patients. The aim of this study was to describe the scintigraphic patterns of joint arthropathy at the CVJ on bone SPECT/CT in patients with suboccipital/neck pain and cervicogenic headache. Patients with more than 3 months of suboccipital/neck pain/cervicogenic headache and abnormal SPECT/CT findings at the CVJ were included. Patients with known/suspected malignancy, trauma, infectious processes and previous surgery at the CVJ were excluded. Neck disability index (NDI), visual analogue scale (VAS) and treatment were recorded for each patient. Patterns of osteoblastic activity at the CVJ on bone SPECT/CT were described and correlated with arthritic changes on conventional scans. Eighteen patients were included (10 females, mean age 68). Mean NDI score was 22. Mean VAS was 7.5. On bone SPECT/CT, it was found that 13 patients had high osteoblastic activity unilaterally at the atlanto-axial joint (AAJ); two patients at the atlanto-dental joint (ADJ), one at the occipito-atlantal joint (OAJ), one at both OAJ and ADJ and one at the level of C2 pars/pedicle unilaterally. Metabolic activity on SPECT/CT was associated with severe degenerative changes on CT scans. The ability of hybrid bone SPECT/CT to precisely localize osteoblastic activity at the CVJ may provide significant improvement in the diagnosis and treatment of patients with suboccipital/neck pain and joint arthropathy at the CVJ. Further clinical studies are needed to establish the real clinical impact of bone SPECT/CT in the treatment of patients with suboccipital neck pain.

PMID: 27848263 [PubMed - as supplied by publisher]

http://ift.tt/2gjQkAS