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Σάββατο 18 Μαρτίου 2017

Cognitive Functional Therapy (CFT) for chronic non-specific neck pain

Publication date: Available online 18 March 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Ney Meziat-Filho, Maicom Lima, Jessica Fernandez, Felipe J.J. Reis
This case report presents the effect of Cognitive Functional Therapy (CFT) in a patient with chronic non-specific neck pain. The patient believed that pain signified tissue damage, and demonstrated pain catastrophizing, hypervigilance, stress sensitivity, and movement impairment of the neck, during extension and rotation. The CFT intervention integrated a cognitive approach with manual therapy and active exercises to encourage the patient to trust her neck again. One month after the first appointment, the patient had recovered confidence, and the pain and disability had disappeared almost entirely.



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Abnormal Trajectories in Cerebellum and Brainstem Volumes in Carriers of the Fragile X Premutation

Publication date: Available online 18 March 2017
Source:Neurobiology of Aging
Author(s): Jun Yi Wang, David Hessl, Randi J. Hagerman, Tony J. Simon, Flora Tassone, Emilio Ferrer, Susan M. Rivera
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder typically affecting male premutation carriers with 55-200 CGG repeat expansions in the FMR1 gene after age 50. The aim of this study was to examine whether cerebellar and brainstem changes emerge during development or aging in late life. We retrospectively analyzed MRI scans from 322 males (age 8-81 years). Volume changes in the cerebellum and brainstem were contrasted with those in the ventricles and whole brain. Compared to the controls, premutation carriers without FXTAS showed significantly accelerated volume decrease in the cerebellum and whole brain, flatter inverted U-shaped trajectory of the brainstem, and larger ventricles. Compared to both older controls and premutation carriers without FXTAS, carriers with FXTAS exhibited significant volume decrease in the cerebellum and whole brain and accelerated volume decrease in the brainstem. We therefore conclude that cerebellar and brainstem volumes were likely affected during both development and progression of neurodegeneration in premutation carriers, suggesting that interventions may need to start early in adulthood to be most effective.



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N-type Ca2+ channels are affected by full-length mutant huntingtin expression in a mouse model of Huntington’s disease

Publication date: Available online 18 March 2017
Source:Neurobiology of Aging
Author(s): Flavia R. Silva, Artur S. Miranda, Rebeca P.M. Santos, Isabella G. Olmo, Gerald W. Zamponi, Tomas Dobransky, Jader S. Cruz, Luciene B. Vieira, Fabiola M. Ribeiro
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a polyglutamine expansion in the amino-terminal region of the huntingtin (htt) protein. In addition to facilitating neurodegeneration, mutant htt is implicated in HD-related alterations of neurotransmission. Previous data showed that htt can modulate N-type voltage-gated Ca2+ channels (Cav2.2), which are essential for presynaptic neurotransmitter release. Thus, to elucidate the mechanism underlying mutant htt-mediated alterations in neurotransmission, we investigated how Cav2.2 is affected by full-length mutant htt expression in a mouse model of HD (BACHD). Our data indicate that young BACHD mice exhibit increased striatal glutamate release, which is reduced to WT levels following Cav2.2 block. Cav2.2 Ca2+ current density and plasma membrane expression are increased in BACHD mice, which could account for increased glutamate release. Moreover, mutant htt affects the interaction between Cav2.2 and two major channel regulators, namely syntaxin 1A and Gβγ protein. Notably, 12 month old BACHD mice exhibit decreased Cav2.2 cell surface expression and glutamate release, suggesting that Cav2.2 alterations vary according to disease stage.



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Spatio-temporal patterns of event-related potentials related to audiovisual synchrony judgements in older adults

Publication date: Available online 18 March 2017
Source:Neurobiology of Aging
Author(s): Yu Man Chan, Michael Julian Pianta, Stefan Bode, Allison Maree McKendrick
Older adults have altered perception of the relative timing between auditory and visual stimuli, even when stimuli are scaled to equate detectability. To help understand why, this study investigated the neural correlates of audiovisual synchrony judgements in older adults using electroencephalography (EEG). Fourteen younger (18–32 years old) and sixteen older (61–74 years old) adults performed an audiovisual synchrony judgement task on flash-pip stimuli while EEG was recorded. All participants were assessed to have healthy vision and hearing for their age. Observers responded to whether audiovisual pairs were perceived as synchronous or asynchronous via a button press. The results showed that the onset of predictive sensory information for synchrony judgements was not different between groups. Channels over auditory areas contributed more to this predictive sensory information than visual areas. The spatial-temporal profile of the EEG activity also indicates that older adults utilised different resources to maintain a similar level of performance in audiovisual synchrony judgements compared to younger adults.



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3T Hippocampal Glutamate-Glutamine Complex Reflects Verbal Memory Decline in Aging

Publication date: Available online 18 March 2017
Source:Neurobiology of Aging
Author(s): S. Nikolova, S.M. Stark, C.E.L. Stark
The hippocampus is a critical site for alterations that are responsible for age-related changes in memory. Here, we present a relatively novel approach of examining the relationship between memory performance and Glutamate-Glutamine levels using short echo time magnetic resonance spectroscopy (MRS). Specifically, we investigated the relationship between Glx (a composite of glutamate and glutamine) levels in the hippocampus, performance on a word recall task and resting state functional connectivity (RSFC). While there was no overall difference in Glx intensity between young and aging adults, we identified a positive correlation between delayed word-list recall and Glx, bilaterally in older adults, but not in young adults. Collapsed across age, we also discovered a negative relationship between Glx intensity and RSFC between the anterior hippocampus and regions in the subcallosal gyrus, replicating a recent finding by Wagner et al., (2016). These findings demonstrate the possibly utility of Glx in identifying age-related changes in the brain and behavior and provide encouragement that MRS can be useful in predicting age-related decline before any physical abnormalities are present.



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Genetic or pharmacological activation of the Drosophila PGC-1α ortholog spargel rescues the disease phenotypes of genetic models of Parkinson’s disease

Publication date: Available online 18 March 2017
Source:Neurobiology of Aging
Author(s): Chee-Hoe Ng, Adeline H. Basil, Liting Hang, Royston Tan, Kian-Leong Goh, Sharon O'Neill, Xiaodong Zhang, Fengwei Yu, Kah-Leong Lim
Despite intensive research, the etiology of Parkinson's disease (PD) remains poorly understood and the disease remains incurable. However, compelling evidence gathered over decades of research strongly support a role for mitochondrial dysfunction in PD pathogenesis. Related to this, PGC-1α, a key regulator of mitochondrial biogenesis, has recently been proposed to be an attractive target for intervention in PD. Here, we showed that silencing of expression of the Drosophila PGC-1α ortholog spargel results in PD-related phenotypes in flies and also seem to negate the effects of AMPK activation, which we have previously demonstrated to be neuroprotective, i.e. AMPK-mediated neuroprotection appears to require PGC-1α. Importantly, we further showed that genetic or pharmacological activation of the Drosophila PGC-1α ortholog spargel is sufficient to rescue the disease phenotypes of Parkin and LRRK2 genetic fly models of PD, thus supporting the proposed use of PGC-1α-related strategies for neuroprotection in PD.



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Dosimetric comparison between treatment plans of patients treated with low-dose–rate vs. high-dose–rate interstitial prostate brachytherapy as monotherapy: Initial findings of a randomized clinical trial

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Publication date: Available online 18 March 2017
Source:Brachytherapy
Author(s): T. Major, C. Polgár, K. Jorgo, G. Stelczer, P. Ágoston
PurposeThe aim of this study was to compare the dosimetry of intraoperative dose plans of prostate cancer patients treated with low-dose–rate (LDR) and high-dose–rate (HDR) interstitial brachytherapy (BT).Methods and MaterialsA randomized clinical trial was initiated at our institution to compare the results and side effects of LDR and HDR BT as monotherapy in the treatment of early, organ-confined prostate cancer patients. Eighty-seven patients were randomly assigned to receive HDR afterloading BT with one fraction of 19 Gy or permanent LDR 125I seed BT with 145 Gy. Inverse optimization algorithms were used for planning. Stranded seeds were implanted using live ultrasound imaging after preimplant treatment planning. Final dosimetry of HDR treatments was based on updated needle and contour positions. Statistical comparisons with nonparametric test were performed between the corresponding dose–volume parameters.ResultsThe V100 and V150 were 99% and 61%, respectively, for LDR, whereas 98% and 32% for HDR treatments. The D90 was less for HDR (122% vs. 110%). The dose distributions were more homogeneous and conformal with HDR technique (dose homogeneity index, 0.39 vs. 0.67; conformal index, 0.65 vs. 0.80). The urethra and rectum received significantly less dose with HDR. The D10 and D30 for urethra were 133% and 128%, respectively, for LDR and 114% and 111% for HDR treatments. The D2cm3 for rectum was 68% and 55% for LDR and HDR technique, respectively.ConclusionsBoth techniques provided acceptable target volume coverage with a slightly higher value with the LDR technique. The dose distributions were more homogeneous and conformal, and both urethra and rectum were better protected with the HDR technique.



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A Modified Dual-plane Technique Using the Serratus Anterior Fascia in Primary Breast Augmentation

imageBackground: Breast augmentations are commonly performed aesthetic surgical procedures. As the breast is a changeable structure, the ideal location of an implant would be a plane that can adjust to the dynamic changes of the breast. We present a modified dual-plane technique for breast augmentation using the fascia for thin patients. Methods: Between June 2014 and June 2015, 27 patients with small breasts underwent breast augmentation using the modified dual-plane technique. The average age was 29.4 years (range, 20–41 y). The mean body mass index was 18.9 kg/m2 (range, 17.6–20.4 kg/m2). Results: The mean size of the implant was 288.9 ml (range, 255–360 ml) on the right side and 281.6 ml (range, 255–360 ml) on the left side. All the patients returned to daily-life activities within 1 week. There have been no complications during minimum follow-up periods of 18 months. The mean follow-up was 25.6 months (range, 18–36 mo). Conclusions: Visible, palpable implants and rippling after breast augmentation with implants are relatively common problems. Our modified dual-plane technique with the serratus anterior fascia can reduce visible rippling and yields a natural-looking breast, especially in thin patients.

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Dual lanthanide-doped complexes: the development of a time-resolved ratiometric fluorescent probe for anthrax biomarker and a paper-based visual sensor

Publication date: 15 August 2017
Source:Biosensors and Bioelectronics, Volume 94
Author(s): Qi-Xian Wang, Shi-Fan Xue, Zi-Han Chen, Shi-Hui Ma, Shengqiang Zhang, Guoyue Shi, Min Zhang
In this work, a novel time-resolved ratiometric fluorescent probe based on dual lanthanide (Tb: terbium, and Eu: europium)-doped complexes (Tb/DPA@SiO2-Eu/GMP) has been designed for detecting anthrax biomarker (dipicolinic acid, DPA), a unique and major component of anthrax spores. In such complexes-based probe, Tb/DPA@SiO2 can serve as a stable reference signal with green fluorescence and Eu/GMP act as a sensitive response signal with red fluorescence for ratiometric fluorescent sensing DPA. Additionally, the probe exhibits long fluorescence lifetime, which can significantly reduce the autofluorescence interferences from biological samples by using time-resolved fluorescence measurement. More significantly, a paper-based visual sensor for DPA has been devised by using filter paper embedded with Tb/DPA@SiO2-Eu/GMP, and we have proved its utility for fluorescent detection of DPA, in which only a handheld UV lamp is used. In the presence of DPA, the paper-based visual sensor, illuminated by a handheld UV lamp, would result in an obvious fluorescence color change from green to red, which can be easily observed with naked eyes. The paper-based visual sensor is stable, portable, disposable, cost-effective and easy-to-use. The feasibility of using a smartphone with easy-to-access color-scanning APP as the detection platform for quantitative scanometric assays has been also demonstrated by coupled with our proposed paper-based visual sensor. This work unveils an effective method for accurate, sensitive and selective monitoring anthrax biomarker with backgroud-free and self-calibrating properties.

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Rape myth acceptance in convicted rapists: A systematic review of the literature

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Publication date: Available online 18 March 2017
Source:Aggression and Violent Behavior
Author(s): Larissa Gabrielle Johnson, Anthony Beech
AimThe review examines studies on rape myth acceptance (RMA) within populations of convicted sexual offenders, changes in RMA due to interventions, comparisons between sexual offenders and community controls, comparisons within the offending population, and relationships between RMA and other psychological constructs linked to criminogenic need.MethodThe search employed electronic databases, OvidSP, Web of Science, and Proquest; hand searching reference lists; and contacting 35 experts in the field. Inclusion/exclusion and quality appraisal criteria were applied to each study.ResultsEight studies met the inclusion criteria. Results highlighted differences in subgroups of rapists for different aspects of RMA; while rapists can be distinguished from non-offenders and non-sexual offenders on measures of RMA, they cannot be significantly discriminated from child molesters; rapists and sexual murders cannot be distinguished using RMA scores; RMA was not found to be a significant predictor of sexual or violence recidivism; and significant positive change in RMA was reported after sex offenders completed treatment programs.ConclusionsDifferences in scores on RMA subscales amongst rapists' typologies were discovered, which may indicate differences in beliefs within each type. Implications for practice are discussed.



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Alcohol abuse, personality disorders, and aggression: The quest for a common underlying mechanism

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Publication date: Available online 18 March 2017
Source:Aggression and Violent Behavior
Author(s): Carlo Garofalo, Aidan G.C. Wright
Alcohol abuse and personality disorders are often comorbid, and their co-occurrence is associated with worse prognostic expectations, poor therapeutic outcomes, as well as deleterious behavioral and interpersonal consequences. The current review aims at untangling the association among alcohol abuse, personality disorders, and aggression. After reviewing the relevant literature on alcohol abuse, personality disorders, and related aggression, we propose that their association could be better understood by acknowledging common underlying mechanisms. Accordingly, we outline different potential avenues that can explain their association. In particular, we focus on impulsivity and emotion dysregulation as possible triggers of alcohol abuse and personality disorders, ultimately leading to self-harm and interpersonal violence. Also, the critical role of contextual influences in exacerbating both subjective and interpersonal dysfunctions is considered. Finally, we argue that emotion dysregulation and impulsivity could serve as useful intervention targets to treat clients with personality disorders and alcohol abuse who engage in aggressive behavior, by tackling these mechanisms underlying their complex pathology. Relevant implications for both clinical and research purposes are also highlighted.



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Ventricular wall biomaterial injection therapy after myocardial infarction: Advances in material design, mechanistic insight and early clinical experiences

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Publication date: June 2017
Source:Biomaterials, Volume 129
Author(s): Yang Zhu, Yasumoto Matsumura, William R. Wagner
Intramyocardial biomaterial injection therapy for myocardial infarction has made significant progress since concept initiation more than 10 years ago. The interim successes and progress in the first 5 years have been extensively reviewed. During the last 5 years, two phase II clinical trials have reported their long term follow up results and many additional biomaterial candidates have reached preclinical and clinical testing. Also in recent years deeper investigations into the mechanisms behind the beneficial effects associated with biomaterial injection therapy have been pursued, and a variety of process and material parameters have been evaluated for their impact on therapeutic outcomes. This review explores the advances made in this biomaterial-centered approach to ischemic cardiomyopathy and discusses potential future research directions as this therapy seeks to positively impact patients suffering from one of the world's most common sources of mortality.



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Biomaterials for intervertebral disc regeneration and repair

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Publication date: June 2017
Source:Biomaterials, Volume 129
Author(s): Robert D. Bowles, Lori A. Setton
The intervertebral disc contributes to motion, weight bearing, and flexibility of the spine, but is susceptible to damage and morphological changes that contribute to pathology with age and injury. Engineering strategies that rely upon synthetic materials or composite implants that do not interface with the biological components of the disc have not met with widespread use or desirable outcomes in the treatment of intervertebral disc pathology. Here we review bioengineering advances to treat disc disorders, using cell-supplemented materials, or acellular, biologically based materials, that provide opportunity for cell-material interactions and remodeling in the treatment of intervertebral disc disorders. While a field still in early development, bioengineering-based strategies employing novel biomaterials are emerging as promising alternatives for clinical treatment of intervertebral disc disorders.



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Croconaine nanoparticles with enhanced tumor accumulation for multimodality cancer theranostics

Publication date: June 2017
Source:Biomaterials, Volume 129
Author(s): Longguang Tang, Fuwu Zhang, Fei Yu, Wenjing Sun, Menglin Song, Xiaoyuan Chen, Xianzhong Zhang, Xiaolian Sun
A novel nanoparticle self-assembled by polyethylene glycol (PEG) modified croconaine dye (CR780) is presented for photoacoustic (PA)/near-infrared (NIR) fluorescence imaging-guided photothermal therapy (PTT). The simple PEGylation made CR780 amphiphilic, and led to their self-assembly into well-defined and uniform nanostructures with size tunable by controlling the assembly conditions. The CR780-PEG5K not only displayed the strength of small molecules (including rapid distribution to different organs, fast renal clearance and minimal accumulation to normal tissues), but also demonstrated the advantages of nanomaterials (including high physiological stability, multimodal theranostic ability, high tumor accumulation and retention). These facilely synthesized molecular nanoprobes showed great clinical translation potential as a versatile theranostic agent.

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Long-term bioavailability of redox nanoparticles effectively reduces organ dysfunctions and death in whole-body irradiated mice

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Publication date: June 2017
Source:Biomaterials, Volume 129
Author(s): Chitho P. Feliciano, Koji Tsuboi, Kenshi Suzuki, Hiroyuki Kimura, Yukio Nagasaki
Radioprotective agents have been developed to protect patients against the damaging and lethal effects of ionizing radiation. However, in addition to the intrinsic ability to target reactive oxygen species (ROS), the ability to retain a significant level of bioavailability is desirable in radioprotective agents because that would increase and prolong their radioprotective efficacy and improve its safety. Here, we report the development of a novel nanoparticle-based radioprotective agent with improved bioavailability, which suppressed the adverse effects typically associated with low-molecular-weight (LMW) antioxidants. We developed biocompatible and colloidally stable nanoparticles in which nitroxide radicals that were covalently conjugated (redox nanoparticles, RNPN) effectively scavenged radiation-induced ROS with a characteristically prolonged bioavailability and tissue-residence time compared with that of conventional LMW antioxidants. The confinement of the nitroxide radicals in the RNPN core prevented its rapid metabolism and excretion out of the body. The nano-sized formulation prevented internalization of RNPN in healthy cells, thereby preserving the normal function of the redox reactions in the cell. This improved pharmacological performance dramatically reduced the radiation-induced organ dysfunctions and increased the survival time of the lethally irradiated mice when the nanoparticles were administered 3–24 h before whole-body irradiation.



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Thyroid Top-Cited Articles March 2017

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FREE ACCESS through March 30, 2017.
Read now:

Latest Impact Factor: 3.784
The Official Journal of: American Thyroid Association

Impact of the Multi-Gene ThyroSeq Next-Generation Sequencing Assay on Cancer Diagnosis in Thyroid Nodules with Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance Cytology
Yuri E. Nikiforov, Sally E. Carty, Simon I. Chiosea, Christopher Coyne, Umamaheswar Duvvuri, Robert L. Ferris, William E. Gooding, Shane O. LeBeau, N. Paul Ohori, Raja R. Seethala, Mitchell E. Tublin, Linwah Yip, Marina N. Nikiforova

BRAF Inhibitor Dabrafenib in Patients with Metastatic BRAF-Mutant Thyroid Cancer
Gerald S. Falchook, Michael Millward, David Hong, Aung Naing, Sarina Piha-Paul, Steven G. Waguespack, Maria E. Cabanillas, Steven I. Sherman, Bo Ma, Martin Curtis, Vicki Goodman, Razelle Kurzrock

Thyroid Ultrasound Features and Risk of Carcinoma: A Systematic Review and Meta-Analysis of Observational Studies
Luciana Reck Remonti, Caroline Kaercher Kramer, Cristiane Bauermann Leitão, Lana Catani F. Pinto, Jorge Luiz Gross

The Impact of Noninvasive Follicular Variant of Papillary Thyroid Carcinoma on Rates of Malignancy for Fine-Needle Aspiration Diagnostic Categories
Kyle C. Strickland, Brooke E. Howitt, Ellen Marqusee, Erik K. Alexander, Edmund S. Cibas, Jeffrey F. Krane, Justine A. Barletta

Circadian and Circannual Rhythms in Thyroid Hormones: Determining the TSH and Free T4 Reference Intervals Based Upon Time of Day, Age, and Sex
Joel Ehrenkranz, Phillip R. Bach, Gregory L. Snow, Alison Schneider, Jo Lynn Lee, Sarah Ilstrup, Sterling T. Bennett, Salvatore Benvenga

The Impact of Subclinical Disease and Mechanism of Detection on the Rise in Thyroid Cancer Incidence: A Population-Based Study in Olmsted County, Minnesota During 1935 Through 2012
Juan P. Brito, Alaa Al Nofal, Victor M. Montori, Ian D. Hay, John C. Morris

The post Thyroid Top-Cited Articles March 2017 appeared first on American Thyroid Association.



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The Neandertal vertebral column 2: The lumbar spine

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Publication date: May 2017
Source:Journal of Human Evolution, Volume 106
Author(s): Asier Gómez-Olivencia, Mikel Arlegi, Alon Barash, Jay T. Stock, Ella Been
Here we provide the most extensive metric and morphological analysis performed to date on the Neandertal lumbar spine. Neandertal lumbar vertebrae show differences from modern humans in both the vertebral body and in the neural arch, although not all Neandertal lumbar vertebrae differ from modern humans in the same way. Differences in the vertebral foramen are restricted to the lowermost lumbar vertebrae (L4 and L5), differences in the orientation of the upper articular facets appear in the uppermost lumbar vertebrae (probably in L1 and L2–L3), and differences in the horizontal angle of the transverse process appear in L2–L4. Neandertals, when compared to modern humans, show a smaller degree of lumbar lordosis. Based on a still limited fossil sample, early hominins (australopiths and Homo erectus) had a lumbar lordosis that was similar to but below the mean of modern humans. Here, we hypothesize that from this ancestral degree of lumbar lordosis, the Neandertal lineage decreased their lumbar lordosis and Homo sapiens slightly increased theirs. From a postural point of view, the lower degree of lordosis is related to a more vertical position of the sacrum, which is also positioned more ventrally with respect to the dorsal end of the pelvis. This results in a spino-pelvic alignment that, though different from modern humans, maintained an economic postural equilibrium. Some features, such as a lower degree of lumbar lordosis, were already present in the middle Pleistocene populations ancestral to Neandertals. However, these middle Pleistocene populations do not show the full suite of Neandertal lumbar morphologies, which probably means that the characteristic features of the Neandertal lumbar spine did not arise all at once.



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Favorable ecological circumstances promote life expectancy in chimpanzees similar to that of human hunter-gatherers

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Publication date: April 2017
Source:Journal of Human Evolution, Volume 105
Author(s): Brian M. Wood, David P. Watts, John C. Mitani, Kevin E. Langergraber
Demographic data on wild chimpanzees are crucial for understanding the evolution of chimpanzee and hominin life histories, but most data come from populations affected by disease outbreaks and anthropogenic disturbance. We present survivorship data from a relatively undisturbed and exceptionally large community of eastern chimpanzees (Pan troglodytes schweinfurthii) at Ngogo, Kibale National Park, Uganda. We monitored births, deaths, immigrations, and emigrations in the community between 1995 and 2016. Using known and estimated ages, we calculated survivorship curves for the whole community, for males and females separately, and for individuals ≤2 years old when identified. We used a novel method to address age estimation error by calculating stochastic survivorship curves. We compared Ngogo life expectancy, survivorship, and mortality rates to those from other chimpanzee communities and human hunter-gatherers. Life expectancy at birth for both sexes combined was 32.8 years, far exceeding estimates of chimpanzee life expectancy in other communities, and falling within the range of human hunter-gatherers (i.e., 27–37 years). Overall, the pattern of survivorship at Ngogo was more similar to that of human hunter-gatherers than to other chimpanzee communities. Maximum lifespan for the Ngogo chimpanzees, however, was similar to that reported at other chimpanzee research sites and was less than that of human-hunter gatherers. The absence of predation by large carnivores may contribute to some of the higher survivorship at Ngogo, but this cannot explain the much higher survivorship at Ngogo than at Kanyawara, another chimpanzee community in the same forest, which also lacks large carnivores. Higher survivorship at Ngogo appears to be an adaptive response to a food supply that is more abundant and varies less than that of Kanyawara. Future analyses of hominin life history evolution should take these results into account.



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A comparative analysis of infraorbital foramen size in Paleogene euarchontans

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Publication date: April 2017
Source:Journal of Human Evolution, Volume 105
Author(s): Magdalena N. Muchlinski, E. Christopher Kirk
The size of the infraorbital foramen (IOF) is correlated with the size of the infraorbital nerve and number of mystacial vibrissae in mammals. Accordingly, IOF cross-sectional area has been used to infer both the rostral mechanoreceptive acuity and phylogenetic relationships of extinct crown primates and plesiadapiforms. Among living mammals, extant primates, scandentians, and dermopterans (Euarchonta) exhibit smaller IOF cross-sectional areas than most other mammals. Here we assess whether fossil adapoids, omomyoids, and plesiadapiforms show a reduction in relative IOF area similar to that characterizing extant euarchontans. The IOFs of 12 adapoid, 7 omomyoid, 15 plesiadapiform, and 3 fossil gliran species were measured and compared to a diverse extant mammalian sample. These data demonstrate that adapoids and omomyoids have IOFs that are similar in relative size to those of extant euarchontans. Conversely, IOFs of plesiadapiforms are on average about twice as large as those of extant euarchontans and are more comparable in size to those of extant non-euarchontan mammals. These results indicate that crown primates share a derived reduction in relative IOF size with treeshrews and colugos. Accordingly, a decreased reliance on the muzzle and an increased reliance on the hands for environmental exploration may have first evolved in the euarchontan stem lineage. However, the relatively large IOFs of plesiadapiforms imply a continued reliance on the muzzle for close exploration of objects. This finding may indicate that either parallel evolutionary decreases in IOF size occurred within Euarchonta or that plesiadapiforms lie outside the euarchontan crown group.



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The chronostratigraphy of the Haua Fteah cave (Cyrenaica, northeast Libya) — Optical dating of early human occupation during Marine Isotope Stages 4, 5 and 6

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Publication date: April 2017
Source:Journal of Human Evolution, Volume 105
Author(s): Zenobia Jacobs, Bo Li, Lucy Farr, Evan Hill, Chris Hunt, Sacha Jones, Ryan Rabett, Tim Reynolds, Richard G. Roberts, David Simpson, Graeme Barker
The paper presents the results of optical dating of potassium-rich feldspar grains obtained from the Haua Fteah cave in Cyrenaica, northeast Libya, focussing on the chronology of the Deep Sounding excavated by Charles McBurney in the 1950s and re-excavated recently. Samples were also collected from a 1.25 m-deep trench (Trench S) excavated during the present project below the basal level of the Deep Sounding. Optically stimulated luminescence (OSL) data sets for multi-grain, single aliquots of quartz for samples from the Middle Trench were previously published. Re-analyses of these OSL data confirm significant variation in the dose saturation levels of the quartz signal, but allow the most robust OSL ages to be determined for comparison with previous age estimates and with those obtained in this study for potassium-rich feldspars from the Deep Sounding. The latter indicate that humans may have started to visit the cave as early as ∼150 ka ago, but that major use of the cave occurred during MIS 5, with the accumulation of the Deep Sounding sediments. Correlations between optical ages and episodes of "Pre-Aurignacian" artefact discard indicate that human use of the cave during MIS 5 was highly intermittent. The earliest phases of human activity appear to have occurred during interstadial conditions (5e and 5c), with a later phase of lithic discard associated with more stadial conditions, possibly MIS 5b. We argue that the "Pre-Aurignacian" assemblage can probably be linked with modern humans, like the succeeding "Levalloiso-Mousterian" assemblage; two modern human mandibles associated with the latter are associated with a modelled age of 73–65 ka. If this attribution is correct, then the new chronology implies that modern humans using "Pre-Aurignacian" technologies were in Cyrenaica as early as modern humans equipped with "Aterian" technologies were in the Maghreb, raising new questions about variability among lithic technologies during the initial phases of modern human dispersals into North Africa.



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Excision of hypoglossal neurinoma by condyle sparing suboccipital keyhole approach

Harjinder Bhatoe

Asian Journal of Neurosurgery 2017 12(1):120-122

Hypoglossal neurinomas are rare tumors that present with gradually worsening unilateral wasting of the tongue. The tumors often attain large size prior to detection and often extend into the hypoglossal canal. Large tumors can distort the brainstem and cerebellum. Preoperative diagnosis can often be made by magnetic resonance imaging (MRI) with contrast enhancement. Traditionally, surgery for these tumors has entailed large transcondylar approaches, often necessitating occipitocervical stabilization. We managed one 23-year-old female patient with a large hypoglossal neurinoma. The tumor could be excised completely by a condyle-sparing minimally invasive suboccipital keyhole approach.

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Bilateral cervico-dorsal gossypiboma presenting as discharging sinus

Sushil Kumar, Pooja Abbey, Amit Handa

Asian Journal of Neurosurgery 2017 12(1):92-94

Retained surgical sponge is an uncommon complication after laminectomy. A 67-year-old male presented with a discharging sinus in the cervical region following cervical laminectomy. Magnetic resonance imaging (MRI) revealed bilateral symmetrical lesions in the paraspinal area. Re-exploration revealed gauze pieces on either side under the muscle. Persistent discharging wound after surgery should arouse the possibility of a foreign body. Because of the rarity of bilateral lesions, the present case is being reported.

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Perioperative complications in endovascular neurosurgery: Anesthesiologist's perspective

Megha U Sharma, Pragati Ganjoo, Daljit Singh, Monica S Tandon, Jyotsna Agarwal, Durga P Sharma, Anita Jagetia

Asian Journal of Neurosurgery 2017 12(1):6-12

Background: Endovascular neurosurgery is known to be associated with potentially serious perioperative complications that can impact the course and outcome of anesthesia. We present here our institutional experience in the anesthetic management of various endovascular neurosurgical procedures and their related complications over a 10-year period. Methods: Data was obtained in 240 patients pertaining to their preoperative status, details of anesthesia and surgery, perioperative course and surgery-related complications. Information regarding hemodynamic alterations, temperature variability, fluid-electrolyte imbalance, coagulation abnormalities and alterations in the anesthesia course was specifically noted. Results: Among the important complications observed were aneurysm rupture (2.5%), vasospasm (6.67%), thromboembolism (4.16%), contrast reactions, hemodynamic alterations, electrolyte abnormalities, hypothermia, delayed emergence from anesthesia, groin hematomas and early postoperative mortality (5.14%). Conclusion: Awareness of the unique challenges of endovascular neurosurgery and prompt and appropriate management of the associated complications by an experienced neuroanesthesiologist is vital to the outcome of these procedures.

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Economic and outcome following severe head injury

Somsri Wiwanitkit, Viroj Wiwanitkit

Asian Journal of Neurosurgery 2017 12(1):147-147



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Post ventriculoperitoneal shunt abdominal pseudocyst: Challenges posed in management

Raashid Hamid, Aejaz A Baba, Nisar A Bhat, Gowhar Mufti, Younis A Mir, Wani Sajad

Asian Journal of Neurosurgery 2017 12(1):13-16

Background: In patients with hydrocephalus, the abdominal cavity has been used for absorption of cerebrospinal fluid (CSF) since 1905. Ventriculoperitoneal (VP) shunt operation is followed by abdominal complications in about 5-47% cases. Abdominal CSF pseudo cyst is an uncommon, but well described complication. Aim: This survey was conducted to study the clinical profile and management of this entity. We present our experience with cases of CSF pseudo cyst in children. Materials and Methods: Retrospective analysis of 4 cases diagnosed to have abdominal pseudo cyst following VP shunt between 2008 and 2013. All the four cases were suspected clinically and diagnosis was confirmed by abdominal ultrasonography. Results: In three patients, the cyst was multilocular and of varying size. Fourth one had a unilocular cyst at the lower end of VP shunt. All the four patients had features of varying degree raised intracranial pressure and a two patients had abdominal signs also. All the patients needed open exploration. Cyst fluid was drained and partial to complete excision of the cyst was done along with the repositioning of the shunt in abdominal cavity in three patients and exteriorization of shunt in one patient. Patients were followed for any further complication over a period of 1-year. Conclusion: Abdominal pseudo cyst is a rare complication after VP Shunt and could result in shunt malfunction or abdominal symptoms and signs. Whenever suspected it should be confirmed by imaging, followed by open exploration and repositioning of the shunt.

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Challenges in a case of ophthalmic artery aneurysm associated with abnormal internal carotid arteries

Eduard B Dinca, Felix Brehar, Andrei Giovani, Alexandru V Ciurea

Asian Journal of Neurosurgery 2017 12(1):106-108

Ophthalmic artery aneurysms account for 5% of all cerebral aneurysms and are an important cause of morbidity and mortality related to subarachnoid hemorrhage. The diagnosis is often made only when the aneurysm is large enough to become symptomatic. They remain technically challenging for both neurosurgeon and interventional radiologist. We present the case of a 62-year-old woman admitted for transient loss of consciousness, followed by generalized tonic-clonic seizures. Computed tomography (CT) showed a subarachnoid hemorrhage (SAH), clinically graded as Hunt and Hess III. Magnetic resonance imaging (angioMR) and the four-vessel digital subtraction angiography (DSA) identified a ruptured, 8 mm left ophthalmic artery aneurysm. Embolization was the first therapeutic choice. Nevertheless, the attempt had to be aborted due to a combination of a hypoplastic right internal carotid artery (ICA) and an irregular atheromatous plaque on the left ICA, rendering the procedure unduly hazardous. Therefore, microsurgical clipping of the aneurysm became the procedure of choice. Postoperatively, the patient was in good condition, with no visual and neurological deficits. At 6 months follow up, she was assigned maximum scores of 5 and 8 on the Glasgow Outcome Scale (GOS) and Extended GOS (GOS-E), respectively. Aneurysm rupture represents a neurosurgical emergency and an early intervention (less than 48 h) is recommended to maximize the chances of deficit-free survival. The peculiarities of this case consisted in the combination between the size and the location of the aneurysm, abrupt presentation, and the impossibility of embolization due to bilateral ICA abnormalities, congenital (hypoplastic right ICA) and acquired (extensively atherosclerotic left ICA).

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Neuroendoscopy - Is it safe?

Manas Panigrahi, Bharat Gupta, Rajesh Reddy

Asian Journal of Neurosurgery 2017 12(1):17-21

Background: The effect of heat in endoscopic instruments used for laparoscopy and hysteroscopy has been well-studied. Reports of thermal injury from nasal endoscopes have also been reported. However, there are no experimental studies, which have objectively documented and provided recommendations for safe use of endoscopes in neurosurgery. Objectives: To study the heat generated at the tip of the endoscope and the subsequent thermal damage caused to a cotton drape placed in proximity, by varying the intensity of light delivered through different optical cables, ambient (operating room) temperatures and working distances. Materials and Methods: The study was carried out in the operation theater using a 300 watt xenon light source connected to the endoscope with 3.5 mm and 4.8 mm optical cables. A digital thermometer was used to record the heat generated at the tip of the endoscope. Results: The heat generated at the tip of the endoscope reached its peak in the first 6 min and attained a plateau at 15 min after turning on a light source of 60% intensity. Thermal injury to the cotton drape took a longer time with a 3.8 mm cable compared with 4.8 mm cable. The heat generated at the tip of the endoscope, and thereby the thermal injury caused was found to be lower when the ambient temperature was close to 20°C. Conclusions: Complications related to thermal injuries caused by heat generated at the tip of an endoscope can be reduced by using a smaller diameter cable, light intensity of 60%, increasing the working distance (as permissible), reducing the time spent for dissection while keeping the endoscope very close to the target and lowering the ambient temperature to 20°C.

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C2 Primary leiomyoma in an immunocompetent woman: A case report and review of literature

Mohana Rao Patibandla, Madhukar T Nayak, AK Purohit, Megha Uppin, Sundaram Challa, Gokul Chowdary Addagada, Manisha Nukavarapu

Asian Journal of Neurosurgery 2017 12(1):134-138

Clinical case report and review of the literature. This is the first case of primary leiomyoma in an immunocompetent woman without previous history of uterine leiomyoma being reported in the literature to the best of our knowledge.Leiomyoma, a type of smooth muscle cell tumor, involving the vertebra is extremely rare. There were very few primary leiomyoma in patients with AIDS or in the immune-suppressed patients.This 48-year-old female came with H/o neck pain, weakness and bladder retention. On examination, tone increased in all four limbs, power on the right side of the limbs 4/5, power on the left upper limb 0/5, lower limb 3/5, left plantar was up going, decreased sensation over the left second cervical vertebra (C2) dermatome and all modalities decreased below C2. X-ray and magnetic resonance imaging (MRI) of the cervical spine showed kyphosis of the cervical spine with destruction of the C2 vertebral body along with pathological fracture. The patient underwent decompression of the C2 lesion through the C2 right pedicle with occipito-C1-C3 lateral mass screws fixation. Lesion anterior to the cord was reached by a transpedicular approach and decompression was performed.The lesion was pinkish grey, firm and moderately vascular and was destroying the C2 vertebral body. The patient improved symptomatically in power in the left upper limb and lower limb over the next 1 week duration from 0/5 to 4+/5. Histopathology revealed primary leiomyoma. The patient was evaluated with ultrasound abdomen and contrast tomogram of the chest, abdomen and pelvis to rule out other possible lesions in the lung, intestines and uterus.We suggest that leiomyoma should be included in the differential diagnosis of destructive lytic lesions involving the C2 vertebra. Histopathological examination with immunohistochemistry is necessary for the definitive diagnosis. Treatment of choice is surgery with complete removal.

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First report of important causal relationship between the Adamkiewicz artery vasospasm and dorsal root ganglion cell degeneration in spinal subarachnoid hemorrhage: An experimental study using a rabbit model

Osman N Turkmenoglu, Ayhan Kanat, Coskun Yolas, Mehmet Dumlu Aydin, Naci Ezirmik, Cemal Gundogdu

Asian Journal of Neurosurgery 2017 12(1):22-27

Background: The blood supply of the lower spinal cord is heavily dependent on the artery of Adamkiewicz. The goal of this study was to elucidate the effects of lumbar subarachnoid hemorrhage (SAH) on the lumbar 4 dorsal root ganglion (L4DRG) cells secondary to Adamkiewicz artery (AKA) vasospasm. Materials and Methods: This study was conducted on 20 rabbits, which were randomly divided into three groups: Spinal SAH (n = 8), serum saline (SS) (SS; n = 6) and control (n = 6) groups. Experimental spinal SAH was performed. After 20 days, volume values of AKA and neuron density of L4DRG were analyzed. Results: The mean alive neuron density of the L4DRG was 15420 ± 1240/mm3 and degenerated neuron density was 1045 ± 260/mm3 in the control group. Whereas, the density of living and degenerated neurons density were 12930 ± 1060/mm3 and 1365 ± 480/mm3 in serum saline (SS), 9845 ± 1028/mm3 and 4560 ± 1340/mm3 in the SAH group. The mean volume of imaginary AKAs was estimated as 1,250 ± 0,310 mm3 in the control group and 1,030 ± 0,240 mm3 in the SF group and 0,910 ± 0,170 mm3 in SAH group. Volume reduction of the AKAs and neuron density L4DRG were significantly different between the SAH and other two groups (P < 0.05). Conclusion: Decreased volume of the lumen of the artery of Adamkiewicz was observed in animals with SAH compared with controls. Increased degeneration the L4 dorsal root ganglion in animals with SAH was also noted. Our findings will aid in the planning of future experimental studies and determining the clinical relevance on such studies.

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Predictors of visual outcome with transsphenoidal excision of pituitary adenomas having suprasellar extension: A prospective series of 100 cases and brief review of the literature

Amit Kumar Thotakura, Mohana Rao Patibandla, Manas K Panigrahi, Gokul Chowdary Addagada

Asian Journal of Neurosurgery 2017 12(1):1-5

Objective: The aim was to assess the factors influencing the visual outcome following trans-sphenoidal excision of pituitary adenomas. Materials and Methods: One hundred consecutive patients of pituitary adenomas with suprasellar extension (SSE) were operated by trans-sphenoidal approach from July 2003 to December 2006. There were 52 male and 48 female patients with a mean age of 42.47 years. The visual impairment score, which was used to evaluate the visual outcome was produced by adding the scores for visual acuity and visual field defects of each patient (from the tables of the German Ophthalmological Society). The mean diameter, the SSE and the parasellar extension of the lesion were noted in the magnetic resonance imaging study. The average follow-up was 43.5 months. Results: The mean diameter of the tumor was 32.97 mm, and the mean SSE was 14.95 mm. The parasellar extension was present in 27 patients. The vision improved in 61 of the 71 patients (85.91%). The shorter the duration of visual symptoms and smaller the size of the lesion resulted in better visual outcome. The age and the preoperative visual impairment did not show any correlation with the visual outcome. Conclusions: Patients with visual symptoms of <1-year duration (P < 0.01) and adenomas of <36.5 mm diameter (P < 0.009) have better visual outcome.

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Clinical predictors for survival and treatment outcome of high-grade glioma in Prasat Neurological Institute

Raywat Noiphithak, Kullapat Veerasarn

Asian Journal of Neurosurgery 2017 12(1):28-33

Objective: The aim was to identify clinical predictors for survival and examine treatment outcome in patients with high-grade glioma (HGG). Materials and Methods: The authors retrospectively reviewed medical records of patients who was diagnosed HGG between January 2007 and December 2009. Demographic data, radiological data and treatment data of patients were reviewed and analyzed. Results: A total of 100 patients were analyzed. There was no difference in demographic data between Grade III and IV glioma. Patients with HGG had median survival time (MST) 18 months, The MST of patients with Grade III and IV glioma were 26 and 13 months, respectively. In this study, only anaplastic oligoastrocytoma and radiotherapy did impact strongly on survival of patients with HGG. In patients with Grade III and IV glioma, radiotherapy found to have influence on survival. Conclusion: Patients with HGG in Prasat Neurological Institute had short survival resemble to other previous study. The clinical predictors for survival of patients were identified on multivariate analysis.

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Supratentorial intermediate grade meningeal melanocytoma with intratumoral bleed in the background of neurocutaneous melanosis: Report of an unusual case and review of literature

Kuntal Das, Anup Nair, Sushila Jaiswal, Rabi Sahu, Arun Srivastava, Raj Kumar, Anant Mehrotra

Asian Journal of Neurosurgery 2017 12(1):98-102

Primary melanocytic tumours of the central nervous system (CNS) are rare. According to the WHO classification (2007), these tumours include diffuse leptomeningeal melanosis, melanomatosis, melanocytoma, and primary CNS melanoma. Meningeal melanocytoma, most commonly seen in the infratentorial compartment and cervical spinal cord, is a benign primary melanocytic neoplasm. Primary CNS melanoma, on the other hand, represents the malignant end of the spectrum. Intermediate grade melanocytoma is a rare histological subtype of primary meningeal tumours and is characterised by the clinicopathological features between the two extremes. Neurocutaneous melanosis (NCM) is a rare phacomatosis characterised by melanotic lesions on the skin and leptomeninges. Leptomeningeal manifestation in NCM may be observed either in the form of diffuse leptomeningeal melanosis or primary CNS melanoma. Melanocytomas are focal lesions and their association with NCM is extremely rare. In this report, we present an unusual case of NCM accompanied by right frontal intermediate grade melanocytoma with intratumoral bleeding in a 17-year-old boy. A brief literature review is also presented.

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An evaluation of neuroendocrine dysfunction following acute aneurysmal subarachnoid hemorrhage: A prospective study

Awadhesh Kumar Jaiswal, Subhash Yadav, Rabi Narayan Sahu, Anant Mehrotra, Sanjay Behari, Ashok Kumar Mahapatra

Asian Journal of Neurosurgery 2017 12(1):34-36

Objective: The aim was to investigate the incidence and pattern of neuroendocrine changes in cases of acute aneurysmal subarachnoid hemorrhage (SAH). Materials and Methods: Endocrine assessment was performed in 100 consecutive cases of acute aneurysmal SAH presenting within 7 days of ictus. The gonadotropic, somatotrophic, thyrotropic, and corticotrophic axes were evaluated for their possible dysfunction. Results: A total of 100 cases (38 males, 62 females; age range - 17-76 years; mean age - 43.6 years) of acute SAH were studied. The aneurysms were located in the anterior circulation (n = 95) and posterior circulation (n = 5). The most common hormone deficiency was of growth hormone (n = 67), followed by gonadotrophin (n = 50), corticotrophin (n = 49) and thyrotrophin (n = 35). Hyperprolactinemia was noted in 10 cases. One-pituitary hormone axis deficiency was noted in 26 cases while 67 cases had two or more pituitary hormone axes dysfunction. A total of 93 cases had hormonal dysfunction in one or more pituitary hormone axes, and seven cases had no hormonal dysfunction. Conclusions: Endocrine dysfunction occurs in 93% cases of acute SAH and multiple pituitary hormone axes dysfunction occurs in 67% cases. It is suggested that hormonal evaluation should be considered as part of management of acute SAH.

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Alveolar soft part sarcoma with brain metastases

Vinodh Vayara Perumall, Rahmat Harun, Pulivendhan Sellamuthu, Mohd Shariman Md Shah

Asian Journal of Neurosurgery 2017 12(1):112-115

Metastatic tumors are the most common mass lesions in the brain. This case reports a rare form of sarcoma with metastasis to the brain. The appropriate management of a patient with metastatic alveolar soft part sarcoma to the brain is discussed. Author describes a 32-year-old gentleman diagnosed with primary tumor at gluteus and distant metastases at lower lobe of right lung and the brain. Histopathology proves diagnosis as alveolar soft part sarcoma. Craniotomy with excision of brain lesion was done. Repeated magnetic resonance imaging of the brain after 2 months showed rapidly growing new lesions. The next step of management was made by the oncology team as recurrence rate was high and due to multi-systemic involvement. Patient was planned for palliative chemotherapy and to be reassessed later. This case report discusses the appropriate approach to any form of brain metastases and the role of early follow-up especially after surgery for better outcome and choice of post operative management such as radiotherapy or chemotherapy or both for malignant tumors. Based on this report, it was concluded that every brain tumor patient should be frequently monitored even in the outpatient setting as most of them are metastatic and rapidly spreading. The patient should be considered for radiotherapy or chemotherapy or both after surgery if the histopathology result is suggestive of malignancy.

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Outcome after operative intervention for traumatic brain injuries in the elderly

Lai-Fung Li, Wai-Man Lui, Heidi Hay-Tai Wong, Wai-Kei Yuen, Gilberto Ka-Kit Leung

Asian Journal of Neurosurgery 2017 12(1):37-43

Introduction: The management of traumatic brain injuries in the elderly (age ≥ 65 years) is a constant dilemma. The aim of this study is to investigate for factors that may predict outcome of operative treatment in this group of patients. Materials and Methods: A retrospective analysis was conducted on 68 elderly patients who had been operated in a designated center from 2006 to 2010. Patients' age, Glasgow Coma score (GCS), pupillary responses, imaging findings, medical conditions, and the use of anticoagulant/antiplatelet agents on patient outcomes were studied. Results: The overall mortality rate was 55.9%. Older age, abnormal pupillary response, low GCS, the presence of midline shift and cistern obliteration on computerized tomography were associated with poor survival. Patient aged 75-84 with normal bilateral pupillary response still had an overall survival rate of 52.6% and good outcomes (Glasgow outcome score: 4 or 5) in 36.8% of patients. Abnormal pupillary response in at least one eye and preoperative GCS ≤ 12 were associated with very poor prognosis. Conclusions: More advanced age was found to be associated with progressively worse outcome. A subgroup patients aged below 85 would survive and could achieve good clinical outcome. The prognosis of those aged over 85 with moderate or severe head injuries was extremely poor.

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Dissecting intracranial aneurysm in pregnancy: A rare association

Manasi Mehrotra, Anant Mehrotra, Anup Nair, Arun Srivastava, Rabi Narayan Sahu, Mandakini Pradhan, Raj Kumar

Asian Journal of Neurosurgery 2017 12(1):127-130

We report a case of dissecting aneurysm of the right posterior cerebral artery presenting with sudden onset headache and altered behavior during labor. A 26-year-old P1001 with uncomplicated antenatal period, except history of headache off and on since 32 weeks of pregnancy, developed sudden onset headache and altered behavior during 3rd stage of labor. She had vaginal delivery and a live born male baby was delivered with good Apgar score. The CT was suggestive of subarachnoid hemorrhage and DSA was suggestive of dissecting aneurysm of the right P2 segment with hypoplasia of right P1 segment and A1 segment of posterior and anterior cerebral artery, respectively. The patient was managed conservatively. At 4-month follow-up, the patient was doing well. We discuss about the rare association of a dissecting aneurysm and pregnancy, especially dissection of the posterior cerebral artery.

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Unusual site of Rathke's cleft cyst: A case report and review of literature

Vivek Agarwal, Deepak Palande, Vernon Velho, Rachana S Binayke

Asian Journal of Neurosurgery 2017 12(1):44-46

We report an eight years female child of symptomatic giant Rathke's cleft cyst extending from right parasellar, paraventricular region to right fronto-temporo-parietal cortical surface which is an unusual site for Rathke's cyst. MRI Brain scans of patient who presented with diminution of vision in right eye with headache and vomiting revealed a large cystic mass in right parasellar, paraventricular region with peripheral enhancement and midline shift. In this case, we performed the right fronto-temporo-parietal craniotomy with drainage and marsupilization of cyst wall. Histopathologically, it was inflamed Rathke's cleft cyst with focal epithelial metaplasia.

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Intracranial hemorrhage from giant aneurysm in pregnancy: A rare association

Manasi Mehrotra, Anant Mehrotra, Anup Nair, Arun Srivastava, Rabi Narayan Sahu, Mandakini Pradhan, Raj Kumar

Asian Journal of Neurosurgery 2017 12(1):142-144

We report a case of giant aneurysm causing subarachnoid hemorrhage in a pregnant female. A 25-year-old female presented with sudden onset of severe headache and vomiting with altered sensorium and right hemiplegia. On investigation, she had a giant supraclinoid segment internal carotid artery (ICA) aneurysm. She was planned for digital substraction angiography, but during the procedure she deteriorated neurologically and went into spontaneous labor. The baby was a male child with weight of 1.1 kg. She was taken up for surgery and aneurysm was clipped. We discuss the rare occurrence of intracranial hemorrhage in pregnancy due to a giant ICA aneurysm.

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Spontaneous extradural and subgaleal hematoma: A rare neurosurgical crisis of sickle cell disease

Sudhansu S Mishra, Satya B Senapati, Amiya K Gouda, Sanjay K Behera, Ashis Patnaik

Asian Journal of Neurosurgery 2017 12(1):47-50

Extradural hematoma (EDH) in absence of trauma is a rare entity with only few cases reported in literature. The various causes reported include: Vascular malformation of dura, coagulopathies, sinus infection, middle ear or orbital infection, and tumor. Occurrence of spontaneous EDH as a complication of sickle cell disease is even much rarer. We report a case with sickle cell disease who presented with spontaneous extradural and subgaleal hematomas following an episode of vaso-oclusive crisis. He was managed successfully with surgery. The association of epidural hematomas in sickling hemoglobinopathies is reviewed. In all cases, we noticed one episode of sickle cell crisis just before the occurrence of spontaneous EDH. Perhaps this crisis puts an extra demand over the hematopoietic skull tissue disrupting inner and outer skull margins leading to spontaneous EDH and subgaleal hematoma.

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Severe hypotension in transforaminal lumbar interbody fusion surgery: Is it vasovagal or?

Tumul Chowdhury, Harsh Sapra, Sudhir Dubey

Asian Journal of Neurosurgery 2017 12(1):149-150



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Assessment of in vivo experiments: The newly synthesized porphyrin with proper light source enhanced effectiveness of PDT comparing to 5-ALA-mediated PDT

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Publication date: June 2017
Source:Photodiagnosis and Photodynamic Therapy, Volume 18
Author(s): Kamil Jurczyszyn, Marta Woźniak, Krzysztof Symonowicz, Natasza Sprutta, Lechosław Latos-Grażyński, Piotr Ziółkowski, Yurij Ivonyak, Piotr Tuchowski, Witold Trzeciakowski
BackgroundThe search for new photosensitizers for application in photodynamic therapy has quite a long history. In the past, a large number of potent photosensitizers were used in both basic and clinical studies; however, only a few turned out to be effective and safe.MethodsIn the present study, two compounds were used: 5-aminolevulinic acid in two formulations (free and liposomal), and the newly synthesized porphyrin, 5,10,15,20-tetra-p-tolyl-22,24-dithiadibenzocarbaporphyrin, termed DTDB. Two different light sources, a halogen lamp (wavelength 450+/−20nm) and a diode laser (wavelength 450nm), were used to sensitize the compounds. The entire experiment was performed on mice bearing mouse mammary carcinoma, 4T1.ResultsThe results showed that the DTDB-PDT applied by means of a laser proved to be most effective and caused the 83.3% necrosis of treated tumors. The overall effect of laser PDT was more potent than that of the halogen lamp-mediated PDT.ConclusionsIn the present study, we would like to show that modifications of porphyrins lead to an increase in the effectiveness of PDT and that this effect could also be potentiated by using a proper light source.



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Comparison of photoinactivation of T. rubrum by new methylene blue (NMB) and indocyanine green (EmunDo®)

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Publication date: June 2017
Source:Photodiagnosis and Photodynamic Therapy, Volume 18
Author(s): Reza Fekrazad, Arash Poorsattar Bejeh Mir, Mina Kahyaie Aghdam, Vadood Ghasemi Barghi
BackgroundSuperficial mycotic skin infections which are predominantly caused by Trichophyton rubrum, poorly responsd to conventional therapies. A great amount of attention has focused on finding more effective treatments. The current work is aimed to compare the effectiveness of phoinactivation of Trichophyton rubrum by two relatively new photosensitizers: a phenothiazinium dye(New methylene blue) and Indocyanine green (EmunDo®).Materials and methodsA Final inoculum of T. rubrum which corresponded to 106 colony forming unit per milliliter (CFUml−1) was prepared. Antimicrobial Photodynamic treatment (aPDT) of T. rubrum was carried out by either EmunDo® (1mg/ml, Infra-red laser (IRL, λ=810nm, Energy Density 55J/cm2)) or NMB (10μM, Red laser (RL), λ=630nm, Energy Density of 5J/cm2). The suspensions thereafter were subcultured on Sabouraud dextrose agar (SDA) and were counted on due time. based on colony-forming unit per milliliter (CFU/ml).ResultsaPDT with either EmunDo® (E) or NMB (N) considerably diminished the viability of inoculated T. rubrum with respective reduction of 0.64 log and 0.4 log compared to the control group (P<0.001). No significant difference was found between two laser only groups (P=0.79) and two aPDT groups (P=0.73), however significant reduction of T. rubrum in red laser only group (P=0.04) and EmunDo® only group (P=0.04) was found as compared to the control group (P<0.05).ConclusionThe study provides evidence regarding satisfactory photodynamic inactivation of T. rubrum with EmunDo® or NMB as photosensitizers. Irradiation by only red laser source was found superior to only infra-red laser source. Dark toxicity of EmunDo® was more successful than new methylene blue dye.



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A quantitative study of in vivo protoporphyrin IX fluorescence build up during occlusive treatment phases

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Publication date: June 2017
Source:Photodiagnosis and Photodynamic Therapy, Volume 18
Author(s): C Louise Campbell, C Tom A Brown, Kenneth Wood, Ana Gabriela Salvio, Natalia M Inada, Vanderlei S Bagnato, Harry Moseley
BackgroundTopical photodynamic therapy (PDT) is a non-invasive light based therapy used to treat non-melanoma skin cancer (NMSC) and dysplasia. During PDT, the light sensitive molecule protoporphyrin IX (PpIX) is activated, resulting in the production of singlet oxygen, which subsequently leads to cell death. PpIX is metabolised from a topically applied pro-drug and the strong fluorescence signal associated with PpIX can be utilised as an indicator of the amount of PpIX present within the tumour tissue. In this work we measure the build up PpIX during the occlusive treatment phase and investigate how the PpIX production rate is affected by different lesion and patient characteristics.MethodsFluorescence measurements were used to investigate the build up of PpIX within the tumour tissue during the 3h long occlusive treatment prior to irradiation. The study included in vivo measurements of 38 lesions from 38 individual patients. Actinic keratosis (AK) and basal cell carcinoma (BCC) were the lesion types included in this study. The resulting data from the study was analysed using generalised linear mixed effects models.ResultsIt was found that the surface fluorescence signal linearly increased with occlusive treatment time. The predictive models suggest that there is a significant difference in PpIX production between lesion location, however no significant difference is demonstrated between different lesion types, gender and skin type.ConclusionsThe study extends and supports previous knowledge of PpIX production during the occlusive treatment phase.



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Influence of iron oxide nanoparticles (Fe3O4) on erythrocyte photohemolysis via photofrin and Rose Bengal sensitization

Publication date: June 2017
Source:Photodiagnosis and Photodynamic Therapy, Volume 18
Author(s): M-Ali H. Al-Akhras, Khaled Aljarrah, Borhan Albiss, Duaa Al-Khalili
BackgroundIron oxide (Fe3O4) nanoparticles (IO-NP) were recently employed in medical applications as a diagnostic tool and drug carrier. Photofrin (PF) is a photosensitizer that clinically is used in Photodynamic therapy (PDT).Study designThe photosensitivity of PF and Rose Bengal (RB) mixed with (IO-NP) on red blood cells (RBCs) lysis was investigated. Second, Photohemolysis for post-irradiation (delayed) and during irradiation (continuous) with PF, RB and IO-NP combinations at different concentrations was investigated. Third, the photohemolysis rate, relative lysis steepness and power-concentration dependant parameter were evaluated by modeling and fitting the data using Gompertz function and power law.MethodsRBCs were isolated from healthy male human volunteer. Washed cells (7.86×106 cells/mm3) were incubated with PF only or with IO-NP for 45min at 37°C then irradiated to a range of temperatures (4–41°C). CPH results were recorded and evaluated using Gompertz function.ResultsThe relative steepness of the photohemolysis curves was approximately independent on light dose for delayed irradiation. The presence of IO-NP increases the rupturing time for 50% of the RBCs. Photohemolysis rate for delayed irradiation using the power law, led to 1.7 and 2.3 power dependence, respectively, for PF only and PF mixed with IO-NP. The power dependence of continuous irradiation measurements showed inverse proportionality for different concentrations of IO-NP combined with 2μg/ml PF concentration and 1.5μg/ml for RB concentration.ConclusionPhotosensitization of RBC with PF or RB mixed with IO-NP inhibited rupturing erythrocyte membrane and therefore a consideration should be taken against their combination in clinical applications.



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ALA—Photodynamic treatment in Lichen sclerosus—clinical and immunological outcome focusing on the assesment of antinuclear antibodies

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Publication date: June 2017
Source:Photodiagnosis and Photodynamic Therapy, Volume 18
Author(s): Anita Olejek, Iwona Gabriel, Anna Bilska-Janosik, Iwona Kozak-Darmas, Aleksandra Kawczyk-Krupka
BackgroundLichen sclerosus (LS) is a difficult to treat, often relapsing disease with unknown background. Autoimmune diseases also coexist with LS. Over recent years photodynamic therapy (PDT) has been shown to be a noninvasive and successful therapeutic approach for the effective treatment of many conditions. However, the change of immune status of the patients based on ANA antibodies has not been yet reported. Our aim was to observe the clinical response followed by possible changes in autoimmune antibodies levels before and after PDT for LS.Material and MethodsWe enrolled 100 women with Lichen sclerosus with or without a concomitant autoimmune disease. All patients received 10 cycles of PDT (65 treated with DIOMED Light, 35 with PhotoDYN Light). We assessed autoimmune antibodies before and after PDT in addition to the clinical response evaluation.Two-year prospective controlled before-and-after study.ResultsFollowing PDT, patients showed a significant attenuation in symptoms' intensity (itching, pruritus, vulvar discomfort). After therapy 41% of patients had partial response, 51% of patients had no symptoms and 8% had persistent or worsened symptoms. The most frequent autoimmune disease were thyroid disorders, followed by vitiligo and arthritis. 57% patients with an additional autoimmune disease before PDT had ANA antibodies. The mean level of ANA in this group diminished significantly after PDT treatment (261.74 IU/ml before vs. 123.20 IU/ml after treatment).ConclusionBased on our results, we assume that PDT may influence the immune status of patients with Lichen sclerosus.



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Photodynamic therapy enhances the efficacy of gene-directed enzyme prodrug therapy

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Publication date: June 2017
Source:Photodiagnosis and Photodynamic Therapy, Volume 18
Author(s): Catherine Christie, Aftin Pomeroy, Rohit Nair, Kristian Berg, Henry Hirschberg
IntroductionGene-directed enzyme prodrug therapy (GDEPT) employing the cytosine deaminase (CD) gene, which encodes an enzyme that converts the nontoxic agent 5-fluorocytosine (5-FC) into the chemotherapeutic drug 5-fluorouracil (5-FU), has shown promise both in experimental animals and in clinical trials. Nevertheless, with the transfection systems available presently the percentage of tumor cells incorporating the desired gene is usually too low for successful therapy. We have examined the ability of photodynamic therapy (PDT) to enhance the efficacy of the metabolites, converted from 5-FC by CD gene transfected rat glioma cells.MethodsHybrid tumor cell spheroids consisting of CD poitive and CD negative F98 glioma cells in varying ratios were used as in vitro tumor models. PDT was performed with the photosensitizer AlPcS2a and λ=670nm laser irradiance, both before and after confrontation with 5-FC.ResultsPDT increased the toxicity of 5-FU either as pure drug or derived from monolayers of CD positive cells chalanged with 5-FC. PDT in combination with 5-FC resulted in a significantly enhanced inhibition of hybrid spheroid growth compared to non light treated controls. This was the case even at tumor to producer cell ratios as high as 40:1.ConclusionThe results of the present study show that GDEPT and PDT interact in a synergistic manner over a range of prodrug concentration and tumor to transfected cell ratios. The degree of synergy was significant regardless if PDT treatment was given before or after 5-FC administration. The highest degree of interaction was observed though, when PDT was delivered prior to prodrug exposure.



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In silico identification of a therapeutic target for photo-activated disinfection with indocyanine green: Modeling and virtual screening analysis of Arg-gingipain from Porphyromonas gingivalis

Publication date: June 2017
Source:Photodiagnosis and Photodynamic Therapy, Volume 18
Author(s): Maryam Pourhajibagher, Abbas Bahador
BackgroundPorphyromonas gingivalis is a momentous bacterial etiological agent associated with periodontitis, peri-implantitis as well as endodontic infections. The potential advantage of Photo-activated disinfection (PAD) as a promising novel approach is the choice of a suitable target site, specific photosensitizer, and wavelength of light for delivery of the light from source to target. Since Arg-gingipain is a cysteine proteinase that is involved in the virulence of P. gingivalis, it was evaluated as a target site for PAD with indocyanine green (ICG) as a photosensitizer.MethodsIn this study, we used a range of in silico strategies, bioinformatics tools, biological databases, and computer simulation molecular modeling to evaluate the capacity of Arg-gingipain.ResultsThe predicted structure of Arg-gingipain indicated that it is located outside the cell and has nine domains and 17 ligands, including two calcium ions and three sodium ions with positive charges which can be a site of interaction for anionic ICG.ConclusionBased on the results of this study, anionic ICG desires to bind and interact with residues of Arg-gingipain during PAD as a main site to enhance the yield of treatment of endo-periodontal lesions.



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Real-time light dosimetry for intra-cavity photodynamic therapy: Application for pleural mesothelioma treatment

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Publication date: June 2017
Source:Photodiagnosis and Photodynamic Therapy, Volume 18
Author(s): Nacim Betrouni, Camille Munck, Wael Bensoltana, Grégory Baert, Anne-Sophie Dewalle-Vignion, Arnaud Scherpereel, Serge Mordon
Complete and homogeneous illumination of the target is necessary for the success of a photodynamic therapy (PDT) procedure. In most applications, light dosimetry is done using detectors placed at strategic locations of the target. In this study we propose a novel approach based on the combination of light distribution modeling with spatial localization of the light applicator for real time estimation and display of the applied dose on medical images. The feasibility approach is demonstrated for intrapleural PDT of malignant pleural mesothelioma.



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Liposomal delivery of ferrous chlorophyllin: A novel third generation photosensitizer for in vitro PDT of melanoma

Publication date: June 2017
Source:Photodiagnosis and Photodynamic Therapy, Volume 18
Author(s): Iman Gomaa, Aya Sebak, Nagia Afifi, Mahmoud Abdel-Kader
BackgroundCutaneous melanoma (CM) has substantially increased among Caucasian populations in the past few decades. This increased the number of CM deaths throughout the world. Pigmentation of melanoma reduces the efficacy of photodynamic therapy (PDT). Third generation photosensitizers (PSs) are characterized by improved targeting to the diseased tissue and reduced systemic side effects. This study is directed towards synthesis and characterization of liposomes encapsulating sodium ferrous chlorophyllin (Fe-CHL) and assessing its efficacy as a PS in PDT of melanoma.MethodsPhenylthiourea (PTU) was used as a melanin synthesis inhibitor. PDT has been applied on de-pigmented melanoma cells using liposomes-encapsulated Fe-CHL. Cell death mechanisms after PDT were evaluated.ResultsTreatment of melanoma cells with 200μM of PTU for 48h provided 49.9% melanin inhibition without significant cytotoxicity. Transmission electron microscope (TEM) results proved an increase in the cellular uptake of liposomes by increasing incubation period from 6 to 24h via endocytosis with preferential accumulation in the mitochondria and the nucleus. Following de-pigmentation, PDT was applied resulting in LC50 of 18.20 and 1.77μM after 24 and 48h incubation with liposomes-encapsulated Fe-CHL respectively and exposure to 56.2J/cm2 monochromatic red laser of wavelength of 652nm. Mechanism of cell death of Fe-CHL mediated PDT was found to be a combination of both apoptosis and necrosis.ConclusionsLiposomes could be efficiently employed as a potential sustained release delivery system in the Fe-CHL-mediated PDT of de-pigmented melanoma.

Graphical abstract

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Risk factors for overweight and obesity in children aged 2–6 years

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Anonymity and Electronics

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Publication date: Available online 18 March 2017
Source:Academic Radiology
Author(s): Teresa Chapman, Janet R. Reid, Erin E. O'Conner
Rationale and ObjectivesDiagnostic radiology resident assessment has evolved from a traditional oral examination to computerized testing. Teaching faculty struggle to reconcile the differences between traditional teaching methods and residents' new preferences for computerized testing models generated by new examination styles. We aim to summarize the collective experiences of senior residents at three different teaching hospitals who participated in case review sessions using a computer-based, interactive, anonymous teaching tool, rather than the Socratic method.Materials and MethodsFeedback was collected from radiology residents following participation in a senior resident case review session using Nearpod, which allows residents to anonymously respond to the teaching material.ResultsSubjective resident feedback was uniformly enthusiastic. Ninety percent of residents favor a case-based board review incorporating multiple-choice questions, and 94% favor an anonymous response system.ConclusionsNearpod allows for inclusion of multiple-choice questions while also providing direct feedback to the teaching faculty, helping to direct the instruction and clarify residents' gaps in knowledge before the Core Examination.



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The rationale of indoleamine 2,3-dioxygenase inhibition for cancer therapy

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Publication date: May 2017
Source:European Journal of Cancer, Volume 76
Author(s): Lieve Brochez, Ines Chevolet, Vibeke Kruse
Indoleamine 2,3-dioxygenase (IDO, also referred to as IDO1) has been demonstrated to be a normal endogenous mechanism of acquired peripheral immune tolerance in vivo.In the field of oncology, IDO expression and/or activity has been observed in several cancer types and has usually been associated with negative prognostic factors and worse outcome measures.This manuscript reviews current available data on the role of IDO in cancer and the current results obtained with IDO inhibition, both in animal models and in phase 1 and 2 clinical trials in humans. Preliminary results with IDO inhibitors, usually combined with other anti-cancer drugs, seem encouraging. Further studies are needed to clarify the conditions in which IDO inhibitors can be of value as an anti-cancer strategy. In addition, further research should address whether the expression of IDO in tissue or blood can be a marker to select patients who can benefit most from IDO inhibition.



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Biological mechanisms of immune escape and implications for immunotherapy in head and neck squamous cell carcinoma

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Publication date: May 2017
Source:European Journal of Cancer, Volume 76
Author(s): Jennifer D. Moy, Jessica M. Moskovitz, Robert L. Ferris
Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with high morbidity and mortality. Despite advances in cytotoxic therapies and surgical techniques, overall survival (OS) has not improved over the past few decades. This emphasises the need for intense investigation into novel therapies with good tumour control and minimal toxicity. Cancer immunotherapy has led this endeavour, attempting to improve tumour recognition and expand immune responses against tumour cells. While various forms of HNSCC immunotherapy are in preclinical trials, the most promising direction thus far has been with monoclonal antibodies (mAbs), targeting growth factor and immune checkpoint receptors. Preclinical and early phase trials have shown unprecedented efficacy with minimal adverse effects. This article will review biological mechanisms of immune escape and implications for immunotherapy in HNSCC.



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Impaired quality of life in patients with treated acromegaly despite long-term biochemically stable disease: results from a 5-year prospective study

Abstract

Objective

Patients with acromegaly demonstrate impaired quality of life (QoL), but data on long-term QoL changes in treated acromegaly are limited. This study evaluates and identifies factors that influence QoL in patients with long-term biochemical remission.

Design

The study consists of a cross-sectional arm comparing QoL between patients with treated and controlled acromegaly and healthy controls; and a longitudinal arm assessing QoL changes in patients with biochemically stable disease during 5.7±0.6yrs of follow-up.

Patients

58 patients and 116 matched controls were recruited for the cross-sectional arm; 28 patients completed the longitudinal arm.

Measurements

Three generic questionnaires [Psychological General Well-Being Schedule (PGWBS), 36-item Short-Form (SF-36), EuroQoL (EQ-5D)] and the disease-specific acromegaly QoL questionnaire (AcroQoL) were applied.

Results

QoL assessment was performed 11.6±8.2yrs following diagnosis and treatment of acromegaly. Patients with treated acromegaly had lower QoL scores compared with controls in all questionnaires with the exception of the PGWBS "Anxiety" subscale. The AcroQoL "Appearance" subscale and the "physical function" subscales of the remaining questionnaires were the most underscored domains. No difference in the total and subscale scores of all questionnaires was observed between baseline and follow-up, with the exception of the SF-36 "Physical Function", where a decline was found (58.5±24.7% vs. 43.1±31.1%; p=0.002). However, after adjusting for covariates, no significant change in any of the QoL scores was seen. Duration of IGF-1/GH control was positively correlated with QoL scores in most questionnaires at baseline, whereas use of GH lowering therapy at the time of QoL assessment was a negative predictive factor of QoL.

Conclusions

Patients with biochemically controlled acromegaly demonstrate impaired QoL, which persists despite long-term disease control. This primarily consists of impaired physical function and secondly of impaired psycho-social well-being. Duration of biochemical disease control and current use of GH lowering therapy were the predominant factors determining patients' QoL.

This article is protected by copyright. All rights reserved.



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The effects of DASH diet on weight loss, anti-Müllerian hormone and metabolic profiles in women with polycystic ovary syndrome: a randomized clinical trial

Summary

Objective

This study was designed to evaluate the effects of the Dietary Approaches to Stop Hypertension (DASH diet) on weight loss, anti-Müllerian hormone (AMH) and metabolic profiles in women with polycystic ovary syndrome (PCOS).

Design, Patients and Measurements

A randomized controlled clinical trial was conducted among 60 overweight or obese patients with PCOS. Patients were randomly assigned to receive either low-calorie DASH (N=30) or control diet (N=30) for 12 weeks. The DASH and control diets were consisted of 52-55% carbohydrates, 16-18% proteins and 30% total fats; however, the DASH diet was designed to be rich in fruits, vegetables, whole grains, low-fat dairy products, cholesterol and refined grains. Both diets were equicaloric.

Results

Adherence to the DASH diet, compared to the control diet, resulted in a significant decrease in BMI (-1.6±0.5 vs. -1.2±0.7 kg/m2, P=0.02). Significant decreases in AMH (-1.1±3.1 vs. +0.3±0.7 ng/mL, P=0.01), insulin (-25.2±51.0 vs. -1.2±28.8 pmol/L, P=0.02), homeostasis model of assessment-estimated insulin resistance (-0.9±2.0 vs. -0.1±1.0, P=0.02), free androgen index (FAI) (-0.03±0.09 vs. +0.06±0.21, P=0.02) and malondialdehyde (MDA) levels (-0.5±0.4 vs. +0.2±0.3 μmol/L, P<0.001), and significant increases in quantitative insulin sensitivity check index (+0.01±0.03 vs. -0.004±0.01, P=0.02), sex hormone-binding globulin (SHBG) (+3.7±8.5 vs. -1.5±7.2 nmol/L, P=0.01) and nitric oxide (NO) (+9.0±4.9 vs. +0.6±2.3 μmol/L, P<0.001) were also seen in the DASH group compared with the control group .

Conclusions

Adherence to the DASH diet for 12 weeks among PCOS women had beneficial effects on BMI, AMH, insulin metabolism, SHBG, FAI, NO and MDA levels.

This article is protected by copyright. All rights reserved.



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Biological predictors of radiosensitivity in head and neck squamous cell carcinoma

Abstract

Objectives

The aim of this study is to investigate the influence of prognostic biomarkers on radiosensitivity and survival of advanced head and neck squamous cell carcinomas treated by primary (chemo)radiation.

Material and methods

The clinicopathological data and immunohistochemical staining of p16, c-Met, survivin, PD-1, and PD-L1 of 82 primarily (chemo)irradiated patients with head and neck squamous cell carcinoma were analyzed. Associations with local and locoregional radiation response, overall survival (OS), disease-free (DFS), and disease-specific survival (DSS) were assessed.

Results

Complete tumor response was associated with increased patient age (p = 0.007), N0-status (p = 0.022), M0-status (p = 0.007), and p16-positivity (p = 0.022). High PD-L1 was associated with M0-status (p = 0.026) and indicated tumor response to irradiation (p = 0.057); survivin expression showed higher rates of response failure (p = 0.073). Low PD-1 was associated with increased T-stage (p = 0.029) and local recurrence (p = 0.014). High PD-1 was strongly correlated with PD-L1-positive tumor infiltrating lymphocytes (p < 0.001). Low PD-L1 showed a significant correlation with high c-Met expression (p = 0.01). Significant predictors for unfavorable univariate survival were incomplete tumor response (DSS, p < 0.001), single radiotherapy (DSS, p = 0.002), M1-status (DSS, p < 0.001), decreased radiation dose (DSS, p = 0.014), high survivin (DSS, p = 0.045), and high c-Met (OS, p < 0.05). Survivin and c-Met also showed prognostic significance in multivariate survival analysis.

Conclusions

P16 and PD-L1 indicate radiosensitivity, whereas survivin and c-Met implicate radioresistance in primarily (chemo)irradiated head and neck squamous cell carcinomas. The role of the PD-1/PD-L1 immune checkpoints in radiation response and survival merits further investigation.

Clinical relevance

The findings may improve patient-specific therapy according to individual tumor characteristics.



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Exogenous application of plant growth regulators (PGRs) induces chilling tolerance in short-duration hybrid maize

Abstract

Chilling stress hampers the optimal performance of maize under field conditions precipitously by inducing oxidative stress. To confer the damaging effects of chilling stress, the present study aimed to investigate the effects of some natural and synthetic plant growth regulators, i.e., salicylic acid (SA), thiourea (TU), sorghum water extract (SWE), and moringa leaf extract (MLE) on chilling stress tolerance in autumn maize hybrid. Foliar application of growth regulators at low concentrations was carried out at six leaf (V6) and tasseling stages. An increase in crop growth rate (CGR), leaf area index (LAI), leaf area duration (LAD), plant height (PH), grain yield (GY), and total dry matter accumulation (TDM) was observed in exogenously applied plants as compared to control. In addition, improved physio-biochemical, phenological, and grain nutritional quality attributes were noticed in foliar-treated maize plots as compared to non-treated ones. SA-treated plants reduced 20% electrolyte leakage in cell membrane against control. MLE and SA were proved best in improving total phenolic, relative water (19–23%), and chlorophyll contents among other applications. A similar trend was found for photosynthetic and transpiration rates, whereas MLE and SWE were found better in improving CGR, LAI, LAD, TDM, PH, GY, grains per cob, 1000 grain weight, and biological yield among all treatments including control. TU and MLE have significantly reduced the duration in phenological events of crop at the reproductive stage. MLE, TU, and SA also improved the grain protein, oil, and starch contents as compared to control. Enhanced crop water productivity was also observed in MLE-treated plants. Economic analysis suggested that MLE and SA applications were more economical in inducing chilling stress tolerance under field conditions. Although eliciting behavior of all growth regulators improved morpho-physiological attributes against suboptimal temperature stress conditions, MLE and SA acted as leading agents which proved to be better stress alleviators by improving plant physio-biochemical attributes and maize growth.



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Toxic elements and bio-metals in Cantharellus mushrooms from Poland and China

Abstract

Data on multi-trace element composition and content relationships have been obtained for Cantharellus cibarius, C. tubaeformis, and C. minor mushrooms from Poland and China by inductive coupled plasma–dynamic reaction cell–mass spectroscopy. There is no previous data published on As, Li, V, Tl, and U in chanterelles from Poland and on Ba, Co, Cr, Ni, Rb, and Sr in chanterelles from China. The results implied a role of the soil background geochemistry at the collection site with the occurrence of Ag, As, Ba, Cr, Cs, Li, Mn, Pb, Rb, Sr, U, and V in the fruiting bodies. Both geogenic Cd and anthropogenic Cd can contribute in load of this element in chanterelles from the Świetokrzyskie Mts. region in Poland, while geogenic source can be highly dominant in the background areas of Yunnan. An essentiality of Cu and Zn and effort by mushroom to maintain their physiological regulation could be reflected by data for Cantharellus mushrooms from both regions of the world, but its geogenic source (and possibly anthropogenic) can matter also in the region of the Świetokrzyskie Mountains in Poland. The elements Co, Ni, and Tl were at the same order of magnitude in contents in C. cibarius in Poland and Yunnan, China. C. tubaeformis differed from C. cibarius by a lower content of correlated Co, Ni, and Zn. Soil which is polymetallic and highly weathered in Yunnan can be suggested as a natural geogenic source of greater concentrations of As, Ba, Cr, Li, Pb, Sr, U, and V in the chanterelles there while lower of Mn and Rb, when related to chanterelles in Poland. A difference in Cs content between the sites can be attributed as an effect of the 137Cs release from the Chernobyl accident, in which Poland was much more affected than Yunnan, where deposition was negligible.



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Biodegradation of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) by Phanerochaete chrysosporium in the presence of Cd 2+

Abstract

Aerobic biodegradation of 2,2′,4,4′-tetrabrominated diphenyl ether (BDE-47) by Phanerochaete chrysosporium in the presence of Cd2+ was investigated in this study. The results showed that P. chrysosporium could effectively degrade BDE-47, and its extracellular enzyme played an important role in the process of decomposition. BDE-47 biodegradation by fungi was more tolerant than extracellular enzyme in the presence of Cd2+. Also, both of the activity of two typical enzymes, MnP and LiP, descended with ascended Cd2+ concentration. Based on the four mono-hydroxylated PBDEs (5-OH-BDE-47, 4′-OH-BDE-17, 6-OH-BDE-47, and 2′-OH-BDE-28) and two bromophenols (2,4-DBP, 4-BP) detected, three possible degradation pathways were proposed, inferring that BDE-47 was more easily to transform via hydroxylation. With addition of Cd2+, the types of degradation products did not change, merely a variation of the content of these products observed. Meanwhile, the major metabolites of BDE-47, bromophenol compounds, have been found to be transformed or even mineralized by P. chrysosporium quickly, which also helped better explain why the amounts of BDE-47 decomposed did not match with that of the metabolites detected.



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Changes and relations of photosynthesis and iron cycling in anoxic paddy soil amended with high concentrations of sulfate

Abstract

Sulfate contamination is an increasingly serious environmental problem related to microbial reduction processes in anoxic paddy soil. This study revealed the changes and interrelations of ferric iron [Fe(III)] reduction, ferrous iron [Fe(II)] oxidation, and oxygenic photosynthesis in an anoxic paddy soil (Fe-accumuli-Stagnic Anthrosols) amended with a range of high sulfate concentrations. Soil slurries mixed with 0 (control), 50, 100, 200, and 400 mmol kg−1 Na2SO4 were incubated anaerobically under dark and light conditions. The changes in chlorophyll a (Chl a), Fe(II), pH levels, and the chlorophyll absorption spectrum were determined over a 42-day period. Fe(II) concentrations increased with the addition of sulfate under dark conditions, while Fe(III) reduction potential was enhanced by increasing sulfate addition. The effect of light on Fe(II) concentration was observed after 16 days of incubation, when Fe(II) started to decrease markedly in the control. The decrease in Fe(II) slowed with increasing sulfate addition. The concentrations of Chl a increased in all treatments after 16 days of incubation under light conditions. There was a reduction in Chl a accumulation with increasing sulfate at the same incubation time. The absorption peaks of chlorophyll remained shorter than the 700-nm wavelength throughout the incubation period. The pH of all treatments decreased in the first week and then increased thereafter. The pH increased with sulfate addition and light conditions. In conclusion, contamination with high concentrations of sulfate could accelerate Fe(III) reduction while inhibiting oxygenic photosynthesis, which correspondingly slows chemical Fe(II) oxidation in an anoxic paddy soil.



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Nitrogen removal and microbial community shift in an aerobic denitrification reactor bioaugmented with a Pseudomonas strain for coal-based ethylene glycol industry wastewater treatment

Abstract

An aerobic denitrification system, initially bioaugmented with Pseudomonas strain T13, was established to treat coal-based ethylene glycol industry wastewater, which contained 3219 ± 86 mg/L total nitrogen (TN) and 1978 ± 14 mg/L NO3-N. In the current study, a stable denitrification efficiency of 53.7 ± 4.7% and nitrite removal efficiency of 40.1 ± 2.7% were achieved at different diluted influent concentrations. Toxicity evaluation showed that a lower toxicity of effluent was achieved when industry wastewater was treated by stuffing biofilm communities compared to suspended communities. Relatively high TN removal (~50%) and chemical oxygen demand removal percentages (>65%) were obtained when the influent concentration was controlled at below 50% of the raw industry wastewater. However, a further increased concentration led to a 20–30% decrease in nitrate and nitrite removal. Microbial network evaluation showed that a reduction in Pseudomonas abundance was induced during the succession of the microbial community. The napA gene analysis indicated that the decrease in nitrate and nitrite removal happened when abundance of Pseudomonas was reduced to less than 10% of the overall stuffing biofilm communities. Meanwhile, other denitrifying bacteria, such as Paracoccus, Brevundimonas, and Brucella, were subsequently enriched through symbiosis in the whole microbial network.



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Treatment of municipal wastewater in full-scale on-site sand filter reduces BOD efficiently but does not reach requirements for nitrogen and phosphorus removal

Abstract

A traditional sand filter for treatment of household wastewater was constructed in the fall of 2012 at Biolinja 12, Turku, Finland. Construction work was led and monitored by an authorized wastewater treatment consultant. The filter was placed on a field bordered by open ditches from all sides in order to collect excess rain and snowmelt waters. The filter was constructed and insulated from the environment so that all outflowing water was accounted for. Untreated, mainly municipal, wastewater from Varissuo suburb was pumped from a sewer separately via three septic tanks (volume = 1 m3 each) into the filters. Normally, wastewater was distributed to ground filters automatically according to pre-programmed schedule. Initially, the daily flow was 1200 L day−1 to reflect the average organic load of a household of five persons (load: ca 237 g day−1 BOD; 73 g day−1 total N; and 10.4 g day−1 total P). Later in the test, the flow rate was decreased first to 900 and then to 600 L day−1 to better reflect the average volume produced by five persons. Volumes of inlet wastewater as well as treated water were monitored by magnetic flow meters. Samples were withdrawn from the inlet water, from the water entering the filters after the third septic tank, and from the outflowing water. After an initial adaption time, the reductions in BOD and chemical oxygen demand were constantly between 92 and 98%, showing that the biological degradation process in the filters functioned optimally and clearly comply with the national and EU standards. The reduction in total nitrogen and total phosphorus, however, reached required levels only during the first months of testing, apparently when buildup of microbial biomass was still ongoing. After this initial period of 3 months showing satisfactory reduction levels, the reduction of total nitrogen varied between 5 and 25% and total phosphorus mostly between 50 and 65%. Nitrification was efficient in the filter, but as indicated by high nitrate levels and poor nitrogen reductions, denitrification was inefficient or absent. During the winter period, the temperature in the filter dropped to near freezing, but at all time points, the flow of water was unaffected by freezing. During snowmelt and heavy rain, occasional flooding was observed. Such situations may lead to dilution rather than purification of the wastewater. In conclusion, the sand filter tested worked well for reduction of the organic load in municipal wastewater but failed to sufficiently reduce nitrogen and phosphorus levels.



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The influence of TNF-α and Ang II on the proliferation, migration and invasion of HepG2 cells by regulating the expression of GRK2

Abstract

Purpose

Hepatocellular carcinoma (HCC) is a common digestive system malignancy that is associated with a poor prognosis. This study researched the interaction of tumor necrosis factor-α (TNF-α) and angiotensin II (Ang II) in HCC cells proliferation, migration and invasion and examined their influence on the expression of G protein-coupled receptor kinase 2 (GRK2) and relevant receptors.

Methods

Cell Counting Kit-8 and Transwell assays were performed to evaluate the effects of TNF-α and Ang II on HepG2 cells proliferation, migration and invasion. Flow cytometry was used to investigate the expression of tumor necrosis factor receptor 1 (TNFR1), angiotensin II type 1 (AT1R) and type 2 receptors (AT2R) on the surface of HepG2 cells. Additionally, Western blot was performed to assess the modulation of GRK2 expression by TNF-α and Ang II in HepG2 cells. Meanwhile, GRK2 siRNA-transfected HepG2 cells were used to confirm the effects of GRK2, TNF-α and Ang II on the proliferation, migration and invasion of GRK2-knockdown HCC cells. Finally, the expression of TNF-α, Ang II, TNFR1, AT1R, AT2R and GRK2 proteins in HCC, tumor-adjacent and normal liver tissues were tested by immunohistochemistry.

Results

The data demonstrated that TNF-α and Ang II can enhance the proliferation, migration and invasion of HepG2 cells through suppressing GRK2 expression but that the two reagents combined did not have synergistic effects. Moreover,overexpression of TNFR1 and AT1R perhaps promoted the formation and progression of HCC, while high AT2R expression had the opposite effect.

Conclusions

This study provides new ideas for the prevention and treatment of HCC by researching the interaction and probable mechanism of different bioactive factors associated with HCC.



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Inhibition of GOT1 sensitizes colorectal cancer cells to 5-fluorouracil

Abstract

Purpose

Almost all colorectal cancer (CRC) cell lines are known to overexpress aspartate aminotransferase (GOT1), which potentially regulates the intracellular levels of reactive oxygen species (ROS) via the production of NADPH, and supports tumor growth. In our study, the role of GOT1 in the anticancer efficacy of 5-fluorouracil (5-FU) was examined.

Methods

HCT116, SW480, and HT-29 cells were transfected with lentiviral vectors expressing short hairpin RNA (shRNA) against GOT1. Following 5-FU treatment, cellular proliferation was evaluated, the NADP+/NADPH ratio was monitored, ROS was measured, and intracellular levels of glutamine (Gln), Aspartate (Asp), oxaloacetate (OAA), malate, and pyruvate were investigated using liquid chromatography–mass spectrometry (LC-MS). A CRC subcutaneous tumor model was performed to determine the impact of GOT1 inhibition on 5-FU efficacy in vivo.

Results

In response to 5-FU administration, CRC cells undergo metabolic adaptation, resulting in increased glutamine flux for the synthesis of aspartate. GOT1 is responsible for the conversion of glutamine-derived aspartate into OAA, which subsequently can be converted into malate and pyruvate. The GOT1-mediated metabolic process is able to maintain the NADP+/NADPH ratio, which counteracts 5-FU-induced oxidative stress. Inhibition of GOT1 impaired the defense against 5-FU-induced ROS, thereby sensitizing cells to 5-FU. The importance of GOT1 in supporting tumor growth during 5-FU treatment was also indicated in an in vivo tumor model of CRC.

Conclusion

These findings show that GOT1 could serve as a promising target for increasing the anticancer efficacy of the conventional therapy in patients with CRC.



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