Publication date: Available online 27 December 2016
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Chien-Ho Wang, Chang-Yo Yang, Reyin Lien, Shih-Ming Chu, Jen-Fu Hsu, Ren-Huei Fu, Ming-Chou Chiang
BackgroundAlthough we've made big strides in perinatal and neonatal care, auditory handicap remains a serious complication in those who were born very premature.ObjectivesThe aim was to determine the prevalence and analyze possible risk factors of hearing impairment in very-low-birth-weight (VLBW) infants.Materials and MethodsThis was a retrospective study by reviewing medical records of all VLBW infants (BW ≤ 1500 g) admitted to NICU of Chang Gung Children's Hospital over 2 years period from Jan. 2010 to 2011. Brainstem auditory evoked potentials (BAEP) hearing screening was performed at 3 months postnatal corrective age and repeated if failed the 1st time, then refer to ENT doctor if BAEP confirmed abnormal. All VLBW infants examined for hearing impairment were included and data were retrieved retrospectively and analyzed for neonatal risk factors using logistic regression.ResultsOver the period, 309 VLBW infants were screened. Prevalence of uni- or bilateral hearing impairment was 3.9% (12/309; 95% CI 2.6-4.1). The mean corrective age on diagnosed of hearing impairment was 2.9±1.1 (range 1-5) months. Mean gestational age was 27.9 weeks (SD 1.4) and mean birth weight was 1028 g (SD 180). By univariant analysis for hearing impairment, severe birth asphyxia, craniofacial anomalies, ventilator dependence, patent ductus arteriosus ligation, and use of postnatal ototoxins yielded good prediction of hearing impairment in this population. However, using multivariate analysis revealed that the only independent risk factors for hearing impairment were ototoxins (OR: 3.62; CI: 1.67-7.82), PDA ligation (OR: 4.96; CI: 2.34-10.52) , craniofacial anomalies (OR: 3.42; CI: 1.70-6.88)and assisted prolonged use of oxygen at gestational age of >36 weeks (OR: 5.94; CI: 2.61-13.54).ConclusionThe incidence of hearing impairment among VLBW infants was 3.9%. Prolonged supplemental oxygen use is a marker for predicting hearing impairment; this requires detailed analysis of the pathophysiologic features, to reduce the prevalence of hearing impairment.
http://ift.tt/2i63xxo
Τρίτη 27 Δεκεμβρίου 2016
Prevalence and Independent Risk Factors for Hearing Impairment Among Very Low Birth Weight Infants
Carcinoid-Like/Labyrinthine Pattern in Sebaceous Neoplasms Represents a Sebaceous Mantle Phenotype: Immunohistochemical Analysis of Aberrant Vimentin Expression and Cytokeratin 20-Positive Merkel Cell Distribution.
http://ift.tt/2ipNQPx
Altered Expression of Toll-like Receptors in Human Oral Epithelium in Oral Lichenoid Reactions.
http://ift.tt/2ig3X4M
Differentiating Intralymphatic Histiocytosis, Intravascular Histiocytosis, and Subtypes of Reactive Angioendotheliomatosis: Review of Clinical and Histologic Features of All Cases Reported to Date.
http://ift.tt/2ipOJYr
m-Health Self-Management Program for the Smartphone Generation
http://ift.tt/2i6bToM
Amplification, Auditory Training for Hearing Aid, Cochlear Implant Users
http://ift.tt/2i6gSWy
Smartphone-based National Hearing Test Launched in South Africa
http://ift.tt/2i65Gt1
Effects of gait training with body weight support on a treadmill vs. overground for individuals with stroke
Publication date: Available online 27 December 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Gabriela L. Gama, Melissa L. Celestino, José A. Barela, Larry Forrester, Jill Whitall, Ana M.F. Barela
ObjectiveTo investigate the effects of gait training with body weight support on a treadmill vs. overground in individuals with chronic stroke.DesignRandomized controlled trial.SettingUniversity research laboratoryParticipantsTwenty-eight individuals with chronic stroke (> 6 months).InterventionsParticipants were randomly assigned to receive gait training with BWS on a treadmill (n=14) or overground (n=14) three times a week for six weeks.Main Outcome MeasuresOverground gait speed, 6-minute walk test, motor domain of the functional independence measure, lower extremity domain of Fugl-Meyer movement assessment, step length, step-length symmetry ratio and single limb support duration. Measurements were obtained at baseline (T0), immediately after (T1) and six weeks after (T2) the training session.ResultsAt T1, both groups improved in all outcome measures except paretic step-length and step-symmetry, which were only improved in the overground group (p=0.01 and p=0.01 respectively). At T2, all improvements remained and the treadmill group also improved paretic step length (p<0.001) but not step-symmetry (p>0.05).ConclusionsIndividuals with chronic stroke equally improve gait speed and other gait parameters after 18 sessions of BWS gait training on either treadmill or overground. Only the overground group improved step symmetry, suggesting a role for integrating overground walking into BWS interventions post-stroke.
http://ift.tt/2iCy5rB
Validation of the QuickDASH and DASH in Patients with Distal Radius Fractures through Agreement Analysis
Publication date: Available online 27 December 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Philemon Tsang, David Walton, Ruby Grewal, Joy MacDermid
ObjectiveTo examine the agreement of scores between the Disability of Arm, Shoulder and Hand (DASH) and QuickDASH Questionnaires in patients with distal radius fractures (DRF) and their score's concurrent validity with PRWE scores.DesignValidity StudySettingHand and upper limb clinicParticipantsOne hundred and seventy-seven patients with Distal Radius Fractures over the age of 18 were included in this study.InterventionsN/AMain Outcome MeasuresMeasurements of the DASH, QuickDASH, and Patient Reported Wrist Evaluation (PRWE) were taken at baseline and 1-year follow-up. QuickDASH scores were extracted from the DASH scores. Agreement analysis of the DASH and QuickDASH were evaluated using Bland-Altman's technique. Item difficultly analysis was performed to examine the distribution of QuickDASH items amongst DASH items. Responsiveness of the DASH, QuickDASH, and PRWE were also evaluated by calculating standardized response means.ResultsQuickDASH scores were higher than DASH scores, particularly at baseline. A mean difference of 3.8 and 1.2 points were observed at baseline and 1-year follow-up, respectively. The limits of agreement (LOA) were wide at baseline with a range of 24.8 points at baseline, but decreased to 12.5 points at 1-year follow-up. Item difficulty analysis revealed that QuickDASH items were not evenly distributed at baseline. Finally, the responsiveness of the DASH, QuickDASH and PRWE were similar from baseline to 1-year follow-up (standardized response mean of 2.13, 2.17, and 2.19, respectively).ConclusionWhen changing from the DASH to the QuickDASH in the context of DRF, a systematic bias of higher scores on the QuickDASH should be considered by the user. However, the QuickDASH still demonstrated good concurrent validity and responsiveness.
http://ift.tt/2hmNPdl
Qualitative Development of a Discrete Choice Experiment for Physical Activity Interventions to Improve Knee Osteoarthritis
Publication date: Available online 27 December 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Daniel Pinto, Margaret Danilovich, Paul Hansen, Daniel J. Finn, Rowland W. Chang, Jane L. Holl, Allen W. Heinemann, Ulf Bockenholt
ObjectiveTo describe the qualitative process used to develop attributes and attribute levels for inclusion in a discrete choice experiments (DCE) for older adult physical activity interventions.DesignFive focus groups (a total of 41 participants) were conducted, grounded in the Health Action Process Approach framework. Discussion emphasized identification and prioritization attributes for a DCE on physical activity. Semi-structured interviews (n=6) investigated attribute levels and lay-language for the DCE. A focus group with physical activity researchers and health care providers was the final stakeholder group used to establish a comprehensive approach for the generation of attributes and levels. A DCE pilot test was then conducted with individuals of the target patient population. All transcripts were analyzed using a constant comparative approach.SettingGeneral community and university-based research settingParticipantsVolunteers with age greater than 45 years and knee pain, aches or stiffness for at least one month over the previous 12 months.InterventionsNot applicable.Main outcome measuresInterview guides, attributes, attribute levels, discrete choice experiment.ResultsThe most influential identified attributes for physical activity were time, effort, cost, convenience, enjoyment, and health benefits. Each attribute had three levels that were understandable in the pilot test of the DCE.ConclusionsThe identification of six physical activity attributes that are most salient to adults with knee osteoarthritis resulted from a systematic qualitative process including attribute-ranking exercises. A DCE will provide insight into the relative importance of these attributes for participating in physical activity, which can guide intervention development.
http://ift.tt/2hvssLM
Relationship between subacromial bursitis on ultrasonography and efficacy of subacromial corticosteroid injection in rotator cuff disease: a prospective comparison study
Publication date: Available online 27 December 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Doo-Hyung Lee, Ji Yeon Hong, Michael Young Lee, Kyu-Sung Kwack, Seung-Hyun Yoon
ObjectiveTo evaluate the correlations between subacromial bursitis (bursal thickening and effusion) on ultrasonography and its response to subacromial corticosteroid injection in rotator cuff disease patients.DesignProspective, longitudinal comparison study.SettingUniversity-affiliated tertiary care hospital.ParticipantsPatients with rotator cuff disease (N=69) were classified into three groups based on ultrasonographic findings; (1) normal bursa group (group 1, n=23): bursa and effusion thickness <1 mm, (2) bursa thickening group (group 2, n=22): bursa thickness >2 mm and effusion thickness <1 mm, (3) bursa effusion group (group 3, n=24): bursa thickness <1 mm and effusion thickness >2 mm.InterventionA single subacromial injection with 20 mg of triamcinolone acetonide.Main Outcome Measures: Visual analog scale (VAS) of the shoulder pain, Shoulder Disability Questionnaire (SDQ), angles of active shoulder range of motion (flexion, abduction, external rotation, and internal rotation), and bursa and effusion thickness at pre-treatment and post-treatment at week 8.ResultsThere were no significant differences between the 3 groups in demographic characteristics pre-treatment. Groups 2 and 3 showed a significant difference compared to group 1 in changes of VAS and abduction; group 3 showed a significant difference compared to group 1 in changes of SDQ, internal rotation and external rotation; and all groups showed significant differences when compared to each other (1 and 3, 2 and 3, and 1 and 2) in changes of thickness.ConclusionA patient with ultrasonographic observation of subacromial bursitis, instead of normal bursa, can expect better outcome with subacromial corticosteroid injection. Therefore, we recommend a careful selection of patients using ultrasonography prior to injection.
http://ift.tt/2iCFEyK
qSOFA should replace SIRS as the screening tool for sepsis
No description available
http://ift.tt/2i5UNre
qSOFA should replace SIRS as the screening tool for sepsis
No description available
http://ift.tt/2i5UNre
qSOFA should replace SIRS as the screening tool for sepsis
No description available
http://ift.tt/2i5UNre
qSOFA should replace SIRS as the screening tool for sepsis
No description available
http://ift.tt/2i5UNre
qSOFA should replace SIRS as the screening tool for sepsis
No description available
http://ift.tt/2i5UNre
qSOFA should replace SIRS as the screening tool for sepsis
No description available
http://ift.tt/2i5UNre
Early Pregnancy Thyroid Function Test Abnormalities in Biobank Sera from Women Clinically Diagnosed with Thyroid Dysfunction Before or After Pregnancy
http://ift.tt/2hrSU7p
Fusion Oncogenes Are the Main Genetic Events Found in Sporadic Papillary Thyroid Carcinomas from Children
http://ift.tt/2icBY3B
Elevated Microsatellite Alterations at Selected Tetranucleotide Repeats (EMAST) and Microsatellite Instability in Patients with Colorectal Cancer and Its Clinical Features
Purpose: Recently, a different type of microsatellite instability (MSI) instability designated 'elevated microsatellite alterations at selected tetranucleotide repeats' (EMAST) has been reported in several neoplasms, but its clinical implications remain unclear. We aimed to determine the relationships among EMAST, MSI and clinicopathologic characteristics, including oncologic outcomes, in colorectal cancer (CRC). <p></p> Materials and Methods: We evaluated 100 sporadic CRC cases subjected to surgery using five markers (MYCL1, D9S242, D20S85, D8S321, and D20S82) for EMAST and the Bethesda panel for MSI status. Immunohistochemical detection of hMSH3, c-erbB2, EGFR and thymidylate synthase was performed. Clinical characteristics and prognostic relevance were assessed. <p></p> Results: We identified 22 EMAST-positive tumors (22.0%) and 32 MSI-high (MSI-H) tumors (32.0%). EMAST was more frequent in colon cancer than rectal cancer (p=0.033), and associated with MSI-H phenotype (p<0.001), low expression of hMSH3 (p=0.004), and overexpression of thymidylate synthase (p=0.006). Among the 38 MSI-L tumors, only one (4.5%) showed EMAST. Long-term oncologic results in terms of overall and disease-free survival were similar between EMAST and non-EMAST tumors. <p></p> Conclusion: EMAST is more closely related to MSI-H than MSI-L or MSS status. The clinical and molecular characteristics of EMAST were distinct in terms of tumor location, thymidylate synthase expression, MSI status and hMSH3 expression. Our preliminary findings support the utility of EMAST as a new potential classifier in CRC. <p></p>
http://ift.tt/2i6bIK3
A Review of Clinical Trials of Belimumab in the Management of Systemic Lupus Erythematosus
There have been few changes over the last 50 years in the treatment of Systemic lupus erythematosus (SLE), using non-specific anti-inflammatory agents such as: nonsteroidal anti-inflammatory drugs along with the immune cell modulating agent hydroxychloroquine for mild disease, and broad spectrum immunosuppressants plus antiinflammatories such as corticosteroids, azathioprine, cyclophosphamide, or mycophenolate during flares or severe disease with organ involvement. In some patients, the response is inadequate and side effects appear from mild unpleasant up to severe toxicity. Drug metabolism and clearance may be severely compromised. Therefore, it is a priority to develop better treatments with fewer adverse events that can be used at different stages of disease activity. <p></p> In recent years, a member of the tumor necrosis factor (TNF) family, soluble human B Lymphocyte Stimulator protein (BLyS), also referred to as B-cell activating factor (BAFF) and TNFSF13B has been studied extensively. This protein is synthesized by myeloid cell lines, specifically interacts with B lymphocytes and increases their life-span. BlyS plays a key role in the selection, maturation and survival of B cells and it has a significant role in the pathogenesis of SLE. <p></p> In this review, we analyzed the role of BLyS as a diagnostic/prognostic marker and/or therapeutic target for lupus patients, and the different clinical studies published using belimumab. <p></p>
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Therapeutic Potential of Targeting TREM-1 in Inflammatory Diseases and Cancer
The triggering receptor expressed on myeloid cells (TREM)-1 is a member of the Ig-like immunoregulatory receptor family and a major amplifier of innate immune responses. TREM- 1 has been implicated in the development and perpetuation of a number of inflammatory disorders, and soluble TREM-1 levels are a clinically valuable diagnostic and prognostic biomarker in patients with sepsis and other types of acute and chronic inflammation- associated diseases, easily detectable in biological fluids. High TREM-1 expression in macrophages infiltrating human tumors and increased concentrations of soluble TREM-1 also correlate with aggressive tumor behavior and recurrence and are a relevant independent predictor of poor patient survival. Pharmacological inhibition of TREM-1 has proven effective in preclinical mouse models of infectious and non-infectious inflammatory disorders and malignancies, conferring survival advantages and protecting from organ damage or tumor growth by attenuating inflammatory responses. This review aims at providing a comprehensive overview of the state of the art on TREM-1 research. We review the literature addressing TREM-1 role in the amplification of myeloid cell inflammatory responses at pathologic sites and its relevance in the development, severity, and progression of inflammatory diseases and cancer. Furthermore, we discuss recent advances in the pharmacological use of TREM-1 inhibitors in mouse preclinical models, emphasizing their potential in new strategies for the treatment of acute and chronic inflammatory conditions and for therapeutic intervention in cancer. This information will be of value to investigators in the field of pharmacology, drawing attention to novel therapeutic opportunities to complement current treatment approaches.
http://ift.tt/2iCdYKq
qSOFA should replace SIRS as the screening tool for sepsis
No description available
http://ift.tt/2i5UNre
Early Pregnancy Thyroid Function Test Abnormalities in Biobank Sera from Women Clinically Diagnosed with Thyroid Dysfunction Before or After Pregnancy
http://ift.tt/2hrSU7p
Fusion Oncogenes Are the Main Genetic Events Found in Sporadic Papillary Thyroid Carcinomas from Children
http://ift.tt/2icBY3B
qSOFA should replace SIRS as the screening tool for sepsis
No description available
http://ift.tt/2i5UNre
qSOFA should replace SIRS as the screening tool for sepsis
No description available
http://ift.tt/2i5UNre
qSOFA should replace SIRS as the screening tool for sepsis
No description available
http://ift.tt/2i5UNre
The Association of Sleep Duration and Morbid Obesity in a Working Population: The Baptist Health South Florida Employee Study
Metabolic Syndrome and Related Disorders , Vol. 0, No. 0.
http://ift.tt/2iCPi0j
qSOFA should replace SIRS as the screening tool for sepsis
No description available
http://ift.tt/2i5UNre
qSOFA should replace SIRS as the screening tool for sepsis
No description available
http://ift.tt/2i5UNre
qSOFA should replace SIRS as the screening tool for sepsis
No description available
http://ift.tt/2i5UNre
Minispectrometer with handheld probe for 5-ALA based fluorescence-guided surgery of brain tumors: preliminary study for clinical applications
Source:Photodiagnosis and Photodynamic Therapy
Author(s): J.F. Cornelius, J.M. Placke, J. Knipps, I. Fischer, M. Kamp, H.J. Steiger
IntroductionRecently a mini-spectrometer with a handheld probe quantifying 5-aminolevulinic acid (5-ALA) based fluorescence intensity of brain tumors was developped by Kim and co-workers to improve fluorescence-guided neurosurgery.ObjectiveTo evaluate if this new tool is capable to discriminate nuances of fluorescence intensity of strongly fluorescing tumors (glioblastomas (GBM) and meningiomas (MM)). To study different modes of measurement (touch/no-touch). To determine protoporphyrin IX (PPIX) concentration in tumor tissue as compared to a laboratory spectrometer.Material and MethodsThe tumor tissue was resected from patients operated in the neurosurgical department of University Hospital Duesseldorf, Germany between 01/2014 and 06/2014. Two spectrometers, one custom-built with a handheld probe ("mini-spectrometer") and one commercial laboratory spectrometer were employed. After calibration they were used to detect and compare fluorescence intensity of human brain tumor samples ex vivo under standardized conditions. The mini-spectrometer was tested at different distances to the tumor. PPIX concentrations of tumor lysates were determined by both spectrometers.ResultsIn total n=11 tumors (5 MM and 6 GBM) resulting in 17 tumor biopsies were studied. All GBM showed significant higher fluorescence intensity as compared to MM (Z=−3.123, p=0.001). The fluorescence signal was inversely proportional to the square of the distance (GBM: R2=0.226; F=4.683; p<0.5; MM: R2=0255; F=8.042; p<0.01). The mini-spectrometer recorded fluorescence signals up to 2 millimeters ("no-touch"). Determination of PPIX concentration in tumor by the mini-spectrometer did not differ from a laboratory spectrometer.ConclusionThe mini-spectrometer was a very sensitive tool for detection of 5-ALA based fluorescence of human brain tumors. Fluorescence intensity of glioblastoma and meningioma were significantly different. A no-touch mode of measurement was possible. PPIX concentration in tumor tissue could be determined as precisely as with a laboratory spectrometer. In future clinical trials the practicability of using such a tool in vivo has to be further evaluated.
http://ift.tt/2hmxeWU
Treatment of Sweat gland carcinoma with Topical Aminolevulinic Acid Photodynamic therapy: An effective treatment method to improve surgical outcomes
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Xian He, Yadong Yang, Yang Yang, Yuanyuan Wang, Wensheng Wang, Yanying Song, Yongfang Zen, Yunchuan Yang, Xingcun Zhang, Guoling Li, Yang Gao, Yuangang Lu
BackgroundSweat gland carcinoma is an extremely rare skin cancer, which is hard to diagnose and completely exsect without causing functional and cosmetic problems. Moreover, the high rate of recurrence is hard to handle in the treatment of sweat gland carcinoma. Photodynamic therapy is a novel treatment protocol which can selectively destroy tumor cell with good functional and cosmetic outcomes.MethodsThis is a case about a 53 years old patient with sweat gland carcinoma on his right foot, which received surgery and photodynamic therapy.ResultsThere is no recurrence in one year after treatment of surgery and photodynamic therapy.ConclusionsExcision combined with photodynamic therapy during operation is a promising strategy towards tumors which is hard to exsect thoroughly and have a high risk of recurrence.
http://ift.tt/2iCiVmp
Evidence for an Optimal Algorithm Underlying Signal Combination in Human Visual Cortex
How does the cortex combine information from multiple sources? We tested several computational models against data from steady-state electroencephalography (EEG) experiments in humans, using periodic visual stimuli combined across either retinal location or eye-of-presentation. A model in which signals are raised to an exponent before being summed in both the numerator and the denominator of a gain control nonlinearity gave the best account of the data. This model also predicted the pattern of responses in a range of additional conditions accurately and with no free parameters, as well as predicting responses at harmonic and intermodulation frequencies between 1 and 30 Hz. We speculate that this model implements the optimal algorithm for combining multiple noisy inputs, in which responses are proportional to the weighted sum of both inputs. This suggests a novel purpose for cortical gain control: implementing optimal signal combination via mutual inhibition, perhaps explaining its ubiquity as a neural computation.
http://ift.tt/2hmoJvb
DMRT5 Together with DMRT3 Directly Controls Hippocampus Development and Neocortical Area Map Formation
Mice that are constitutively null for the zinc finger doublesex and mab-3 related (Dmrt) gene, Dmrt5/Dmrta2, show a variety of patterning abnormalities in the cerebral cortex, including the loss of the cortical hem, a powerful cortical signaling center. In conditional Dmrt5 gain of function and loss of function mouse models, we generated bidirectional changes in the neocortical area map without affecting the hem. Analysis indicated that DMRT5, independent of the hem, directs the rostral-to-caudal pattern of the neocortical area map. Thus, DMRT5 joins a small number of transcription factors shown to control directly area size and position in the neocortex. Dmrt5 deletion after hem formation also reduced hippocampal size and shifted the position of the neocortical/paleocortical boundary. Dmrt3, like Dmrt5, is expressed in a gradient across the cortical primordium. Mice lacking Dmrt3 show cortical patterning defects akin to but milder than those in Dmrt5 mutants, perhaps in part because Dmrt5 expression increases in the absence of Dmrt3. DMRT5 upregulates Dmrt3 expression and negatively regulates its own expression, which may stabilize the level of DMRT5. Together, our findings indicate that finely tuned levels of DMRT5, together with DMRT3, regulate patterning of the cerebral cortex.
http://ift.tt/2iCpjdq
Whole-brain functional connectivity during acquisition of novel grammar: Distinct functional networks depend on language learning abilities
Source:Behavioural Brain Research, Volume 320
Author(s): Olga Kepinska, Mischa de Rover, Johanneke Caspers, Niels O. Schiller
In an effort to advance the understanding of brain function and organisation accompanying second language learning, we investigate the neural substrates of novel grammar learning in a group of healthy adults, consisting of participants with high and average language analytical abilities (LAA). By means of an Independent Components Analysis, a data-driven approach to functional connectivity of the brain, the fMRI data collected during a grammar-learning task were decomposed into maps representing separate cognitive processes. These included the default mode, task-positive, working memory, visual, cerebellar and emotional networks. We further tested for differences within the components, representing individual differences between the High and Average LAA learners. We found high analytical abilities to be coupled with stronger contributions to the task-positive network from areas adjacent to bilateral Broca's region, stronger connectivity within the working memory network and within the emotional network. Average LAA participants displayed stronger engagement within the task-positive network from areas adjacent to the right-hemisphere homologue of Broca's region and typical to lower level processing (visual word recognition), and increased connectivity within the default mode network. The significance of each of the identified networks for the grammar learning process is presented next to a discussion on the established markers of inter-individual learners' differences. We conclude that in terms of functional connectivity, the engagement of brain's networks during grammar acquisition is coupled with one's language learning abilities.
http://ift.tt/2hvoUsM
Immediate and delayed anxiety- and depression-like profiles in the adolescent Wistar-Kyoto rat model of endogenous depression following postweaning social isolation
Source:Behavioural Brain Research, Volume 320
Author(s): Reshma A. Shetty, Monika Sadananda
In order to understand links that exist between inherited risk or predisposition, brain and behavioural development, endocrine regulation and social/environmental stimuli, animal models are crucial. The Wistar-Kyoto (WKY) rat has been shown to have validity as a model of adult and adolescent depression. While sex- and age-specific differences in some of the face, predictive and construct validities of the model such as depression-like behaviours have been established, anhedonia and anxiety using other induced anxiety paradigms such as elevated plus maze remain equivocal. First, post-weaning social isolation effects on inherent and induced anxiety behaviours were tested during two critical time periods, early- and mid-adolescence. Isolation induced immediate effects on novel environment-induced hyperactivity and anxiety-related behaviours. Adolescent WKYs demonstrated reduced 50-kHz ultrasonic vocalizations suggesting agoraphobia-like behaviours. Second, isolated rats, despite being subsequently social-/group-housed demonstrated longer lasting effects on social interaction measures and anhedonia. This establishes that the depression-like profile observed during early- and mid-adolescence persists into late adolescence and early adulthood in WKY. Further, that interventions at a later stage during adolescence may not be able to reverse early adolescent effects in the context of pre-disposition, thus highlighting the irreversibility of being double-hit during critical time periods of brain and behavioural development and maturation.
http://ift.tt/2hMaBMz
Mid-face toddler excoriation syndrome (MiTES): a new paediatric diagnosis
Summary
Chronic ulcerating lesions on the face are rarely seen in toddlers. Blistering disease, vasculitis, infections and self-mutilation due to neurometabolic disease can usually be excluded on clinical and histological grounds. In the absence of identifiable disease, such lesions are sometimes attributed to child abuse or fabricated illness. We describe three toddlers with chronic mid-face erosions, two from India and one from the UK. One had moderate developmental delay and one had had seizures. The lesions appeared to be self-inflicted, no underlying disease was identified and there was no suspicion of child abuse. Recognition of the same disease pattern in different continents implies a distinct pathological entity. The pattern closely resembles that seen in some patients with mutations in the pain-insensitivity genes PRDM12 and SCN11A. We suggest the term 'mid-face toddler excoriation syndrome' (MiTES) to acknowledge the existence of this condition, encourage further reports and help clarify the pathogenesis.
http://ift.tt/2iCiHvu
Possible association between germline methylenetetrahydrofolate reductase gene polymorphisms and psoriasis risk in a Turkish population
Summary
Background
Psoriasis is a common chronic inflammatory skin disease caused by genetic and epigenetic factors. There are conflicting results in the literature about the association between psoriasis and the methylenetetrahydrofolate reductase gene (MTHFR), ranging from strong linkage to no association.
Aim
To investigate the association between the germline MTHFR polymorphisms C677T and A1298C with psoriasis risk in a Turkish population.
Methods
The study enrolled 84 patients with psoriasis and 212 healthy controls (HCs) without any history of psoriasis. DNA was extracted from peripheral blood samples of patients and HCs, and real-time PCR was used for genotyping. Results were compared by Pearson χ² test and multiple logistic regression models.
Results
The frequency of both the MTHFR 677TT and A1298C (homozygous) genotypes was statistically significantly different from HCs. Point mutations were detected in all patients with early-onset psoriasis (before the age of 20 years). The T allele of MTHFR 677 and the C allele of MTHFR 1298 increased psoriasis risk by 12.4- and 17.0-fold, respectively, in patients compared with HCs.
Conclusion
A possible association was detected betweengermline MTHFR 677 C>T and 1298 A>C genotypes and psoriasis risk in a Turkish population. These results need to be confirmed in further studies with larger sample sizes.
http://ift.tt/2iChZhX
Cutaneous protothecosis on the bilateral wrists of a food handler
Summary
Cutaneous protothecosis is caused by the achlorophyllic algae Prototheca, typically presenting as a localized plaque in immunocompetent individuals. We report a patient with bilateral erythematous plaques and pustules on her forearms, which had initially been treated with steroids for presumed eczema. Histology showed spherical spore-like bodies with internal morula-like septation, which were positive for periodic-acid–Schiff (PAS) staining, consistent with cutaneous protothecosis. Definitive treatment with oral itraconazole resulted in resolution of the lesions.
http://ift.tt/2iCkDE8
British Association of Dermatologists’ national audit on nonmelanoma skin cancer excision, 2014
Summary
Background
Diagnosis and management of nonmelanoma skin cancer (NMSC) represents a large part of the dermatology workload, and complete excision is a required surgical standard for treatment.
Aim
To conduct an audit of the surgical practice for the treatment of NMSC by dermatologists in the UK.
Methods
Data on 10 consecutive nonmicrographic excisions of nonmelanoma skin cancer by UK dermatologists. Data collected included site, preoperative diagnosis, histological diagnosis, proximity to previous scars, and histological deep and peripheral margins.
Results
A total of 227 responses from 135 centres reported 2739 excisions. Excisions on the head and neck accounted for 58.3% of cases. Tumour diameter (mean ± SD) was 10.61 ± 6.9 mm (maximum 130 mm), and 96.7% of cases were primary excisions, with 3.3% being re-excisions. Basal cell carcinomas (BCCs) accounted for 79.1% (n = 2167) of the total cases and squamous cell carcinomas (SCCs) for 17.9% n = 491). Of the suspected BCCs and SCCS, 94.4% (n = 2045) and 66.8% (328), respectively, were confirmed histologically to be the respective carcinomas. Similar proportions of BCC and SCC cases were within 10 mm of a previous excision. Lateral and deep margins were clear in 98.3% and 99.2% of BCC cases, respectively, and in 98.4% and 97.1% of SCC cases, respectively. Reported surgical complication rate in the audit was 3.4%.
Conclusions
The majority of excisions for NMSC are for BCC and SCC. Our figures for diagnostic accuracy are at the upper range of previously published figures. Most patients were not followed up in secondary care, hence complication rates may be under-reported.
http://ift.tt/2hmvYTQ
Mid-face toddler excoriation syndrome (MiTES): a new paediatric diagnosis
Summary
Chronic ulcerating lesions on the face are rarely seen in toddlers. Blistering disease, vasculitis, infections and self-mutilation due to neurometabolic disease can usually be excluded on clinical and histological grounds. In the absence of identifiable disease, such lesions are sometimes attributed to child abuse or fabricated illness. We describe three toddlers with chronic mid-face erosions, two from India and one from the UK. One had moderate developmental delay and one had had seizures. The lesions appeared to be self-inflicted, no underlying disease was identified and there was no suspicion of child abuse. Recognition of the same disease pattern in different continents implies a distinct pathological entity. The pattern closely resembles that seen in some patients with mutations in the pain-insensitivity genes PRDM12 and SCN11A. We suggest the term 'mid-face toddler excoriation syndrome' (MiTES) to acknowledge the existence of this condition, encourage further reports and help clarify the pathogenesis.
http://ift.tt/2iCiHvu
Possible association between germline methylenetetrahydrofolate reductase gene polymorphisms and psoriasis risk in a Turkish population
Summary
Background
Psoriasis is a common chronic inflammatory skin disease caused by genetic and epigenetic factors. There are conflicting results in the literature about the association between psoriasis and the methylenetetrahydrofolate reductase gene (MTHFR), ranging from strong linkage to no association.
Aim
To investigate the association between the germline MTHFR polymorphisms C677T and A1298C with psoriasis risk in a Turkish population.
Methods
The study enrolled 84 patients with psoriasis and 212 healthy controls (HCs) without any history of psoriasis. DNA was extracted from peripheral blood samples of patients and HCs, and real-time PCR was used for genotyping. Results were compared by Pearson χ² test and multiple logistic regression models.
Results
The frequency of both the MTHFR 677TT and A1298C (homozygous) genotypes was statistically significantly different from HCs. Point mutations were detected in all patients with early-onset psoriasis (before the age of 20 years). The T allele of MTHFR 677 and the C allele of MTHFR 1298 increased psoriasis risk by 12.4- and 17.0-fold, respectively, in patients compared with HCs.
Conclusion
A possible association was detected betweengermline MTHFR 677 C>T and 1298 A>C genotypes and psoriasis risk in a Turkish population. These results need to be confirmed in further studies with larger sample sizes.
http://ift.tt/2iChZhX
Cutaneous protothecosis on the bilateral wrists of a food handler
Summary
Cutaneous protothecosis is caused by the achlorophyllic algae Prototheca, typically presenting as a localized plaque in immunocompetent individuals. We report a patient with bilateral erythematous plaques and pustules on her forearms, which had initially been treated with steroids for presumed eczema. Histology showed spherical spore-like bodies with internal morula-like septation, which were positive for periodic-acid–Schiff (PAS) staining, consistent with cutaneous protothecosis. Definitive treatment with oral itraconazole resulted in resolution of the lesions.
http://ift.tt/2iCkDE8
British Association of Dermatologists’ national audit on nonmelanoma skin cancer excision, 2014
Summary
Background
Diagnosis and management of nonmelanoma skin cancer (NMSC) represents a large part of the dermatology workload, and complete excision is a required surgical standard for treatment.
Aim
To conduct an audit of the surgical practice for the treatment of NMSC by dermatologists in the UK.
Methods
Data on 10 consecutive nonmicrographic excisions of nonmelanoma skin cancer by UK dermatologists. Data collected included site, preoperative diagnosis, histological diagnosis, proximity to previous scars, and histological deep and peripheral margins.
Results
A total of 227 responses from 135 centres reported 2739 excisions. Excisions on the head and neck accounted for 58.3% of cases. Tumour diameter (mean ± SD) was 10.61 ± 6.9 mm (maximum 130 mm), and 96.7% of cases were primary excisions, with 3.3% being re-excisions. Basal cell carcinomas (BCCs) accounted for 79.1% (n = 2167) of the total cases and squamous cell carcinomas (SCCs) for 17.9% n = 491). Of the suspected BCCs and SCCS, 94.4% (n = 2045) and 66.8% (328), respectively, were confirmed histologically to be the respective carcinomas. Similar proportions of BCC and SCC cases were within 10 mm of a previous excision. Lateral and deep margins were clear in 98.3% and 99.2% of BCC cases, respectively, and in 98.4% and 97.1% of SCC cases, respectively. Reported surgical complication rate in the audit was 3.4%.
Conclusions
The majority of excisions for NMSC are for BCC and SCC. Our figures for diagnostic accuracy are at the upper range of previously published figures. Most patients were not followed up in secondary care, hence complication rates may be under-reported.
http://ift.tt/2hmvYTQ
Spectrum of Pregnancy and Lactation Related Benign Breast Findings
Source:Current Problems in Diagnostic Radiology
Author(s): Scott Parker, Megan Saettele, Matthew Morgan, Matthew Stein, Nicole Winkler
http://ift.tt/2iCdHHf
The Champion′s Creed: Shared values of athletes and academicians
Source:Current Problems in Diagnostic Radiology
Author(s): Laura M. Fayad, Lisa Morales
While the pursuit of sports may be dismissed as unimportant by those in the academic fields, sports are pervasive, and in our society, elite athletes are revered. There are lessons to be appreciated from the training journey and ultimate achievements of such athletes, that parallel the development and sustainment of the academic radiologist on many fronts, including educational training, clinical work, the pursuit of research, and for some, the culmination of a career in a leadership role.
http://ift.tt/2hmll3p
Decellularized adipose tissue microcarriers as a dynamic culture platform for human adipose-derived stem/stromal cell expansion
Publication date: March 2017
Source:Biomaterials, Volume 120
Author(s): Claire Yu, Anna Kornmuller, Cody Brown, Todd Hoare, Lauren E. Flynn
With the goal of designing a clinically-relevant expansion strategy for human adipose-derived stem/stromal cells (ASCs), methods were developed to synthesize porous microcarriers derived purely from human decellularized adipose tissue (DAT). An electrospraying approach was applied to generate spherical DAT microcarriers with an average diameter of 428 ± 41 μm, which were soft, compliant, and stable in long-term culture without chemical crosslinking. Human ASCs demonstrated enhanced proliferation on the DAT microcarriers relative to commercially-sourced Cultispher-S microcarriers within a spinner culture system over 1 month. ASC immunophenotype was maintained post expansion, with a trend for reduced expression of the cell adhesion receptors CD73, CD105, and CD29 under dynamic conditions. Upregulation of the early lineage-specific genes PPARγ, LPL, and COMP was observed in the ASCs expanded on the DAT microcarriers, but the cells retained their multilineage differentiation capacity. Comparison of adipogenic and osteogenic differentiation in 2-D cultures prepared with ASCs pre-expanded on the DAT microcarriers or Cultispher-S microcarriers revealed similar adipogenic and enhanced osteogenic marker expression in the DAT microcarrier group, which had undergone a higher population fold change. Further, histological staining results suggested a more homogeneous differentiation response in the ASCs expanded on the DAT microcarriers as compared to either Cultispher-S microcarriers or tissue culture polystyrene. A pilot chondrogenesis study revealed higher levels of chondrogenic gene and protein expression in the ASCs expanded on the DAT microcarriers relative to all other groups, including the baseline controls. Overall, this study demonstrates the promise of applying dynamic culture with tissue-specific DAT microcarriers as a means of deriving regenerative cell populations.
Graphical abstract
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Comprehensive chemical characterization of industrial PM2.5 from steel industry activities
Publication date: March 2017
Source:Atmospheric Environment, Volume 152
Author(s): Alexandre Sylvestre, Aurélie Mizzi, Sébastien Mathiot, Fanny Masson, Jean L. Jaffrezo, Julien Dron, Boualem Mesbah, Henri Wortham, Nicolas Marchand
Industrial sources are among the least documented PM (Particulate Matter) source in terms of chemical composition, which limits our understanding of their effective impact on ambient PM concentrations. We report 4 chemical emission profiles of PM2.5 for multiple activities located in a vast metallurgical complex. Emissions profiles were calculated as the difference of species concentrations between an upwind and a downwind site normalized by the absolute PM2.5 enrichment between both sites. We characterized the PM2.5 emissions profiles of the industrial activities related to the cast iron (complex 1) and the iron ore conversion processes (complex 2), as well as 2 storage areas: a blast furnace slag area (complex 3) and an ore terminal (complex 4). PM2.5 major fractions (Organic Carbon (OC) and Elemental Carbon (EC), major ions), organic markers as well as metals/trace elements are reported for the 4 industrial complexes. Among the trace elements, iron is the most emitted for the complex 1 (146.0 mg g−1 of PM2.5), the complex 2 (70.07 mg g−1) and the complex 3 (124.4 mg g−1) followed by Al, Mn and Zn. A strong emission of Polycyclic Aromatic Hydrocarbons (PAH), representing 1.3% of the Organic Matter (OM), is observed for the iron ore transformation complex (complex 2) which merges the activities of coke and iron sinter production and the blast furnace processes. In addition to unsubstituted PAHs, sulfur containing PAHs (SPAHs) are also significantly emitted (between 0.011 and 0.068 mg g−1) by the complex 2 and could become very useful organic markers of steel industry activities. For the complexes 1 and 2 (cast iron and iron ore converters), a strong fraction of sulfate ranging from 0.284 to 0.336 g g−1) and only partially neutralized by ammonium, is observed indicating that sulfates, if not directly emitted by the industrial activity, are formed very quickly in the plume. Emission from complex 4 (Ore terminal) are characterized by high contribution of Al (125.7 mg g−1 of PM2.5) but also, in a lesser extent, of Fe, Mn, Ti and Zn. We also highlighted high contribution of calcium ranging from 0.123 to 0.558 g g−1 for all of the industrial complexes under study. Since calcium is also widely used as a proxy of the dust contributions in source apportionment studies, our results suggest that this assumption should be reexamined in environments impacted by industrial emissions.
Graphical abstract
http://ift.tt/2iCHETv
Dry deposition and canopy uptake in Mediterranean holm-oak forests estimated with a canopy budget model: A focus on N estimations
Source:Atmospheric Environment, Volume 152
Author(s): L. Aguillaume, S. Izquieta-Rojano, H. García-Gómez, D. Elustondo, J.M. Santamaría, R. Alonso, A. Avila
Bulk/wet and throughfall fluxes of major compounds were measured from June 2011 to June 2013 at four Mediterranean holm-oak (Quercus ilex) forests in the Iberian Peninsula. Regression analysis between net throughfall fluxes and precipitation indicated that the best defined canopy process was leaching for K+ and uptake for NH4+ at all sites. A more variable response between sites was found for Na+, Ca2+, SO42- and Cl−, which suggests that the interplay of dry deposition, leaching and uptake at the canopy was different depending on site climate and air quality characteristics.A canopy budget model (CBM) was used to try to discriminate between the canopy processes and enable to estimate dry deposition and uptake fluxes at three of the sites that complied with the model specifications. To derive N uptake, an efficiency factor of NH4+vs. NO3− uptake (xNH4) corresponding to moles of NH4+ taken up for each NO3− mol, has to be determined. Up to now, a value of 6 has been proposed for temperate forests, but we lack information for Mediterranean forests. Experimental determination of N absorption on Quercus ilex seedlings in Spain suggests efficiency factors from 1 to 6. Based on these values, a sensitivity analysis for xNH4 was performed and the NH4N and NO3N modeled dry deposition was compared with dry deposition estimated with independent methods (inferential modeling and washing of branches). At two sites in NE Spain under a milder Mediterranean climate, the best match was obtained for xNH4 = 6, corroborating results from European temperate forests. Based on this value, total DIN deposition was 12–13 kg N ha−1 y−1 at these sites. However, for a site in central Spain under drier conditions, variation of the NH4+ efficiency factor had little effect on DD estimates (which ranged from 2 to 2.6 kg N ha−1 y−1 with varying xNH4); when added to wet deposition, this produced a total N deposition in the range 2.6–3.4 kg N ha−1 y−1. Dry deposition was the predominant pathway for N, accounting for 60–80% of total deposition, while for base cations wet deposition dominated (55–65%). Nitrogen deposition values at the northwestern sites were close to the empirical critical load proposed for evergreen sclerophyllous Mediterranean forests (15–17 kg N ha−1 y−1). When organic N deposition at these forests is added (3 kg N ha−1 y−1), the total N input to the sites in NE Spain are close to the critical loads for Mediterranean evergreen oak forests.
http://ift.tt/2iCvKsD
Ambient air quality measurements from a continuously moving mobile platform: Estimation of area-wide, fuel-based, mobile source emission factors using absolute principal component scores
Source:Atmospheric Environment, Volume 152
Author(s): Timothy Larson, Timothy Gould, Erin A. Riley, Elena Austin, Jonathan Fintzi, Lianne Sheppard, Michael Yost, Christopher Simpson
We have applied the absolute principal component scores (APCS) receptor model to on-road, background-adjusted measurements of NOx, CO, CO2, black carbon (BC), and particle number (PN) obtained from a continuously moving platform deployed over nine afternoon sampling periods in Seattle, WA. Two Varimax-rotated principal component features described 75% of the overall variance of the observations. A heavy-duty vehicle feature was correlated with black carbon and particle number, whereas a light-duty feature was correlated with CO and CO2. NOx had moderate correlation with both features. The bootstrapped APCS model predictions were used to estimate area-wide, average fuel-based emission factors and their respective 95% confidence limits. The average emission factors for NOx, CO, BC and PN (14.8, 18.9, 0.40 g/kg, and 4.3 × 1015 particles/kg for heavy duty vehicles, and 3.2, 22.4, 0.016 g/kg, and 0.19 × 1015 particles/kg for light-duty vehicles, respectively) are consistent with previous estimates based on remote sensing, vehicle chase studies, and recent dynamometer tests. Information on the spatial distribution of the concentrations contributed by these two vehicle categories relative to background during the sampling period was also obtained.
http://ift.tt/2i5BRsq
Intraoperative cerebral oxygenation, oxidative injury, and delirium following cardiac surgery
Publication date: Available online 27 December 2016
Source:Free Radical Biology and Medicine
Author(s): Marcos G. Lopez, Pratik Pandharipande, Jennifer Morse, Matthew S. Shotwell, Ginger L. Milne, Mias Pretorius, Andrew D. Shaw, L. Jackson Roberts, Frederic T. Billings
BackgroundDelirium affects 20–30% of patients after cardiac surgery and is associated with increased mortality and persistent cognitive decline. Hyperoxic reperfusion of ischemic tissues increases oxidative injury, but oxygen administration remains high during cardiac surgery. We tested the hypothesis that intraoperative hyperoxic cerebral reperfusion is associated with increased postoperative delirium and that oxidative injury mediates this association.MethodsWe prospectively measured cerebral oxygenation with bilateral oximetry monitors in 310 cardiac surgery patients, quantified intraoperative hyperoxic cerebral reperfusion by measuring the magnitude of cerebral oxygenation above baseline after any ischemic event, and assessed patients for delirium twice daily in the ICU following surgery using the confusion assessment method for ICU (CAM-ICU). We examined the association between hyperoxic cerebral reperfusion and postoperative delirium, adjusted for the extent of cerebral hypoxia, the extent of cerebral hyperoxia prior to any ischemia, and additional potential confounders and risk factors for delirium. To assess oxidative injury mediation, we examined the association between hyperoxic cerebral reperfusion and delirium after further adjusting for plasma levels of F2-isoprostanes and isofurans at baseline and ICU admission, the association between hyperoxic cerebral reperfusion and these markers of oxidative injury, and the association between these markers and delirium.ResultsNinety of the 310 patients developed delirium following surgery. Every 10%·hour of intraoperative hyperoxic cerebral reperfusion was independently associated with a 65% increase in the odds of delirium (OR, 1.65 [1.12 to 2.44]; P=0.01). Hyperoxia prior to ischemia was also independently associated with delirium (1.10 [95% CI, 1.01 to 1.19]; P=0.02), but hypoxia was not (1.12 [95% CI, 0.97 to 1.29]; P=0.11). Increased hyperoxic cerebral reperfusion was associated with increased concentrations of F2-isoprostanes and isofurans at ICU admission, increased concentrations of these markers were associated with increased delirium, and the association between hyperoxic cerebral reperfusion and delirium was weaker after adjusting for these markers of oxidative injury.ConclusionsIntraoperative hyperoxic cerebral reperfusion was associated with increased postoperative delirium, and increased oxidative injury following hyperoxic cerebral reperfusion may partially mediate this association. Further research is needed to assess the potential deleterious role of cerebral hyper-oxygenation during surgery.
Graphical abstract
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Hyperbaric oxygen treatment reverses radiation induced pro-fibrotic and oxidative stress responses in a rat model
Publication date: Available online 27 December 2016
Source:Free Radical Biology and Medicine
Author(s): N. Oscarsson, L. Ny, J. Mölne, F. Lind, S-E. Ricksten, H. Seeman-Lodding, D. Giglio
PurposeRadiotherapy is effective in the treatment of tumors in the pelvic area but is associated with side effects such as cystitis and proctitis. Hyperbaric Oxygen Therapy (HBOT) has emerged as a treatment modality for radiation-induced side effects. In a rat model for radiation cystitis, we studied the effects of HBOT on oxidative stress and pro-fibrotic factors.Materials and MethodsSedated Sprague-Dawley rats underwent bladder irradiation of 20Gy with and without 20 sessions of HBOT during a fortnight. Control animals were treated with and without HBOT. All four groups of animals were euthanized 28 days later. Histopathological examinations, immunohistochemistry and quantitative polymerase chain reaction (qPCR) were used to analyze changes in oxidative stress (8-OHdG), anti-oxidative responses (SOD-1, SOD2, HO-1 and NRFα) and a panel of Th1-type and Th2-type cytokines (IL-1β, IL-4, IL-5, IL-6, IL-10, IL-13, TNF, TGF-β, IFN-γ) in the urinary bladder.ResultsBladder irradiation increased the expression of 8-OHdG, SOD2, HO-1, NRFα, IL-10, TNF and tended to increase TGF-β. These changes were completely reversed by HBOT while HBOT in control animals had no effects on the studied markers for oxidative stress, anti-oxidative responses and Th1-type and Th2-type cytokines.ConclusionsRadiation induced a significant elevation of oxidative stress, antioxidants and pro-fibrotic factors in our animal model for radiation cystitis that were completely reversed and normalized by HBOT. Our findings indicate that HBOT may prevent radiation-induced changes by affecting oxidative stress and inflammatory cascades induced by radiation.SummaryRadiotherapy may cause the development of chronic inflammation and fibrosis, significantly impairing organ function. We hypothesized that bladder irradiation induces an oxidative stress reaction, thereby triggering the redox system and thus initiating an inflammatory and pro-fibrotic response. We aimed to assess whether these changes would be reversed by hyperbaric oxygen using an animal model for radiation cystitis. Our study show that hyperbaric oxygen may reverse oxidative stress and pro-inflammatory factors induced by radiation.
Graphical abstract
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Protein disulfide isomerase externalization in endothelial cells follows classical and unconventional routes
Publication date: Available online 27 December 2016
Source:Free Radical Biology and Medicine
Author(s): Thaís L.S. Araujo, Julianna D. Zeidler, Percíllia V.S. Oliveira, Matheus H. Dias, Hugo A. Armelin, Francisco R.M. Laurindo
Extracellular protein disulfide isomerase (PDIA1) pool mediates thrombosis and vascular remodeling, however its externalization mechanisms remain unclear. We performed systematic pharmacological screening of secretory pathways affecting extracellular PDIA1 in endothelial cells (EC). We identified cell-surface (csPDIA1) and secreted non-particulated PDIA1 pools in EC. Such Golgi bypass also occurred for secreted PDIA1 in EC at baseline or after PMA, thrombin or ATP stimulation. Inhibitors of Type I, II and III unconventional routes, secretory lysosomes and recycling endosomes, including syntaxin-12 deletion, did not impair EC PDIA1 externalization. This suggests predominantly Golgi-independent unconventional secretory route(s), which were GRASP55-independent. Also, these data reinforce a vesicular-type traffic for PDIA1. We further showed that PDIA1 traffic is ATP-independent, while actin or tubulin cytoskeletal disruption markedly increased EC PDIA1 secretion. Clathrin inhibition enhanced extracellular soluble PDIA1, suggesting dynamic cycling. Externalized PDIA1 represents <2% of intracellular PDIA1. PDIA1 was robustly secreted by physiological levels of arterial laminar shear in EC and supported alpha 5 integrin thiol oxidation. Such results help clarify signaling and homeostatic mechanisms involved in multiple (patho)physiological extracellular PDIA1 functions.
Graphical abstract
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Proteasome activation enhances stemness and lifespan of human mesenchymal stem cells
Publication date: Available online 27 December 2016
Source:Free Radical Biology and Medicine
Author(s): Marianna Kapetanou, Niki Chondrogianni, Spyros Petrakis, George Koliakos, Efstathios S. Gonos
The age-associated decline of adult stem cell function contributes to the physiological failure of homeostasis during aging. The proteasome plays a key role in the maintenance of proteostasis and its failure is associated with various biological phenomena including senescence and aging. Although stem cell biology has attracted intense attention, the role of proteasome in stemness and its age-dependent deterioration remains largely unclear. By employing both Wharton's-Jelly- and Adipose-derived human adult mesenchymal stem cells (hMSCs), we reveal a significant age-related decline in proteasome content and peptidase activities, accompanied by alterations of proteasomal complexes. Additionally, we show that senescence and the concomitant failure of proteostasis negatively affects stemness. Remarkably, the loss of proliferative capacity and stemness of hMSCs can be counteracted through proteasome activation. At the mechanistic level, we demonstrate for the first time that Oct4 binds at the promoter region of β2 and β5 proteasome subunits and thus possibly regulates their expression. A firm understanding of the mechanisms regulating proteostasis in stem cells will pave the way to innovative stem cell-based interventions to improve healthspan and lifespan.
Graphical abstract
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Learning and memory improvement and neuroprotection of Gardenia jasminoides (Fructus gardenia) extract on ischemic brain injury rats
Publication date: 20 January 2017
Source:Journal of Ethnopharmacology, Volume 196
Author(s): Haiyan Zhang, Qiong Lai, Yan Li, Yang Liu, Ming Yang
Ethnopharmacological relevanceGardenia jasminoides Ellis is a traditional Chinese medicine (TCM) that containing a variety of effective active ingredients and exhibits diverse pharmacological functions, such as anti-inflammatory, antioxidant and nerve protection.Aim of the studyThis study investigated the effect of Gardenia jasminoides extract (GJE) and Geniposide on learning and memory improvement and neuroprotection in a rat model with chronic cerebral ischemia, as well as explore the underlying mechanisms.Materials and methodsThe crude GJE was prepared using the methods of water extraction and alcohol precipitation, and refined by macroporous adsorption resin. The chronic cerebral ischemia model was simulated by permanent occlusion of bilateral common carotid arteries in rats. GJE was taken at three doses groups (150mg/kg, 100mg/kg, 50mg/kg), Geniposide group (50mg/kg), and oral administration for 30 days. Memory function was assessed using Morris water maze test. The morphological changes of hippocampus and related parts of brain in rats by Hematoxylin and Eosin (HE) staining were observed. Moreover, the levels of Acetylcholin Esterase (AchE), Nitric Oxide Synthase (NOS), Malondialdehyde (MDA), Superoxide Dismutase (SOD) in the brain tissue were quantified.ResultsGJE contained 27% gardenoside and 72% total iridoid glycoside. The chronic cerebral ischemia rat model has been proved successfully. The memory function of the rats assessed using Morris water maze test showed that GJE significantly shortened the escape latency of rats, but had no significant improvement on the number of times crossing the platform and the percentage of time spent in the target quadrant. HE staining showed that the apoptosis and necrosis of the cortex and hippocampus in the GJE group were significantly reduced. In addition, it was found that GJE could significantly improved the content of SOD, inhibited NOS and AchE activity in brain tissue, but did not show a significant reduction in the content of MDA. The effect of medium dosage of GJE was the best among these three dose groups and also better than Geniposide according to the results of all the detection index.ConclusionsGJE had the functions of learning and memory improvement and the neuroprotection on chronic cerebral ischemia model rats. The mechanisms were found to be strongly correlated with antioxygen free radical, reduction of NO toxicity and AChE activity, and brain neuron protective effect. GJE could be able to play a better effect on improving chronic cerebral ischemia than Geniposide.
Graphical abstract
http://ift.tt/2icwlm0
Effect of St.John's wort (Hypericum perforatum) oily extract for the care and treatment of pressure sores; a case report
Publication date: 20 January 2017
Source:Journal of Ethnopharmacology, Volume 196
Author(s): Ali Yücel, Yüksel Kan, Erdem Yesilada, Onat Akın
Ethnopharmacological relevanceTopical formulations such as oily extracts or ointments prepared with the flowering aerial parts of St. John's wort (Hypericum perforatum L., Hypericaceae) have been used in the management of a wide range dermatological problems including superficial wounds and burns, bruises, contusions and many others in the worldwide traditional medicines.Aim of the studyThis is the first case study reporting the beneficial effects of an oily extract of St. John's wort in the treatment of pressure sores in a intensive care unit (ICU) patient.Material and methodsThe oily extract of St. John's wort was applied to a volunteer patient at ICU daily for forty successive days for wound care and treatment. Healing status was monitored macroscopically by measuring the wound size and stages at certain intervals as well as histopathological evaluation of the tissue sections taken at the initial and final dates of treatment.ResultsEvaluation of the results obtained from the macroscopical and histopathological experimentation have shown that oily extract of St. John's wort provided significant efficacy for the treatment of pressure sore wounds.ConclusionSt. John's wort oily extract may be suggested as a cost-effective option for the prevention or treatment of pressure sores in ICU patients.
Graphical abstract
http://ift.tt/2icvDVC
Dissociable Effects of Stimulus Range on Perception and Action
Source:Cortex
Author(s): Gal Namdar, Daniel Algom, Tzvi Ganel
We have recently reported the discovery that the ability to detect a minimum increment to a stimulus depends on the spread of the other stimuli for which this just noticeable difference (JND) is being measured (Namdar, Ganel, & Algom, 2016). In particular, the JND around a standard stimulus was larger when the other standards tested within the same experimental session spread a larger range. In this study we show that this range of standards effect (RSE) is limited to perceptual estimations and does not extend to action. The JND remained invariant when the participants grasped the objects rather than perceptually estimated their size. This difference supports the hypothesis that visual perception, on the one hand, and visually controlled action, on the other hand, are governed by separate rules and mediated by different mechanisms.
http://ift.tt/2iC5YJn
Clinical Question - Should we be offering fertility preservation by surgical sperm retrieval to men with Klinefelter's Syndrome?
Abstract
The diagnosis of Klinefelter's syndrome was made at 11 years of age. The patient was born normally at full term and, although his mother noticed occasions when he was "different" from his siblings, he encountered no major problems until 6-7 years of age when he gained weight excessively and began exhibiting "difficult" behaviour with delayed motor and neurocognitive milestones. Following his presentation to children's community services with pertussis aged 10 these developmental issues began to be explored, culminating in his karyotype being checked.
This article is protected by copyright. All rights reserved.
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Thyroid Abnormalities following the use of CTLA-4 and PD-1 Inhibitors in the treatment of melanoma
Abstract
Context
Checkpoint inhibitors are emerging as important cancer therapies, but are associated with a high rate of immune side effects, including endocrinopathy.
Objective
To determine the burden of thyroid dysfunction in patients with melanoma treated with immune checkpoint inhibitors and describe the clinical course.
Design and Patients
Consecutive patients with melanoma treated with either Ipilimumab, Nivolumab, Pembrolizumab or the combination of Ipilimumab and Nivolumab were identified. Baseline thyroid function tests were used to exclude those with pre-existing thyroid abnormalities, and thyroid function tests during treatment used to identify those with thyroid dysfunction.
Results
Rates of overt thyroid dysfunction were in keeping with the published Phase 3 trials. Hypothyroidism occurred in 13.0% treated with a PD-1 inhibitor and 22.2% with a combination of PD-1 inhibitor and Ipilimumab. Transient subclinical hyperthyroidism was observed in 13.0% treated with a PD-1 inhibitor, 15.9% following a PD-1 inhibitor, and 22.2% following combination treatment with investigations suggesting a thyroiditic mechanism rather than Graves' disease, and a high frequency of subsequent hypothyroidism. Any thyroid abnormality occurred in 23.0% following Ipilimimab, 39.1% following a PD-1 inhibitor and 50% following combination treatment.Abnormal thyroid function was more common in female patients.
Conclusion
Thyroid dysfunction occurs commonly in patients with melanoma treated with immune checkpoint inhibitors, with rates, including sub-clinical dysfunction, occurring in up to 50%.
This article is protected by copyright. All rights reserved.
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Neuronal insulin receptor mediates a positive feedback regulation of insulin biosynthesis in Drosophila
Source:Journal of Genetics and Genomics
Author(s): Jie Ye, Danping Chen, Yue Yu, Liming Wang
http://ift.tt/2ip8EXn
LMM5.1 and LMM5.4, two eukaryotic translation elongation factor 1A-like gene family members, negatively affect cell death and disease resistance in rice
Source:Journal of Genetics and Genomics
Author(s): Jiying Zhao, Pengcheng Liu, Chunrong Li, Yanyan Wang, Lequn Guo, Guanghuai Jiang, Wenxue Zhai
Lesion mimic mutant (LMM) genes, stimulating lesion formation in the absence of pathogens, play significant roles in immune response. In this study, we characterized a rice lesion mimic mutant, lmm5, which displayed light-dependent spontaneous lesions. Additionally, lmm5 plants also exhibited enhanced resistance to all of the tested races of Magnaporthe oryzae and Xanthomonas oryzae pv. oryzae (Xoo) by increasing the expression of defense-related genes and the accumulation of hydrogen peroxide. Genetic analysis showed that the lesion mimic phenotype of lmm5 was controlled by two genes, lmm5.1 and lmm5.4, which were isolated with a map-based cloning strategy. Remarkably, LMM5.1 and LMM5.4 share a 97.4% amino acid sequence identity, and they each encode a eukaryotic translation elongation factor 1A (eEF1A)-like protein. Besides, LMM5.1 and LMM5.4 were expressed in a tissue-specific and an indica-specific manner, respectively. In addition, high-throughput mRNA sequencing analysis confirmed that the basal immunity was constitutively activated in the lmm5 mutant. Taken together, these results suggested that the homologous eEF1A-like genes, LMM5.1 and LMM5.4, negatively affect cell death and disease resistance in rice.
http://ift.tt/2ifvgwk
Thermal imidization process of polyimide film: Interplay between solvent evaporation and imidization
Publication date: 27 January 2017
Source:Polymer, Volume 109
Author(s): Wenjuan Chen, Wei Chen, Baoqing Zhang, Shiyong Yang, Chen-Yang Liu
The thermal imidization process of 1,2,4,5-benzenetetracaboxylic (PMDA)/4,4'-diamnodiphenyl ether (4,4′-ODA) solutions in N-methyl-2-pyrrolidone (NMP) from polyimide (PI) precursor, poly (amic acid) (PAA), was systematically investigated through a series of characterization methods, such as Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and dynamic mechanical analysis (DMA). At the low-temperature drying stage, mechanical properties and Tg of polymer films were increased as a result of solvent removal. TGA method was used to quantitatively monitor the evaporations of hydrogen-bonded solvents on PAA and of the dehydration during the imidization reaction that occurred above 150 °C. During the imidization stage, the interplay between the solvent evaporation and the imidization was the key factor that determined the enhancement of the mechanical properties and Tg. The degree of imidization approached 94% when the temperature was increased to 250 °C. A "complete" imidization was achieved by annealing between 350 and 400 °C. The enhancement in the mechanical properties of final PI films may result from the increased Tg and the crystallized structure formed during the annealing stage.
Graphical abstract
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Influence of structural relaxation on thermomechanical and shape memory performances of amorphous polymers
Publication date: 27 January 2017
Source:Polymer, Volume 109
Author(s): Ming Lei, Kai Yu, Haibao Lu, H. Jerry Qi
AbstractShape memory polymers (SMPs) have been intensively studied for a wide range of potential applications, including biomedical devices, morphing structures, and 4D printing. For amorphous polymers, the glass transition temperature measured by dynamic mechanical analysis (DMA) is an important consideration in designing SMPs. However, typical DMA curves are cooling- and heating-rate dependent and the cooling and heating traces for storage modulus form a (sometimes large) hysteresis loop. This paper first experimentally studies temperature-rate effects on DMA results. A constitutive relation is then developed based on the assumption that the stress relaxation behavior depends on both temperature and structural relaxation state. Good agreement is obtained between the experimental and the modeling results. This model is then applied to study the shape memory behaviors, showing that structural relaxation plays an important role in the free recovery; the model without considering structural relaxation tends to predict a fast recovery.
Graphical abstract
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Synergistic effects of Janus particles and triblock terpolymers on toughness of immiscible polymer blends
Publication date: 27 January 2017
Source:Polymer, Volume 109
Author(s): Ronak Bahrami, Tina I. Löbling, Holger Schmalz, Axel H.E. Müller, Volker Altstädt
By influencing both the interfacial adhesion and the morphology, compatibilizers determine the mechanical properties of polymer blends. Here, we study the mechanical properties, in particular the fatigue crack propagation (FCP) of immiscible blends of poly(2,6-dimethyl-1,4-phenylene ether)/poly(styrene-co-acrylonitrile) (PPE/SAN), compatibilized with Janus nanoparticles (JPs) and linear polystyrene-block-polybutadiene-block-poly(methyl methacrylate) (SBM) triblock terpolymers. Synergistic effects of a mixture of both compatibilizers improve the FCP behavior and reveal the important role of interface stiffness and flexibility on the mechanical properties of polymer blends. The triblock terpolymer and JPs allow at the same time an elastic and stiff linkage at the blend interface and induce multiple deformation mechanisms such as crack bridging and matrix fibrillation that can dissipate energy and contribute to an improved FCP behavior. The presented concept allows tailoring macro-mechanical properties of immiscible polymer blends by adjusting blend morphology and interfacial properties.
Graphical abstract
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Material properties of the cyanobacterial reserve polymer multi-l-arginyl-poly-l-aspartate (cyanophycin)
Publication date: 27 January 2017
Source:Polymer, Volume 109
Author(s): Nikita A. Khlystov, Wui Yarn Chan, Aditya M. Kunjapur, Weichao Shi, Kristala L.J. Prather, Bradley D. Olsen
Bio-sourced macromolecules such as cyanophycin are an attractive source for alternative, sustainable plastics. While the chemical structure and biological function of cyanophycin have been previously investigated, its material properties remain largely unexplored. This study investigates the structural, thermal, mechanical, and solution properties of cyanophycin produced from recombinant Escherichia coli. Unplasticized, it has an elastic compression modulus of about 560 MPa and undergoes brittle failure at 78 MPa. Cyanophycin exhibits thermal stability in air up to 200 °C and does not undergo glass transition within its limit of thermal stability. The polypeptide is amorphous and has no long-range ordering in the solid state. In solution, water-soluble cyanophycin is thermoresponsive, exhibiting both upper and lower critical solution temperatures. Because the feasibility of industrial scale cyanophycin production through fermentation has been well studied, an expanded understanding of its materials properties should contribute to the development of new applications for this biopolymer.
Graphical abstract
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Development of 3D printable formulations containing CNT with enhanced electrical properties
Publication date: 27 January 2017
Source:Polymer, Volume 109
Author(s): Gustavo Gonzalez, Annalisa Chiappone, Ignazio Roppolo, Erika Fantino, Valentina Bertana, Francesco Perrucci, Luciano Scaltrito, Fabrizio Pirri, Marco Sangermano
This study demonstrates the feasibility of printing 3D composite objects based on acrylic photocurable formulations containing CNTs, by using an unmodified commercial DLP-printer. In the preliminary investigations, the most suitable formulation was developed. Viscosity and dispersion stability were adjusted by the addition of a reactive diluent to the acrylic formulation. FT-IR analyses in real time and photorheology tests allowed finding the best composition and printing parameters.Printing conditions were adjusted to get 3D structures from formulations with a content up to 0.3 wt % of CNTs. The presence of the filler causes a decrease of the crosslinking density, which could be overcome using higher intensity light sources. Electrical conductivity measurements performed on the printed samples give promising results for the use of the developed formulation for the building of 3D structures with electrical properties.
Graphical abstract
http://ift.tt/2hM58Wk
On the validity of representation of the inter-particle forces of a polymer-colloid cluster by linear springs
Publication date: 27 January 2017
Source:Polymer, Volume 109
Author(s): Roozbeh Dargazany, Hsieh Chen, Jiaqi Lin, Ali Imani Azad, Alfredo Alexander-Katz
We have investigated the validity of the popular assumption of identical linear spring (ILS) in polymer-colloids aggregated clusters. The ILS assumption suggests that all inter-particle bonds in an aggregated cluster of polymer chains and colloid particles can be represented by identical linear springs. The assumption has been challenged by several experiments that showed the bond stiffness varies across the cluster based on the connectivity of their associated particles. Yet, the predictions of the computational models that used ILS assumption are surprisingly well-aligned with the experiments in some materials. By coupling the coarse-grain Brownian dynamics simulation to a Multi-body dynamics model, a systematic pathway for analyzing the effect of connectivity of particles on elasticity of polymer-colloids aggregated clusters is presented. ILS assumption is found to be valid for systems with a stress path formation mechanism such as close-packed polymer-colloid clusters. We found the assumption irrelevant in systems with wave-like stress distribution mechanism, such as with granular materials, sand piles and jammed systems. Keywords Mechanics; polymer-colloid clusters; Identical springs assumption.
Graphical abstract
http://ift.tt/2hM2Fev
Fascio-cutaneous flaps for chest wall reconstruction after massive inflammatory breast cancer: a case series
Abstract
Background
Inflammatory breast cancer represents a rare condition that presents poor prognosis with high risk of recurrences and greatly affects patients' quality of life. The resective surgical treatment frequently requires challenging reconstructive solutions to restore a proper tissue layer for the chest wall. Reconstructive methods are nowadays still matter of debate.
Methods
A retrospective review of all cases of massive inflammatory breast cancer that underwent mastectomy and reconstruction with fasciocutaneous flaps from October 2009 to September 2014 was performed at our department. Patient demographics, indications, flap specifics, complications, and number of operations were collected.
Results
Our review identified five cases. A lateral thoracic flap was planned in two cases, a modified lateral thoraco-dorsal flap in one case, a combination of scapular and pubic flaps in other case, and a thoraco-epigastric and lateral thoracic flap association in the remaining case. The mean patient age was 60 years (range, 35 to 76 years). Flap dimensions ranged from 9cm to 14 cm in width and 20 to 24 cm in length. Partial necrosis of the flap distal part occurred in two cases requiring minor flap revision.
Conclusions
Resective surgical treatment of inflammatory breast cancer might require a challenging reconstructive planning. In this scenario, fasciocutaneous flaps are an interesting option due to their versatility, easiness of harvesting, low morbidity, and complications rate.
Level of Evidence: Level IV, therapeutic study.
http://ift.tt/2hM3GmQ
Transgenerational transmission of an anticholinergic endophenotype with memory dysfunction
Publication date: March 2017
Source:Neurobiology of Aging, Volume 51
Author(s): Wolfram Doehner, Lieselotte Praße, James Wolpers, Martina K. Brückner, Uwe Ueberham, Thomas Arendt
Impaired cholinergic neurotransmission associated with cognitive dysfunction occurs in various mental disorders of different etiologies including Alzheimer's disease and postalcoholic dementia and others. To address the question whether there exists a common endophenotype with a defined genetic and/or epigenetic signature causing mental dysfunction in these disorders, we investigated 2 generations of offspring born to alcohol-treated mothers. Here, we show that memory impairment and reduced synthesis of acetylcholine occurs in both F1 (exposed to ethanol in utero) and F2 generation (never been exposed to ethanol). Effects in the F2 generation are most likely consequences of transgenerationally transmitted epigenetic modifications in stem cells induced by alcohol. This clearly documents the role of ancestral history of drug abuse on the brain development of subsequent generations. The results further suggest an epigenetic trait for an anticholinergic endophenotype associated with cognitive dysfunction which might be relevant to our understanding of mental impairment in neurodegenerative disorders such as Alzheimer's disease and related disorders.
http://ift.tt/2iBYAgL
Ultrastructural evidence for impaired mitochondrial fission in the aged rhesus monkey dorsolateral prefrontal cortex
Publication date: March 2017
Source:Neurobiology of Aging, Volume 51
Author(s): Yury M. Morozov, Dibyadeep Datta, Constantinos D. Paspalas, Amy F.T. Arnsten
Dorsolateral prefrontal cortex mediates high-order cognitive functions that are impaired early in the aging process in monkeys and humans. Here, we report pronounced changes in mitochondrial morphology in dendrites of dorsolateral prefrontal cortex neurons from aged rhesus macaques. Electron microscopy paired with 3D reconstruction from serial sections revealed an age-related increase in mitochondria with thin segments that intermingled with enlarged ones, the 'mitochondria-on-a-string' phenotype, similar to those recently reported in patients with Alzheimer's disease. The thin mitochondrial segments were associated with endoplasmic reticulum cisterns, and the mitochondrial proteins Fis1 and Drp1, all of which initiate mitochondrial fission. These data suggest that the 'mitochondria-on-a-string' phenotype may reflect malfunction in mitochondrial dynamics, whereby fission is initiated, but the process is incomplete due to malfunction of subsequent step(s). Thus, aged rhesus monkeys may be particularly helpful in exploring the age-related changes that render higher cortical circuits so vulnerable to degeneration.
http://ift.tt/2hmhHGS
Preconditioning tDCS facilitates subsequent tDCS effect on skill acquisition in older adults
Publication date: March 2017
Source:Neurobiology of Aging, Volume 51
Author(s): Hakuei Fujiyama, Mark R. Hinder, Azadeh Barzideh, Charis Van de Vijver, Andreea C. Badache, Maria Nathalya Manrique-C, Paola Reissig, Xue Zhang, Oron Levin, Jeffery J. Summers, Stephan P. Swinnen
Functional motor declines that often occur with advancing age—including reduced efficacy to learn new skills—can have a substantial impact on the quality of life. Recent studies using noninvasive brain stimulation indicate that priming the corticospinal system by lowering the threshold for the induction of long-term potentiation–like plasticity before skill training may facilitate subsequent skill learning. Here, we used "priming" protocol, in which we used transcranial direct current stimulation (tDCS) applying the cathode over the primary motor cortex (M1) before the anode placed over M1 during unimanual isometric force control training (FORCEtraining). Older individuals who received tDCS with the cathode placed over M1 before tDCS with the anode placed over M1 concurrent with FORCEtraining showed greater skill improvement and corticospinal excitability increases following the tDCS/FORCEtraining protocol compared with both young and older individuals who did not receive the preceding tDCS with the cathode placed over M1. The results suggested that priming tDCS protocols may be used in clinical settings to improve motor function and thus maintain the functional independence of older adults.
http://ift.tt/2hmbWbY
Life events, salivary cortisol, and cognitive performance in nondemented subjects: a population-based study
Publication date: March 2017
Source:Neurobiology of Aging, Volume 51
Author(s): Sami Ouanes, Enrique Castelao, Sirak Gebreab, Armin von Gunten, Martin Preisig, Julius Popp
Older people are particularly exposed to stressful events, known to activate the hypothalamus-pituitary-adrenal axis resulting in increased cortisol levels. High cortisol has been associated with deleterious effects on cognition. We hypothesized that stressful life events could increase cortisol secretion leading to cognitive impairment. A cross-sectional analysis was conducted using data from Colaus/PsyColaus, a longitudinal population-based study among Lausanne residents. Salivary cortisol samples were obtained from 796 nondemented subjects aged at least 65. A neuropsychological battery was used to assess cognitive performance and determine the Clinical Dementia Rating Sum of Boxes (CDRSOB). Lifetime life events and their subjective impact were assessed using a validated questionnaire. The total impact of life events was associated neither with cortisol area under the curve (AUC) nor with CDRSOB nor with any cognitive domain performance. The CDRSOB was associated with the cortisol AUC, controlling for age, sex, body mass index, education and depressive symptoms (p = 0.003; B = 0.686 [0.240; 1.333]; r = 0.114). This association between CDRSOB and the cortisol AUC remained significant after controlling for life events total impact (p = 0.040; B = 0.591 [0.027; 1.155]; r = 0.106). These findings do not support the hypothesis that stressful life events increase cortisol secretion leading to cognitive impairment. The association of higher cortisol levels with poorer cognition might be not a mere reflection of stressful events but rather explained by other factors, yet to be elucidated.
http://ift.tt/2iBX26E
Medial temporal lobe subregional morphometry using high resolution MRI in Alzheimer's disease
Publication date: January 2017
Source:Neurobiology of Aging, Volume 49
Author(s): David A. Wolk, Sandhitsu R. Das, Susanne G. Mueller, Michael W. Weiner, Paul A. Yushkevich
Autopsy studies of Alzheimer's disease (AD) have found that neurofibrillary tangle (NFT) pathology of the medial temporal lobe (MTL) demonstrates selective topography with relatively stereotyped subregional involvement at early disease stages, prompting interest in more granular measurement of these structures with in vivo magnetic resonance imaging. We applied a novel, automated method for measurement of hippocampal subfields and extrahippocampal MTL cortical regions. The cohort included cognitively normal (CN) adults (n = 86), early mild cognitive impairment (n = 43), late MCI (n = 22), and mild AD (n = 40) patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI). For pseudolongitudinal analysis of the continuum from preclinical to mild AD dementia, the groups were further divided according to amyloid status based on positron emission tomography. Specific subregions associated with the early NFT pathology of AD were more sensitive to preclinical and early prodromal AD than whole hippocampal volume while more diffuse involvement was found in later stages. In particular, BA35, the first region associated with NFT deposition, was the only region to discriminate preclinical AD from amyloid negative cognitively normal adults ("normal aging"). In general, patterns of atrophy in the pseudolongitudinal analysis largely recapitulated Braak staging of NFTs within the MTL.
http://ift.tt/2hmhFie
Mutation analysis of sporadic early-onset Alzheimer's disease using the NeuroX array
Publication date: January 2017
Source:Neurobiology of Aging, Volume 49
Author(s): Imelda S. Barber, Anne Braae, Naomi Clement, Tulsi Patel, Tamar Guetta-Baranes, Keeley Brookes, Christopher Medway, Sally Chappell, Rita Guerreiro, Jose Bras, Dena Hernandez, Andrew Singleton, John Hardy, David M. Mann, Kevin Morgan
We have screened sporadic early-onset Alzheimer's disease (sEOAD, n = 408) samples using the NeuroX array for known causative and predicted pathogenic variants in 16 genes linked to familial forms of neurodegeneration. We found 2 sEOAD individuals harboring a known causative variant in PARK2 known to cause early-onset Parkinson's disease; p.T240M (n = 1) and p.Q34fs delAG (n = 1). In addition, we identified 3 sEOAD individuals harboring a predicted pathogenic variant in MAPT (p.A469T), which has previously been associated with AD. It is currently unknown if these variants affect susceptibility to sEOAD, further studies would be needed to establish this. This work highlights the need to screen sEOAD individuals for variants that are more classically attributed to other forms of neurodegeneration.
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Gray matter network differences between behavioral variant frontotemporal dementia and Alzheimer's disease.
Publication date: February 2017
Source:Neurobiology of Aging, Volume 50
Author(s): E.G.B. Vijverberg, B.M. Tijms, J. Dopp, Y.J. Hong, C.E. Teunissen, F. Barkhof, P. Scheltens, Y.A.L. Pijnenburg
We set out to study whether single-subject gray matter (GM) networks show disturbances that are specific for Alzheimer's disease (AD; n = 90) or behavioral variant frontotemporal dementia (bvFTD; n = 59), and whether such disturbances would be related to cognitive deficits measured with mini-mental state examination and a neuropsychological battery, using subjective cognitive decline subjects as reference. AD and bvFTD patients had a lower degree, connectivity density, clustering, path length, betweenness centrality, and small world values compared with subjective cognitive decline. AD patients had a lower connectivity density than bvFTD patients (F = 5.79, p = 0.02; mean ± standard deviation bvFTD 16.10 ± 1.19%; mean ± standard deviation AD 15.64 ± 1.02%). Lasso logistic regression showed that connectivity differences between bvFTD and AD were specific to 23 anatomical areas, in terms of local GM volume, degree, and clustering. Lower clustering values and lower degree values were specifically associated with worse mini-mental state examination scores and lower performance on the neuropsychological tests. GM showed disease-specific alterations, when comparing bvFTD with AD patients, and these alterations were associated with cognitive deficits.
http://ift.tt/2hm08Xe
Aldose reductase deficiency leads to oxidative stress-induced dopaminergic neuronal loss and autophagic abnormality in an animal model of Parkinson's disease
Publication date: February 2017
Source:Neurobiology of Aging, Volume 50
Author(s): Patrick K.K. Yeung, Angela K.W. Lai, Hyo Jin Son, Xu Zhang, Onyou Hwang, Stephen S.M. Chung, Sookja K. Chung
Fungicide exposure causes degeneration of dopaminergic neurons and contributes to Parkinson's disease (PD). Benomyl inhibits enzymes responsible for detoxifying the reactive dopamine metabolite 3,4-dihydroxyphenylacetaldehyde. Aldose reductase (AR) is known as tetrahydrobiopterin (BH4) reductase that generates BH4, a cofactor for tyrosine hydroxylase (TH) involved in dopamine synthesis. AR also acts as an aldehyde reductase involved in detoxifying 3,4-dihydroxyphenylacetaldehyde. In PD patients, the level of AR is significantly lower in the cerebellum. To determine if AR deficiency contributes to PD, AR wild-type (AR+/+) and knockout (AR−/−) mice were administrated with 1-methyl-4-phenyl -1,2,3,6- tetrahydropyridine (MPTP). The MPTP-treated AR−/− mice showed more severe behavioral deficits and brain damage than that of AR+/+ mice. Contrary to expectation, under normal or MPTP-treated condition, AR−/− mice showed a significant elevation of BH4 and dopamine in the midbrain, suggesting that either AR does not contribute to BH4 production, or other BH4 synthetic pathways are induced. The AR−/− brain showed upregulation of peroxynitrite, inducible nitric oxide synthase and downregulation of antioxidant enzymes, Cu/Zn superoxide dismutase (SOD) and peroxiredoxin 2 (Prx2), which indicate an increase in oxidative stress. In line with the animal data, pretreating the SH-SY5Y cells with AR inhibitors (Fidarestat or Epalrestat) before MPP+ treatment, increased severe cell death and mitochondrial fragmentation with downregulation of SOD were observed when compared to the MPP+ treatment alone. Cycloxygenase 2 (COX2), which can lead to the oxidation of dopamine, was upregulated in AR−/− brains. Autophagic proteins, beclin-1 and LC3B were also downregulated. The loss of dopaminergic neurons was associated with activation of p-ERK1/2. These findings suggest that AR plays an important role in protecting dopaminergic neuron against neurotoxic metabolites in PD.
http://ift.tt/2iBWHkp
Age-related differences in the structural complexity of subcortical and ventricular structures
Publication date: February 2017
Source:Neurobiology of Aging, Volume 50
Author(s): Christopher R. Madan, Elizabeth A. Kensinger
It has been well established that the volume of several subcortical structures decreases in relation to age. Different metrics of cortical structure (e.g., volume, thickness, surface area, and gyrification) have been shown to index distinct characteristics of interindividual differences; thus, it is important to consider the relation of age to multiple structural measures. Here, we compare age-related differences in subcortical and ventricular volume to those differences revealed with a measure of structural complexity, quantified as fractal dimensionality. Across 3 large data sets, totaling nearly 900 individuals across the adult lifespan (aged 18–94 years), we found greater age-related differences in complexity than volume for the subcortical structures, particularly in the caudate and thalamus. The structural complexity of ventricular structures was not more strongly related to age than volume. These results demonstrate that considering shape-related characteristics improves sensitivity to detect age-related differences in subcortical structures.
Graphical abstract
http://ift.tt/2iBZ9at