Παρασκευή 6 Οκτωβρίου 2017
Future Horizons in Allergy
There are several advances in diagnosis and management for the otolaryngologist treating allergy. These include new technologies and the refinement of current techniques, and reflect overall trends in health care toward personalized medicine. Local immunoglobulin, urinary leukotriene E4, lipidomics, microRNA within extracellular vesicles, and optical rhinometry all offer to improve the diagnostic accuracy of allergy and related nonallergic conditions. New delivery systems for intranasal steroids and antihistamines, recombinant allergens, advances in allergen immunotherapy delivery, and biologics will improve current management options. These developments will aid the otolaryngologist in diagnosing and treating allergy and related diseases.
http://ift.tt/2z53vMf
The Role of Allergy in Otologic Disease
Allergy is commonly associated with conditions such as rhinitis, sinusitis, and asthma, but the relationship between allergy and otologic diseases is less clear. This article examines the evidence for a relationship between allergic disease and several common otologic conditions, including otitis media with effusion, eosinophilic otitis media, and Ménière's disease.
http://ift.tt/2y0J2KO
Future Horizons in Allergy
There are several advances in diagnosis and management for the otolaryngologist treating allergy. These include new technologies and the refinement of current techniques, and reflect overall trends in health care toward personalized medicine. Local immunoglobulin, urinary leukotriene E4, lipidomics, microRNA within extracellular vesicles, and optical rhinometry all offer to improve the diagnostic accuracy of allergy and related nonallergic conditions. New delivery systems for intranasal steroids and antihistamines, recombinant allergens, advances in allergen immunotherapy delivery, and biologics will improve current management options. These developments will aid the otolaryngologist in diagnosing and treating allergy and related diseases.
http://ift.tt/2z53vMf
The Role of Allergy in Otologic Disease
Allergy is commonly associated with conditions such as rhinitis, sinusitis, and asthma, but the relationship between allergy and otologic diseases is less clear. This article examines the evidence for a relationship between allergic disease and several common otologic conditions, including otitis media with effusion, eosinophilic otitis media, and Ménière's disease.
http://ift.tt/2y0J2KO
Diagnostic flaws in oral lichen planus and related lesions
There has been a constant debate as to the exact prevalence and malignant potential of oral lichen planus (OLP). The present ambiguity is due to the existence of lesions which have a clinicopathological resemblance to OLP [1]. Our research team had conducted a retrospective study on OLP and related lesions like oral epithelial dysplasia (OED), OLP, OLP with dysplasia and oral lichenoid lesions (OLL), and have commented on the possible existence of "oral lichenoid dysplasia" (OLD) which is a primary epithelial dysplasia with secondary lichenoid features as opposed to "OLP with dysplasia" which is a lichen planus with secondary dysplastic features [2].
http://ift.tt/2hSGfx4
Poor early response to methotrexate portends inadequate long-term outcomes in patients with moderate-to-severe psoriasis: Evidence from 2 phase 3 clinical trials
Most methotrexate-treated psoriasis patients do not achieve a long-term PASI75 (75% reduction from baseline Psoriasis Area and Severity Index score) response. Indications of nonresponse can be apparent after only 4 weeks of treatment.
http://ift.tt/2yNd7dM
Promoting sunscreen use and sun-protective practices in NCAA athletes: Impact of SUNSPORT educational intervention for student-athletes, athletic trainers, and coaches
Student-athletes (SAs) have an increased skin cancer risk on account of significant ultraviolet exposure; however, their sun-protective practices are suboptimal. A novel program, Stanford University Network for Sun Protection, Outreach, Research, and Teamwork (SUNSPORT), was designed to target SAs, coaches, and athletic trainers (ATs).
http://ift.tt/2fYqCUa
Epidemiology of Hyperhidrosis in Two Population-Based Healthcare Databases
Hyperhidrosis has a range of reported prevalence estimates with the most often cited equal to 2.8%.We describe methods using a combination of diagnosis, symptom, and prescription codes from healthcare databases to ascertain hyperhidrosis cases.This study estimates population prevalences of 1% - 1.6% for patients seeking healthcare for hyperhidrosis.
http://ift.tt/2y5OLOR
Adalimumab for nail psoriasis: Efficacy and safety from the first 26 weeks of a phase 3, randomized, placebo-controlled trial
Previous clinical trials have not evaluated improvement in nail psoriasis as a primary end point.
http://ift.tt/2yOeM2N
Diagnosis and management of diaper dermatitis in infants with emphasis on skin microbiota in the diaper area
Abstract
Diaper dermatitis is the most common inflammatory skin eruption within the diaper area in infants and toddlers. Although it rarely causes problems for prolonged periods of time, it causes considerable distress for both infants and parents. Diapered skin is exposed to friction, excessive hydration, varying pH, and is in constant contact with urine and feces, both of which are highly irritant to the skin. The three most common types of diaper dermatitis include chaffing dermatitis, irritant contact dermatitis, and diaper candidiasis. However, a variety of other skin conditions may manifest in the diaper area. Candida albicans and Staphylococcus aureus are most frequently isolated from the affected area and are thought to have a predominant role in diaper dermatitis. The review includes an overview of the epidemiology, etiology, and common skin microbiota in the diaper area. State-of-the-art strategies for diagnosis, management, and prevention of diaper dermatitis are also included. Appropriate skin care can help in the prevention of diaper dermatitis and can aid the reparation of the skin. This review discusses common causes, skin microbiota within the diapered area, differential diagnosis, and finally possible prevention and treatment recommendations. Recent findings have proven that the key to efficient eradication of irritant diaper dermatitis lies in its prevention.
http://ift.tt/2y6g6Aw
Micro-autologous fat transplantation for rejuvenation of the dorsal surface of the ageing hand
Rejuvenation of the dorsal surface of the hand for various conditions, such as cutaneous dyschromia, fine wrinkling, skin laxity, visible extensor tendons, and varicosities appear vital to prevent wrist and digit flexion resulting from hiding of the aged appearance of the hand. Numerous fillers have been applied to re-contour the ageing dorsal surface of the hand; the results were variable. The micro-autologous fat transplantation (MAFT) technique, proposed by Lin et al. in 2006, has demonstrated its feasibility in facial rejuvenation.
http://ift.tt/2wDnlgf
Systematic review and meta-analysis of dropout rates in individual psychotherapy for generalized anxiety disorder
Source:Journal of Anxiety Disorders
Author(s): Elon Gersh, David J. Hallford, Simon M. Rice, Nikolaos Kazantzis, Hannah Gersh, Benji Gersh, Carolyn A. McCarty
BackgroundDespite being a relatively prevalent and debilitating disorder, Generalized Anxiety Disorder (GAD) is the second least studied anxiety disorder and among the most difficult to treat. Dropout from psychotherapy is concerning as it is associated with poorer outcomes, leads to service inefficiencies and can disproportionately affect disadvantaged populations. No study to date has calculated a weighted mean dropout rate for GAD and explored associated correlates.MethodsA systematic review was conducted using PsycINFO, Medline and Embase databases, identifying studies investigating individual psychotherapies for adults with GAD. Forty-five studies, involving 2224 participants, were identified for meta-analysis.ResultsThe weighted mean dropout rate was 16.99% (95% confidence interval 14.42%-19.91%). The Q-statistic indicated significant heterogeneity among studies. Moderator analysis and meta-regressions indicated no statistically significant effect of client age, sex, symptom severity, comorbidity, treatment type, study type (randomized trial or not), study quality, number of sessions or therapist experience.ConclusionsIn research investigating psychotherapy for GAD, approximately one in six clients can be expected to drop out of treatment. Dropout rate was not significantly moderated by the client, therapist or treatment variables investigated. Future research should specify the definition of dropout, reasons for dropout and associated correlates to assist the field's progression.
http://ift.tt/2xp9ZZ8
Comparative Study of Head and Neck Mucosal Melanoma in 66 patients vs. 226 patients with Cutaneous Melanoma: A survival analysis
Abstract
Sixty-six patients (22%) had HNMM and 226 (78%) HNCM and the higher prevalence was seen in females with a similar distribution amongst the two diagnoses (p=0.8).
Symptoms were present in all patients with HNCM and in only 15% of patients with HNMM (p=0.000).
Lymph node involvement at diagnosis was present in 51% of HNMM vs. 33% of HNCM (p=0.007) and were bilateral in 44% of HNMM while in HNCM they were only ipsilateral (p=0.000).
Metastatic disease at diagnosis was similar in both groups (p=0.9).
Relapses were more frequent in the HNMM group in ~70% of the cases compared with 23% in HNCM group (p=0.000).
When comparing HNCM vs. HNMM, Overall Survival is similar, without statistical difference.
This article is protected by copyright. All rights reserved.
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A study on the clinical characteristics of treating nevus of Ota by Q-switched Nd:YAG laser
Abstract
The purpose of this study was to retrospectively analyze the clinical characteristics of treating nevus of Ota by Q-switched Nd:YAG laser in Laser Cosmetology Center of Department of Dermatology, the Second Hospital, Xi'an Jiaotong University. The data of 1168 patients of nevus of Ota were analyzed retrospectively, which included the correlation among lesion color, treatment sessions, sex, age, lesion types, and effect. The Q-switched (QS) Nd:YAG laser system had a higher number of treatment sessions which were positively associated with a better response to treatment. Other variables, including gender, age, the categorization of the lesion according to Tanino's classification, and the color of the lesion, were not associated with the response to treatment. The treatment of nevus of Ota with QS Nd:YAG laser is safe and effective, with rare complications.
http://ift.tt/2xoifso
Comparative Study of Head and Neck Mucosal Melanoma in 66 patients vs. 226 patients with Cutaneous Melanoma: A survival analysis
Abstract
Sixty-six patients (22%) had HNMM and 226 (78%) HNCM and the higher prevalence was seen in females with a similar distribution amongst the two diagnoses (p=0.8).
Symptoms were present in all patients with HNCM and in only 15% of patients with HNMM (p=0.000).
Lymph node involvement at diagnosis was present in 51% of HNMM vs. 33% of HNCM (p=0.007) and were bilateral in 44% of HNMM while in HNCM they were only ipsilateral (p=0.000).
Metastatic disease at diagnosis was similar in both groups (p=0.9).
Relapses were more frequent in the HNMM group in ~70% of the cases compared with 23% in HNCM group (p=0.000).
When comparing HNCM vs. HNMM, Overall Survival is similar, without statistical difference.
This article is protected by copyright. All rights reserved.
http://ift.tt/2fRLlFu
Relationships between soil parameters and vegetation in abandoned terrace fields vs. non-terraced fields in arid lands (Lanzarote, Spain): An opportunity for restoration
Source:Acta Oecologica, Volume 85
Author(s): José Ramón Arévalo, Silvia Fernández-Lugo, J. Alfredo Reyes-Betancort, Marisa Tejedor, Concepción Jiménez, Francisco J. Díaz
Over 90% of terraced fields have been abandoned on the island of Lanzarote in the last 40 years. The present work analyses the effects of abandonment on the soil and vegetation recovery of terraced field agroecosystems by comparing them with adjacent non-terraced fields in Lanzarote, Canary Islands (Spain). This information is necessary to take the appropriate management actions to achieve goals such as soil protection and biodiversity conservation. Results indicate that terraced fields display better soil quality than non-terraced ones, as shown by the significant differences found in parameters such as SAR, exchangeable Na, CaCO3, B content, moisture content or soil depth. Moreover, the terraced fields' plant community has more species similarities with the native plant community when compared with non-terraced areas. Owing to characteristics such as deeper soils, more water capacity, lower salinity and less sodic soils, terraced soils provide better conditions for passive restoration of both soil and vegetation. Therefore, the recovery and maintenance of wall structures and revegetation with native/endemic species are proposed to promote the restoration of native systems and preserve a landscape with cultural and aesthetic value.
http://ift.tt/2hTwIFV
Seed-deposition and recruitment patterns of Clusia species in a disturbed tropical montane forest in Bolivia
Source:Acta Oecologica, Volume 85
Author(s): Francisco Saavedra, Isabell Hensen, Amira Apaza Quevedo, Eike Lena Neuschulz, Matthias Schleuning
Spatial patterns of seed dispersal and recruitment of fleshy-fruited plants in tropical forests are supposed to be driven by the activity of animal seed dispersers, but the spatial patterns of seed dispersal, seedlings and saplings have rarely been analyzed simultaneously. We studied seed deposition and recruitment patterns of three Clusia species in a tropical montane forest of the Bolivian Andes and tested whether these patterns changed between habitat types (forest edge vs. forest interior), distance to the fruiting tree and consecutive recruitment stages of the seedlings. We recorded the number of seeds deposited in seed traps to assess the local seed-deposition pattern and the abundance and distribution of seedlings and saplings to evaluate the spatial pattern of recruitment. More seeds were removed and deposited at the forest edge than in the interior. The number of deposited seeds decreased with distance from the fruiting tree and was spatially clustered in both habitat types. The density of 1-yr-old seedlings and saplings was higher at forest edges, whereas the density of 2-yr-old seedlings was similar in both habitat types. While seedlings were almost randomly distributed, seeds and saplings were spatially clustered in both habitat types. Our findings demonstrate systematic changes in spatial patterns of recruits across the plant regeneration cycle and suggest that the differential effects of biotic and abiotic factors determine plant recruitment at the edges and in the interior of tropical montane forests. These differences in the spatial distribution of individuals across recruitment stages may have strong effects on plant community dynamics and influence plant species coexistence in disturbed tropical forests.
http://ift.tt/2hTC0Bi
Investigating psychological and physiological responses to the Trier social stress test in young adults with insomnia: a preliminary study
Stress and hyperarousal both contribute to insomnia. Elevated stress-related sleep reactivity is associated with hyperarousal, and might constitute a vulnerability to future insomnia. The present study examined acute stress-induced arousal and its association with nocturnal sleep.
http://ift.tt/2xY17t4
Comparison of the trapping effect and antioxidant enzymatic activities using three different light sources in cockchafers
Abstract
Light traps have been widely used for controlling underground pests. However, very little is known regarding the relationship between trapping effect and antioxidant enzymatic activities using light irradiation in underground pests. Thus, we determined the trapping effect of three light sources of the frequoscillation pest-killing lamp on two species of cockchafers, Serica orientalis Motschulsky (Coleoptera: Melolonthidae) and Anomala corpulenta Motschulsky (Coleoptera: Rutelidae), and evaluated the effect of the same three light sources on the activities of their antioxidant enzymes. The catches of S. orientalis were significantly higher compared to A. corpulenta using light source A in peanut fields in China. After irradiation by light source A, the malondialdehyde (MDA) contents and activities of superoxide dismutase (SOD) and glutathione S-transferases (GST) in S. orientalis were significantly and marginally significantly lower compared to A. corpulenta. Taken together, these results indicated a weaker antioxidant enzyme activity response to light stress and a larger quantity of trapping catches using light irradiation in cockchafers. Thus, we proposed a potential negative relationship between trapping effect and antioxidant enzymatic activities in response to light irradiation in cockchafers.
http://ift.tt/2yNTv9n
Attention profiles in childhood absence epilepsy compared with attention-deficit/hyperactivity disorder
Source:Brain and Development
Author(s): Hyun-Jeong Lee, Eun-Hee Kim, Mi-Sun Yum, Tae-Sung Ko, Hyo-Won Kim
ObjectiveThis study aimed to compare the attention profiles of subjects with childhood absence epilepsy (CAE) to those of children with attention-deficit/hyperactivity disorder (ADHD) and controls.MethodWe retrospectively reviewed the medical records of 20 children (age 7.2 ± 1.6 years, 5 boys) in whom CAE was diagnosed at the Department of Pediatric Neurology of Asan Medical Center, Seoul, Korea. ADHD and control subjects were selected from children who visited the Department of Pediatric Psychiatry and were confirmed as having or not having ADHD based on Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL). The 20 children with CAE, 20 with ADHD and 20 controls completed the Advanced Test of Attention (ATA), which is a computerized continuous performance task.ResultsThe CAE subjects without ADHD showed increased Omission errors (p=.013) on the visual ATA and Response time (p=0.044) on the auditory ATA than the controls, although these differences did not remain significant after multiple comparison correction. The CAE subjects without ADHD had significantly decreased Response time variability on the visual ATA than the ADHD group (p<0.001). The CAE subjects with comorbid ADHD showed increased Commission errors (p=0.020) and Response time variability (p=0.016) on the visual ATA and increased Commission errors (p=0.022) on the auditory ATA than the CAE subjects without ADHD, although statistical significance disappeared after multiple comparison adjustments.ConclusionThese findings suggest that selective attention is impaired in children with CAE and comorbid ADHD contributes to further impairment of sustained attention and response inhibition.
http://ift.tt/2wDPXWt
Self-rated health and associated factors in elderly patients with non-Hodgkin lymphoma
Source:Cancer Epidemiology, Volume 51
Author(s): Lívia Maria Santiago, Daniel Richard Mercante, Inês Echenique Mattos
BackgroundSelf-rated health is a useful indicator for understanding health issues in elderly populations and considered to be a predictor of adverse health outcomes in this group. This study aims to identify factors associated with self-rated health in elderly people with non-Hodgkin's lymphoma.MethodsCross-sectional study performed at a cancer referral hospital in Rio de Janeiro, Brazil, included 162 patients, aged 60 or more years. All patients received a Multidimensional Geriatric Assessment, including seven health dimensions, and socio-demographic, epidemiological and it were collected clinical data. Descriptive analyses were performed and prevalence ratios were calculated to assess associations between self-rated health and the independent variables. Multivariate analysis was performed using Poisson's regression, to a ≤0.05 level of statistical significance.ResultsThe study population mean age was 68.8 (SD=7.1) years; most were women, lived with a partner and had little education. Prevalence of fair/poor self-rated health was 33.6%. Being female, not living with a partner, functional dependence, depressive symptoms and nutritional risk/malnutrion showed associations with fair/poor self-rated health. In the multiple model, dependence in instrumental activities of daily living (PR 2.96; 95%CI 1.66-5.30) and presence of depressive symptoms (PR 1.78; 95%CI 1.15-2.75) remained associated with fair/poor health.ConclusionVariation in perceived health status supports the hypothesis that self-rated health is related to multiple issues, regardless of disease status. The risk profile for poor self-rated health identified may be a useful tool in care for older cancer patients, as it points to those at higher risk of adverse health outcomes.
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NO 2 inhalation enhances asthma susceptibility in a rat model
Abstract
Nitrogen dioxide (NO2) is a major air pollutant. Epidemiologic studies have found that NO2 exposure is associated with an increased risk of asthma. Nevertheless, the potential molecular mechanisms remain unclear. In this study, we investigated the effect of NO2 inhalation on the occurrence of allergic airway inflammation and its underlying mechanisms. Firstly, male Wistar rats were exposed to 2 and 5 mg/m3 NO2 (28 days, 5 h/day). The results showed that NO2 exposure could induce pulmonary inflammatory response, mucus formation, and Th1/Th2 imbalance in the lung of normal rats, resulting in allergic asthma-like features. Secondly, male Wistar rats were exposed to 5 mg/m3 NO2 (42 days, 5 h/day), sensitized with ovalbumin (OVA), challenged with aerosolized OVA, and characterized in asthma models. Results showed that NO2 exposure aggravated lung inflammation in the OVA-sensitized rats, accompanied by the increase in inflammatory cell infiltration, mucus hypersecretion, and collagen deposition. Furthermore, NO2 exposure promoted the increase in the expression of mucin gene (MUC5AC) and pro-inflammatory factors [interleukin (IL)-1β, intercellular adhesion molecule-1 (ICAM-1), and IL-6] as well as serum OVA-specific immunoglobulin E (IgE) production. Taken together, we established that NO2 exposure promotes allergic airway inflammation and increases the asthma susceptibility. The underlying mechanisms involve the promotion of activation of interleukin-4/signal transducer and activator of transcription-6 (IL-4/STAT6) pathway [IL-4 receptor (IL-4R) α, janus kinase (JAK) 1, JAK 3, and STAT6] and related transcription factor [T cell-specific protein-tyrosine kinase (Lck), extracellular-regulated kinase (ERK)1/2, and nuclear factor-κB (NF-κB)]. In particular, the imbalance of Th1/Th2 cell differentiation [IL-4, interferon (IFN)-γ, GATA-binding protein-3 (GATA-3), and T-box expressed in T cells (T-bet)] plays a pivotal role in NO2-induced inflammatory responses. These findings may provide a better understanding of mechanism of NO2-associated respiratory diseases.
http://ift.tt/2ghJoTu
Investigations of electronic and thermoelectric properties of half-Heusler alloys XMgN (X=Li, Na, K) by first-principles calculations
Publication date: 15 December 2017
Source:Materials & Design, Volume 136
Author(s): Rashid Ahmed, Nor Safikah Masuri, Bakhtiar Ul Haq, A. Shaari, S. AlFaifi, Faheem K. Butt, Mohamed Noor Muhamad, M. Ahmed, Sohail Afzal Tahir
The rapid depletion of the fossil fuels and their environment repercussion can be resolved wisely by exploring the efficient and sustainable materials which have the ability to convert waste heat into electricity. Half-Heusler materials are also considered one of the promising class for the thermoelectric applications. In this paper, the investigations on the thermoelectric properties of half-Heusler compounds, XMgN (X=Li, Na, K) are reported. The study is carried out within full potential linearised augmented plane wave plus local orbital approach (FP-LAPW+lo) in conjunction with the semi-empirical Boltzmann theory. To incorporate exchange-correlation energy/potential part, Perdew and Wang (PW) suggested local density approximation (LDA), parameterized generalized gradient approximation (GGA) by Perdew-Berke-Ernzerhof (PBE) and the modified Becke-Johnson (mBJ) exchange potential by Trans-Blaha are used. Our electronic band structure calculations show that the KMgN is indirect band gap material, whereas LiMgN and NaMgN demonstrate their direct electronic band gap structure. To comprehend their thermoelectric character, the calculations of the Seebeck coefficient, electrical conductivity, thermal conductivity, power factor and figure of merit (ZT) are carried out at temperatures of values 300K, 600K, and 900K. From our calculations, the optimal value of Seebeck coefficient for the all three materials although was found at 300K, the results of the Seebeck coefficient for the LiMgN were found more good as compared to NaMgN and KMgN and in coordination with the Lee et al. study as well. Similarly, electrical conductivity results endorse the Wiedemann-Franz law. The calculated results of the ZT parameter (ZT~1) for the all three materials (LiMgN, NaMgN, and KMgN) revealing that the investigated materials have a potential to be used for thermoelectric applications.
Graphical abstract
http://ift.tt/2xorfch
Aggressive differentiated thyroid cancer
Publication date: Available online 6 October 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Noor Janjua, Volkert B. Wreesmann
Differentiated thyroid cancer is characteristically associated with an innocuous clinical course, but a minority may manifest surprisingly aggressive behaviour. The latter are not only directly responsible for the majority of thyroid cancer related deaths, but also contribute indirectly to increased DTC-related morbidity, because our inability to differentiate these tumours from innocuous DTC at an early stage contributes to a significant degree of overtreatment that is observed for DTC around the globe. In the present paper we describe how improved understanding of the clinicopathological thyroid tumour progression model and optimization of clinical staging systems continues to improve our ability to diagnose and treat aggressive DTC. Early recognition of aggressive DTC allows instillation of an aggressive management strategy which is based upon oncologic completeness, and minimization of treatment-related sequelae through continued development of reconstructive options and focussed delivery of adjuvant treatments.
http://ift.tt/2y799Qc
Stereotactic vacuum-assisted breast biopsy: comparison between 11- and 8-gauge needles
Publication date: Available online 6 October 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Irene Ruggirello, Jacopo Nori, Isacco Desideri, Calogero Saieva, Elisabetta Giannotti, Giulia Bicchierai, Diego De Benedetto, Giulio Francolini, Simonetta Bianchi, Vania Vezzosi, Luis Sanchez, Tommaso Susini, Lorenzo Orzalesi, Icro Meattini, Lorenzo Livi, Vittorio Miele
PurposeThe 11-gauge (11G) stereotactic vacuum-assisted breast biopsy (VABB) showed a better profile than 14G-VABB in terms of feasibility, safety, microcalcification sampling, and accuracy. Underestimation rates were significantly lower with 11G-VABB than with 14G-VABB. Thus, the introduction of an even larger needle at the VABB procedure could reduce this rate further. The purpose of this study was to compare the overall performance of stereotactic VABB with 8G and 11G needles.Materials and methodsFour hundred and three VABBs performed between July 2012 and February 2015 at the Breast Diagnostic Unit of Careggi Hospital in Florence were retrospectively analyzed; 197 were performed with 11G-VABB and 206 with 8G-VABB. Lesions were classified according to mammographical patterns in microcalcifications, architectural distortions, or opacities, and all biopsy targets were classified according to BIRADS classification as BIRADS III, IV or V. Data were collected on radiological classification of targets, imaging presentation, procedure time, number of specimens per procedure, and microcalcification retrieval on histological findings. Surgery was always performed when high-risk or malignant lesions (B3 or B5) were detected; the final diagnosis was made on surgical pathology.ResultsCompared to VABB with an 11G needle, 8G-VABB allows a reduction in the time needed to complete the procedure (20.6 versus 27.4, P < 0.00001) and the number of specimens collected per lesion (21.6 versus 12.2, P < 0.00001). Moreover, 8G-VABB resulted in the same diagnostic accuracy, and the underestimation rates were comparable between the two groups for both B3 and DCIS lesions.ConclusionsThe 8G needle should be considered as a valid alternative option in VABB for breast lesions.
http://ift.tt/2fZm9AN
Cortical β-Amyloid Burden, Gray Matter, and Memory in Adults at Varying APOE ε4 Risk for Alzheimer's Disease
Source:Neurobiology of Aging
Author(s): Adam P. Mecca, Nicole M. Barcelos, Shuo Wang, Anna Brück, Nabeel Nabulsi, Beata Planeta-Wilson, Jennifer Nadelmann, Amanda L. Benincasa, Jim Ropchan, Yiyun Huang, Joel Gelernter, Peter H. Van Ness, Richard E. Carson, Christopher H. van Dyck
Models of preclinical Alzheimer's disease (AD) propose that cerebral amyloidosis leads to neurodegeneration and subsequent cognitive decline. This study investigated whether APOE genotype is related to β-amyloid (Aβ) burden in brain regions preferentially affected by AD and whether Aβ burden is associated with gray matter fraction (as a marker of neurodegeneration) and episodic memory performance in cognitively normal middle-aged individuals at varying genetic risk for AD. Three groups of cognitively normal participants aged 50-65 with a first-degree family history of AD [APOE genotype ε4ε4 (n=15), ε3ε4 (n=15), and ε3ε3 (n=15)], underwent [11C]PiB PET scans to quantify cortical Aβ, brain MRI and neuropsychological testing. APOE ε4ε4 participants demonstrated significantly higher cortical Aβ burden than APOE ε3ε3 (p<0.001). Furthermore, cortical Aβ burden was inversely associated with cortical gray matter fraction (p=0.017), but not episodic memory performance. In cognitively normal, middle-aged individuals, Aβ burden is significantly associated with gray matter fraction but not episodic memory performance. These findings are consistent with models of preclinical AD in which neurodegeneration occurs before manifest cognitive decline.
http://ift.tt/2wD80Mu
Recollection-related increases in functional connectivity across the healthy adult lifespan
Source:Neurobiology of Aging
Author(s): Danielle R. King, Marianne de Chastelaine, Michael D. Rugg
In young adults, recollection-sensitive brain regions exhibit enhanced connectivity with a widely distributed set of other regions during successful versus unsuccessful recollection, and the magnitude of connectivity change correlates with individual differences in recollection accuracy. Here, we examined whether recollection-related changes in connectivity and their relationship with performance varied across samples of young, middle-aged, and older adults. Psychophysiological interactions (PPI) analyses identified recollection-related increases in connectivity both with recollection-sensitive seed regions and among regions distributed throughout the whole brain. The seed-based approach failed to identify age-related differences in recollection-related connectivity change. However, the whole-brain analysis revealed a number of age-related effects. Numerous pairs of regions exhibited a main effect of age on connectivity change, mostly due to decreased change with increasing age. After controlling for recollection accuracy, however, these effects of age were for the most part no longer significant, and those effects that were detected now reflected age-related increases in connectivity change. A subset of pairs of regions also exhibited an age by performance interaction, driven mostly by a weaker relationship between connectivity change and recollection accuracy with increasing age. We conjecture that these effects reflect age-related differences in neuromodulation.
http://ift.tt/2giocg1
A bell-shaped dependence between amyloidosis and GABA accumulation in astrocytes in a mouse model of Alzheimer’s disease
Source:Neurobiology of Aging
Author(s): Bianca Brawek, Robert Chesters, Daniel Klement, Julia Müller, Chommanad Lerdkrai, Marina Hermes, Olga Garaschuk
Functioning at the interface between the nervous and immune systems, in the amyloid-depositing brain astrocytes become hypertrophic and accumulate around senile plaques. Moreover, hippocampal astrocytes upregulate their GABA content and enhance tonic inhibition, likely causing local circuit imbalance. It remains, however, unclear whether this effect is hippocampus-specific and how it is regulated during disease progression. Here, we studied changes in astrocytic morphology and GABA content in the frontal cortex and dentate gyrus of control and amyloid-depositing mice. Healthy aging was accompanied by a transient increase in astrocytic GABA content at middle age and region-specific alterations of soma size. In contrast, amyloid deposition caused a gradual cortex-accentuated increase in soma size. Importantly, our data uncovered a bell-shaped relationship between the mouse age and astrocytic GABA content in both brain regions. Moreover, in mice carrying an Alzheimer's disease (AD)-related mutation in presenilin 1, astrocytes accumulated GABA even in the absence of amyloidosis. These data question the proposed inhibition of astrocytic GABA synthesis as a universal strategy for treating network dysfunction in AD.
http://ift.tt/2wCk3JV
Reversal of age-related cognitive impairments in mice by an extremely low dose of tetrahydrocannabinol (THC)
Source:Neurobiology of Aging
Author(s): Yosef Sarne, Roni Toledano, Lital Rachmany, Effrat Sasson, Ravid Doron
This study was designed to test our hypothesis that an ultra-low dose of THC (delta-9 tetrahydrocannabinol) reverses age-dependent cognitive impairments in old mice, and to examine the possible biological mechanisms that underlie this behavioral effect. Old female mice aged 24 months that had been injected once with 0.002 mg/kg THC (3-4 orders of magnitudes lower than doses that induce the conventional cannabinoid effects in mice) performed significantly better than vehicle-treated old mice, and performed similarly to naive young mice aged 2 months, in 6 different behavioral assays that measured various aspects of memory and learning. The beneficial effect of THC lasted for at least 7 weeks. The single injection of THC increased the level of Sirtuin1, an enzyme that has been previously shown to be involved in neuroprotection and neuroplasticity, in the hippocampus and in the frontal cortex of old mice, for at least 7 weeks. Magnetic Resonance Imaging (MRI) demonstrated a larger volume and higher tissue density in various regions of the brain of THC-treated old mice. These findings suggest that extremely low doses of THC that are devoid of any psychotropic effect and do not induce desensitization, may provide a safe and effective treatment for cognitive decline in aging humans.
http://ift.tt/2giyIUI
Inhibition of cathepsin L alleviates the microglia-mediated neuroinflammatory responses through caspase-8 and NF-κB pathways
Source:Neurobiology of Aging
Author(s): Shaoqing Xu, Hui Zhang, Xiaodong Yang, Yiwei Qian, Qin Xiao
Cathepsin L (CTSL) has been shown to participate in the microglia-mediated neuroinflammation. However, role of CTSL in neuroinflammation remains to be elucidated. In this study, CTSL was found to be up-regulated upon lipopolysaccharide (LPS) stimulation. The neuroinflammatory responses upon LPS stimulation were ameliorated by inhibition or deficiency of CTSL in vitro or vivo. Treatment with conditioned medium of activated BV2 cells in SH-SY5Y cells showed that CTSL inhibition reduced microglia-mediated neurotoxicity. Further analysis indicated that CTSL was involved in the activation of caspase-8 and NF-κB, and overexpression of CTSL enhanced expression of inflammatory mediators in response to LPS via caspase-8 and NF-κB pathways. Moreover, mRNA level of CTSL in peripheral blood mononuclear cells from patients with Parkinson's disease (PD) was higher compared with controls. Level of CTSL was positively correlated with expression of inflammatory mediators and NF-κB in PD patients. Taken together, these findings suggested that inhibition of CTSL alleviated the neuroinflammatory responses through caspase-8 and NF-κB pathways, and blocking CTSL might provide some clues to control the excessive neuroinflammation.
http://ift.tt/2wCjXlx
Grey matter network measures are associated with cognitive decline in mild cognitive impairment
Source:Neurobiology of Aging
Author(s): Ellen Dicks, Betty M. Tijms, Mara ten Kate, Alida A. Gouw, Marije R. Benedictus, Charlotte E. Teunissen, Frederik Barkhof, Philip Scheltens, Wiesje M. van der Flier
Grey matter networks are disrupted in Alzheimer's disease and related to cognitive impairment. However, it is still unclear whether these disruptions are associated with cognitive decline over time. Here, we studied this question in a large sample of patients with mild cognitive impairment with extensive longitudinal neuropsychological assessments. Grey matter networks were extracted from baseline structural MRI and we tested associations of network measures and cognitive decline in MMSE and five cognitive domains (i.e., memory, attention, executive function, visuospatial and language). Disrupted network properties were cross-sectionally related to worse cognitive impairment. Longitudinally, lower small-world coefficient values were associated with a steeper decline in almost all domains. Lower betweenness centrality values correlated with a faster decline in MMSE and memory and, at a regional level, these associations were specific for the precuneus, medial frontal and temporal cortex. Furthermore, network measures showed additive value over established biomarkers in predicting cognitive decline. Our results suggest that grey matter network measures might have use in identifying patients who will show fast disease progression.
http://ift.tt/2giOr69
A phase IB dose-escalation study of the safety and pharmacokinetics of pictilisib in combination with either paclitaxel and carboplatin (with or without bevacizumab) or pemetrexed and cisplatin (with or without bevacizumab) in patients with advanced non–small cell lung cancer
Source:European Journal of Cancer, Volume 86
Author(s): Jean-Charles Soria, Alex A. Adjei, Rastilav Bahleda, Benjamin Besse, Charles Ferte, David Planchard, Jing Zhou, Joseph Ware, Kari Morrissey, Geetha Shankar, Wei Lin, Jennifer L. Schutzman, Grace K. Dy, Harry J.M. Groen
AimThe phosphatidylinositol 3-kinase (PI3K) pathway is a potential therapeutic target in non–small cell lung cancer (NSCLC). This study aimed to evaluate the pan-PI3K inhibitor pictilisib in combination with first-line treatment regimens that were the standard of care at the time of study, in patients with NSCLC.Patients and methodsA 3 + 3 dose-escalation study was performed using a starting daily dose of 60 mg pictilisib on days 1–14 of a 21-day cycle. Depending on bevacizumab eligibility and NSCLC histology, patients also received either paclitaxel + carboplatin or pemetrexed + cisplatin, ± bevacizumab every 3 weeks. The primary objectives of the study were to assess safety and tolerability and to identify dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD) and a recommended phase II dose (RP2D), for each combination.ResultsAll 66 treated patients experienced at least one adverse event (AE). Grade ≥III AEs, serious AEs and deaths occurred in 57 (86.4%), 56 (84.8%) and 9 (13.6%) patients, respectively. Three patients reported DLTs across the four arms of the study. The MTD was not reached in any arm and the RP2D of pictilisib was determined to be 330 mg (capsules) or 340 mg (tablets) on a '14 days on, 7 days off' schedule. The best confirmed response was partial response in 29 (43.9%) patients and stable disease in 20 (30.9%) patients.ConclusionCombining pictilisib with various standard-of-care first-line treatment regimens is feasible from a safety perspective in patients with NSCLC, and encouraging preliminary anti-tumour activity was observed.
http://ift.tt/2yvpH5l
Diarrhoea during checkpoint blockade, not always colitis
Source:European Journal of Cancer
Author(s): Josephine J. Koldenhof, Karijn P.M. Suijkerbuijk
http://ift.tt/2xo8NRd
Potential role of polymorphisms in the transporter genes ENT1 and MATE1/OCT2 in predicting TAS-102 efficacy and toxicity in patients with refractory metastatic colorectal cancer
Source:European Journal of Cancer, Volume 86
Author(s): Mitsukuni Suenaga, Marta Schirripa, Shu Cao, Wu Zhang, Dongyun Yang, Vincenzo Dadduzio, Lisa Salvatore, Beatrice Borelli, Filippo Pietrantonio, Yan Ning, Satoshi Okazaki, Martin D. Berger, Yuji Miyamoto, Roel Gopez, Afsaneh Barzi, Toshiharu Yamaguchi, Fotios Loupakis, Heinz-Josef Lenz
BackgroundTrifluridine (FTD) is an active cytotoxic component of the metastatic colorectal cancer (mCRC) drug TAS-102, and thymidine phosphorylase inhibitor (TPI) inhibits the rapid degradation of FTD. We tested whether single nucleotide polymorphisms (SNPs) in genes involved in FTD metabolism and TPI excretion could predict outcome in patients with mCRC treated with TAS-102.Patients and methodsWe investigated three different cohorts: a training cohort (n = 52) and a testing cohort (n = 129) both receiving TAS-102 and a control cohort (n = 52) receiving regorafenib. SNPs of TK1, ENT1, CNT1, MATE1, MATE2 and OCT2 were analysed by polymerase chain reaction-based direct DNA sequencing.ResultsIn the training cohort, patients with any ENT1 rs760370 G allele had a significantly longer progression-free survival (PFS; 3.5 versus 2.1 months, respectively, hazard ratio [HR] 0.44, P = 0.004) and overall survival (OS; 8.7 versus 5.3 months, respectively, HR 0.27, P = 0.003) than the A/A genotype. These findings were validated in the testing cohort (P = 0.021 and 0.009 for PFS and OS, respectively). In addition, the combination of ENT1 rs760370, MATE1 rs2289669 and OCT2 rs316019 SNPs significantly stratified patients with the risk of PFS and OS in both cohorts (P < 0.001 for PFS and OS in the training cohort; P = 0.053 and 0.025 for PFS and OS, respectively, in the testing cohort). No significant differences were observed in the control group.ConclusionsThe combination of ENT1, MATE1 and OCT2 SNPs may serve as a predictive and prognostic marker in mCRC patients treated with TAS-102.
http://ift.tt/2yvpv67
Bridging the gap between the randomised clinical trial world and the real world by combination of population-based registry and electronic health record data: A case study in haemato-oncology
Source:European Journal of Cancer, Volume 86
Author(s): R.E. Kibbelaar, B.E. Oortgiesen, A.M. van der Wal-Oost, K. Boslooper, J.W. Coebergh, N.J.G.M. Veeger, P. Joosten, H. Storm, E.N. van Roon, M. Hoogendoorn
Randomised clinical trials (RCTs) are considered the basis of evidence-based medicine. It is recognised more and more that application of RCT results in daily practice of clinical decision-making is limited because the RCT world does not correspond with the clinical real world. Recent strategies aiming at substitution of RCT databases by improved population-based registries (PBRs) or by improved electronic health record (EHR) systems to provide significant data for clinical science are discussed. A novel approach exemplified by the HemoBase haemato-oncology project is presented. In this approach, a PBR is combined with an advanced EHR, providing high-quality data for observational studies and support of best practice development. This PBR + EHR approach opens a perspective on randomised registry trials.
http://ift.tt/2xojrqZ
A 3D-printed modular device for imaging the brain of small birds
Source:Journal of Neuroscience Methods
Author(s): Christine R. Lattin, Maxwell A. Emerson, Jean-Dominique Gallezot, Tim Mulnix, J. Elliott Brown, Richard E. Carson
BackgroundOne potential barrier to using in vivo imaging in any new animal species is solving the basic problem of how to hold animals safely and securely during scans.New MethodIn this paper, we describe the design, fabrication, use, and positional reproducibility of a 3D-printed plastic device (the Avian Imaging Device, or AID) for imaging the brain of 1 or 2 small songbirds. We designed two different types of head cones to use with this device: one that was not contoured and designed for anesthesia induction, and one contoured to the shape of a house sparrow head, designed to be used with a pre-anesthetized animal.ResultsCompared to no holder, using the AID with both contoured and non-contoured head cones significantly reduced the amount of translation necessary to align the head in pairs of CT scans (by 78% and 90%, respectively); using the contoured head cone also significantly reduced the amount of rotation necessary for head alignment in registering pairs of scans (by 90%).Comparison with Existing Method(s)Using an animal holder that can not only securely hold animals but which has high positional reproducibility is essential to take advantage of the maximum resolution possible with small animal imaging. 3D-printed materials are also compatible with PET and CT, environmentally stable, and fast and inexpensive to make.ConclusionsResearchers can learn from the design of the AID and use our CAD models as a starting point for fabricating devices for multiple small-animal imaging needs.
http://ift.tt/2y6sAYV
A Novel Technology to Model Pressure-Induced Cellular Injuries in the Brain
Publication date: Available online 6 October 2017
Source:Journal of Neuroscience Methods
Author(s): Michael E. Smith, Ramin Eskandari
BackgroundElevated intracranial pressure (ICP) accompanying a number of neurological emergencies is poorly understood, and lacks a model to determine cellular pathophysiology. This limits our ability to identify cellular and molecular biomarkers associated with the pathological progression from physiologic to pathologic ICP.New MethodWe developed an ex vivo model of pressure-induced brain injury, which combines 3D neural cell cultures and a newly developed Pressure Controlled Cell Culture Incubator (PC3I). Human astrocytes and neurons maintained in 3D peptide-conjugated alginate hydrogels were subjected to pressures that mimic both physiologic and pathologic levels of ICP for up to 48hours to evaluate the earliest impacts of isolated pressure on cellular viability and quantify early indicators of pressure-induced cellular injury.ResultsCompared to control cell cultures grown under physiologic pressure, sustained pathologic pressure exposure increased the release of intracellular ATP in a cell-specific manner. Eighteen hours of sustained pressure resulted in increased ATP release from neurons but not astrocytes.Comparison with Existing MethodsCell culture incubators maintain cultures at normal atmospheric pressure. Based on multiple literature searches, we are not aware of any other cell culture incubator systems that modify the pressure at which primary CNS cells are maintained.ConclusionThis model simulates the clinical features of elevated ICP encountered in patients with hydrocephalus, and provides a first estimate of the pathological signaling encountered during the earliest perid of progression in neonatal hydrocephalus. This model should provide a means to better understand the pathological biomarkers associated with the earliest stages of elevated ICP.
Graphical abstract
http://ift.tt/2y1QG5w
Preparation of polysomal fractions from mouse brain synaptoneurosomes and analysis of polysomal-bound mRNAs
Source:Journal of Neuroscience Methods
Author(s): Bozena Kuzniewska, Magdalena Chojnacka, Jacek Milek, Magdalena Dziembowska
BackgroundHere we describe a detailed, reliable protocol for isolation of polysomal fractions from mouse brain synaptoneurosomes. This method is an important tool to study local protein synthesis in neurons.New MethodWe combined rapid preparation of synaptoneurosomes by filtration with polysome profiling. We provide a detailed protocol highlighting difficulties and critical steps of: i) preparation of synaptoneurosomes; ii) polyribosome fractionation from synaptoneurosomes; iii) extraction of proteins and RNA from sucrose gradient fractions.Resultsand Comparison with Existing Methods We fractionated polyribosomes from synaptoneurosomes and detected the association of Mmp9, Camk2a and Stx1B mRNA with polysomes in the unstimulated conditions. Synaptic stimulation led to increased levels of Mmp9 and Camk2a mRNA in the heavy polysomal fractions. We compared our protocol with existing methodsConclusionsWe have developed a reliable, effective method to prepare polyribosomal fractions from synaptoneurosomes to study polyribosomal binding of mRNAs as an aspect of synaptic translation in vitro.
http://ift.tt/2y1dXVd
A distinctive subgroup of oral EBV+ B-cell neoplasm with polymorphous features is potentially identical to EBV+ mucocutaneous ulcer
Publication date: Available online 6 October 2017
Source:Human Pathology
Author(s): Yae Ohata, Anna Tatsuzawa, Yoshio Ohyama, Ayako Ichikawa, Yumi Mochizuki, Sachiko Ishibashi, Yuri Itakura, Kei Sakamoto, Tohru Ikeda, Masanobu Kitagawa, Kouhei Yamamoto
EBV-positive mucocutaneous ulcer (EBVMCU) is a newly recognized provisional entity, included in mature B-cell neoplasm in the latest 2016 World Health Organization Classification. It has a self-limited growth potential with a high predilection for oral cavities, and occurs in age-related or iatrogenic immunodeficiency with indolent clinical courses. However, it shares histological features with EBV-positive diffuse large B-cell lymphoma (DLBCL), and this often leads to diagnostic challenges and controversies in patients with an oral EBV-positive B-cell neoplasm. The aim of this study was to better characterize and comprehend the pathophysiology of DLBCL and EBVMCU in the oral cavity. We conducted clinicopathologic and recurrent gene mutation analysis of 49 cases (14 EBV-positive, 35 EBV-negative) including cases diagnosed as DLBCL or B-cell lymphoproliferative disorders with high-grade morphology in the oral cavity. All EBV-positive cases matched the criteria of EBVMCU, with significantly earlier clinical stages than the EBV-negative group (P=.0006). Besides, histological analysis showed that all EBV-positive cases presented polymorphous features, while 91.4% (32/35) of the EBV-negative cases showed diffuse and monotonous proliferation (P<.0001). Further, EBV-positive cases presented favorable clinical outcomes without disease-related death or recurrence. Gene mutation analysis (MYD88, CD79A, CD79B, CARD11, and EZH2) revealed that 33.3% (9/27) of EBV-negative cases harbored at least one gene mutation, while no gene mutation was observed in the EBV-positive group (0/11). These results suggest that oral EBV-positive B-cell lymphoid proliferation with polymorphous features often fulfill the criteria for EBVMCU, with clinicopathologically and genetically distinctive properties.
http://ift.tt/2gh44Lh
Therapies for Inner Ear Disorders Are One Step Closer to Reality
Spiral Therapeutics (http://ift.tt/2xooDek), a pre-clinical stage company developing first-in-class therapies targeting inner ear disorders, has received positive feedback from the U.S. Drug and Food Administration (FDA) regarding its first Pre-Investigational New Drug (Pre-IND) package submission. The FDA answered Spiral's product development questions related to manufacturing and non-clinical testing, and concurred with the company's clinical development plans for its LPT99 program for preventing chemotherapy-induced hearing loss in pediatric patients. Pre-IND is a program through which the FDA's Office of Antimicrobial Products could provide advice on drug development before it begins. Spiral plans to raise additional funds for an initial Phase 1 trial, the development of new preclinical data, and the company's operations for the next 18 months.
Published: 10/6/2017 1:51:00 PM
http://ift.tt/2yvLGcg
Transfer of radionuclides to plants of natural ecosystems at the Semipalatinsk Test Site
Source:Journal of Environmental Radioactivity
Author(s): N.V. Larionova, S.N. Lukashenko, A.M. Kabdyrakova, A.Ye. Kunduzbayeva, A.V. Panitskiy, A.R. Ivanova
A systematic study devoted to 137Cs, 90Sr, 241Am, 239+240Pu radionuclides in vegetation cover from several spots of the Semipalatinsk test site (STS) is summarised in this paper, highlighting the main findings obtained. The analysed spots are characterized by various types of radioactive contamination.Transfer factors (Tf) required for the quantitative description of the radionuclides transition from the soil to aboveground plant parts were determined, being found that, on average, the minimum Tf for all the radionuclides concerned were determined on the "Experimental Field" ground, followed by the determined ones in the "plumes" of radioactive fallout and in the conditionally "background" territories analysed. The highest transfer factors were characteristic of zones of radioactive streamflows and places of warfare radioactive agent (WRA) tests.On the other hand, ordering the radionuclide transferring factors in descending order, the following sequence was obtained: 90Sr Tf > Cs Tf > 239+240Pu Tf > 241Am Tf, with the 90Sr Tf, on the average, exceeding the 137Cs Tf by 8 times and exceeding the 239+240Pu Tf by up 16 times. 239+240Pu Tf values were up to 3 times higher than the 241Am Tf. The exception to the indicated radionuclide Tf descending order corresponded to places of WRA tests where Tf of radionuclides of interest by plants follows the sequence 90Sr > 239+240Pu > 137Cs.
http://ift.tt/2wCfGOV
Have we pushed the needle for treatment of Type 1 diabetes?
Source:Current Opinion in Immunology, Volume 49
Author(s): Nida Naushad, Ana Luisa Perdigoto, Jinxiu Rui, Kevan C Herold
Studies with immunologics have shown that the natural history of Type 1 diabetes can be modified. These studies have targeted key mediators of the disease and recent analyses, together with studies in preclinical models have identified mechanisms that may be involved in the clinical effects. Several issues remain including specificity of the interventions, adverse effects of the treatments, and duration of their effects. Future studies are likely to include more specific approaches with agents such as cell therapies with selected immune regulatory subsets, antigen specific therapies, and combinations of agents with complementary mechanisms of activity.
http://ift.tt/2ggIbf4
Pathogenesis of infections in HIV-infected individuals: insights from primary immunodeficiencies
Source:Current Opinion in Immunology, Volume 48
Author(s): Qian Zhang, Pierre Frange, Stéphane Blanche, Jean-Laurent Casanova
Following infection with almost any given microorganism other than an emerging pathogen, only a minority of individuals develop life-threatening clinical disease, implying that these individuals have some form of immunodeficiency. A growing number of inherited and acquired immunodeficiencies have been deciphered over the last 50 years. HIV infection is probably the best-known acquired immunodeficiency. It emerged about 40 years ago and precipitates various severe infections, the occurrence of which is associated with a fall in circulating CD4+ T cells. However, despite the strength of this correlation, infection rates differ between patients with similar levels and durations of CD4+ T lymphopenia in the presence or absence of antiretroviral treatment. Moreover, a few infections seem to be less dependent on total CD4+ T-cell levels. The fine detail of the mechanisms underlying these infections is unknown. We discuss here how studies of the human genetics and immunology of some of these infections in patients with primary immunodeficiencies (PIDs) have provided unique insights into their molecular and cellular basis. Defects of specific CD4+ Th-cell subsets account for some of these infections, as best exemplified by Th1* for mycobacteriosis and Th17 for candidiasis. PIDs are individually rare, but collectively much more common than initially thought, with new disorders being discovered at an ever-increasing pace and a global prevalence worldwide approaching that of HIV infection. Studies of known and new PIDs should make it possible to dissect the pathogenesis of most human infections at an unprecedented level of molecular and cellular precision. The predictive, preventive, and therapeutic implications of studies of immunity to infection in PIDs may extend to HIV-infected patients and patients with infectious diseases in other settings.
http://ift.tt/2y63U2T
Patients’ preferences for headache acute and preventive treatment
We aimed to explore patients' preferences for headache treatments with a self-administered questionnaire including the Q-No questionnaire for nocebo.
http://ift.tt/2yNLIZf
The relative effects of dexmedetomidine and propofol on cerebral blood flow velocity and regional brain oxygenation: A randomised noninferiority trial
BACKGROUND: Dexmedetomidine constricts cerebral blood vessels without a concomitant reduction in cerebral metabolic oxygen consumption. Its safety as a sedative in patients with neurological diseases thus remains uncertain. OBJECTIVE: Our primary objective was to test the hypothesis that dexmedetomidine is noninferior to propofol as regards cerebral blood flow (CBF) velocity and brain oxygenation. DESIGN: Unblinded randomised trial. SETTING: Cleveland Clinic Hospital, Cleveland, from November 2010 to July 2013. PATIENTS: Forty-four patients scheduled for insertion of a deep-brain stimulating electrodes. INTERVENTIONS: Patients were randomised to receive either dexmedetomidine or propofol sedation during deep-brain stimulating electrode insertion. MAIN OUTCOME MEASURES: Intraoperative CBF velocity was measured with transcranial Doppler, and brain oxygenation was assessed with near-infrared spectroscopy. Noninferiority of dexmedetomidine to propofol was defined as a less than 20% difference in means. RESULTS: Twenty-three patients were given dexmedetomidine and 21 propofol. Baseline characteristics and operative management were similar in each group. Dexmedetomidine was noninferior to propofol on both CBF and brain oxygenation, confirming our primary hypothesis. For cerebral flood flow, the estimated ratio of means (dexmedetomidine/propofol) was 0.94 [90% CI: 0.84 to 1.05], P = 0.011 for noninferiority. For brain oxygenation, the estimated ratio of means was 0.99 [90% CI: 0.96 to 1.02], P http://ift.tt/2xZP24i
Sevoflurane attenuates systemic inflammation compared with propofol, but does not modulate neuro-inflammation: A laboratory rat study
BACKGROUND: Septic encephalopathy is believed to be a result of neuro-inflammation possibly triggered by endotoxins, such as lipopolysaccharides (LPS). Modulation of the immune system is a property of volatile anaesthetics. OBJECTIVE: We aimed to investigate the systemic and cerebral inflammatory response in a LPS-induced sepsis model in rats. We compared two different sedation strategies, intravenous propofol and the volatile anaesthetic sevoflurane, with the hypothesis that the latter may attenuate neuro-inflammatory processes. DESIGN: Laboratory rat study. SETTING: Basic research laboratories at the University Hospital Zurich and University Zurich Irchel between August 2014 and June 2016. PATIENTS: A total of 32 adult male Wistar rats. INTERVENTIONS: After tracheotomy and mechanical ventilation, the anaesthetised rats were monitored before sepsis was induced by using intravenous LPS or phosphate-buffered saline as control. Rats were sedated with propofol (10 mg kg−1 h−1) or sevoflurane (2 vol%) continuously for 12 h. MAIN OUTCOME MEASURES: Systemic inflammatory markers such as cytokine-induced neutrophil chemo-attractant protein 1, monocyte chemo-tactic protein-1 and IL-6 were determined. The same cytokines were measured in brain tissue. Cellular response in the brain was assessed by defining neutrophil accumulation with myeloperoxidase and also activation of microglia with ionised calcium-binding adaptor molecule-1 and astrocytes with glial fibrillary acidic protein. Finally, brain injury was determined. RESULTS: Animals were haemodynamically stable in both sedation groups treated with LPS. Blood cytokine peak values were lower in the sevoflurane-LPS compared with propofol-LPS animals. In brain tissue of LPS animals, chemoattractant protein-1 was the only significantly increased cytokine (P = 0.003), however with no significance between propofol and sevoflurane. After LPS challenge, cerebral accumulation of neutrophils was observed. Microglia activation was pronounced in the hippocampus of animals treated with LPS (P = 0.006). LPS induced prominent astrogliosis (P http://ift.tt/2y0DwFK
The impact of continuous non-invasive arterial blood pressure monitoring on blood pressure stability during general anaesthesia in orthopaedic patients: A randomised trial
BACKGROUND: In patients undergoing general anaesthesia, intraoperative hypotension occurs frequently and is associated with adverse outcomes such as postoperative acute kidney failure, myocardial infarction or stroke. A history of chronic hypertension renders patients more susceptible to a decrease in blood pressure (BP) after induction of general anaesthesia. As a patient's BP is generally monitored intermittently via an upper arm cuff, there may be a delay in the detection of hypotension by the anaesthetist. OBJECTIVE: The current study investigates whether the presence of continuous BP monitoring leads to improved BP stability. DESIGN: Randomised, controlled and single-centre study. PATIENTS: A total of 160 orthopaedic patients undergoing general anaesthesia with a history of chronic hypertension. INTERVENTION: The patients were randomised to either a study group (n = 77) that received continuous non-invasive BP monitoring in addition to oscillometric intermittent monitoring, or a control group (n = 83) whose BP was monitored intermittently only. The interval for oscillometric measurements in both groups was set to 3 min. After induction of general anaesthesia, oscillometric BP values of the two groups were compared for the first hour of the procedure. Anaesthetists were blinded to the purpose of the study. MAIN OUTCOME MEASURE: BP stability and hypotensive events. RESULTS: There was no difference in baseline BP between the groups. After adjustment for multiple testing, mean arterial BP in the study group was significantly higher than in the control group at 12 and 15 min. Mean ± SD for study and control group, respectively were: 12 min, 102 ± 24 vs. 90 ± 26 mmHg (P = 0.039) and 15 min, 102 ± 21 vs. 90 ± 23 mmHg (P = 0.023). Hypotensive readings below a mean pressure of 55 mmHg occurred more often in the control group (25 vs. 7, P = 0.047). CONCLUSION: Continuous monitoring contributes to BP stability in the studied population. TRIAL REGISTRATION: NCT02519101.http://ift.tt/2yv6TDh
Validation of radial artery-based uncalibrated pulse contour method (PulsioFlex) in critically ill patients: A observational study
BACKGROUND: Because of their simplicity, uncalibrated pulse contour (UPC) methods have been introduced into clinical practice in critical care but are often validated with a femoral arterial waveform. OBJECTIVE: We aimed to test the accuracy of cardiac index (CI) measurements and trending ability from a radial artery with one UPC. DESIGN: An observational study. SETTING: Tertiary care mixed-surgical ICU. Data were obtained from April 2015 to July 2016. PATIENTS: We studied 20 critically ill mechanically ventilated patients monitored by UPC (PulsioFlex; Pulsion Medical Systems SE, Feldkirchen, Germany). We used transpulmonary thermodilution (PiCCO2) as a reference. MAIN OUTCOME MEASURES: Bland–Altman-analyses with percentage errors were calculated to assess the accuracy of CI values from radial pulse contour analysis (CIRAD), autocalibration (CIAC) and femoral pulse contour analysis (CIFEM). All were compared with a reference (CITD) at 4-h intervals for 24 h. Trending ability was assessed by polar-plots and four-quadrant-plots. CI is given in l min−1 m−2. RESULTS: Bland–Altman-analyses: for CIRAD, the mean bias was −0.1 with limits of agreement (LOA) of −2.9 to 2.7 and a percentage error of 70%; for CIAC, the mean bias was 0 with LOA −2.8 to 2.7 and a percentage error of 70%; for CIFEM, the mean bias was 0 with LOA −1.2 to 1.2 and a percentage error of 30%, respectively. Polar plots for trending: for CIRAD, the angular bias was 12° with radial LOA of 39°, a polar concordance rate of 73% and a concordance rate of 67% in the four-quadrant-plot; for CIAC, the angular bias was 4° with radial LOA of 41°, polar concordance rate of 79% and a concordance rate of 74% in the four quadrant plot; for CIFEM, the angular bias was −2° with radial LOA of 50°, polar concordance rate of 74% and a concordance rate of 81%. CONCLUSION: In critically ill patients, the PulsioFlex system connected to a radial arterial catheter is inaccurate for CI measurements and does not track changes in CI adequately. We therefore recommend using validated thermodilution techniques for monitoring in the critical care setting.http://ift.tt/2yvNlyH
The relative effects of dexmedetomidine and propofol on cerebral blood flow velocity and regional brain oxygenation: A randomised noninferiority trial
BACKGROUND: Dexmedetomidine constricts cerebral blood vessels without a concomitant reduction in cerebral metabolic oxygen consumption. Its safety as a sedative in patients with neurological diseases thus remains uncertain. OBJECTIVE: Our primary objective was to test the hypothesis that dexmedetomidine is noninferior to propofol as regards cerebral blood flow (CBF) velocity and brain oxygenation. DESIGN: Unblinded randomised trial. SETTING: Cleveland Clinic Hospital, Cleveland, from November 2010 to July 2013. PATIENTS: Forty-four patients scheduled for insertion of a deep-brain stimulating electrodes. INTERVENTIONS: Patients were randomised to receive either dexmedetomidine or propofol sedation during deep-brain stimulating electrode insertion. MAIN OUTCOME MEASURES: Intraoperative CBF velocity was measured with transcranial Doppler, and brain oxygenation was assessed with near-infrared spectroscopy. Noninferiority of dexmedetomidine to propofol was defined as a less than 20% difference in means. RESULTS: Twenty-three patients were given dexmedetomidine and 21 propofol. Baseline characteristics and operative management were similar in each group. Dexmedetomidine was noninferior to propofol on both CBF and brain oxygenation, confirming our primary hypothesis. For cerebral flood flow, the estimated ratio of means (dexmedetomidine/propofol) was 0.94 [90% CI: 0.84 to 1.05], P = 0.011 for noninferiority. For brain oxygenation, the estimated ratio of means was 0.99 [90% CI: 0.96 to 1.02], P http://ift.tt/2xZP24i
Evaluation of preoperative oral carbohydrate administration on insulin resistance in off-pump coronary artery bypass patients: A randomised trial
BACKGROUND: In fasting cardiac surgery patients, preoperative carbohydrate (CHO) drink intake attenuated insulin resistance and improved cardiac metabolism, although its beneficial effects were not evident after cardiac surgery possibly due to cardiopulmonary bypass-related extreme systemic inflammation. OBJECTIVE: We aimed to evaluate whether preoperative CHO intake affected insulin resistance and free-fatty acid (FFA) concentrations in off-pump coronary revascularisation. DESIGN: A randomised controlled trial. SETTING: Primary care in a university hospital in Korea from January 2015 to July 2016. PATIENTS: Sixty patients who underwent elective multi-vessel off-pump coronary revascularisation were randomised into two groups. Three patients were excluded from analysis and 57 patients completed study. INTERVENTION: The CHO group received oral CHO (400 ml) the prior evening and 2 to 3 h before surgery, and the control group was fasted from food and water according to standard protocol. MAIN OUTCOME MEASURES: Insulin resistance was assessed twice, after anaesthetic induction and after surgery via short insulin tolerance test. FFA, C-reactive protein and creatine kinase-myocardial band concentrations were determined serially for 48 h after surgery. RESULTS: Insulin sensitivity was greater (P = 0.002) and plasma FFA concentrations were lower (P = 0.001) after anaesthetic induction in the CHO group compared with the Control group, although there were no intergroup differences after surgery. The postoperative peak creatine kinase-myocardial band concentration was significantly lower in the CHO group compared with the Control group [8.8 (5.4 to 18.2) vs. 6.4 (3.5 to 9.7) ng ml−1, P = 0.031]. CONCLUSION: A preoperative CHO supplement significantly reduced insulin resistance and FFA concentrations compared with fasting at the beginning of the surgery, but these benefits were lost after off-pump coronary revascularisation. Despite their transient nature, these beneficial effects resulted in less myocardial injury, mandating further studies focused on the impact of preoperative CHO on myocardial ischaemia and cardiac function after coronary revascularisation. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT 02330263.http://ift.tt/2y1165p
Rethinking indicators of problematic cannabis use in the era of medical cannabis legalization
Source:Addictive Behaviors, Volume 77
Author(s): Sharon R. Sznitman, Robin Room
IntroductionRecent rapid changes in medical cannabis policies and increases in medical use of cannabis have raised new research questions related to potential effects of medical cannabis legalization on cannabis use problems. In order to investigate such effects there is a need for screening tools that are sensitive to the fact that people may be using for medical and/or recreational purposes. This article critically assesses whether screening tools designed to measure cannabis use problems in recreational users are meaningful as measures of problems resulting from medical use.Results and conclusionsIt is possible that existing cannabis problem screening tools are not equally valid across medical and recreational users, since individual screening items have different implications for recreational and medical users. For instance, items that measure use that deviates from common patterns of recreational use (use before midday and use alone) reflect normative assumptions that non-problematic recreational use will occur in contexts of parties or social gatherings. However, use before midday and alone are how people typically take medication for chronic medical health problems. There is thus a need to develop and validate criteria for problematic use in medical cannabis patients.
http://ift.tt/2z2sKPj
Emerging role for the medial prefrontal cortex in alcohol-seeking behaviors
Source:Addictive Behaviors, Volume 77
Author(s): Paul M. Klenowski
The medial prefrontal cortex (mPFC) plays an important role in high-order executive processes and sends highly organized projections to sub-cortical regions controlling mood, motivation and impulsivity. Recent preclinical and clinical studies have demonstrated alcohol-induced effects on the activity and composition of the PFC which are implicated in associative learning processes and may disrupt executive control over impulsivity, leading to an inability to self-limit alcohol intake. Animal studies have begun to dissect the role of the mPFC circuitry in alcohol-seeking behavior and withdrawal, and have identified a key role for projections to sub-cortical sites including the extended amygdala and the nucleus accumbens (NAc). Importantly, these studies have highlighted that alcohol can have contrasting effects on the mPFC compared to other addictive substances and also produce differential effects on the structure and activity of the mPFC following short-term versus long-term consumption. Because of these differences, how the mPFC influences the initial aspects of alcohol-seeking behavior and how we can better understand the long-term effects of alcohol use on the activity and connectivity of the mPFC need to be considered. Given the lack of preclinical data from long-term drinking models, an increased focus should be directed towards identifying how long-term alcohol use changes the mPFC, in order to provide new insights into the mechanisms underlying the transition to dependence.
http://ift.tt/2xZDLDD
Efficacy and outcomes of a mobile app targeting alcohol use in young people
Source:Addictive Behaviors, Volume 77
Author(s): Leanne Hides, Catherine Quinn, Wendell Cockshaw, Stoyan Stoyanov, Oksana Zelenko, Daniel Johnson, Dian Tjondronegoro, Lake-Hui Quek, David J. Kavanagh
Mobile apps provide a highly accessible way of reducing alcohol use in young people. This paper determines the 1-month efficacy and 2, 3 and 6month outcomes of the Ray's Night Out app, which aims to increase alcohol knowledge and reduce alcohol use in young people. User-experience design and agile development processes, informed by the Information-Motivation-Behavioral skills model and evidence-based motivational interviewing treatment approaches guided app development. A randomized controlled trial comparing immediate versus 1-month delayed access to the app was conducted in 197 young people (16 to 25years) who drank alcohol in the previous month. Participants were assessed at baseline, 1, 2, 3 and 6months. Alcohol knowledge, alcohol use and related harms and the severity of problematic drinking were assessed. App quality was evaluated after 1-month of app use. Participants in the immediate access group achieved a significantly greater increase in alcohol knowledge than the delayed access group at 1-month, but no differences in alcohol use or related problems were found. Both groups achieved significant reductions in the typical number of drinks on a drinking occasion over time. A reduction in maximum drinks consumed was also found at 1month. These reductions were most likely to occur in males and problem drinkers. Reductions in alcohol-related harm were also found. The app received a high mean quality (M=3.82/5, SD=0.51). The Ray app provides a youth-friendly and easily-accessible way of increasing young people's alcohol knowledge but further testing is required to determine its impact on alcohol use and related problems.
http://ift.tt/2xng7MS
Simultaneous alcohol & tobacco use expectancies in young adult co-users
Source:Addictive Behaviors, Volume 77
Author(s): Ryan S. Trim, Neal Doran
http://ift.tt/2z4iPZu
Sirolimus precipitating diabetes mellitus in a patient with congenital hyperinsulinaemic hypoglycaemia due to autosomal dominant ABCC8 mutation
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
http://ift.tt/2giif2C
Adipose-derived stem cell sheet encapsulated construct of micro-porous decellularized cartilage debris and hydrogel for cartilage defect repair.
Source:Medical Hypotheses
Author(s): Yuxiang Zhang, Zhong Lei, Yiying Qi, Tuoyu Di, Guoqi Li, Wenkai Zhang, Weiqi Yan
Challenges of repairing injuries and damage to the cartilage still remain in orthopedics. The characteristics of cartilage structure, especially avascular, make it a limited capacity of self-renewal. Articular cartilage defect or damage result from various causes will lead to degenerative osteoarthritis (OA). Surgical treatment and non-surgical treatment can temporarily alleviate symptoms to some extent but can't fundamentally restore the normal structure and function of cartilage, and therefore give rise to progressive degeneration. Autologous or allogeneic cartilage transplantation has been employed to the treatment of osteoarthritis for years. Nevertheless, the major deficiency of cartilage grafting is the inability and insufficiency to repair large cartilage defect. Implants are also unable to integrate with native tissue well. Adipose-derived stem cells (ASCs) can be easily isolated from subcutaneous fat tissues and harvest as intact cell sheets containing extracellular matrix (ECM), intercellular connect, ion channel, growth factor receptors, nexin and other important cell surface proteins by means of temperature-responsive culture dish (TCD). A cell sheet can provide a large amount of extracellular matrix, fibronectin, and cells contributing to the integration of cartilage. Decellularized extracellular matrix (DECM) of cartilage debris with excellent cell affinity and signal transduction is capable of driving cartilage homeostasis and regeneration. Appropriate decellularization process would remove cellular remnants of cartilage debris, keep the mechanical properties, and avoid the adverse immune response of allografts effectively. Micro-porous cartilage debris conduces to cell migration and angiogenesis. The cell-round shape of adipose-derived stem cells cultured in the three-dimensional (3D) system provided by hydrogel is more susceptible to chondrogenic stimulation and prevents it from fibroblast-like phenotypic conversion. We hypothesize that adipose-derived stem cell sheet encapsulated construct of micro-porous decellularized cartilage debris and hydrogel can effectively promote regeneration of cartilage defect. The construct of decellularized cartilage debris and hydrogel provide a favorable microenvironment for stem cells. Adipose-derived stem cells sheet supply fibronectin, collagen, and cells contributing to integration and regeneration of cartilage restore. Moreover, the constructs can be shaped and fabricated according to the configuration of target defect, especially in osteoarthritis, which is promising for clinical application.
http://ift.tt/2yNPIZw
Can memory exist outside of brain and be transferred? Historical review, issues & ways forward
Source:Medical Hypotheses
Author(s): Ghulam Abbas, Wajahat Mahmood, Faisal Khan
Learning and memory are among the executive functions attributed to intelligent forms of life. Unfortunately, there is a lack of clear understanding regarding the underlying mechanisms governing these functions. Most of the modern day scientists attribute these functions solely to brain. However, in the latter half of last century, a number of reports suggested existence of extra-cranial memory and potential of its transfer between animals. Some have linked this phenomenon to RNA while others believed that peptides were responsible. The terms like "educated RNA" and "scotophobin" were coined. This atypical work involving flatworms, yeast RNA and scotophobin was received with deep skepticism and ultimately disregarded. However, the recent reproduction of some of this earlier work by scientists at Tufts University has reignited the debate on the mechanisms of learning and memory. Keeping this in view, we believe it is high time to summarize this historical work and discuss the possibilities to delineate these atypical claims. The objective is to incite the present day researchers to explore this opportunity under the perspective of newer advancements in science.
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Dynamics of oogenesis in ghost shrimp Callichirus major (Crustacea: Axiidea): a morphofunctional and histochemical study
Source:Acta Histochemica
Author(s): Tugstênio L. Souza, Adriane A. Braga, Laura S. López-Greco, Erika T. Nunes
Callichirus major, popularly known as ghost shrimp, is a species of great importance in the fishing industry, because of its use as live bait. This study aimed to describe the different stages of the developing ovaries in C. major. Shrimps were collected along the Corujão beach, Piuma, Brazil (20°50'41.6"S 40°44'15.7"W), and the gonads were dissected for histological and histochemical analysis. The ovary consists of two elongated filaments covered by a connective tissue that divides the organ into lobules, where somatic and germ cells are found. It was possible to classify five types of germ cells: Oogonia (Oog), previtellogenic oocyte (Oc1), early vitellogenic oocyte (Oc2), late vitellogenic oocyte (Oc3) and mature oocyte (Oc4) based on their vitellogenic stage, cytoplasmic, nuclear and morphometric characteristics. The histochemical analysis demonstrated an intense reaction for proteins and polysaccharides in peripheral cytoplasm of Oc3 comparing to others cell types. According to size, volume, color intensity and distribution of oocyte types the gonads were classified into: immature, developing, developed and spent, being in females at this last stage, observed empty follicles and oocytes in reabsorption process. During oogenesis was observed a gradual increase in cytoplasmic acidophilia due to accumulation of yolk granules and the intense histochemical reaction in periphery of Oc3, which indicate the beginning of an extravitellogenic source of nutrients. Based on the microscopic analysis of the vitellogenesis, shrimp C. major showed the initial short phase of oocyte growth following with a fast vitellogenic cycle.
http://ift.tt/2y6gaR3
The amount of postural change experienced by adolescent computer users developing seated –related upper quadrant musculoskeletal pain
Publication date: Available online 6 October 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Yolandi Brink, Quinette Louw, Karen Grimmer
BackgroundImproved techniques of measuring sitting posture have not led to a more comprehensive understanding of poor posture, nor its association with pain. There is also an evidence gap regarding critical thresholds of sitting postural change over time related to pain production. This paper describes postural angle changes over a 12-month period, and describes the process of placing defensible cut-points in the angle change data, to better understand associations between posture change over time, and onset of upper quadrant musculoskeletal pain (UQMP).MethodsThis paper reports on data captured at baseline and 12-month follow-up, in adolescents in school using computers. Four sitting postural angles, head flexion (HF), neck flexion (NF), craniocervical angle (CCA) and trunk flexion (TF), and self-reported seated UQMP in the previous month were captured at each time-point. Research questions were: 1) What is the magnitude and direction of change in each postural angle over 12 months? 2) What are best cut-points in the continuous posture change distribution to most sensitively test the association between posture change and UQMP? 3) Is gender-specific cut-points required? The 12-month posture angle change data was divided into quintiles (0–20th%; 21-40th%, 41-60th%, 61-80th%, >80th%), and the odds of UQMP occurring in each posture change quintile were calculated using logistic regression models.ResultsTwo hundred and eleven students participated at baseline, of which 153 were followed-up at one year. Both males and females with postural change into extension (which represents lesser flexion range) were more at risk for the development of UQMP, than any other group. The best cut-point for HF was 40th% (≤−3.9°), NF was 20th% (≤−2.9°) and TF was 40th% (≤−1.1°). For CCA however, change at or beyond 40th % for extension or beyond 60% for flexion was associated with UQMP.ConclusionsIdentification of critical postural angle change cut-points assists in considering the pain-producing mechanisms for adolescents using desk top computers.
http://ift.tt/2ghUKXE
Role of manganese dioxide in the recovery of oxide–sulphide zinc ore
Publication date: 5 February 2018
Source:Journal of Hazardous Materials, Volume 343
Author(s): Kun Yang, Libo Zhang, Xingcai Zhu, Jinhui Peng, Shiwei Li, Aiyuan Ma, Haoyu Li, Fei Zhu
In this article, the role of MnO2 in the recovery of oxide–sulphide zinc ore discussed. Through adopting various modern analysis techniques (such as X-ray diffraction pattern, X-ray photoelectron spectroscopy, scanning electron microscope, energy dispersive X-ray analysis, and fourier transform infrared spectroscopy), the function and mechanism of MnO2 during the phase transformation process is found out. Thermodynamic mechanisms involved in the phase transformation process with or without addition of manganese dioxide investigated by exploiting the Equilib module of FactSage. What's more, XRD patterns, XPS spectra and SEM-EDAX analyses of zinc calcines verify well the calculations of FactSage. Results reveal that the addition of MnO2 will produce an aggregation of ZnMn2O4, a valuable energy material, while roasting on its own, results in generating undesirable Zn2SiO4, the oxidation degree being relatively low. Moreover, XRD pattern of zinc calcine and FT-IR spectrum of yellow product collected in the calcination process prove that the sulphur-fixing value of the additive MnO2, which can promote transforming to the elemental sulphur. The volatile S can be collected through a simple guiding device. In this process, the emission of SO2 effectively avoids, thus MnO2 deems as a potential additive in the recovery of oxide–sulphide zinc ore.
Graphical abstract
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Gender proteomics II. Which proteins in sexual organs
Publication date: Available online 6 October 2017
Source:Journal of Proteomics
Author(s): Elisabetta Gianazza, Ingrid Miller, Uliano Guerrini, Luca Palazzolo, Chiara Parravicini, Ivano Eberini
In continuity with the review dealing with differences by gender in non-sexual organs [1], this review collects data on the proteomes of the sexual organs as involved in human reproduction, under both physiological and pathological conditions. It also collects data on the tissue structures and biological fluids typical of pregnancy, such as placenta and amniotic fluid, as well as what may be tested on preimplantation embryos during medically assisted reproduction. The review includes as well mention to all fluids and secretions connected with sex organs and/or reproduction, including sperm and milk, to exemplify two distinctive items in male and female physiology.SignificanceThe causes of infertility are only incompletely understood; the same holds for the causes, and even the early markers, of the most frequent complications of pregnancy. To these established medical challenges, present day practice adds new issues connected with medically assisted reproduction. Omics approaches, including proteomics, are building the database for basic knowledge to possibly translate into clinical testing and eventually into medical routine in this critical branch of health care.
Graphical abstract
http://ift.tt/2giJGcA
Comprehensive proteomic profiles of mouse AApoAII amyloid fibrils provide insights into the involvement of lipoproteins in the pathology of amyloidosis
Publication date: Available online 6 October 2017
Source:Journal of Proteomics
Author(s): Hiroki Miyahara, Jinko Sawashita, Eri Ishikawa, Mu Yang, Xin Ding, Yingye Liu, Naomi Hachiya, Fuyuki Kametani, Masahide Yazaki, Masayuki Mori, Keiichi Higuchi
Amyloidosis is a disorder characterized by extracellular fibrillar deposits of misfolded proteins. The amyloid deposits commonly contain several non-fibrillar proteins as amyloid-associated proteins, but their roles in amyloidosis pathology are still unknown. In mouse senile amyloidosis, apolipoprotein A-II (ApoA-II) forms extracellular amyloid fibril (AApoAII) deposits with other proteins (AApoAII-associated proteins) in many organs. We previously reported that R1.P1-Apoa2c mice provide a reproducible model of AApoAII amyloidosis. In order to investigate the sequential alterations of AApoAII-associated protein, we performed a proteomic analysis of amyloid fibrils extracted from mouse liver tissues that contained different levels of AApoAII deposition. We identified 6 AApoAII-associated proteins that constituted 20 of the top-ranked proteins in mice with severe AApoAII deposition. Although the amount of AApoAII-associated proteins increased with the progression of amyloidosis, the relative abundance of AApoAII-associated proteins changed little throughout the progression of amyloidosis. On the other hand, plasma levels of these proteins showed dramatic changes during the progression of amyloidosis. In addition, we confirmed that AApoAII-associated proteins were significantly associated with lipid metabolism based on functional enrichment analysis, and lipids were co-deposited with AApoAII fibrils from early stages of development of amyloidosis. Thus, these results demonstrate that lipoproteins are involved in AApoAII amyloidosis pathology.SignificanceThis study presented proteomic profiles of AApoAII amyloidosis during disease progression and it revealed co-deposition of lipids with AApoAII deposits based on functional analyses. The relative abundance of AApoAII-associated proteins in the amyloid fibril fractions did not change over the course of development of AApoAII amyloidosis pathology. However, their concentrations in plasma changed dramatically with progression of the disease. Interestingly, several AApoAII-associated proteins have been found as constituents of lipid-rich lesions of other degenerative diseases, such as atherosclerosis and age-related macular degeneration. The common protein components among these diseases with lipid-rich deposits could be accounted for by a lipoprotein retention model.
Graphical abstract
http://ift.tt/2gimJGK
Gender proteomics I. Which proteins in non-sexual organs
Publication date: Available online 6 October 2017
Source:Journal of Proteomics
Author(s): Elisabetta Gianazza, Ingrid Miller, Uliano Guerrini, Luca Palazzolo, Chiara Parravicini, Ivano Eberini
Differences related to gender have long been neglected but recent investigations show that they are widespread and may be recognized with all types of omics approaches, both in tissues and in biological fluids. Our review compiles evidence collected with proteomics techniques in our species, mainly focusing on baseline parameters in non-sexual organs in healthy men and women. Data from human specimens had to be replaced with information from other mammals every time invasive procedures of sample procurement were involved.SignificanceAs our knowledge, and the methods to build it, get refined, gender differences need to receive more and more attention, as they influence the outcome of all aspects in lifestyle, including diet, exercise and environmental factors. In turn this background modulates a differential susceptibility to some disease, or a different pathogenetic mechanism, depending on gender, and a different response to pharmacological therapy. Preparing this review we meant to raise awareness about the gender issue. We anticipate that more and more often, in the future, separate evaluations will be carried out on male and female subjects as an alternative – and an upgrade – to the current approach of reference and test groups being 'matched for age and sex'.
http://ift.tt/2ggXNze
Expanding horizons in complement drug discovery: challenges and emerging strategies
Abstract
The complement system is best known for its role in innate immunity, providing a first line of defence against infection, maintaining tissue homeostasis by flagging apoptotic cells and debris for removal, and orchestrating crosstalk between adaptive and innate immunity. In a growing number of diseases, complement is known to drive pathogenesis or to contribute as an inflammatory amplifier of a disease trigger. Association of complement with common and devastating diseases has driven an upsurge in complement drug discovery, but despite a wealth of knowledge in the complexities of the cascade, and many decades of effort, very few drugs have progressed to late-stage clinical studies. The reasons for this are becoming clear with difficulties including high target concentration and turnover, lack of clarity around disease mechanism and unwanted side effects. Lessons learnt from drugs which are either approved, or are currently in late-stage development, or have failed and dropped off the drug development landscape, have been invaluable to drive a new generation of innovative drugs which are progressing through clinical development. In this review, the challenges associated with complement drug discovery are discussed and the current drug development landscape is reviewed. The latest approaches to improve drug characteristics are explored and those agents which employ these technologies to improve accessibility to patients are highlighted.
http://ift.tt/2yN0hft
High pressure Raman spectroscopic studies on ultrananocrystalline diamond thin films: Anharmonicity and thermal properties of the grain boundary
Publication date: Available online 6 October 2017
Source:Diamond and Related Materials
Author(s): K.K. Mishra, Revati Rani, N. Kumar, T.R. Ravindran, K.J. Sankaran, I-Nan Lin
Ultrananocrystalline diamond (UNCD) thin film has been attracted widely to scientific community due to its attractive thermal and mechanical properties. Herein, we report the high-pressure behavior of grain boundary (GB) originated phonon modes and their correlation with thermal properties in UNCD film grown by microwave plasma enhanced chemical vapor deposition (MPECVD) method. Spherical ultranano grains with size 3–4nm in these films were investigated by high-resolution transmission electron microscopy (HRTEM). Raman spectroscopic studies of UNCD with a pressure transmitting medium (up to 16GPa) and uniaxial pressure (up to 28GPa) revealed the presence of grain boundary phonons which are found to harden upon compression. GB phonons contribution to the specific heat of UNCD at room temperature is estimated to be 4.7314J/mol-K, which is ~80% of the reported theoretical Cv value (5.568J/mol-K). Using our experimentally obtained mode Grüneisen parameters, GB contribution to the thermal expansion coefficient of UNCD is estimated to be 0.5×10−6K−1. Grain boundaries of UNCD are found to be highly stable and Raman spectra showed reversible behavior upon release of pressure. Phonon spectra as a function of temperature down to 90K were used to obtain the anharmonicity of GB phonon modes. The first order temperature coefficient of transpolyacetylene modes (ν1, ν2 and ν3) and E2g in-plane (G-band) modes of GB are obtained as −0.38×10−2, 1.69×10−2, −1.55×10−2 and −1.41×10−2cm−1K−1, respectively.
Graphical abstract
http://ift.tt/2hRB8gC
Role of endogenous melatoninergic system in development of hyperalgesia and tolerance induced by chronic morphine administration in rats
Source:Brain Research Bulletin
Author(s): Yuchao Fan, Xiao Liang, Rurong Wang, Li Song
Morphine is a widely used analgesic for various types of pain. However, its efficacy is impeded by development of hyperalgesia and tolerance. Melatonin has antinociceptive effect and is involved in morphine-induced hyperalgesia and tolerance but the mechanism of its involvement remains to be defined. In this study, we established a rat model of morphine-induced hyperalgesia and tolerance. We determined the serum level of melatonin and expression of μ-opioid receptor (MOR), melatonin receptor (MT1, MT2) and protein kinase C γ(PKCγ)in the spinal dorsal horn of the rats with morphine-induced hyperalgesia and tolerance. Comparing with control group (n=6), the group (n=6) of rats with morphine-induced hyperalgesia and tolerance exhibited a significant lower serum melatonin level, reduction in expression of the MT1, but up-regulation of the PKCγ in the spinal dorsal horn. These results may facilitate revealing the mechanism of opioid-induced hyperalgesia and tolerance and exploring new therapeutic remedy for pain management.
http://ift.tt/2fPTqKR
A chamber study of alkyl nitrate production formed by terpene ozonolysis in the presence of NO and alkanes
Source:Atmospheric Environment
Author(s): Stephen R. Jackson, Joel C. Harrison, Jason E. Ham, J.R. Wells
Organic nitrates are relatively long-lived species and have been shown to have a potential impact on atmospheric chemistry on local, regional, and even global scales. However, the significance of these compounds in the indoor environment remains to be seen. This work describes an impinger-based sampling and analysis technique for organic nitrate species, focusing on formation via terpene ozonolysis in the presence of nitric oxide (NO). Experiments were conducted in a Teflon film environmental chamber to measure the formation of alkyl nitrates produced from α-pinene ozonolysis in the presence of NO and alkanes using gas chromatography with an electron capture detector. For the different concentrations of NO and O3 analyzed, the concentration ratio of [O3]/[NO] around 1 was found to produce the highest organic nitrate concentration, with [O3] = 100 ppb & [NO] = 105 ppb resulting in the most organic nitrate formation, roughly 5 ppb. The experiments on α-pinene ozonolysis in the presence of NO suggest that organic nitrates have the potential to form in indoor air between infiltrated ozone/NO and terpenes from household and consumer products.
http://ift.tt/2yuDB7N
Effects of inorganic seeds on secondary organic aerosol formation from photochemical oxidation of acetone in a chamber
Source:Atmospheric Environment, Volume 170
Author(s): Shuangshuang Ge, Yongfu Xu, Long Jia
Photochemical oxidations of acetone were studied under different inorganic seed (NaCl, (NH4)2SO4 and NaNO3) conditions in a self-made chamber. The results show that no secondary organic aerosol (SOA) can be formed in the experiments either in the absence of artificially added seed particles or in the presence of solid status of the added particles. Liquid water content is the key factor for the formation of SOA in the experiments with seeds. The amount of SOA was only about 4–7 μg m−3 in the experiments with the initial acetone of ∼15 ppm under different seed conditions. The analysis of SOA compositions by Exactive-Orbitrap mass spectrometer equipped with electro-spray interface (ESI-MS) shows that chlorine-containing and sulfur-containing compounds were detected in SOA formed from the experiments with NaCl and (NH4)2SO4 seeds, respectively, which were not identified in SOA from those with NaNO3. The compositions of SOA were mainly esters, organonitrates, hydroperoxides, etc. It is concluded that inorganic seed particles participated into the formation of SOA. Acetone SOA was mainly formed in the aqueous phase in which dissolved SOA precursors underwent further oxidation reactions, esterification reactions and/or radical-radical reactions. Our experiments further demonstrate that low-molecular-weight VOCs, such as acetone, can form SOA under certain conditions in the atmosphere, although their contributions to SOA may not be large.
http://ift.tt/2yumanL
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