Tsunami run-up and inundation along the coast of Sabah and Sarawak, Malaysia due to a potential Brunei submarine mass failure

Abstract

Submarine landslides, also known as submarine mass failures (SMFs), are major natural marine disasters that could critically damage coastal facilities such as nuclear power plants and oil and gas platforms. It is therefore essential to investigate submarine landslides for potential tsunami hazard assessment. Three-dimensional seismic data from offshore Brunei have revealed a giant seabed mass deposited by a previous SMF. The submarine mass extends over 120 km from the continental slope of the Baram Canyon at 200 m water depth to the deep basin floor of the Northwest Borneo Trough. A suite of in-house two-dimensional depth-averaged tsunami simulation model TUNA (Tsunami-tracking Utilities and Application) is developed to assess the vulnerability of coastal communities in Sabah and Sarawak subject to potential SMF tsunami. The submarine slide is modeled as a rigid body moving along a planar slope with the center of mass motion parallel to the planar slope and subject to external forces due to added mass, gravity, and dissipation. The nonlinear shallow water equations are utilized to simulate tsunami propagation from deepwater up to the shallow offshore areas. A wetting-drying algorithm is used when a tsunami wave reaches the shoreline to compute run up of tsunami along the shoreline. Run-up wave height and inundation maps are provided for seven densely populated locations in Sabah and Sarawak to highlight potential risks at each location, subject to two scenarios of slide slopes: 2° and 4°. The first wave may arrive at Kudat as early as 0.4 h after the SMF, giving local communities little time to evacuate. Over a small area, maximum inundated depths reaching 20.3 m at Kudat, 26.1 m at Kota Kinabalu, and 15.5 m at Miri are projected, while the maximum inundation distance of 4.86 km is expected at Miri due to its low-lying coast. In view of the vulnerability of some locations to the SMF tsunami, it is important to develop and implement community resilience program to reduce the potential damage that could be inflicted by SMF tsunamis.

http://ift.tt/2nSEDVq

Characterization of PM 2.5 chemical composition at the Demokritos suburban station, in Athens Greece. The influence of Saharan dust

Abstract

The aim of this work is to study the atmospheric concentrations of selected major and trace elements and ions found in PM_2.5, at a suburban site in Athens, Greece, and discuss on the impact of the different sources. Special focus is given to the influence of Saharan dust episodes. The seasonal variability in the metal and ion concentrations is also examined. The results show that PM_2.5 mass concentrations are significantly influenced by Saharan dust events; it is observed that when the PM_2.5 concentration is higher than 25 μg/m³, five out of six times, the air mass crossed North Africa at an altitude within the boundary layer. Fe is found to be the element with the more significant seasonal variability, displaying much higher concentrations during cold period. The frequent Saharan dust intrusions in the cold period of this dataset may explain this result. Mineral dust and secondary aerosol are the main PM_2.5 components (29 and 34%, respectively). During Saharan dust events, the concentration of mineral dust is increased by 35% compared to the days without dust intrusions, while an increase of 68% of the sea salt is also observed. During event days, PM_2.5 concentrations are also increased by 14%. Anthropogenic components do not decrease during those days, while sulfate displays even a slight increase, suggesting enrichment of mineral dust with secondary sulfates. The results indicate that African dust intrusions add a rather significant PM pollution load even in the PM_2.5 fraction, with implication to population exposure and human health.

http://ift.tt/2njl2e8

Expression of the cyanobacterial enzyme cyanase increases cyanate metabolism and cyanate tolerance in Arabidopsis

Abstract

Cyanate and its derivatives are considered as environmental hazardous materials. Cyanate is released to the environment through many chemical industries and mining wastewater. Cyanase enzyme converts cyanate into CO₂ and NH₃ in a bicarbonate-dependent reaction. At low cyanate concentrations, the endogenous plant cyanases play a vital role in cyanate detoxification. However, such cyanate biodegradation system is probably insufficient due to the excess cyanate concentrations at contaminated sites. In this study, we have transferred the activity of the cyanobacterial cyanase into Arabidopsis thaliana plants in order to enhance plant resistance against cyanate toxicity. The enzyme was shown to be active in planta. Transgenic plants exposed to cyanate, either applied by foliar spray or supplemented in growth medium, showed less reduction in pigment contents, antioxidant enzymes, carbohydrate contents, and reduced levels of plant growth retardation. Plant growth assays under cyanate stress showed enhanced growth and biomass accumulation in cyanase overexpressors compared to control plants. Results of this study provide evidence for developing novel eco-friendly phytoremediation systems for cyanate detoxification.

http://ift.tt/2nSDNbd

HLA-A*31:01 and lamotrigine-induced severe cutaneous adverse drug reactions in a Korean population

Publication date: Available online 25 March 2017
Source:Annals of Allergy, Asthma & Immunology
Author(s): Byung-Keun Kim, Jae-Woo Jung, Tae-Bum Kim, Yoon-Seok Chang, Hae-Sim Park, Jangsup Moon, Soon-Tae Lee, Keun-Hwa Jung, Ki-Young Jung, Kon Chu, Sang Kun Lee, Hye-Ryun Kang, Heung-Woo Park




http://ift.tt/2nVbmK5

Quality Survival with Fertility after Gynaecological and other Cancers

Introduction: Earlier, diagnosis of cancer ultimately led to death but now with complex therapies, not only many survive, but they have quality life too. Even preservation of fertility is possible. In addition to this, with early diagnosis, complete cure is possible. <p></p> Objectives: To look into the existing evidence, challenges and possibilities. <p></p> Methodology: Simple review of literature was done with the help of various search engines, Pubmed, Google, Uptodate and other databases to evaluate the relevant studies, reviews and short commentaries to get information as per the objectives. <p></p> Evidence: Because of long-term effects of various cancers and their therapies, problems like quality of life, sexuality and fertility are the real concerns. Gonadal dysfunction is common, especially in gynaecological cancers and their therapies. Germ cell tumors of ovary are most common in young girls but with conservative surgery and chemotherapy the results are excellent. Same is true even for stage I epithelial ovarian cancers. Conservative therapies for cervical cancer, conization, simple / radical trachelectomy can do wonders. Endometrial cancer usually occurs after menopause, and there are no standard recommendations for conservative management, which is possible in younger women. Choriocarcinoma is highly malignant but has high cure rate too. So, quality survival is possible. Studies with Breast cancer, Hodgkin lymphoma have also revealed menstrual function resumption after chemotherapy. Presurgery assessment and close follow-up are necessary. Side effects of radiochemotherapy are real. Effects are drug, dose, and age dependent with possibilities of infertility and adverse pregnancy outcomes. Gonadotoxic effects may cause early menopause. Challenges increase if cancer occurs during pregnancy. <p></p> Preventive Possibilities and Conclusion: Mission of any cancer therapy needs to be quality long life, preservation of pregnancy prospects: natural or assisted. Prepubertal ovary is least susceptible to gonadotoxicity with chances of better reproductive life. Ovarian transposition / shielding or transplantation is possible. Ovarian tissue rather than oocyte or embryo cryopreservation is better. Early diagnosis and safe therapy can do miracles for women who are diagnosed with cancer. Conservative surgery, safe chemotherapy and focused radiation can reduce gonadotoxicity and preserve fertility. Multidisciplinary treatments are essential. Role of psychotherapy is important. For quality survival with reduced risk of cardiac, renal, neurological problems, bone osteoporosis and also for preservation of fertility, therapy needs proper planning for all cancers. <p></p>

http://ift.tt/2jGgJuz

Organotin(IV) Carboxylates as Promising Potential Drug Candidates in the Field of Cancer Chemotherapy

Medicinal inorganic chemistry plays an important role in exploring the properties of metal ions for the designing of new drugs. The field has been stimulated by the success of cis-platin, the world best selling anticancer drug and platinum complexes with reduced toxicity, oral activity and activity against resistant tumors are currently on clinical trial. The use of cis-platin is, however, severely limited by its toxic side-effects. This has stimulated chemists to employ different strategies in the development of new metal-based anticancer agents with different mechanisms of action. The discovery of new non-covalent interactions with the classical target, DNA, was the first developing step in the treatment of cancer. The use of organometallic compounds as a medicine is very common now a days because it offers potential advantages over the more common organic-based drugs. In this article we have highlighted the anticancer activity of the organotin(IV) carboxylates published in the last few years (from 2008 to 2016). In most cases they present lower IC₅₀ values than those of cisplatin, which indicates their high activity against the cancer cell lines. The summarized data reveal that every year new organotin(IV) carboxylate complexes are synthesized with the aim of new anticancer agent with much better results than the than the corresponding activity of cis-platin or other clinically approved drugs. In addition to the advantages of high activity, compared to the platinum compound, tin complexes are much cheaper. Thus by using organotin carboxylate for clinical medicine, cost reduction, dosage reduction and effect enhancement will be reached.

http://ift.tt/2n676mX

Incidental metastatic mediastinal atypical carcinoid in a patient with parathyroid adenoma: a case report

Atypical carcinoid arising from the mediastinal tissue is a rare neuroendocrine tumor and an association with parathyroid adenoma is very unusual. We report an unusual case of atypical carcinoid of mediastinum...

http://ift.tt/2oihdVU

Spontaneous Iliopsoas Hematoma following Microvascular Free Tissue Transfer

Spontaneous hematoma within the iliopsoas muscle (SIH) is a rare complication most commonly seen in coagulopathic patients. Often, patients undergoing microvascular free tissue transfer are anticoagulated for anastomotic patency. Here we describe two cases of postoperative SIH following contralateral anterolateral thigh (ALT) free tissue transfer for reconstruction of oncologic head and neck defects. Both patients described hip pain after mobilization and had a corresponding acute blood loss anemia. Diagnosis of SIH was confirmed by CT and both patients were managed conservatively. Given that anticoagulation is a common practice following head and neck free tissue transfer, surgeons should be aware of this potential complication.

http://ift.tt/2nRYpQI

Spontaneous Iliopsoas Hematoma following Microvascular Free Tissue Transfer

Spontaneous hematoma within the iliopsoas muscle (SIH) is a rare complication most commonly seen in coagulopathic patients. Often, patients undergoing microvascular free tissue transfer are anticoagulated for anastomotic patency. Here we describe two cases of postoperative SIH following contralateral anterolateral thigh (ALT) free tissue transfer for reconstruction of oncologic head and neck defects. Both patients described hip pain after mobilization and had a corresponding acute blood loss anemia. Diagnosis of SIH was confirmed by CT and both patients were managed conservatively. Given that anticoagulation is a common practice following head and neck free tissue transfer, surgeons should be aware of this potential complication.

http://ift.tt/2nRYpQI

Incidental metastatic mediastinal atypical carcinoid in a patient with parathyroid adenoma: a case report

Atypical carcinoid arising from the mediastinal tissue is a rare neuroendocrine tumor and an association with parathyroid adenoma is very unusual. We report an unusual case of atypical carcinoid of mediastinum...

http://ift.tt/2oihdVU

Correlates of sleep quality in midlife and beyond: a machine learning analysis

In older adults, traditional metrics derived from polysomnography (PSG) are not well correlated with subjective sleep quality. Little is known about whether the association between PSG and subjective sleep quality changes with age, or whether quantitative assessment of EEG (qEEG) is associated with sleep quality. We therefore examined the relationship between subjective sleep quality and objective sleep characteristics (standard polysomnography and qEEG) across middle to older adulthood.

http://ift.tt/2n3Zalt

Treatment of Insomnia with Tricyclic Antidepressants: A Meta-Analysis of Polysomnographic Randomized Controlled Trials

Insomnia represents a significant public health burden worldwide. Antidepressants have often been the insomnia treatment of choice in recent decades. Some tricyclic antidepressants (TCAs) have been shown to improve sleep efficiency.

http://ift.tt/2nS1NeC

Natural killer cell response is a predictor of good outcome in MCPyV+ Merkel cell carcinoma: A case series of 23 patients

To the Editor: Merkel cell carcinoma (MCC) represents a rare, aggressive cutaneous neuroendocrine carcinoma. The majority of MCCs are positive for genomic insertions of Merkel cell polyomavirus (MCPyV). Favorable outcomes have been reported for MCPyV+ versus MCPyV− MCCs1 and a high level of tumor-infiltrating lymphocytes.2-4 In addition, higher numbers of natural killer (NK) cells have been identified in MCPyV+ versus MCPyV−,3 but the prognostic significance of this remains to be determined.

http://ift.tt/2mCII0c

Management of Toxic Epidermal Necrolysis with Plasmapheresis and Cyclosporine A: Our 10 Years’ Experience

Background: The management of toxic epidermal necrolysis (TEN) is controversial and there is no uniform strategy. Objective: To share our 10 years' experience in treating severe TEN with a novel protocol based on the association of cyclosporine A and plasmapheresis. Methods: In this case series, we retrospectively collected and assessed the 12 cases of severe TEN treated from 2005 to 2015 at the Burn Unit of the University of Bari Policlinico hospital. Results: Average body surface area was 77; average SCORETEN was 4.3. The 12 patients had been treated with culprit drug withdrawal, systemic corticosteroids, and/or cyclosporine A with no response. The protocol was successfully administered in all 12 cases. Average time to response from protocol start was 4.9 days. Average time to remission from protocol start was 22 days; average hospital stay at our unit was 24.8 days. Four patients developed severe complications; 1 patient died. No complications linked to the protocol therapeutic measures were observed. The relatively small number of cases given the rarity of the condition is a limitation of this report. Conclusion: Our protocol based on the association of cyclosporine A and plasmapheresis is safe and efficacious in treating severe TEN.

http://ift.tt/2n00lqm

HLA-A*31:01 and lamotrigine-induced severe cutaneous adverse drug reactions in a Korean population

Lamotrigine (LTG) was first synthesized in the early 1980s and approved by the US Food and Drug Administration in 1994. Since then, it has been used worldwide as an effective anticonvulsant and as a mood stabilizer. However, LTG can cause adverse reactions including cutaneous adverse drug reactions with approximately 10% probability.1 Severe cutaneous adverse reactions (SCARs) are the most serious form and include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS).

http://ift.tt/2noc6pE

HLA-A*31:01 and lamotrigine-induced severe cutaneous adverse drug reactions in a Korean population

Lamotrigine (LTG) was first synthesized in the early 1980s and approved by the US Food and Drug Administration in 1994. Since then, it has been used worldwide as an effective anticonvulsant and as a mood stabilizer. However, LTG can cause adverse reactions including cutaneous adverse drug reactions with approximately 10% probability.1 Severe cutaneous adverse reactions (SCARs) are the most serious form and include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS).

http://ift.tt/2noc6pE

Gender differences in obstructive sleep apnoea, insomnia and restless legs syndrome in adults - what do we know? A clinical update

Research in sleep medicine over the last decades has involved a broad variety of sleep disorders in both men and women. Gender differences have been identified in sleep physiology as well as in the three most common sleep disorders: obstructive sleep apnoea (OSA), insomnia and restless legs syndrome (RLS). However, research on gender differences in sleep medicine appears limited. This clinical review aims to give an updated overview of gender differences, in relation to prevalence, clinical presentation, treatment and quality of life in OSA, insomnia and RLS.

http://ift.tt/2n5C5Q4

Corrigendum to “Dry eye disease and uveitis: A closer look at immune mechanisms in animal models of two ocular autoimmune diseases” [AUTREV 15-12 (2016) 1181–1192]

Publication date: Available online 25 March 2017
Source:Autoimmunity Reviews
Author(s): Tanima Bose, Maria Diedrichs-Möhring, Gerhild Wildner




http://ift.tt/2nipl9D

Corrigendum to “Dry eye disease and uveitis: A closer look at immune mechanisms in animal models of two ocular autoimmune diseases” [AUTREV 15-12 (2016) 1181–1192]

Publication date: Available online 25 March 2017
Source:Autoimmunity Reviews
Author(s): Tanima Bose, Maria Diedrichs-Möhring, Gerhild Wildner




http://ift.tt/2nipl9D

Preprosthetic surgery, fault-lines, and scholarly leadership

Publication date: Available online 24 March 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Stephen F. Rosenstiel, George A. Zarb




http://ift.tt/2ohRWv5

Multifaceted link between metabolism and cancer

Publication date: Available online 25 March 2017
Source:Molecular and Cellular Endocrinology
Author(s): Paula Saavedra-García, Lavender Yuen-Nam Fan, Eric W-F. Lam




http://ift.tt/2nRnsmX

Interaction of IRF9 and STAT2 synergistically up-regulates IFN and PKR transcription in Ctenopharyngodon idella

Publication date: May 2017
Source:Molecular Immunology, Volume 85
Author(s): Zhen Wu, Liqiang Wang, Xiaowen Xu, Gang Lin, Huiling Mao, Xiaoqin Ran, Tao Zhang, Keyi Huang, Haizhou Wang, Qingli Huang, Qun Xu, Chengyu Hu
IRF9 is a key factor in the JAK-STAT pathway. Under the stimulation of type I IFN, IRF9 interacts with STAT1 and STAT2 to form the IFN-I-stimulated gene factor 3 (ISGF3) which activates the transcription of ISG. However, many studies also showed that the dimmer IRF9/STAT2 rather than the tripolymer IRF9/STAT1/STAT2 acts as the ISGF3 in cells in response to IFN signals. In the present study, the full-length cDNA sequence of IRF9 (termed CiIRF9, KT601055) and STAT2 (term CiSTAT2, KT781914) from grass carp were cloned and identified. A low level of constitutive expression of CiIRF9 was detected by RT-PCR in grass carp tissues, but it was significantly up-regulated by LPS and poly I:C stimulation. In vitro, a high-affinity interaction between CiIRF9 and the promoter of CiIFN or CiPKR was demonstrated by gel mobility shift assay. In vivo, the promoter activities of CiIFN and CiPKR were not only increased by transient transfection of CiIRF9, but also prominently increased by co-transfection of CiIRF9 and CiSTAT2. Moreover, the interaction of CiIRF9 and CiSTAT2 was further investigated by in vivo and in vitro protein interaction assays. Recombinant CiIRF9 and CiSTAT2, both tagged with FLAG (or HA), were expressed in HEK 293T cells by transient transfection experiment. Co-immunoprecipitation assays showed that CiIRF9 can interact with CiSTAT2 in vivo. Soluble GST-ST2-936 (containing the N-terminal and coiled-coil domain of CiSTAT2) was expressed and purified from E. coli. A GST pull-down assay suggested that GST-tagged ST2-936 efficiently bound to FLAG-tagged IRF9. The data indicated that interaction of IRF9 and STAT2 synergistically up-regulated the transcriptional level of IFN and ISG genes.



http://ift.tt/2ohOT6g

Interaction of IRF9 and STAT2 synergistically up-regulates IFN and PKR transcription in Ctenopharyngodon idella

Publication date: May 2017
Source:Molecular Immunology, Volume 85
Author(s): Zhen Wu, Liqiang Wang, Xiaowen Xu, Gang Lin, Huiling Mao, Xiaoqin Ran, Tao Zhang, Keyi Huang, Haizhou Wang, Qingli Huang, Qun Xu, Chengyu Hu
IRF9 is a key factor in the JAK-STAT pathway. Under the stimulation of type I IFN, IRF9 interacts with STAT1 and STAT2 to form the IFN-I-stimulated gene factor 3 (ISGF3) which activates the transcription of ISG. However, many studies also showed that the dimmer IRF9/STAT2 rather than the tripolymer IRF9/STAT1/STAT2 acts as the ISGF3 in cells in response to IFN signals. In the present study, the full-length cDNA sequence of IRF9 (termed CiIRF9, KT601055) and STAT2 (term CiSTAT2, KT781914) from grass carp were cloned and identified. A low level of constitutive expression of CiIRF9 was detected by RT-PCR in grass carp tissues, but it was significantly up-regulated by LPS and poly I:C stimulation. In vitro, a high-affinity interaction between CiIRF9 and the promoter of CiIFN or CiPKR was demonstrated by gel mobility shift assay. In vivo, the promoter activities of CiIFN and CiPKR were not only increased by transient transfection of CiIRF9, but also prominently increased by co-transfection of CiIRF9 and CiSTAT2. Moreover, the interaction of CiIRF9 and CiSTAT2 was further investigated by in vivo and in vitro protein interaction assays. Recombinant CiIRF9 and CiSTAT2, both tagged with FLAG (or HA), were expressed in HEK 293T cells by transient transfection experiment. Co-immunoprecipitation assays showed that CiIRF9 can interact with CiSTAT2 in vivo. Soluble GST-ST2-936 (containing the N-terminal and coiled-coil domain of CiSTAT2) was expressed and purified from E. coli. A GST pull-down assay suggested that GST-tagged ST2-936 efficiently bound to FLAG-tagged IRF9. The data indicated that interaction of IRF9 and STAT2 synergistically up-regulated the transcriptional level of IFN and ISG genes.



http://ift.tt/2ohOT6g

Mental Health in Allergic Rhinitis: Depression and Suicidal Behavior

Opinion statement

A high proportion of suicides visit their medical provider in the month prior to death, but depression, suicidal thoughts, and substance use are seldom addressed. For the clinicians routinely treating a substantial patient population with allergic diseases, there are additional concerns, as allergy has been linked with both depression and suicidal behavior. While psychotropic medications may affect diagnosis of allergies, medications used to treat allergies impact mood and behavior. Thus, we present an overview of the overlap of allergic rhinitis with depression and suicidal behavior in adults, based on clinical and epidemiological data, and our research and clinical experience. In summary, we suggest: (1) inquiring among patients with allergies about personal and family history of depression, substance use disorders, suicidal ideation, and attempts; (2) increased mindfulness regarding the potential effects of allergy medications on mood and behavior; and (3) for people identified with certain types of depression or increased suicide risk, a systematic multilevel collaborative approach. While, for practical reasons the majority of patients with depression will continue to be treated by general or family practitioners, the allergy-treating provider should always consider integrated care for bipolar, psychotic, or suicidal depression and incomplete remission, or relapsing and highly recurrent course. While awaiting results of a much needed basic and clinical research to guide the clinical approach to patients with comorbid allergic rhinitis and depression, the simple steps recommended here are expected to lead to improved clinical outcomes in depression, and, perhaps, contributing to lowering the highly resilient suicide mortality.Learning objectives: a) Present overlaps between allergy, allergen exposure, depression, and suicidal behavior in adults and b) Familiarize allergists with the principles of diagnosis and treatment of depression in adults and importance to monitor suicide risk.

http://ift.tt/2mCCEVg

Clinicopathologic and genetic features of primary bronchopulmonary mucoepidermoid carcinoma: the MD Anderson Cancer Center experience and comprehensive review of the literature

Abstract

Primary bronchopulmonary mucoepidermoid carcinoma (BPMEC) is a rare tumor. The fusion protein MECT1-MAML2 has been implicated as a causative genetic event in salivary and BPMECs. Several studies have shown the impact of MECT1-MAML2 on the diagnosis and prognosis of salivary gland mucoepidermoid carcinoma; however, few studies have been published regarding MECT1-MAML2 in the context of primary BPMEC. We describe the clinicopathologic, genetic, and outcome data of 16 patients with BPMEC. Clinicopathologic features were recorded from the electronic medical records. All tumors were reviewed by two expert pulmonary pathologists and graded according to previously established criteria. The presence of MECT1-MAML2 was evaluated with reverse transcription polymerase chain reaction using RNA extracted from formalin-fixed paraffin-embedded tumor tissue. Patients included 9 women and 7 men with a median age of 50 years (range, 7 to 82 years). Tumors exhibited low (n = 14, 88%), and high (n = 2, 12%) grade histologic features. Eight of nine tested tumors (89%) were positive for MECT1-MAML2. The median follow-up time was 40.8 months (range, 1.8–120). Median overall survival for patients with high-grade tumors was 12 months, which was significantly (p = 0.002) shorter than that for patients with low-grade tumors (survival undefined). We also provide a comprehensive review of literature of cases of primary bronchopulmonary mucoepidermoid carcinoma and summarize our findings in this context. MECT1-MAML2 fusion transcript is a driver genetic event in the pathogenesis of primary BPMEC. Histologic grade continues to play a pivotal role in the survival of patients with primary bronchopulmonary mucoepidermoid carcinoma.

http://ift.tt/2nieQ6r

MCPIP1 contributes to the inflammatory response of UVB-treated keratinocytes

Publication date: Available online 25 March 2017
Source:Journal of Dermatological Science
Author(s): Beata Bugara, Piotr Konieczny, Agnieszka Wolnicka-Glubisz, Leopold Eckhart, Heinz Fischer, Lukasz Skalniak, Julia Borowczyk-Michalowska, Justyna Drukala, Jolanta Jura
BackgroundMonocyte chemoattractant protein-1-induced protein-1 (MCPIP1), also known as regnase-1, negatively regulates many cellular processes including the cellular response to inflammatory agents, differentiation, viability, and proliferation. It possesses a PilT N-terminus (PIN) domain that is directly involved in regulating the stability of transcripts and miRNAs by recognizing stem loop structures and degrading them by endonucleolytic cleavage.ObjectiveWe investigated the role of MCPIP1 in the response of human primary keratinocytes to UVB stress.MethodsKeratinocytes were treated with UVB, siRNA against MCPIP1, pharmacological inhibitors of signaling pathways, or subjected to control treatments. The mRNA and protein levels of MCPIP1 and MCPIP1-dependent changes gene expression were analyzed by quantitative (Q)-RT-PCRs and Western blots. Secretion of TNFα and IL-8 was determined by ELISA.ResultsUVB treatment of keratinocytes induced upregulation of MCPIP1 at the mRNA level after 4-8h and at the protein level after 8-16h. MCPIP1 abundance depended on NF-κB activity. Using an siRNA strategy, we found that diminished MCPIP1 resulted in an up-regulation of transcripts coding for IL-8, TNFα, COX-2, and BCL-2, as well as an enhanced release of IL-8. Moreover, decreased phosphorylation of NF-κB and p38 signaling pathways were observed in addition to a slight up-regulation of ERK1/2 directly after UVB treatment. Twenty-four hours later, decreased phosphorylation was observed only for NF-κB and p38. Furthermore, in MCPIP1-suppressed cells, the levels of pro-apoptotic Puma, the phosphorylated form of p53 and the abundance of its target p21 as well as the activity of caspase 3 decreased, while the level of cyclin D1 increased.ConclusionMCPIP1 contributes to the UVB response of keratinocytes by altering metabolic and apoptotic processes and the release of inflammatory mediators.



http://ift.tt/2nUuwQj

Corrigendum to “p62 modulates the intrinsic signaling of UVB-induced apoptosis” [Journal of Dermatological Science 83 (2016) 226–233]

Publication date: Available online 25 March 2017
Source:Journal of Dermatological Science
Author(s): Sachiko Ito, Shintaro Kimura, Eiji Warabi, Yasuhiro Kawachi, Masanobu Yamatoji, Fumihiko Uchida, Naomi Ishibashi-Kanno, Kenji Yamagata, Shogo Hasegawa, Junichi Shoda, Katsuhiko Tabuchi, Satoshi Sakai, Hiroki Bukawa, Mitsuru Sekido, Toru Yanagawa




http://ift.tt/2ohzaUr

Twenty years of the G protein-coupled estrogen receptor GPER: historical and personal perspectives

Publication date: Available online 25 March 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Matthias Barton, Edward J. Filardo, Stephen J. Lolait, Peter Thomas, Marcello Maggiolini, Eric R. Prossnitz
Estrogens play a critical role in many aspects of female physiology, particularly reproductive function, but also in pathophysiology, and are associated with protection from numerous diseases in premenopausal women. Steroids and particularly estrogen action have been known for ∼90 years, with the first evidence for a receptor for estrogen presented ∼50 years ago. The original ancestral steroid receptor, extending back into evolution more than 500 million years, was likely an estrogen receptor, whereas G protein-coupled receptors (GPCRs) trace their origins back into history more than one billion years. The classical estrogen receptors (ERα and ERβ) are ligand-activated transcription factors that confer estrogen sensitivity upon many genes. It was soon apparent that these, or novel receptors may also be responsible for the "'rapid"/"non-genomic" membrane-associated effects of estrogen. The identification of an orphan GPCR (GPR30, published in 1996) opened a new field of research with the description in 2000 that GPR30 expression is required for rapid estrogen signaling. In 2005-2006, the field was greatly stimulated by two studies that described the binding of estrogen to GPR30-expressing cell membranes, followed by the identification of a GPR30-selective agonist (that lacked binding and activity towards ERα and ERβ). Renamed GPER (G protein-coupled estrogen receptor) by IUPHAR in 2007, the total number of articles in PubMed related to this receptor recently surpassed 1000. In this article, the authors present personal perspectives on how they became involved in the discovery and/or advancement of GPER research. These areas include non-genomic effects on vascular tone, receptor cloning, molecular and cellular biology, signal transduction mechanisms and pharmacology of GPER, highlighting the roles of GPER and GPER-selective compounds in diseases such as obesity, diabetes, and cancer and the obligatory role of GPER in propagating cardiovascular aging, arterial hypertension and heart failure through the regulation of Nox expression.



http://ift.tt/2nR2uEU

Prevalence of thyroid dysfunction and its impact on cognition in older mexican adults: (SADEM study)

Abstract

Introduction

Subclinical thyroid dysfunction is a possible risk factor for cognitive impairment in old age, but results are inconsistent. Aim of the present study was to evaluate the prevalence of thyroid dysfunction among older community-dwelling adults and to see whether thyroid function impacts the cognitive status of the elderly.

Methods

We included 1750 participants from the Study on Aging and Dementia in Mexico (SADEM). All subjects were evaluated clinically via specific interviews. TSH levels were analyzed by chemiluminescent immunometry assay. We classified participants into five thyroid state groups: (1) normal TSH levels (0.40–4.0 IU/L) were considered euthyroid; (2) Overt hyperthyroidism: TSH <0.3 IU/l and FT4 >23 pmol/l; (3) Overt hypothyroidism: TSH >4.8 IU/l, FT4 <13 pmol/l; (4) Subclinical hyperthyroidism: TSH <0.3 IU/l, FT4: 13–23 pmol/l; (5) Subclinical hypothyroidism: TSH >4.8 IU/l, FT4: 13–23 pmol/l.

Results

The overall estimated prevalence of thyroid dysfunction in Mexican population was 23.7% (95% CI, 22.66–26.77). Of these, 15.4% older adults were classified as subclinical hypothyroidism, 7.2% overt hypothyroidism, 0.5% subclinical hyperthyroidism, and 0.6% overt hyperthyroidism. The association of thyroid dysfunction with cognitive impairment was most evident in overt hypothyroidism OR = 1.261 (1.185–1.343).

Conclusions

The present study demonstrated a high prevalence of thyroid dysfunction in Mexican elderly people living in the community. A relationship between cognitive impairment and the presence of hypothyroidism was also shown, and to a lesser degree in hyperthyroidism.

http://ift.tt/2nnLghq

Do glucocorticoids induce addiction in humans?

http://ift.tt/2nid8Sk

Ultrasound Stimulation of Insulin Release from Pancreatic Beta Cells as a Potential Novel Treatment for Type 2 Diabetes

Publication date: Available online 25 March 2017
Source:Ultrasound in Medicine & Biology
Author(s): Ivan Suarez Castellanos, Aleksandar Jeremic, Joshua Cohen, Vesna Zderic
Type 2 diabetes mellitus is a complex metabolic disease that has reached epidemic proportions in the United States and around the world. This disease is characterized by loss of insulin secretion and, eventually, destruction of insulin-producing pancreatic beta cells. Controlling type 2 diabetes is often difficult as pharmacological management routinely requires complex therapy with multiple medications, and loses its effectiveness over time. The objective of this study was to explore the effectiveness of a novel, non-pharmacological approach that uses the application of ultrasound energy to augment insulin release from rat INS 832/13 beta cells. The cells were exposed to unfocused ultrasound for 5 min at a peak intensity of 1 W/cm² and frequencies of 400 kHz, 600 kHz, 800 kHz and 1 MHz. Insulin release was measured with enzyme-linked immunosorbent assay and cell viability was assessed via the trypan blue dye exclusion test. A marked release (approximately 150 ng/10⁶ cells, p < 0.05) of insulin was observed when beta cells were exposed to ultrasound at 400 and 600 kHz as compared with their initial control values; however, this release was accompanied by a substantial loss in cell viability. Ultrasound application at frequencies of 800 kHz resulted in 24 ng/10⁶ cells released insulin (p < 0.05) as compared with its unstimulated base level, while retaining cell viability. Insulin release from beta cells caused by application of 800-kHz ultrasound was comparable to that reported by the secretagogue glucose, thus operating within physiological secretory capacity of these cells. Ultrasound has potential as a novel and alternative method to current approaches aimed at correcting secretory deficiencies in patients with type 2 diabetes.



http://ift.tt/2nzOe2Q

A novel method to evaluate salivary flow rates of head and neck cancer patients after radiotherapy: a pilot study

Publication date: Available online 25 March 2017
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Luiz Felipe Palma, Fernanda Aurora Stabile Gonnelli, Marcelo Marcucci, Adelmo José Giordani, Rodrigo Souza Dias, Roberto Araújo Segreto, Helena Regina Comodo Segreto
IntroductionThe procedure used to evaluate salivary flow rate is called sialometry. It can be performed through several techniques, but none appears to be really efficient for post-radiotherapy patients.ObjectiveTo adequate sialometry tests for head and neck cancer patients submitted to radiotherapy.Methods22 xerostomic patients post-radiotherapy (total radiation dose ranging from 60 to 70Gy) were included in this study. Ten patients were evaluated using sialometries originally proposed by the Radiation Therapy Oncology Group and twelve were assessed by our modified methods. Unstimulated and stimulated sialometries were performed and the results were classified according a grading scale and compared between both groups.ResultsThere was no statistically significant difference between the salivary evaluations of both groups (p=0.4487 and p=0.5615). Also, most of these rates were classified as very low and low.ConclusionThis novel method seems to be suitable for patients submitted to radiotherapy.



http://ift.tt/2nQGoCE

Neonatal BCG-vaccination has no effect on recurrent wheeze in the first year of life. A randomized clinical trial

Publication date: Available online 25 March 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Lisbeth Marianne Thøstesen, Lone Graff Stensballe, Gitte Thybo Pihl, Jesper Kjærgaard, Nina Marie Birk, Thomas Nørrelykke Nissen, Aksel Karl Georg Jensen, Peter Aaby, Annette Wind Olesen, Dorthe Lisbeth Jeppesen, Christine Stabell Benn, Poul-Erik Kofoed
BackgroundRecurrent wheeze is frequent in childhood. Studies have suggested that Bacillus Calmette-Guérin (BCG) vaccination may have non-specific effects, reducing general non-tuberculosis morbidity, including respiratory infections and atopic diseases. The mechanisms behind these non-specific effects of BCG are not fully understood, but a shift from Th2 to Th1-response has been suggested as a possible explanation.ObjectiveWe hypothesized that BCG at birth would reduce the cumulative incidence of recurrent wheeze during the first year of life.MethodsThe Danish Calmette Study is a multicenter randomized trial conducted from 2012-2015 at three Danish hospitals. The 4262 newborns of 4184 included mothers were randomized 1:1 to BCG (SSI strain 1331) or to a no-intervention control group within 7 days of birth; siblings were randomized together as one randomization unit. Exclusion criteria were gestational age <32 weeks, birth weight <1000g, known immunodeficiency, or no Danish-speaking parent. Information was collected through telephone interviews and clinical examinations at 3 and 13 months of age; the data collectors were blinded to randomization group.Recurrent wheeze was defined in several ways, the main definition being: "physician-diagnosed and medically treated recurrent wheeze up to 13 months of age".ResultsBy 13 months 211/2100 (10.0%) children in the BCG group and 195/2071 (9.4%) children in the control group had been diagnosed by a medical doctor with recurrent wheeze and received anti-asthmatic treatment (relative risk 1.07 (95% confidence intervals 0.89-1.28)). Supplementary analyses were made, including an analysis of baseline risk factors for developing RW.ConclusionNeonatal BCG had no effect on the development of recurrent wheeze before 13 months of age.

Teaser

Neonatal BCG vaccination cannot be used prophylactically against recurrent wheeze in Denmark, but if a BCG vaccination is necessary for other reasons, the infant can be BCG vaccinated without concerns of recurrent wheeze.


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Rhinovirus-induced first wheezing episode predicts atopic but not non-atopic asthma at school-age

Publication date: Available online 25 March 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Minna Lukkarinen, Annamari Koistinen, Riitta Turunen, Pasi Lehtinen, Tytti Vuorinen, Tuomas Jartti
BackgroundPersistent childhood asthma is mainly atopy-driven. However, limited data exist on the risk factors for childhood asthma phenotypes.ObjectiveTo identify risk factors at the first severe wheezing episode for the current asthma 7 years later, and separately for atopic and non-atopic asthma.MethodsOne hundred and twenty-seven steroid-naive children with the first severe wheezing episode (90% hospitalized/10% emergency room treated) were followed for 7 years. The primary outcome was current asthma at age 8 years, which was also analyzed separately as atopic and non-atopic asthma. Risk factors including sensitization, viral etiology and other main asthma risk factors were analyzed.ResultsAt study entry, median age was 11 months (interquartile range 6;16 months), 17% were sensitized and 98% were virus-positive. Current asthma (n = 37) at 8 years was divided to atopic (n = 19) and non-atopic (n = 18) asthma. The risk factors for current atopic asthma at study entry were sensitization (adjusted odds ratio 12; P<.001), eczema (4.8; P .014, respectively) and wheezing with rhinovirus (5.0; P .035). The risk factors for non-atopic asthma were the first severe respiratory syncytial virus/rhinovirus-negative wheezing episode (adjusted odds ratio 8.0; P .001), first wheezing episode at age <12 months (7.3; P = .007, respectively), and parental smoking (3.8; P .028).ConclusionsThe data suggest diverse asthma phenotypes and mechanisms that can be predicted using simple clinical markers at the time of the first severe wheezing episode. Findings are important in designing early intervention strategies for secondary prevention of asthma. (ClinicalTrials.gov number, NCT00494624 and NCT00731575)

Teaser

The data suggest that sensitization, eczema and the rhinovirus etiology and atopic characteristics already at the first severe wheezing episode predict atopic but not non-atopic asthma at age 8 years, and therefore are worth assessing early.


http://ift.tt/2nTY7t8

Novel Sensitization Trajectories in Childhood revealed by a Cluster Analysis

Publication date: Available online 25 March 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Ann-Marie M. Schoos, Bo L. Chawes, Erik Melén, Anna Bergström, Inger Kull, Magnus Wickman, Klaus Bønnelykke, Hans Bisgaard, Morten A. Rasmussen
BackgroundAssessment of sensitization at an isolated time-point during childhood provides limited clinical information. We hypothesized that sensitization develops as specific patterns with respect to age at debut, development over time, and involved allergens, and that such patterns might be more biologically and clinically relevant.ObjectiveTo explore latent patterns of sensitization during the first 6 years of life and investigate whether such patterns associate to development of asthma, rhinitis, and eczema.MethodsWe investigated 398 children from the at-risk Copenhagen Prospective Studies on Asthma in Childhood 2000 birth cohort (COPSAC2000) with specific-IgE against 13 common food and inhalant allergens at ages ½, 1½, 4, and 6yrs. An unsupervised cluster analysis for three-dimensional data (NNS-PARAFAC) was used to extract latent patterns explicitly characterizing temporal development of sensitization, while clustering allergens and children. Subsequently, these patterns were investigated in relation to asthma, rhinitis, and eczema. Verification was sought in an independent unselected birth cohort, BAMSE, constituting 3051 children with specific-IgE against the same allergens at 4 and 8yrs.ResultsThe NNS-PARAFAC analysis indicated a complex latent structure involving seven age- and allergen-specific patterns in the COPSAC2000 data: (1) dog/cat/horse; (2) timothy grass/birch; (3) molds; (4) house dust mites; (5) peanut/wheat flour/mugwort; (6) peanut/soybean; and (7) egg/milk/wheat flour. Asthma was solely associated with pattern 1 (OR=3.3 [1.5-7.2]), rhinitis with patterns 1-4 and 6 (ORs=2.2–4.3) and eczema with patterns 1-3 and 5-7 (ORs=1.6–2.5). All seven patterns were verified in the independent BAMSE cohort (R²>0.89).ConclusionThis study suggests the presence of specific sensitization patterns in early childhood differentially associated to development of clinical outcomes. Using such patterns in future research might provide more robust and clinically relevant results.

Teaser

Sensitization in young children is a make-up of seven distinct patterns defined by the allergens and temporal profile and with different association to allergic disease.


http://ift.tt/2o43GlD

Impact of School Peanut-Free Policies on Epinephrine Administration

Publication date: Available online 25 March 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Lisa M. Bartnikas, Michelle F. Huffaker, William J. Sheehan, Watcharoot Kanchongkittiphon, Carter R. Petty, Robert Leibowitz, Marissa Hauptman, Michael C. Young, Wanda Phipatanakul
BackgroundChildren with food allergies spend a large proportion of time in school but characteristics of allergic reactions in schools are not well studied. Some schools self-designate as peanut-free or have peanut-free areas, but the impact of policies on clinical outcomes has not been evaluated.ObjectiveWe sought to determine the effect of peanut-free policies on rates of epinephrine administration for allergic reactions in Massachusetts public schools.MethodsIn this retrospective study, we analyzed (1) rates of epinephrine administration in all Massachusetts public schools and (2) Massachusetts public school nurse survey reports of school peanut-free policies from 2006-2011 and whether schools self-designated as "peanut-free" based on policies. Rates of epinephrine administration were compared for schools with or without peanut restrictive policies.ResultsThe percentage of schools with peanut restrictive policies did not change significantly in the study timeframe. There was variability in policies used by schools self-designated as peanut-free. No policy was associated with complete absence of allergic reactions. Both self-designated peanut-free schools and schools banning peanuts from being served in school or brought from home had allergic reactions to nuts. Policies restricting peanuts from home, served in schools or having peanut-free classrooms did not affect epinephrine administration rates. Schools with peanut-free tables, compared to without, had lower rates of epinephrine administration (IR per 10,000 students 0.2 and 0.6, respectively, P=0.009).ConclusionsThese data provide a basis for evidence-based school policies for children with food allergies. Further studies are required before decisions can be made regarding peanut-free policies in schools.

Teaser

In this retrospective study of epinephrine administration in Massachusetts public schools, schools with peanut-free tables, compared to without, had lower epinephrine administration rates. Other peanut restrictive policies did not affect epinephrine administration rates.


http://ift.tt/2nTY5Bw

Liver metastases from gastric carcinoma. Case Report and Review of the literature

Publication date: Available online 24 March 2017
Source:Current Problems in Cancer
Author(s): Beata Polkowska-Pruszyńska, Karol Rawicz-Pruszyński, Bogumiła Ciseł, Robert Sitarz, Grażyna Polkowska, Witold Krupski, Wojciech P. Polkowski
Gastric carcinoma (GC) is the fifth most common malignancy worldwide but the third leading cause of cancer death, and surgery remains the only curative treatment option. Prognosis of patients with liver metastases from gastric carcinoma (LMGC) is poor, and the optimal treatment of metastatic gastric cancer remains a matter of debate. In 2002 a 53-year-old male patient with GC and synchronous oligometastatic lesion in liver VIII segment underwent a total gastrectomy combined with metastasectomy. The pathological diagnosis was stage IV gastric adenocarcinoma (pT3N2M1), which was treated with adjuvant chemotherapy (PELF). In 2012 abdominal ultrasound and percutaneous liver biopsy revealed recurrence of the metastasis in the right liver lobe. Progression of the disease was observed after palliative chemotherapy (EOX). Nevertheless an extended right-hemihepatectomy, with excision of segments 1, 4A, 5, 6, 7 and 8, was still performed. Pathological examination confirmed large KRAS-, and HER2-negative LMGC. The patient is alive and free of disease 47 months after the repeated hepatectomy, and 13 years after removal of the primary GC and synchronous liver metastasis. Based on review of 27 articles, 5-year OS rate following gastrectomy and liver metastasectomy may reach 60%, with median survival time up to 74 months.  Although the combination of aggressive surgical approach with systemic therapy for LMGC is controversial, it may allow favourable outcome. Careful selection of patients based on evaluable predictive factors for R0 surgical resection of both, primary tumour and liver metastases can lead to cure, as shown in our case presentation, where 10 year relapse-free survival was observed, followed by successful repeated hepatectomy due to liver metastases.



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Functional connectivity and activity of white matter in somatosensory pathways under tactile stimulations

Publication date: 15 May 2017
Source:NeuroImage, Volume 152
Author(s): Xi Wu, Zhipeng Yang, Stephen K. Bailey, Jiliu Zhou, Laurie E. Cutting, John C. Gore, Zhaohua Ding
Functional MRI has proven to be effective in detecting neural activity in brain cortices on the basis of blood oxygenation level dependent (BOLD) contrast, but has relatively poor sensitivity for detecting neural activity in white matter. To demonstrate that BOLD signals in white matter are detectable and contain information on neural activity, we stimulated the somatosensory system and examined distributions of BOLD signals in related white matter pathways. The temporal correlation profiles and frequency contents of BOLD signals were compared between stimulation and resting conditions, and between relevant white matter fibers and background regions, as well as between left and right side stimulations. Quantitative analyses show that, overall, MR signals from white matter fiber bundles in the somatosensory system exhibited significantly greater temporal correlations with the primary sensory cortex and greater signal power during tactile stimulations than in a resting state, and were stronger than corresponding measurements for background white matter both during stimulations and in a resting state. The temporal correlation and signal power under stimulation were found to be twice those observed from the same bundle in a resting state, and bore clear relations with the side of stimuli. These indicate that BOLD signals in white matter fibers encode neural activity related to their functional roles connecting cortical volumes, which are detectable with appropriate methods.



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Single or multiple frequency generators in on-going brain activity: A mechanistic whole-brain model of empirical MEG data

Publication date: 15 May 2017
Source:NeuroImage, Volume 152
Author(s): Gustavo Deco, Joana Cabral, Mark W. Woolrich, Angus B.A. Stevner, Tim J. van Hartevelt, Morten L. Kringelbach
During rest, envelopes of band-limited on-going MEG signals co-vary across the brain in consistent patterns, which have been related to resting-state networks measured with fMRI. To investigate the genesis of such envelope correlations, we consider a whole-brain network model assuming two distinct fundamental scenarios: one where each brain area generates oscillations in a single frequency, and a novel one where each brain area can generate oscillations in multiple frequency bands. The models share, as a common generator of damped oscillations, the normal form of a supercritical Hopf bifurcation operating at the critical border between the steady state and the oscillatory regime. The envelopes of the simulated signals are compared with empirical MEG data using new methods to analyse the envelope dynamics in terms of their phase coherence and stability across the spectrum of carrier frequencies.Considering the whole-brain model with a single frequency generator in each brain area, we obtain the best fit with the empirical MEG data when the fundamental frequency is tuned at 12Hz. However, when multiple frequency generators are placed at each local brain area, we obtain an improved fit of the spatio-temporal structure of on-going MEG data across all frequency bands. Our results indicate that the brain is likely to operate on multiple frequency channels during rest, introducing a novel dimension for future models of large-scale brain activity.

Graphical abstract

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Joint prediction of longitudinal development of cortical surfaces and white matter fibers from neonatal MRI

Publication date: 15 May 2017
Source:NeuroImage, Volume 152
Author(s): Islem Rekik, Gang Li, Pew-Thian Yap, Geng Chen, Weili Lin, Dinggang Shen
The human brain can be modeled as multiple interrelated shapes (or a multishape), each for characterizing one aspect of the brain, such as the cortex and white matter pathways. Predicting the developing multishape is a very challenging task due to the contrasting nature of the developmental trajectories of the constituent shapes: smooth for the cortical surface and non-smooth for white matter tracts due to changes such as bifurcation. We recently addressed this problem and proposed an approach for predicting the multishape developmental spatiotemporal trajectories of infant brains based only on neonatal MRI data using a set of geometric, dynamic, and fiber-to-surface connectivity features. In this paper, we propose two key innovations to further improve the prediction of multishape evolution. First, for a more accurate cortical surface prediction, instead of simply relying on one neonatal atlas to guide the prediction of the multishape, we propose to use multiple neonatal atlases to build a spatially heterogeneous atlas using the multidirectional varifold representation. This individualizes the atlas by locally maximizing its similarity to the testing baseline cortical shape for each cortical region, thereby better representing the baseline testing cortical surface, which founds the multishape prediction process. Second, for temporally consistent fiber prediction, we propose to reliably estimate spatiotemporal connectivity features using low-rank tensor completion, thereby capturing the variability and richness of the temporal development of fibers. Experimental results confirm that the proposed variants significantly improve the prediction performance of our original multishape prediction framework for both cortical surfaces and fiber tracts shape at 3, 6, and 9 months of age. Our pioneering model will pave the way for learning how to predict the evolution of anatomical shapes with abnormal changes. Ultimately, devising accurate shape evolution prediction models that can help quantify and predict the severity of a brain disorder as it progresses will be of great aid in individualized treatment planning.



http://ift.tt/2mCiieO

Reduction of across-run variability of temporal SNR in accelerated EPI time-series data through FLEET-based robust autocalibration

Publication date: 15 May 2017
Source:NeuroImage, Volume 152
Author(s): Anna I. Blazejewska, Himanshu Bhat, Lawrence L. Wald, Jonathan R. Polimeni
Temporal signal-to-noise ratio (tSNR) is a key metric for assessing the ability to detect brain activation in fMRI data. A recent study has shown substantial variation of tSNR between multiple runs of accelerated EPI acquisitions reconstructed with the GRAPPA method using protocols commonly used for fMRI experiments. Across-run changes in the location of high-tSNR regions could lead to misinterpretation of the observed brain activation patterns, reduced sensitivity of the fMRI studies, and biased results. We compared conventional EPI autocalibration (ACS) methods with the recently-introduced FLEET ACS method, measuring their tSNR variability, as well as spatial overlap and displacement of high-tSNR clusters across runs in datasets acquired from human subjects at 7T and 3T. FLEET ACS reconstructed data had higher tSNR levels, as previously reported, as well as better temporal consistency and larger overlap of the high-tSNR clusters across runs compared with reconstructions using conventional multi-shot (ms) EPI ACS data. tSNR variability across two different runs of the same protocol using ms-EPI ACS data was about two times larger than for the protocol using FLEET ACS for acceleration factors (R) 2 and 3, and one and half times larger for R=4. The level of across-run tSNR consistency for data reconstructed with FLEET ACS was similar to within-run tSNR consistency. The displacement of high-tSNR clusters across two runs (inter-cluster distance) decreased from ∼8mm in the time-series reconstructed using conventional ms-EPI ACS data to ∼4mm for images reconstructed using FLEET ACS. However, the performance gap between conventional ms-EPI ACS and FLEET ACS narrowed with increasing parallel imaging acceleration factor. Overall, the FLEET ACS method provides a simple solution to the problem of varying tSNR across runs, and therefore helps ensure that an assumption of fMRI analysis—that tSNR is largely consistent across runs—is met for accelerated acquisitions.

Graphical abstract

http://ift.tt/2n4JLlM

Human centromedian-parafascicular complex signals sensory cues for goal-oriented behavior selection

Publication date: 15 May 2017
Source:NeuroImage, Volume 152
Author(s): Inga M. Schepers, Anne-Kathrin Beck, Susann Bräuer, Kerstin Schwabe, Mahmoud Abdallat, Pascale Sandmann, Reinhard Dengler, Jochem W. Rieger, Joachim K. Krauss
Experimental research has shown that the centromedian-parafascicular complex (CM-Pf) of the intralaminar thalamus is activated in attentional orienting and processing of behaviorally relevant stimuli. These observations resulted in the hypothesis that the CM-Pf plays a pivotal role in goal-oriented behavior selection. We here set out to test this hypothesis with electrophysiological recordings from patients with electrodes implanted in CM-Pf for deep brain stimulation (DBS) treatment of chronic neuropathic pain. Six patients participated in (1) an auditory three-class oddball experiment, which required a button press to target tones, but not to standard and deviant tones and in (2) a multi-speaker experiment with a target word that required attention selection and a target image that required response selection. Subjects showed transient neural responses (8–15Hz) to the target tone and the target word. Two subjects additionally showed transient neural responses (15–25Hz) to the target image. All sensory target stimuli were related to an internal goal and required a behavior selection (attention selection, response selection). In group analyses, neural responses were greater to target tones than deviant and standard tones and to target words than other task-relevant words that did not require attention selection. The transient neural responses occurred after the target stimuli but prior to the overt behavioral response. Our results demonstrate that in human subjects the CM-Pf is involved in signaling sensory inputs related to goal-oriented selection of behavior.



http://ift.tt/2n4QvQA

Proportional thresholding in resting-state fMRI functional connectivity networks and consequences for patient-control connectome studies: Issues and recommendations

Publication date: 15 May 2017
Source:NeuroImage, Volume 152
Author(s): Martijn P. van den Heuvel, Siemon C. de Lange, Andrew Zalesky, Caio Seguin, B.T. Thomas Yeo, Ruben Schmidt
Graph theoretical analysis has become an important tool in the examination of brain dysconnectivity in neurological and psychiatric brain disorders. A common analysis step in the construction of the functional graph or network involves "thresholding" of the connectivity matrix, selecting the set of edges that together form the graph on which network organization is evaluated. To avoid systematic differences in absolute number of edges, studies have argued against the use of an "absolute threshold" in case-control studies and have proposed the use of "proportional thresholding" instead, in which a pre-defined number of strongest connections are selected as network edges, ensuring equal network density across datasets. Here, we systematically studied the effect of proportional thresholding on the construction of functional matrices and subsequent graph analysis in patient-control functional connectome studies. In a few simple experiments we show that differences in overall strength of functional connectivity (FC) – as often observed between patients and controls – can have predictable consequences for between-group differences in network organization. In individual networks with lower overall FC the proportional thresholding algorithm has to select more edges based on lower correlations, which have (on average) a higher probability of being spurious, and thus introduces a higher degree of randomness in the resulting network. We show across both empirical and artificial patient-control datasets that lower levels of overall FC in either the patient or control group will most often lead to differences in network efficiency and clustering, suggesting that differences in FC across subjects will be artificially inflated or translated into differences in network organization. Based on the presented case-control findings we inform about the caveats of proportional thresholding in patient-control studies in which groups show a between-group difference in overall FC. We make recommendations on how to examine, report and to take into account overall FC effects in future patient-control functional connectome studies.



http://ift.tt/2mC891E

The IVIM signal in the healthy cerebral gray matter: A play of spherical and non-spherical components

Publication date: 15 May 2017
Source:NeuroImage, Volume 152
Author(s): Tim Finkenstaedt, Markus Klarhoefer, Christian Eberhardt, Anton S. Becker, Gustav Andreisek, Andreas Boss, Cristina Rossi
The intra-voxel incoherent motion (IVIM) model assumes that blood flowing in isotropically distributed capillary segments induces a phase dispersion of the MR signal, which increases the signal attenuation in diffusion-weighted images. However, in most tissue types the capillary network has an anisotropic micro-architecture. In this study, we investigated the possibility to indirectly infer the anisotropy of the capillary network in the healthy cerebral gray matter by evaluating the dependence of the IVIM signal from the direction of the diffusion-encoding.Perfusion-related indices and self-diffusion were modelled as symmetric rank 2 tensors. The geometry of the tensors was quantified pixel-wise by decomposing the tensor in sphere-like, plane-like, and line-like components. Additionally, trace and fractional anisotropy of the tensors were computed.While the self-diffusion tensor is dominated by a spherical geometry with a residual contribution of the non-spherical components, both, fraction of perfusion and pseudo-diffusion, present a substantial (in the order of 30%) contribution of planar and linear components to the tensor metrics.This study shows that the IVIM perfusion estimates in the cerebral gray matter present a detectable deviation from the spherical model. These non-spherical components may reflect the direction-dependent morphology of the microcirculation. Therefore, the tensor generalization of the IVIM model may provide a tool for the non-invasive monitoring of cerebral capillary micro-architecture during development, aging or in pathologies.

Graphical abstract

http://ift.tt/2n4BCh6

Comparing GABA-dependent physiological measures of inhibition with proton magnetic resonance spectroscopy measurement of GABA using ultra-high-field MRI

Publication date: 15 May 2017
Source:NeuroImage, Volume 152
Author(s): Katherine Dyke, Sophia E. Pépés, Chen Chen, Soyoung Kim, Hilmar P. Sigurdsson, Amelia Draper, Masud Husain, Parashkev Nachev, Penelope A. Gowland, Peter G. Morris, Stephen R. Jackson
Imbalances in glutamatergic (excitatory) and GABA (inhibitory) signalling within key brain networks are thought to underlie many brain and mental health disorders, and for this reason there is considerable interest in investigating how individual variability in localised concentrations of these molecules relate to brain disorders. Magnetic resonance spectroscopy (MRS) provides a reliable means of measuring, in vivo, concentrations of neurometabolites such as GABA, glutamate and glutamine that can be correlated with brain function and dysfunction. However, an issue of much debate is whether the GABA observed and measured using MRS represents the entire pool of GABA available for measurement (i.e., metabolic, intracellular, and extracellular) or is instead limited to only some portion of it. GABA function can also be investigated indirectly in humans through the use of non-invasive transcranial magnetic stimulation (TMS) techniques that can be used to measure cortical excitability and GABA-mediated physiological inhibition. To investigate this issue further we collected in a single session both types of measurement, i.e., TMS measures of cortical excitability and physiological inhibition and ultra-high-field (7 T) MRS measures of GABA, glutamate and glutamine, from the left sensorimotor cortex of the same group of right-handed individuals. We found that TMS and MRS measures were largely uncorrelated with one another, save for the plateau of the TMS IO curve that was negatively correlated with MRS-Glutamate (Glu) and intra-cortical facilitation (10ms ISI) that was positively associated with MRS-Glutamate concentration. These findings are consistent with the view that the GABA concentrations measured using the MRS largely represent pools of GABA that are linked to tonic rather than phasic inhibition and thus contribute to the inhibitory tone of a brain area rather than GABAergic synaptic transmission.



http://ift.tt/2n4DAho

Interactions between the anterior cingulate-insula network and the fronto-parietal network during perceptual decision-making

Publication date: 15 May 2017
Source:NeuroImage, Volume 152
Author(s): Ganesh B. Chand, Mukesh Dhamala
Information processing in the human brain during cognitively demanding goal-directed tasks is thought to involve several large-scale brain networks, including the anterior cingulate-insula network (aCIN) and the fronto-parietal network (FPN). Recent functional MRI (fMRI) studies have provided clues that the aCIN initiates activity changes in the FPN. However, when and how often these networks interact remains largely unknown to date. Here, we systematically examined the oscillatory interactions between the aCIN and the FPN by using the spectral Granger causality analysis of reconstructed brain source signals from the scalp electroencephalography (EEG) recorded from human participants performing a face-house perceptual categorization task. We investigated how the aCIN and the FPN interact, what the temporal sequence of events in these nodes is, and what frequency bands of information flow bind these nodes in networks. We found that beta band (13–30Hz) and gamma (30–100Hz) bands of interactions are involved between the aCIN and the FPN during decision-making tasks. In gamma band, the aCIN initiated the Granger causal control over the FPN in 25–225 ms timeframe. In beta band, the FPN achieved a control over the aCIN in 225–425 ms timeframe. These band-specific time-dependent Granger causal controls of the aCIN and the FPN were retained for behaviorally harder decision-making tasks. These findings of times and frequencies of oscillatory interactions in the aCIN and FPN provide us new insights into the general neural mechanisms for sensory information-guided, goal-directed behaviors, including perceptual decision-making processes.



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Knowing what from where: Hippocampal connectivity with temporoparietal cortex at rest is linked to individual differences in semantic and topographic memory

Publication date: 15 May 2017
Source:NeuroImage, Volume 152
Author(s): Mladen Sormaz, Elizabeth Jefferies, Boris C. Bernhardt, Theodoros Karapanagiotidis, Giovanna Mollo, Neda Bernasconi, Andrea Bernasconi, Tom Hartley, Jonathan Smallwood
The hippocampus contributes to episodic, spatial and semantic aspects of memory, yet individual differences within and between these functions are not well-understood. In 136 healthy individuals, we investigated whether these differences reflect variation in the strength of connections between functionally-specialised segments of the hippocampus and diverse cortical regions that participate in different aspects of memory. Better topographical memory was associated with stronger connectivity between lingual gyrus and left anterior, rather than posterior, hippocampus. Better semantic memory was associated with increased connectivity between the intracalcarine/cuneus and left, rather than right, posterior hippocampus. Notably, we observed a double dissociation between semantic and topographical memory: better semantic memory was associated with stronger connectivity between left temporoparietal cortex and left anterior hippocampus, while better topographic memory was linked to stronger connectivity with right anterior hippocampus. Together these data support a division-of-labour account of hippocampal functioning: at the population level, differences in connectivity across the hippocampus reflect functional specialisation for different facets of memory, while variation in these connectivity patterns across individuals is associated with differences in the capacity to retrieve different types of information. In particular, within-hemisphere connectivity between hippocampus and left temporoparietal cortex supports conceptual processing at the expense of spatial ability.



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Teams on the same wavelength perform better: Inter-brain phase synchronization constitutes a neural substrate for social facilitation

Publication date: 15 May 2017
Source:NeuroImage, Volume 152
Author(s): Caroline Szymanski, Ana Pesquita, Allison A. Brennan, Dionysios Perdikis, James T. Enns, Timothy R. Brick, Viktor Müller, Ulman Lindenberger
Working together feels easier with some people than with others. We asked participants to perform a visual search task either alone or with a partner while simultaneously measuring each participant's EEG. Local phase synchronization and inter-brain phase synchronization were generally higher when subjects jointly attended to a visual search task than when they attended to the same task individually. Some participants searched the visual display more efficiently and made faster decisions when working as a team, whereas other dyads did not benefit from working together. These inter-team differences in behavioral performance gain in the visual search task were reliably associated with inter-team differences in local and inter-brain phase synchronization. Our results suggest that phase synchronization constitutes a neural correlate of social facilitation, and may help to explain why some teams perform better than others.



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Tratamiento del cáncer de laringe avanzado y calidad de vida. Revisión sistemática

Publication date: Available online 25 March 2017
Source:Acta Otorrinolaringológica Española
Author(s): Francisco Javier García-León, Raúl García-Estepa, Antonio Romero-Tabares, Jaime Gómez-Millán Borrachina
Introducción y objetivosEl objetivo fue comparar la calidad de vida de los pacientes con cáncer de laringe en estadio avanzado tratados con preservación de órgano respecto a aquellos tratados quirúrgicamente.MétodosSe realizó una revisión sistemática consultando MedLine, EMBASE, y PubMed (1991-2014) y Web of Science (2012-2014). Los términos de búsqueda fueron: cáncer de laringe, preservación de órgano, quimioterapia, laringectomía, resultados de tratamiento y calidad de vida. Se incluyeron revisiones sistemáticas, metaanálisis, informes de evaluación de tecnologías sanitarias y estudios comparativos con grupo control, publicados en idioma español, francés o inglés. La selección y evaluación de la calidad fue realizada por dos investigadores. Se usaron los criterios de la Colaboración Cochrane para evaluar el riesgo de sesgo y los del Scottish Intercollegiate Guidelines Network (SIGN) para el nivel de evidencia.ResultadosDe los 208 estudios identificados en la búsqueda se incluyeron tres: un ensayo clínico y dos estudios observacionales, con un total de 211 pacientes. Su calidad y nivel de evidencia fueron bajos. Los resultados fueron contradictorios, en algunas ocasiones favorables a la cirugía y en otras, a la combinación de radioterapia y quimioterapia, pero en general, sin diferencias significativas entre los tratamientos. Se trataba de estudios heterogéneos, con metodología diferente, tamaño insuficiente, limitaciones en su calidad, con importante riesgo de sesgo y utilización de escalas de medida distintas.ConclusionesCarecemos de estudios de calidad suficiente para establecer si la calidad de vida en los pacientes con cáncer de laringe en estadio avanzado es diferente en función del tratamiento recibido.Introduction and objectivesThe objective was the comparison of the quality of life in patients with advanced laryngeal cancer treated with organ preservation versus surgical treatment.MethodsWe performed a systematic review in the databases MedLine, EMBASE, and PubMed (2014 1991) and Web of Science (2012 - 2014). The search terms were: Laryngeal cancer, organ preservation, chemotherapy, laryngectomy, treatment outcomes and quality of life. Systematic reviews, meta-analysis, reports of health technology assessment and comparative studies with control group, published in Spanish, French or English were included. The selection and quality assessment was made by two researchers. The criteria of the Cochrane Collaboration were used to assess the risk of bias and Scottish Intercollegiate Guidelines Network (SIGN) for the level of evidence.ResultsOf the 208 studies identified in the search, three were included a clinical trial and two observational studies, with a total of 211 patients. Quality and level of evidence was low. The results were contradictory, on occasion they favoured surgery, and on other occasions chemotherapy, but in general there were no statistical differences between the treatments. The studies were heterogeneous, with different methodology, undersized, limitations in quality with high risk of bias and use of different measurement scales.ConclusionsThere are not enough studies of quality to establish differences in the quality of life in patients with advanced laryngeal cancer according to the treatment received.



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Prospective Trial of House Staff Time to Response and Intervention in a Surgical Intensive Care Unit: Pager vs. Smartphone

Publication date: Available online 24 March 2017
Source:Journal of Surgical Education
Author(s): James M. Tatum, Terris White, Christopher Kang, Eric J. Ley, Nicolas Melo, Matthew Bloom, Rodrigo F. Alban
ObjectiveThe objective of the study was to characterize house staff time to response and intervention when notified of a patient care issue by pager vs. smartphone. We hypothesized that smartphones would reduce house staff time to response and intervention.DesignProspective study of all electronic communications was conducted between nurses and house staff between September 2015 and October 2015. The 4-week study period was randomly divided into two 2-week study periods where all electronic communications between intensive care unit nurses and intensive care unit house staff were exclusively by smartphone or by pager, respectively. Time of communication initiation, time of house staff response, and time from response to clinical intervention for each communication were recorded. Outcomes are time from nurse contact to house staff response and intervention.SettingSingle-center surgical intensive care unit of Cedars-Sinai Medical Center in Los Angeles, California, an academic tertiary care and level I trauma center.ParticipantsAll electronic communications occurring between nurses and house staff in the study unit during the study period were considered. During the study period, 205 nurse-house staff electronic communications occurred, 100 in the phone group and 105 in the pager group.ResultsHouse staff response to communication time was significantly shorter in the phone group (0.5 [interquartile range = 1.7] vs. 2 [3]min, p < 0.001). Time to house staff intervention after response was also significantly more rapid in the phone group (0.8 [1.7] vs. 1 [2]min, p = 0.003).ConclusionsDedicated clinical smartphones significantly decrease time to house staff response after electronic nursing communications compared with pagers.



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An Assessment of the Frequency of Palliative Procedures in Thoracic Surgery

Publication date: Available online 24 March 2017
Source:Journal of Surgical Education
Author(s): Richard K. Freeman, Gabriel Arevalo, Anthony J. Ascioti, Megan Dake, Raja S. Mahidhara
ObjectivesPalliative care is a medical specialty focused on improving the quality of life of patients and their families with life threatening illness by preventing or relieving suffering. An assessment of a thoracic surgery service was performed to identify the scope and frequency of care that was considered palliative and any implications the findings might have on the current thoracic surgery residency curriculum.MethodsA retrospective review of a prospectively collected database of general thoracic surgery procedures performed over a 5-year period at a single institution was performed. Procedures considered palliative were reviewed for demographics, diagnoses, palliative prognosis score, treatment, morbidity, operative mortality, and survival. Excluded were referrals from thoracic surgery to other specialties for palliative procedures.ResultsDuring the study period, 3842 procedures were performed of which 884 (23%) were palliative. Indications included pleural or pericardial effusion or both, dysphagia, hemoptysis, tracheobronchial obstruction, bronchopleural fistula, and tracheoesophageal fistula. The majority was related to a malignancy. Only 127 patients (14%) had a palliative care assessment before thoracic surgery consultation. Mean survival following thoracic surgery intervention was 110 days for patients with malignancy.ConclusionsThis investigation found that thoracic surgeons commonly care for patients when the intention or indication or both is palliation. Most of these patients have an associated malignancy, a poor performance status and a projected significantly decreased survival compared with the general population. Thoracic surgeons should be familiar with the concepts of palliative care and consideration should be given to expanding exposure to the principles of palliative care in the cardiothoracic residency training curriculum.



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Application of benchtop and portable near-infrared spectrometers for predicting the optimum harvest time of Verbena officinalis

Publication date: 1 July 2017
Source:Talanta, Volume 169
Author(s): Cornelia K. Pezzei, Stefan A. Schönbichler, Christian G. Kirchler, Julia Schmelzer, Shah Hussain, Verena A. Huck-Pezzei, Michael Popp, Justine Krolitzek, Günther K. Bonn, Christian W. Huck
This study examined the applicability of near-infrared (NIR) spectroscopy coupled with multivariate data analysis (MVA) to determine the ideal harvest time of Verbena officinalis. NIR analyses were performed non-invasively on the fresh plant material based on the quantification of the key constituents verbenalin and verbascoside. Vibrational spectroscopic measurements were performed applying a conventional NIR benchtop device as well as a laboratory independent handheld NIR spectrometer. A novel high performance liquid chromatography (HPLC) method was applied as a reference method. For both instruments partial least squares (PLS) regression models were established performing cross validations (CV) and test-set validations (TSV). Quality parameters obtained for the benchtop device revealed that the newly established NIR method enabled reliable quantifications of the main compounds verbenalin and verbascoside related to the dried and fresh plant material. The results of the miniaturised spectrometer revealed that accurate quantitative calibration models could be developed for verbascoside achieving a comparable prediction power to the benchtop device. PLS models for verbenalin were less precise suggesting the application of portable devices including a different spectral range and resolution. The work demonstrated the feasibility of NIR vibrational spectroscopy performing direct measurements on pharmaceutically relevant fresh plant material enabling a quick and simple determination of the ideal harvest time of Verbena officinalis.

Graphical abstract

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Volatile profiles of green Spanish-style table olives: Application of compositional data analysis for the segregation of their cultivars and production areas

Publication date: 1 July 2017
Source:Talanta, Volume 169
Author(s): A. Garrido-Fernández, A. Montaño, A.H. Sánchez-Gómez, A. Cortés-Delgado, A. López-López
The work presents the application of compositional data methodology to analytical results, taking as an example the study of the volatile profiles of green Spanish-style table olives according to cultivars and production areas. For this purpose, the volatile compounds (analysed by GC-MS and expressed as percentages of the total area) were considered as a compositional data set in the Simplex space and, as a result, analysed by their specific new statistical tools. Application of compositional exploratory tools (variation array, tertiary graphs, biplots, or coda-dendrogram) allowed differentiating cultivars and production areas based on their volatile profiles. Also, the application of Cluster and Principal Component analysis to the ilr transformed values (coordinates), following the new methodology, led to more realistic results than the formally incorrect implementation of the standard multivariate analysis (developed for data from the Euclidean space) to percentages (data in the Simplex). Therefore, the work presents a novel consideration of the volatile profiles of table olives as compositional data and shows their proper analysis by statistical tools specifically developed for them.

Graphical abstract

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Selenoprotein T is required for pathogenic bacteria avoidance in Caenorhabditis elegans

Publication date: Available online 24 March 2017
Source:Free Radical Biology and Medicine
Author(s): Laura Romanelli-Cedrez, Inés Carrera, Lucía Otero, Antonio Miranda-Vizuete, Marco Mariotti, Mark J. Alkema, Gustavo Salinas
Selenoprotein T (SELENOT) is an endoplasmatic reticulum (ER)-associated redoxin that contains the amino acid selenocysteine (Sec, U) within a CXXU motif within a thioredoxin-like fold. Its precise function in multicellular organisms is not completely understood although it has been shown in mammals to be involved in Ca²⁺ homeostasis, antioxidant and neuroendocrine functions. Here, we use the model organism C. elegans to address SELENOT function in a whole organism throughout its life cycle. C. elegans possess two genes encoding SELENOT protein orthologues (SELT-1.1 and SELT-1.2), which lack Sec and contain the CXXC redox motif instead. Our results show that a Sec→Cys replacement and a gene duplication were two major evolutionary events that occurred in the nematode lineage. We find that worm SELT-1.1 localizes to the ER and is expressed in different cell types, including the nervous system. In contrast, SELT-1.2 exclusively localizes in the cytoplasm of the AWB neurons. We find that selt-1.1 and selt-1.2 single mutants as well as the double mutant are viable, but the selt-1.1 mutant is compromised under rotenone-induced oxidative stress. We demonstrate that selt-1.1, but not selt-1.2, is required for avoidance to the bacterial pathogens Serratia marcescens and Pseudomonas aeruginosa. Aversion to the noxious signal 2-nonanone is also significantly impaired in selt-1.1, but not in selt-1.2 mutant animals. Our results suggest that selt-1.1 would be a redox transducer required for nociception and optimal organismal fitness. The results highlight C. elegans as a valuable model organism to study SELENOT-dependent processes.

Graphical abstract

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Persistent blood glucose reduction upon repeated transcranial electric stimulation in men

Publication date: Available online 25 March 2017
Source:Brain Stimulation
Author(s): Alina Kistenmacher, Sebastian Manneck, Ewelina K. Wardzinski, Jan C. Martens, Georg Gohla, Uwe H. Melchert, Kamila Jauch-Chara, Kerstin M. Oltmanns
BackgroundTranscranial direct current stimulation (tDCS) of the human brain increases systemic glucose tolerance.Objective/HypothesisTo investigate whether this effect persists after one week of repeated stimulation. Because systemic glucose uptake relates to brain energy homeostasis, we concomitantly measured cerebral high-energy phosphate metabolites.MethodsIn a sham-controlled crossover design, 14 healthy men were tested under daily anodal tDCS vs. sham for 8 days. Systemic glucose metabolism was examined by concentrations of circulating glucose and insulin. Cerebral energy metabolism – i.e. adenosine triphosphate (ATP) and phosphocreatine (PCr) levels – was assessed by ³¹phosphorous magnetic resonance spectroscopy.ResultsBlood glucose concentrations were distinctly lower upon tDCS compared with sham stimulation on day 1. This effect persisted on day 8, while serum insulin levels remained persistently unchanged. Transcranial stimulation increased mean levels of ATP and PCr compared with sham on day 1 only. Blood glucose concentrations negatively correlated with PCr content after repeated daily stimulation.ConclusionsOur data confirm that tDCS reduces blood glucose through an insulin-independent mechanism. This effect persists after 8 days of repeated stimulation and relates to brain energy metabolism. Therefore, transcranial electric stimulation may be a promising non-pharmacological adjuvant option to treat systemic disorders such as glucose intolerance or type 2 diabetes mellitus with a low side-effect profile.



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Primary Localized Cutaneous Amyloidosis: A Systematic Treatment Review

Abstract

Background

Primary localized cutaneous amyloidosis (PLCA) is characterized by extracellular deposition of heterogenic amyloid proteins in the skin without systemic involvement. Lichen amyloidosis, macular amyloidosis, and (primary localized cutaneous) nodular amyloidosis are different subtypes of PLCA.

Objective

The aim of this study was to review the current reported treatment options for PLCA.

Methods

This systematic review was based on a search in the PubMed database for English and German articles from 1985 to 2016.

Results

Reports on the treatment of PLCA were limited predominantly to case reports or small case series. There were a few clinical trials but these lacked control groups. A variety of treatment options for PLCA were reported including retinoids, corticosteroids, cyclophosphamide, cyclosporine, amitriptyline, colchicine, cepharanthin, tacrolimus, dimethyl sulfoxide, vitamin D₃ analogs, capsaicin, menthol, hydrocolloid dressings, surgical modalities, laser treatment, and phototherapy.

Conclusion

No definitive recommendation of preferable treatment procedures can be made based on the analyzed literature. Randomized controlled trials are needed to offer patients an evidence-based therapy with high-quality standardized treatment regimens for PLCA.

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Analysis of the regulation of surfactant phosphatidylcholine metabolism using stable isotopes

Publication date: Available online 25 March 2017
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): Joost Brandsma, Anthony D. Postle
The pathways and mechanisms that regulate pulmonary surfactant synthesis, processing, secretion and catabolism have been extensively characterised using classical biochemical and analytical approaches. These have constructed a model, largely in experimental animals, for surfactant phospholipid metabolism in the alveolar epithelial cell whereby phospholipid synthesised on the endoplasmic reticulum is selectively transported to lamellar body storage vesicles, where it is subsequently processed before secretion into the alveolus. Surfactant phospholipid is a complex mixture of individual molecular species defined by the combination of esterified fatty acid groups and a comprehensive description of surfactant phospholipid metabolism requires consideration of the interactions between such molecular species. However, until recently, lipid analytical techniques have not kept pace with the considerable advances in understanding of the enzymology and molecular biology of surfactant metabolism. Refinements in electrospray ionisation mass spectrometry (ESI-MS) can now provide very sensitive platforms for the rapid characterisation of surfactant phospholipid composition in molecular detail. The combination of ESI-MS and administration of phospholipid substrates labelled with stable isotopes extends this analytical approach to the quantification of synthesis and turnover of individual molecular species of surfactant phospholipid. As this methodology does not involve radioactivity, it is ideally suited to application in clinical studies. This review will provide an overview of the metabolic processes that regulate the molecular specificity of surfactant phosphatidylcholine together with examples of how the application of stable isotope technologies in vivo has, for the first time, begun to explore regulation of the molecular specificity of surfactant synthesis in human subjects.



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Expression of typical osteoclast markers by PBMCs after PEG-induced fusion as a model for studying osteoclast differentiation

Abstract

Bone is a metabolically active organ subjected to continuous remodeling process that involves resorption by osteoclast and subsequent formation by osteoblasts. Osteoclast involvement in this physiological event is regulated by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL). Fusion of mono-nuclear pre-osteoclasts is a critical event for osteoclast differentiation and for bone resorption. Here we show that PBMCs can be successfully fused with polyethylenglicol (PEG) in order to generated viable osteoclast-like cells that exhibit tartrate-resistant acid phosphatase (TRAP) and bone resorptive activities. PEG-fused PBMCs expressed additional markers compatible with osteoclastogenic differentiation such as carbonic anhydrase II (CAII), calcitonin receptor (CR), cathepsin K (Cat K), vacuolar ATPase (V-ATPase) subunit C1 (V-ATPase), integrin β3, RANK and cell surface aminopeptidase N/CD13. Actin redistribution in PEG-fused cells was found to be affected by cell cycle synchronization at G0/G1 or G2/M phases. PEG-induced fusion also led to expression of tyrosine kinases c-Src and Syk in their phosphorylated state. Scanning electron microscopy images showed morphological features typical of osteoclast-like cells. The results here shown allow concluding that PEG-induced fusion of PBMCs provides a suitable model system for understanding the mechanisms involved in osteoclastogenesis and for assaying new therapeutic strategies.

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Platform technologies for modern vaccine manufacturing

Publication date: Available online 25 March 2017
Source:Vaccine
Author(s): Hayley K. Charlton Hume, Linda H.L. Lua
Improved understanding of antigenic components and their interaction with the immune system, as supported by computational tools, permits a sophisticated approach to modern vaccine design. Vaccine platforms provide an effective tool by which strategically designed peptide and protein antigens are modularized to enhance their immunogenicity. These modular vaccine platforms can overcome issues faced by traditional vaccine manufacturing and have the potential to generate safe vaccines, rapidly and at a low cost. This review introduces two promising platforms based on virus-like particle and liposome, and discusses the methodologies and challenges.



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Modern technology: The preferred biosecurity strategy?

Publication date: Available online 24 March 2017
Source:Vaccine
Author(s): Manon Cox




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Informing pneumococcal conjugate vaccine policy in middle-income countries: The case of Malaysia

Publication date: Available online 24 March 2017
Source:Vaccine
Author(s): Serena Tricarico, Hannah C. McNeil, Michael G. Head, David W. Cleary, Stuart C. Clarke




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Knowledge, attitudes, beliefs, and behaviors of university students, faculty, and staff during a meningococcal serogroup B outbreak vaccination program

Publication date: Available online 24 March 2017
Source:Vaccine
Author(s): D.M. MacDougall, J.M. Langley, L. Li, L. Ye, D. MacKinnon-Cameron, K.A. Top, S.A. McNeil, B.A. Halperin, A. Swain, J.A. Bettinger, E. Dubé, G. De Serres, S.A. Halperin
ObjectivesDuring an outbreak of invasive meningococcal B disease on a university campus, we explored the knowledge, attitudes, beliefs, and behaviors of members of the university community in relation to the disease, the vaccine, and the vaccination program.DesignAll students, faculty and staff were invited by email to participate in a 71-item online survey, which was administered after completion of the mass clinics for the first and second doses of a meningococcal B vaccination program.ResultsA total of 404 individuals responded to the survey; 75.7% were students. Knowledge about meningococcal disease and vaccine was generally high; more than 70% correct responses were received on each knowledge question except for one question about the different meningococcal serogroups. Gender (female) and higher knowledge scores were significantly associated with either being immunized or intending to be immunized (p<0.05). Positive attitudes about immunization, concern about meningococccal infection, a sense of community responsibility, and trust in public health advice also correlated with being vaccinated or intending to be vaccinated (p<0.05).ConclusionsA successful mass vaccination program in a Nova Scotia university was associated with high levels of knowledge, positive attitudes toward vaccination, and positive attitudes toward public health recommendations.



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Primary Cutaneous Anaplastic Large Cell Lymphoma

Primary cutaneous anaplastic large cell lymphoma (PC-ALCL) is a CD30+ lymphoproliferative disorder (LPD) of the skin with a relatively good prognosis in the absence of high-stage disease.[1] CD30+ LPDs comprise approximately 25-30% of primary cutaneous lymphomas and as a group represent the second most common clonal T cell neoplasm of the skin behind mycosis fungoides (MF).

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SOX10 Immunohistochemistry in Sweat Ductal/Glandular Neoplasms

Abstract

Background

SOX10 is a newer Schwannian and melanocytic marker that has generated great interest for its relative sensitivity and specificity in the diagnosis of neural crest-derived tumors. Previous studies with SOX10 have shown positive immunohistochemical expression in cutaneous eccrine glands and negative expression in eccrine ducts, apocrine glands, and hair follicles. Thus, we hypothesized that some sweat gland tumors of presumed eccrine origin would be positive for SOX10, whereas apocrine-derived sweat gland tumors would not.

Methods

A mouse monoclonal anti-SOX10 (clone BC34: Biocare) immunohistochemical antibody was performed on various sweat gland tumors and basal cell carcinoma.

Results

SOX10 showed positivity in spiradenomas (13/13), cylindromas (9/10), hidradenoma papilliferum (10/10), syringocystadenoma papilliferum (8/10), apocrine adenomas (8/10), and negativity in poromas (0/12), syringomas (0/10), and basal cell carcinomas (0/13). There was mixed staining of hidradenomas (6/15).

Conclusions

SOX10 immunohistochemistry may be of utility in distinguishing some of the varying adnexal tumors from each other, and from BCC, but given the staining of both apocrine and eccrine tumors, does not seem to provide information as to their origins as either eccrine or apocrine tumors.

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The EP4 antagonist, L-161,982, induces apoptosis, cell cycle arrest and inhibits prostaglandin E2 induced proliferation in oral squamous carcinoma Tca8113 cells

Abstract

Background

Recent studies suggest that cyclooxygenase 2 (COX-2) inhibitors may enhance the toxic effects of anticancer drugs on tumor cells, including oral squamous cell carcinoma(OSCC), but its long-term use can cause side effects such as stomach ulcers and myocardial infarction. Our aim was to investigate proliferative effects of a downstream product of COX-2, prostaglandin E2(PGE2), in human oral squamous carcinoma cell line Tca8113 and explore the effects of PGE2 receptors, especially EP4 receptor, on the growth of Tca8113 cells.

Methods

To evaluate the effects of PGE2 and EP receptors on Tca8113 cells, CCK8 assay, Western blotting, cell cycle analysis, and apoptosis assay were performed.

Results

We found that the EP4 receptor agonist, PGE1-OH, could mimick PGE2 rescued the inhibitory effect of celecoxib and induced cell growth via ERK phosphorylation, and the EP4 receptor antagonist, L-161,982, completely blocked PGE2-stimulated ERK phosphorylation and proliferation of Tca8113 cells. Furthermore, L-161,982 may induce apoptosis and block cell cycle progression at s phase by upregulating Bax and p21 protein levels and by downregulating Bcl-2, CDK2, and cyclinA2 protein levels.

Conclusions

Our results indicate that EP4 receptor mediates PGE2 induced cell proliferation through ERK signaling, and inhibition of EP4 receptor may represent an alternative therapeutic strategy for the prevention and treatment of OSCC.

This article is protected by copyright. All rights reserved.

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PDGFRA mRNA is overexpressed in oral cancer patients as compared to normal subjects with a significant trend of overexpression among tobacco users

Abstract

Background

Platelet derived growth factors alpha (PDGFA) is a tyrosine kinase receptor activator which known to be amplified in the malignancies and their expression levels are correlated to tumor progression and reduced overall survival. The expression of PDGFRA is different among the tumors and normal tissues, furthermore; their expression level is site-specific. Under a physiological condition, PDGFRA and its ligand are expressed in distinct cell populations and activated in a paracrine manner. Nevertheless, heterodimer characteristic of PDGFRA allows it to be trans-activated by non-specific ligands or via autocrine manner. The future of cancer therapy can be based on PDGFRA receptor blockade and therefore warrants further investigation to determine the differing expression of PDGFRA between controls and Oral Squamous Cell Carcinoma (OSCC) patients.

Methods

We performed a case-control study of 111 patients with newly diagnosed tongue squamous cell carcinoma and 111 control subjects without a cancer diagnosis, matched for age and gender, to evaluate the association between PDGFRA expression level in oral mucosal. We then performed smoking stratification in each cohort. Independent t-test analysis was applied for case-control comparisons.

Results

Mean value of PDGFRA mRNA level (−ΔCt) for normal cohort is -30.242, whereas mean value of PDGFRA mRNA level for OSCC patients is -11.516. PDGFRA mRNA level (−ΔCt) was significantly higher in oral cancer cohort, p<0.001. Smokers have a significantly higher PDGFRA mRNA expression in comparison to non-smokers (p=0.002) among the non-cancer group. Likewise, this trend is observed in cancer cohort too, p=0.044.

Conclusion

PDGFRA expression is significantly higher in oral cancer cohort with or without the establishment of tobacco risk factor.

This article is protected by copyright. All rights reserved.

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