Neural control of sweat secretion: a review

Abstract

Humans have 4 million exocrine sweat glands, which can be classified into two types: eccrine and apocrine glands. Sweat secretion is a constitutive feature, which is directly involved in thermoregulation and metabolism. Sweat secretion is regulated by both the central nervous system¹ and autonomic nervous system.² In peripheral areas, the ANS, especially the sympathetic nervous system (SNS), mediates the transmission of neurotransmitters to sweat glands. Two principal chemical mediators, acetylcholine and noradrenaline (NA)/adrenaline (ADR), are released by the SNS, which stimulate sweat secretion. In the CNS, the thermoregulatory center in the hypothalamus responds to the elevated body temperature by increasing sweating, whereas emotional stresses stimulate the limbic system to induce sweating. The ANS mediates sweating that is due to stimulation of the thermoregulatory center and limbic system. In this review, we focus on the neural control of sweat secretion and the mechanisms by which chemical mediators induce sweating. In addition, we will discuss the sweating disorders associated with neural anomaly as well as the treatments.

This article is protected by copyright. All rights reserved.

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The BRAF and NRAS mutation prevalence in dermoscopic subtypes of acquired naevi reveals constitutive MAPK pathway activation

Summary

Background

Acquired naevi can have unique dermoscopic patterns that correspond to distinct microanatomical growth patterns. Previous studies on acquired naevi stratified according to dermoscopic pattern, focused on the frequency of somatic BRAF mutations, whereas NRAS mutations remained to be elucidated.

Objectives

To investigate the BRAF and NRAS mutation prevalence and activation of the MAPK pathway in distinct dermoscopic subtypes of acquired naevi.

Methods

Common mutations present in BRAF and NRAS were assessed in 40 globular, reticular, and peripheral rim of globules (PG) subtypes of acquired naevi from 27 participants (19 male, 8 female; mean age 46.7 years) selected from 1261 eligible volunteers. Mutations were determined using the highly sensitive and quantitative QX200 droplet digital^™ PCR (ddPCR) system.

Results

The BRAFV600E (c.1799T>A or c.1799_1800delTGinsA) and BRAFV600K mutations were detected in 85% (n=34/40) of naevi. All BRAF wild-type naevi (15%; n=6/40) harboured an NRAS codon 12/13 or 61 mutation. BRAF mutations were present in 92% (n=12/13) of globular and 100% (n=12/12) of PG naevi, whereas reticular naevi were 67% (n=10/15) BRAF and 33% (n=5/15) NRAS mutant (p=0.037).

Conclusions

We discovered that 100% of the assessed acquired naevi had either a BRAF or NRAS mutation. Using sensitive techniques capable of single-cell mutation detection, it is likely that all acquired naevi will be mutated for BRAF or NRAS. Since both of these mutations are prevalent in distinct dermoscopic naevus subsets, our study supports the role of the MAPK pathway in the development of benign melanocytic proliferations, indicating that additional genomic events besides somatic mutations in BRAF or NRAS are required for melanoma development.

This article is protected by copyright. All rights reserved.

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Alpha subunit in clinically non-functioning pituitary adenomas: an immunohistochemical study

Publication date: Available online 16 July 2017
Source:Pathology - Research and Practice
Author(s): Michael Solarski, Fabio Rotondo, Luis V. Syro, Michael D. Cusimano, Kalman Kovacs
Pituitary adenomas may be classified as either functioning or non-functioning, depending on whether excess hormone secretion can be clinically identified. Of the six hormones produced in the anterior pituitary, TSH, FSH and LH are known as glycoproteins and contain two subunits (α and β). While α-subunit is identical within all of them, each β-subunit is unique and biologically specific. Independently, the α- and β-subunits are inactive and only induce a hormonal response when they are non-covalently associated. Studies have shown that in certain cases, pituitary adenomas may abnormally secrete only α-subunit, detectable the serum or through immunohistochemical analysis. In the present study, we examined α-subunit immunoexpression in surgically removed non-functioning pituitary adenomas and analyzed its prognostic value. Results showed that expression of α-subunit in clinically non-functioning pituitary adenomas is not a rare occurrence. While there were no age/gender differences between tumors that expressed α-subunit and those that did not, α-subunit immunonegative adenomas presented with suprasellar extension more frequently and had an Ki67 proliferation more than 3%. The use of immunohistochemical techniques to determine the presence of α-subunit may provide information on tumor cell proliferation and biologic behavior. To fully understand the role of α-subunit in pituitary adenomas more work is needed.



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Letter to the editor: health professionals’ attitudes toward individuals with eating disorders: who do we think they are?

Abstract

Health professionals are not immune to stigmatizing attitudes and stereotypes found in society-at-large. Along with patients and their loved ones, treatment providers are important stakeholders – and gatekeepers – in the successful delivery of mental healthcare. Prevailing attitudes among professionals can facilitate timely recognition, enable access to care and uptake of evidence-based practices, or undermine help-seeking and therapeutic engagement. At an interactive activity at the 2016 Nordic Eating Disorders Society (NEDS) meeting, we asked health professionals to describe individuals with eating disorders. The most common descriptive term used was "anxiety" followed by "thin", "sad", "control", "female", and "suffering/pain". Further research on professionals' attitudes toward individuals with eating disorders is necessary to inform education, awareness, and advocacy efforts following the diagnostic revisions in the DSM-5.

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Twenty-five years of gene therapy for genetic diseases and leukemia: The road to marketing authorization of the first ex vivo gene therapies

Publication date: Available online 16 July 2017
Source:Journal of Autoimmunity
Author(s): Claudio Bordignon




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DNA binding and unwinding by Hel308 helicase requires dual functions of a winged helix domain.

Publication date: Available online 16 July 2017
Source:DNA Repair
Author(s): Sarah J. Northall, Ryan Buckley, Nathan Jones, J. Carlos Penedo, Panos Soultanas, Edward L. Bolt
Hel308 helicases promote genome stability linked to DNA replication in archaea, and have homologues in metazoans. In the crystal structure of archaeal Hel308 bound to a tailed DNA duplex, core helicase domains encircle single-stranded DNA (ssDNA) in a "ratchet" for directional translocation. A winged helix domain (WHD) is also present, but its function is mysterious. We investigated the WHD in full-length Hel308, identifying that mutations in a solvent exposed α-helix resulted in reduced DNA binding and unwinding activities. When isolated from the rest of Hel308, the WHD protein alone bound to duplex DNA but not ssDNA, and DNA binding by WHD protein was abolished by the same mutations as were analyzed in full-length Hel308. Isolated WHD from a human Hel308 homologue (HelQ) also bound to duplex DNA. By disrupting the interface between the Hel308 WHD and a RecA-like domain, a topology typical of Ski2 helicases, we show that this is crucial for ATPase and helicase activities. The data suggest a model in which the WHD promotes activity of Hel308 directly, through binding to duplex DNA that is distinct from ssDNA binding by core helicase, and indirectly through interaction with the RecA-like domain. We propose how the WHD may contribute to ssDNA translocation, resulting in DNA helicase activity or in removal of other DNA bound proteins by "reeling" ssDNA.



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Spectral Doppler ultrasound of peripheral arteries: a pictorial review

Publication date: Available online 16 July 2017
Source:Clinical Imaging
Author(s): Zachary Nuffer, Andrey Rupasov, Neel Bekal, Jacqueline Murtha, Shweta Bhatt
This article reviews the pathophysiology and sonographic findings of peripheral arterial lesions, with emphasis on the spectral Doppler waveforms encountered in each. It discusses the characteristic features of the Doppler spectra in obstructive conditions, including thromboembolism, atherosclerotic disease, bypass graft occlusion, dissection, trauma, and compartment syndrome, as well as non-obstructive conditions, including hyperemia, pseudoaneurysm, and arteriovenous fistula. Familiarity with the commonly-encountered spectral waveforms in the setting of these lesions is necessary for timely and accurate diagnosis and treatment.



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Participation of Colon and Rectal Fellows in Robotic Rectal Cancer Surgery: Effect on Surgical Outcomes

Publication date: Available online 15 July 2017
Source:Journal of Surgical Education
Author(s): Danielle Collins, Nikolaos Machairas, Emilie Duchalais, Ron G. Landmann, Amit Merchea, Dorin T. Colibaseanu, Scott R. Kelley, Kellie L. Mathis, Eric J. Dozois, David W. Larson
ObjectivesTo determine whether involvement of colon and rectal fellows has an effect on short-term surgical and oncological outcomes in robotic rectal cancer surgery.Patients and MethodsFrom a dataset of 263 robotic-assisted rectal cancer operations, 114 case-matched patients over a 5-year period (January 2010-December 2015) were included in the study. Patients who underwent resection with and without fellow involvement were compared. Cases were matched according to age, body mass index, neoadjuvant therapy, and tumor location. Intraoperative, postoperative, and pathological outcomes were compared between the 2 groups.ResultsThere was no difference in tumor grade, type of surgical procedure, presence of an anastomosis, or diverting stoma between groups. In addition, there was no difference in the incidence of intraoperative or postoperative complications between the 2 groups. Estimated blood loss was higher in the fellow group compared to the consultant group (mean difference of 70mL, p = 0.007). For pathological outcomes, there was no difference in surrogate oncological quality indicators, specifically margin positivity and lymph node yield, between the 2 groups. Furthermore, fellow involvement did not adversely affect operative time.ConclusionThis study demonstrates that equivalent short-term surgical and oncological outcomes can be achieved with colorectal fellow participation in the field of robotic-assisted rectal cancer surgery.



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Toward Best Practices for Surgical Morbidity and Mortality Conferences: A Mixed Methods Study

Publication date: Available online 15 July 2017
Source:Journal of Surgical Education
Author(s): Marit S. de Vos, Perla J. Marang-van de Mheen, Ann D. Smith, Danny Mou, Edward E. Whang, Jaap F. Hamming
ObjectiveTo assess formats for surgical morbidity and mortality conferences (M&M) for strengths and challenges.DesignA mixed methods approach with local observations to assess key domains of M&M practice (i.e., goals, structure, and process/content) and surveys to assess participants' expectations and experiences.SettingSurgical departments of two teaching hospitals (Boston, USA and Leiden, Netherlands).ParticipantsParticipants of surgical M&M, including attending surgeons, residents, physician assistants, and medical students (total n = 135).ResultsSurgical M&M practices at both hospitals had education as its overarching goal, but varied in structure and process/content. Expectations were similar at both sites with ≥80% of participants (n = 90; 67% response) expecting M&M to be focused on education as well as quality improvement (QI), blame-free, mandatory for both residents and attendings, and to lead to changes in clinical practice. However, compared to expectations, significantly fewer participants at both sites experienced: a QI focus (both p < 0.001); mandatory faculty attendance (p = 0.004; p < 0.001) and changes to practice (both p < 0.001). In comparison, at the site where an active moderator and QI committee are present, respondents seemed more positive about experiencing a QI focus (73% vs 30%) and changes to practice (44% vs 16%).ConclusionDespite variation in M&M practice, the same (unmet) expectations existed at both hospitals, indicating that certain challenges may be more universal. M&M was reported to be well-focused on education, and certain aspects (e.g., active moderator and QI committee) seemed beneficial, but expectations were not met for the conference's focus and function for QI. Greater exchange of "best practices" for M&M may enhance the conference's value for improving surgical care.



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The terminal latency of the phrenic nerve correlates with respiratory symptoms in amyotrophic lateral sclerosis

Publication date: September 2017
Source:Clinical Neurophysiology, Volume 128, Issue 9
Author(s): Jin-Sung Park, Donghwi Park
ObjectiveThe aim of the study was to investigate the electrophysiological parameters in phrenic nerve conduction studies (NCS) that sensitively reflect latent respiratory insufficiency present in amyotrophic lateral sclerosis (ALS).MethodForty-nine patients with ALS were examined, and after exclusion, 21 patients with ALS and their phrenic NCS results were reviewed. The patients were divided into two groups according to their respiratory sub-score in the ALS functional rating scale - revised (Group A, sub-score 12vs. Group B, sub-score 11). We compared the parameters of phrenic NCS between the two groups.ResultsThere were no significant differences in the clinical characteristics between the two groups. Using a multivariate model, we found that the terminal latency of the phrenic nerve was the only parameter that was associated with early symptoms of respiratory insufficiency (p<0.05). The optimal cutoff value for the terminal latency of the phrenic nerve was 7.65ms (sensitivity 80%, specificity 68.2%).ConclusionThe significantly prolonged terminal latency of the phrenic nerve in our study may reflect a profound distal motor axonal dysfunction of the phrenic nerve in patients with ALS in the early stage of respiratory insufficiency that can be used as a sensitive electrophysiological marker reflecting respiratory symptoms in ALS.SignificanceThe terminal latency of the phrenic nerve is useful for early detection of respiratory insufficiency in patients with ALS.



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Using wheel availability to shape running behavior of the rat towards improved behavioral and neurobiological outcomes

Publication date: Available online 15 July 2017
Source:Journal of Neuroscience Methods
Author(s): Julia C. Basso, Joan I. Morrell
BackgroundThough voluntary wheel running (VWR) has been used extensively to induce changes in both behavior and biology, little attention has been given to the way in which different variables influence VWR. This lack of understanding has led to an inability to utilize this behavior to its full potential, possibly blunting its effects on the endpoints of interest.New MethodWe tested how running experience, sex, gonadal hormones, and wheel apparatus influence VWR in a range of wheel access "doses".ResultsVWR increases over several weeks, with females eventually running 1.5 times farther and faster than males. Limiting wheel access can be used as a tool to motivate subjects to run but restricts maximal running speeds attained by the rodents. Additionally, circulating gonadal hormones regulate wheel running behavior, but are not the sole basis of sex differences in running. Comparison with Existing Method(s): Limitations from previous studies include the predominate use of males, emphasis on distance run, variable amounts of wheel availability, variable light-dark cycles, and possible food and/or water deprivation. We designed a comprehensive set of experiments to address these inconsistencies, providing data regarding the "microfeatures" of running, including distance run, time spent running, running rate, bouting behavior, and daily running patterns.ConclusionsBy systematically altering wheel access, VWR behavior can be finely tuned – a feature that we hypothesize is due to its positive incentive salience. We demonstrate how to maximize VWR, which will allow investigators to optimize exercise-induced changes in their behavioral and/or biological endpoints of interest.

Graphical abstract

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Evolutionary basis of a new approach for the treatment of malignant brain tumors: From mice to humans

Publication date: Available online 15 July 2017
Source:Clinical Immunology
Author(s): Pedro R. Lowenstein, Maria G. Castro
Glioma cells are one of the most aggressive and malignant tumors. Following initial surgery, and radio-chemotherapy they progress rapidly, so that patients' median survival remains under two years. They invade throughout the brain, which makes them difficult to treat, and are universally lethal. Though total resection is always attempted it is not curative. Standard of care in 2016 comprises surgical resection, radiotherapy and chemotherapy (temozolomide). Median survival is currently ~14–20months post-diagnosis though it can be higher in high complexity medical university centers, or during clinical trials. Why the immune system fails to recognize the growing brain tumor is not completely understood. We believe that one reason for this failure is that the brain lacks cells that perform the role that dendritic cells serve in other organs. The lack of functional dendritic cells from the brain causes the brain to be deficient in priming systemic immune responses to glioma antigens. To overcome this drawback we reconstituted the brain immune system for it to initiate and prime anti-glioma immune responses from within the brain. To achieve brain immune reconstitution adenoviral vectors are injected into the resection cavity or remaining tumor. One adenoviral vector expresses the HSV-1 derived thymidine kinase which converts ganciclovir into phospho-ganciclovir which becomes cytotoxic to dividing cells. The second adenovirus expresses the cytokine fms-like tyrosine kinase 3 ligand (Flt3L). Flt3L differentiates precursors into dendritic cells and acts as a chemokine for dendritic cells. This results in HSV-1/ganciclovir killing of tumor cells, and the release of tumor antigens, which are then taken up by dendritic cells recruited to the brain tumor microenvironment by Flt3L. Concomitant release of HMGB1, a TLR2 agonist that activates dendritic cells, stimulates dendritic cells loaded with glioma antigens to migrate to the cervical lymph nodes to prime a systemic CD8+ T cytotoxic killing of brain tumor cells. This induced immune response causes glioma-specific cytotoxicity, induces immunological memory, and does not cause brain toxicity or autoimmunity. A Phase I Clinical Trial, to test our hypothesis in human patients, was opened in December 2013 (see: NCT01811992, Combined Cytotoxic and Immune-Stimulatory Therapy for Glioma, at ClinicalTrials.gov). This trial is a first in person trial to test whether the re-engineering of the brain immune system can serve to treat malignant brain tumors. The long and winding road from the laboratory to the clinical trial follows below.



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Pharmacokinetics of intravenous pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor [ 14 C]copanlisib (BAY 80-6946) in a mass balance study in healthy male volunteers

Abstract

Purpose

To determine the pharmacokinetics of radiolabeled copanlisib (BAY 80-6946) in healthy male volunteers and to investigate the disposition and biotransformation of copanlisib.

Methods

A single dose of 12 mg copanlisib containing 2.76 MBq [¹⁴C]copanlisib was administered as a 1-h intravenous infusion to 6 volunteers with subsequent sampling up to 34 days. Blood, plasma, urine and feces were collected to monitor total radioactivity, parent compound and metabolites.

Results

Copanlisib treatment was well tolerated. Copanlisib was rapidly distributed throughout the body with a volume distribution of 1870 L and an elimination half-life of 52.1-h (range 40.4–67.5-h). Copanlisib was the predominant component in human plasma (84% of total radioactivity AUC) and the morpholinone metabolite M1 was the only circulating metabolite (about 5%). Excretion of drug-derived radioactivity based on all 6 subjects was 86% of the dose within a collection interval of 20–34 days with 64% excreted into feces as major route of elimination and 22% into urine. Unchanged copanlisib was the main component excreted into urine (15% of dose) and feces (30% of dose). Excreted metabolites (41% of dose) of copanlisib resulted from oxidative biotransformation.

Conclusions

Copanlisib was eliminated predominantly in the feces compared to urine as well as by hepatic biotransformation, suggesting that the clearance of copanlisib would more likely be affected by hepatic impairment than by renal dysfunction. The dual mode of elimination via unchanged excretion of copanlisib and oxidative metabolism decreases the risk of clinically relevant PK-related drug–drug interactions.

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Methylation-associated silencing of SFRP1 gene in high-grade serous ovarian carcinomas

Publication date: Available online 15 July 2017
Source:Annals of Diagnostic Pathology
Author(s): Vedran Kardum, Valentina Karin, Mislav Glibo, Anita Skrtic, Tamara Nikuseva Martic, Nermina Ibisevic, Faruk Skenderi, Semir Vranic, Ljiljana Serman
Wnt is a highly conserved signaling pathway responsible for tissue regeneration, maintenance and differentiation of stem cells in adults. Its aberrant activation through reduced expression of Wnt signaling pathway inhibitors, such as proteins from the SFRP family, is commonly seen in many tumors. In the present study we explored SFRP1 protein expression using immunohistochemistry in 11 low-grade serous ovarian carcinomas (LGSC), 42 high-grade serous ovarian carcinomas (HGSC), and 5 normal ovarian tissues (controls). SFRP1 gene methylation was analyzed by methylation-specific PCR in 8 LGSCs, 13 HGSCs and control samples. SFRP1 gene was unmethylated and SFRP1 protein expression was strong in normal ovaries (n=5). Although SFRP1 gene was unmethylated in almost all of the LGSC cases (7/8, 88%), SFRP1 protein expression was significantly lower than in normal ovaries (p<0.05). Seven out of 13 HGSCs (54%) showed SFRP1 gene hypermethylation and protein expression level was also significantly lower than in normal ovaries (p<0.001). Our preliminary data show loss of SFRP1 protein expression caused by the SFRP1 promoter hypermethylation in a subset of HGSCs. SFRP1 protein expression was also lost in LGSCs but different regulatory mechanisms may be involved. Further studies should elucidate the clinical and therapeutic relevance of the observed molecular alterations.



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Fluctuations in routine blood count might signal severe immune-related adverse events in melanoma patients treated with nivolumab.

Publication date: Available online 16 July 2017
Source:Journal of Dermatological Science
Author(s): Yasuhiro Fujisawa, Koji Yoshino, Atsushi Otsuka, Takeru Funakoshi, Taku Fujimura, Yuki Yamamoto, Hiroo Hata, Masahiko Gosho, Ryota Tanaka, Kei Yamaguchi, Yumi Nonomura, Ikuko Hirai, Sadanori Furudate, Hisako Okuhira, Keisuke Imafuku, Megumi Aoki, Shigeto Matsushita
BackgroundAlthough nivolumab significantly prolongs survival of metastatic melanoma, about 10% of patients experience severe, even fatal immune-related adverse events (irAEs). Biomarkers to predict irAEs are, therefore, of great interest.ObjectiveWe aimed to correlate changes in routine blood count parameters to the occurrence of serious irAEs (grade 3/4 [G3/4] or lung/gastrointestinal [lung/GI] irAEs) in patients with melanoma who were treated with nivolumab.MethodsWe retrospectively analyzed data from 101 patient with melanoma treated with nivolumab from 8 institutes in Japan. We used logistic regression analyses to investigate associations between severe irAEs and fluctuations in routine blood count parameters (total white blood cell [WBC] count, relative neutrophil, monocyte, lymphocyte, and eosinophil count) during the treatment. Receiver-operating characteristic curve was used to determine a cutoff value for the blood count parameters and area under the curve (AUC).ResultsUnivariate analysis revealed that G3/4 irAEs were associated with increased total WBC count (P=0.034, cutoff value=+27%, AUC=0.68, odds ratio [OR]=1.58) and decreased relative lymphocyte count (RLC, P=0.042, cutoff value=−23%, AUC=0.65, OR=1.65). However, multivariate analysis showed that the same factors, increased WBC count (P=0.014, cutoff value=+59.1%, AUC=0.79, OR=6.04) and decreased RLC (P=0.012, cutoff value=−32.3%, AUC=0.81, OR=5.01) were independent factors associated with lung/GI irAEs.ConclusionsOur results suggest that increased WBC count and decreased RLC are associated with G3/4 and lung/GI irAEs. Our analysis was based on the data point at which irAE occurrence was noticed and, therefore, these factors are not predictive, however, they could be a "signal" of severe irAE occurrence in patients with melanoma treated with nivolumab.



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Increased frequencies of basophils, type 2 innate lymphoid cells and Th2 cells in skin of patients with atopic dermatitis but not psoriasis

Publication date: Available online 15 July 2017
Source:Journal of Dermatological Science
Author(s): Shunya Mashiko, Heena Mehta, Robert Bissonnette, Marika Sarfati
BackgroundPathogenesis of atopic dermatitis (AD) involves interaction between type 2 cells that include basophils, mast cells, innate lymphoid type 2 cells (ILC2), and Th2 cells. Levels of IL-4 and IL-13 are elevated in AD patients.ObjectiveHere, we investigated the distribution of type 2 cells and the source of IL-4 and IL-13 in skin and blood of AD relative to psoriasis.MethodsLesional skin biopsies and blood were collected from patients. Skin cell suspensions were prepared by mild enzymatic digestion and mechanical dissociation. IL-4 and IL-13 expression was analyzed at single-cell level before or after stimulation using flow cytometry.ResultsFrequencies of basophils, ILC2 and Th2 but not mast cells were significantly elevated in skin, and not blood, of AD relative to psoriasis. IL-4 production by circulating basophils and Th2 cells, and IL-13 by ILCs and Th2 cells was similar in both diseases. In contrast, skin T cells expressed IL-4 and IL-13 prior to stimulation in AD when compared to psoriasis. Moreover, skin basophils, which were detected in AD only, expressed IL-4 following stimulation. Interestingly, basophils and ILC2 were positively correlated in skin whereas skin basophils were inversely correlated with blood ILC2.ConclusionsLesional AD skin harbors a distinctive innate and adaptive type 2 profile, which is characterized by basophils producing IL-4, Th2 cells expressing IL-4 or IL-13, and ILC2. This underlies the therapeutic efficacy of targeting IL-4 and IL-13 signaling pathways in AD.



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Epidemiology and comorbidities of patients with chronic urticaria in Taiwan‏: a nationwide population-based study

Publication date: Available online 15 July 2017
Source:Journal of Dermatological Science
Author(s): Chia-Yu Chu, Yung-Tsu Cho, Jhih-Hua Jiang, Eve I-Chun Lin, Chao-Hsiun Tang
BackgroundComprehensive data regarding the epidemiology of chronic urticaria (CU) in general populations are scant.ObjectivesTo investigate the prevalence, incidence, and comorbidities of CU in general population.MethodsThe data were sourced from the National Health Insurance Research Database (NHIRD) for 2009-2012. Patients who had a primary/secondary ICD-9-CM diagnosis code of 708.1, 708.8, or 708.9 during the year with at least two outpatient visits and an antihistamine prescription, were identified as the cases of CU for each year. The incidence, persistence and comorbidities of CU were examined.ResultsThe prevalence of CU ranged from 0.69% to 0.79% for each year from 2009-2012, and the incidence was around 0.50% per year from 2010-2012. Comparing to the Standard Population, the standardized prevalence ratios (SPRs) for the rheumatic diseases, thyroid disorders, inflammatory diseases, and psychiatric disorders among CU patients were 2.74, 1.81, 1.57 and 1.87, respectively.ConclusionThe prevalence of CU in Taiwan is about 0.69-0.79%. CU is associated with a significantly increased risk of psychiatric disorders, inflammatory diseases, thyroid disorders, and rheumatic diseases. Except for thyroid disorders, the prevalence of these comorbidities tends to increase the longer CU persists.



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Determination of chemical forms of 14C in liquid discharges from nuclear power plants

Publication date: October 2017
Source:Journal of Environmental Radioactivity, Volume 177
Author(s): I. Svetlik, M. Fejgl, P.P. Povinec, T. Kořínková, L. Tomášková, J. Pospíchal, M. Kurfiřt, R. Striegler, M. Kaufmanová
Developments of radioanalytical methods for determination of radiocarbon in wastewaters from nuclear power plants (NPP) with pressurized light water reactors, which would distinguish between the dissolved organic and inorganic forms have been carried out. After preliminary tests, the method was used to process pilot samples from wastewater outlets from the Temelín and Dukovany NPPs (Czech Republic). The results of analysis of pilot water samples collected in 2015 indicate that the instantaneous ¹⁴C releases into the water streams would be about 7.10⁻⁵ (Temelín) and 4.10⁻⁶ (Dukovany) of the total quantity of the ¹⁴C liberated into the environment.



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Langerhans Cells – The Macrophage in Dendritic Cell Clothing

Publication date: Available online 15 July 2017
Source:Trends in Immunology
Author(s): Thomas Doebel, Benjamin Voisin, Keisuke Nagao
Our assumptions on the identity and functions of Langerhans cells (LCs) of the epidermis have undergone considerable changes. Once thought to be prototypic representatives of the dendritic cell (DC) lineage, they are now considered to be a specialized subset of tissue-resident macrophages. Despite this, LCs display a remarkable mixture of properties. Like many tissue macrophages, they self-maintain locally. However, unlike tissue macrophages and similar to DCs, they homeostatically migrate to lymph nodes and present antigen to antigen-specific T cells. Current evidence indicates that the immune responses initiated by LCs are complex and dependent on antigenic properties and localization of the stimulus. This complexity is reflected in the recently demonstrated roles of LCs in type 17, regulatory, and humoral immune responses.



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Prognostic significance of recurrent additional chromosomal abnormalities in adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

Publication date: October 2017
Source:Cancer Genetics, Volumes 216–217
Author(s): Chang Ahn Seol, Young-Uk Cho, Seongsoo Jang, Chan-Jeoung Park, Jung-Hee Lee, Je-Hwan Lee, Kyoo Hyung Lee, Eul-Ju Seo
In Philadelphia (Ph) chromosome-positive acute lymphoblastic leukemia (ALL), additional chromosomal abnormalities (ACAs) are frequently observed. We investigated the cytogenetic characteristics and prognostic significance of ACAs in Ph-positive ALL. We reviewed the clinical data and bone marrow cytogenetic findings of 122 adult Ph-positive ALL patients. The ACAs were examined for partial or whole chromosomal gains or losses, and structural aberrations. The overall survival (OS) and disease-free survival (DFS) of patients who received hematopoietic cell transplantation were compared between the isolated Ph group and ACA group. ACAs were present in 73.0% of all patients. The recurrent ACAs were extra Ph (24.7%), 9/9p loss (20.2%), and 7/7p loss (19.1%). Complex karyotype was found in 28.1% of patients in the ACA group. Younger patients (19–30 years) in the ACA group showed the highest frequency of extra Ph (54%) compared to other age groups. The OS in the ACA group was significantly shorter than in the isolated Ph group. The presence of an extra Ph chromosome or 9/9p loss was significantly associated with shorter OS and DFS, whereas 7/7p loss and complex karyotype were not associated with poorer prognosis. We suggest that subclassification of ACAs could be applied to prognostic investigation of Ph-positive ALL.



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Groin Sentinel Node Biopsy and 18F-FDG PET/CT-supported preoperative lymph node assessment in cN0 patients with vulvar cancer currently unfit for minimally invasive inguinal surgery: The GroSNaPET study

Publication date: Available online 16 July 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Giorgia Garganese, Angela Collarino, Simona M. Fragomeni, Vittoria Rufini, Germano Perotti, Stefano Gentileschi, Maria T. Evangelista, Francesco P. Ieria, Luca Zagaria, Sonia Bove, Alessandro Giordano, Giovanni Scambia
ObjectiveThe study aims were: 1) to verify the role of sentinel node biopsy (SNB) in a subset of patients with clinical N0 (cN0) invasive vulvar cancer (VC) who were still candidates for radical inguinal surgery according to the current guidelines; 2) to investigate whether a preoperative 18F-FDG PET/CT (PET/CT) evaluation could improve the selection of node negative patients.MethodsFrom July 2013 to July 2016, all patients with VC admitted to our Division were evaluated by standard imaging and clinical exam. Among the patients assessed as cN0 we enrolled those unsuitable for SNB, due to: T > 4 cm, multifocal tumors, complete tumor diagnostic excision, contralateral nodal involvement and local recurrence. A preoperative PET/CT was performed. For each patient surgery included SNB, performed using a combined technique (radiotracer plus blue dye), followed by standard inguino-femoral lymphadenectomy. The reference standard was histopathology.ResultsForty-seven patients entered the study for a total of 73 groins. Histopathology revealed 12 metastatic SNs in 9 groins. No false-negative SNs were found (NPV 100%). PET/CT showed a negative predictive value of 93%.ConclusionsOur data suggest that SNB is accurate and safe even in cN0 patients currently excluded from this procedure, providing that a careful preoperative selection is performed. PET/CT allows a reliable assessment of LN status and may be an effective support for the selection of patients who are safe candidates for SNB.



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Improved survival after retrieval of 12 or more regional lymph nodes in appendiceal cancer

Publication date: Available online 15 July 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Isabella Fleischmann, Rene Warschkow, Ulrich Beutner, Lukas Marti, Bruno M. Schmied, Thomas Steffen
BackgroundTo evaluate the role of regional lymph node (RLN) retrieval on stage migration, overall (OS), and cancer-specific survival (CSS) in appendiceal cancer.MethodsBetween 2004 and 2012, 1046 patients with primary stage I-III carcinoma of the appendix were identified in the Surveillance, Epidemiology and End Results database. The impact of the number of RLN removed on OS and CSS was assessed using joinpoint regression, Cox regression, and propensity score methods.ResultsThe rate of node-positive cancer increased with the number of retrieved RLN from 10.5% in patients with one RLN removed to 30.6% in patients with 10 RLNs removed. This leveling off at 10 RLN was confirmed by joinpoint regression analysis (p=0.023).Despite the finding that retrieval of 10 RLN should be sufficient for appendiceal cancer, for the survival analysis the somewhat higher cutoff of 12 RLN was applied, since this cutoff is recommended by the guidelines for colorectal cancer. Retrieval of 12 or more RLN was beneficial compared to less than 12 RLN retrieved for OS (HR=0.60, p<0.001) and CSS (HR=0.67, p=0.020) in multivariable analysis, as well as in propensity score matched analysis (OS: HR=0.58, p=0.001, CSS: HR=0.61, p=0.005).ConclusionThe rate of node-positive cancer increased with the number of retrieved RLN up to about 10 RLN (95%CI: 3.6 to 16.3, p=0.023). Over 10 retrieved RLN, the node-positive cancer rate no longer increased. This correlates with the recommended number of 12 RLN to be retrieved in colorectal cancer, but differs from the guideline for neuroendocrine tumors.



http://ift.tt/2urJsI8

Do some epithelial ovarian cancers originate from a fallopian tube ciliate cell lineage?

Publication date: Available online 16 July 2017
Source:Medical Hypotheses
Author(s): Jan Rohozinski, Conception Diaz-Arrastia, Creighton L. Edwards
There is a general agreement that a large subpopulation of serous ovarian cancers arise from the fallopian tube mucosal epithelium. However, there is still some debate as to whether the cancers originate from a secretory or ciliate cell lineage. One well established method for determining the origin of a cell line is to document the expression of genes and proteins that are cell type specific. Lineage or tissue specific patterns of gene expression are evidence of direct decent from a given cell type within a tissue. It has recently been established that the Tumor Protein TAp73 gene (TP73) is expressed in basal epithelial cells that develop into multiciliate cells. TP73 expression is therefore a marker for basal stem cells that are predestined to differentiate into cells with motile cilia and its expression is maintained in fully differentiated multiciliate cells. Interestingly TP73 expression has also been observed in a high percentage of epithelial ovarian cancers. With this in mind, it is hypothesized that a high percentage of epithelial ovarian cancers which express TP73 originate from a ciliate cell lineage.



http://ift.tt/2tXl4gJ

Decreased Use of Spatial Pattern Separation in Contemporary Lifestyles May Contribute to Hippocampal Atrophy and Diminish Mental Health

Publication date: Available online 15 July 2017
Source:Medical Hypotheses
Author(s): Birkel LP
The spatial pattern separation process has not yet been proposed as a pivotal neural activity affecting hippocampal volume, a metric of mental health. The dentate gyrus/CA3 region is increasingly implicated in hippocampal atrophy and its putative role in spatial pattern separation is impaired in mental health disorders. Spatial pattern separation is thought to utilize the heightened neural plasticity of newborn neurons in the dentate gyrus to distinguish highly similar aspects of scene so that these remain distinct in memory rather than lost. The level of such activity associates with BDNF secretion, which may affect neuroplasticity and therefore hippocampal volume. Distinguishing fine-grained aspects of surroundings was likely of great importance during hunting and gathering for survival in nature. However the need to make subtle environmental discriminations is much reduced in modern survival activity. Ancestrally, exploration and utilization of the spatial pattern separation process may have resulted in detection of potential food items, an activity that was likely followed by intensive effort-based reward (EBR) activity to obtain the food. EBR activity and restorative walking in nature demonstrate positive mental health benefits, while their lack indicates negative effects on mental health. Data support the hypothesis that spatial pattern separation activity and neural circuitry are separate from, and may precede, those of EBR as well as restorative walking in nature. Spatial pattern separation therefore represents an additional nature-related neural process whose modern decrease in use may negatively affect mental health. Interventions that increase spatial pattern separation experiences may enhance BDNF secretion, hippocampal volume and mental health.



http://ift.tt/2ttDfHD

Tumor-associated immune aggregates in oral cancer: their cellular composition and potential prognostic significance

Publication date: Available online 16 July 2017
Source:Medical Hypotheses
Author(s): Maria Luiza Diniz de Sousa Lopes, Yi Liu, Kelly Yi-Ping Liu, Éricka Janine Dantas da Silveira, Catherine F. Poh
There is growing evidence supporting the importance of immune microenvironment in cancer development and progression, especially with the rapid development of immunotherapy. Presence of immune cell aggregates in solid tumors has been associated with clinical outcomes, but little is known about the immune microenvironment in oral squamous cell carcinoma (OSCC), which has high morbidity and mortality. Based on our preliminary observation, we hypothesize that there is the presence of tumor-associated immune aggregates (TaIAs) during oral cancer development. Adapting to the dynamic change of the composition of cellular membership and co-evolving with the tumor at invasion fronts, these TaIAs, either pro-inflammatory or immune suppressive, are associated with clinical consequences. With the unique access to a set of prospectively collected, highly annotated OSCC surgical samples and the use of multi-color immunostaining of key immune cells, the confirmation of our hypothesis may shed light of the underlying biology related to OSCC and the knowledge learned can potentially be used to identify prognostic markers, response predictive markers for immunotherapies, as well as novel therapeutic targets.



http://ift.tt/2tXR3gZ

IgA nephropathy during treatment with TNF-alpha blockers: could it be predicted?

Publication date: Available online 16 July 2017
Source:Medical Hypotheses
Author(s): Vito Di Lernia
Immunoglobulin A (IgA) nephropathy (IgAN) may sometimes be related to exposure to pharmacological agents, among which anti-Tumor Necrosis Factor (TNF)-alpha agents. The characteristic pathological feature is a deposition of IgA-containing immune complexes in vessel walls in the kidney mesangium. The link between TNF-alpha blockers and IgAN may be hypothesized examining diseases which share pathologic features. In this respect, idiopathic IgAN and Henoch Schonlein Purpura have been the object of studies revealing a pathogenetic role of aberrant glycosylation of IgA1 molecules. The Authors suggest that anti-drug antibodies against glycan structures of TNF-alpha inhibitors may cross react against serum aberrant IgA1 leading to large antigen-antibody complexes. These large polymeric IgA complexes are then able to deposit in the mesangium and activate the complement cascade. Such hypothesis may be tested by measuring serum levels of galactose-deficient IgA1 of patients developing IgAN following introduction of TNF-alpha blockers. Such a test would be useful also before administration of anti-TNF alpha agents. The presence of aberrant IgA1 may represent a contraindication for treatment with TNF blockers.



http://ift.tt/2uxfQtM

Syntrophic Imbalance and the Etiology of Bacterial Endoparasitism Diseases

Publication date: Available online 15 July 2017
Source:Medical Hypotheses
Author(s): James F. White
This article outlines the proposed 'syntrophic imbalance hypothesis' for etiology of bacterial endoparasitism diseases. This hypothesis involves microbes (archaea and bacteria) that exist in human body biofilms in syntrophic associations, where bacteria ferment nutrients to produce short chain fatty acids (SCFAs) that are used by methanogenic archaeons to produce methane. Overgrowth of archaea on human tissues (e.g., in association with intestines, teeth or lungs) results in excessive removal of SCFAs from the biofilms and this triggers bacteria in the free-living biofilm state to convert to the endoparasitic state and become intracellular in host cells where they incite inflammation and disease. The proposed model provides the mechanism to explain dysbiosis etiology of several human diseases, including gingivitis, leaky gut syndrome, Crohn's disease, irritable bowel syndrome, among others.



http://ift.tt/2uxa4IA

Scholar : Ειδοποίηση Μελετητή - [ Εξωτε

Ειδοποίηση Μελετητή:[ Εξωτερική ωτίτιδα ]

[PDF] Ανάπτυξη Διαδικτυακής Εφαρμογής Ενημέρωσης-αυτοαξιολόγησης Εμβοών Και Ψυχολογικών Προβλημάτων

Θ Πετρούδης - 2017

... Συνήθως πρόκειται για σύμπτωμα κάποιας πάθησης και εμφανίζεται σαν κουδούνισμα, σφύριγμα
ή άλλου είδους θόρυβος, ενώ δεν υπάρχουν στην πραγματικότητα εξωτερικοί ήχοι [3]. ... η χρόνια
ωτίτιδα, η ωτοσκλήρυνση, τα ακουστικά νευρίσματα, οι κρανιοεγκεφαλικές ...

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Scholar : Ειδοποίηση Μελετητή - [ ΓΛΩΣΣ

Ειδοποίηση Μελετητή:[ ΓΛΩΣΣΙΤΙΣ ]

Antihistamines (H1 Receptor Antagonists)

TS Dougherty - Side Effects of Drugs Annual, 2017

... adverse event was moderate gastroenteritis in the 20 mg bilastine group, resulting in the
participant being withdrawn from the trial on day 4. Diarrhea (1/9, 11.1%) and stomatitis (1/9,
11.1%) were noted in the bilastine 20 mg group, while eczema (1/9, 11.1%), glossitis (1/9, 11.1 ...

Oral Manifestations of Diabetes 32

D Dean, B Gandara - Principles of Diabetes Mellitus, 2017

Page 574. Oral Manifestations of Diabetes 32 David Dean and Beatrice Gandara
Abstract The classic pathophysiologic features of diabe- tes mellitus (DM), including
immune dysregulation, vasculopathy, and neuropathy, predispose ...

[HTML] Lesiones linguales y su relación con afecciones sistémicas

J Harris Ricardo, N Fortich Mesa, A Herrera Herrera… - Avances en …, 2017

... Dorsal Lingual Surface and Halitosis: a Morphological Point of View. Acta stomatologica
Croatica. 2016;50(2):151-7. [ Links ]. 11. Byrd JA, Bruce AJ, Rogers RS. Glossitis and other
tongue disorders. Dermatologic clinics. 2003;21(1):123-34. [ Links ]. 12. ...

[PDF] Anaemia–a pale ale?

GL Muntingh, M Viljoen - South African Family Practice, 2017

... diagnosed by examining the patient's bone marrow. Macrocytosis is often asymptomatic
but in some instances patients might present with tiredness, mild jaundice, glossitis
or neuropathy. Treatment depends on the underlying cause ...

GALLBLADDER AND BILIARY TRACT

S Schimpke, BR Veenstra, K Millikan - Rush University Medical Center Review of …, 2017

Substituted uracils as chymase inhibitors

C Fürstner, J Ackerstaff, A Straub, H Meier, H Tinel… - US Patent 9,695,131, 2017

Substituted uracil derivatives of formula (I), processes for their preparation, their use alone
or in combinations for the treatment and/or prophylaxis of diseases, and their use for preparing
medicaments for the treatment and/or prophylaxis of diseases.

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Scholar : Ειδοποίηση Μελετητή - [ Decannulat

Ειδοποίηση Μελετητή:[ Decannulation ]

Clinical Criteria for Tracheostomy Decannulation in Subjects with Acquired Brain Injury

C Enrichi, I Battel, C Zanetti, I Koch, L Ventura… - Respiratory Care, 2017

BACKGROUND: Patients with acquired brain injury (ABI) often require long periods of
having a tracheostomy tube for airway protection and prolonged mechanical ventilation. It
has been recognized that fast and safe decannulation improves outcomes and facilitates the

[HTML] Revista Americana de Medicina Respiratoria-Volumen 13, Número 2-Junio 2013

JR Bach, LB Quiroga

... and mechanically assisted coughing The purpose of this article is to describe the use of
noninvasive inspiratory and expiratory muscle aids to prevent ventilatory insufficiency and failure,
and to permit the extubation and tracheostomy tube decannulation in "unweanable" patients ...

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Scholar : Ειδοποίηση Μελετητή - [ Εμφυτ

Ειδοποίηση Μελετητή:[ Εμφυτευματα ]

[PDF] Ανάπτυξη Διαδικτυακής Εφαρμογής Ενημέρωσης-αυτοαξιολόγησης Εμβοών Και Ψυχολογικών Προβλημάτων

Θ Πετρούδης - 2017

... από τον μαγνητικό τομογράφο. Στους πάσχοντες με βηματοδότες, κοχλιακά
εμφυτεύματα και άλλες μεταλλικές προθέσεις αντενδείκνυται η μαγνητική τομογραφία
και ως εκ τούτου υποβάλλονται σε αξονική τομογραφία. Η αξονική ...

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Scholar : Scholar Alert - [ intitle:laryngeal ]

Scholar Alert: [ intitle:laryngeal ]

Laryngeal mask airway device

AIJ Brain - US Patent 9,694,150, 2017

A laryngeal-mask airway device including provision for drainage of the esophagus including
an inflatable main-cuff and a backplate having a laryngeal-side and a pharyngeal-side. The
backplate also has an external tube joint adjacent to the proximal region of the main-cuff.

Quality indicators of laryngeal cancer care in commercially insured patients

CJ Britt, HY Chang, H Quon, H Kang, AP Kiess… - The Laryngoscope, 2017

Objective To examine associations between quality, complications, and costs in
commercially insured patients treated for laryngeal cancer. Study Design Retrospective
cross-sectional analysis of MarketScan Commercial Claim and Encounters data (Truven

Laryngeal mask

SEK Poulsen, HT Poh - US Patent D791,305, 2017

... www.google.comhttp://www.google.com/patents/USD791305?utm_source=gb-gplus-sharePatent
USD791305 - Laryngeal mask. Advanced Patent Search. Try the new Google Patents, with
machine-classified Google Scholar results, and Japanese and South Korean patents. Publication

Laryngeal Cysts in Adults: Simplifying Classification and Management

R Heyes, DG Lott - Otolaryngology–Head and Neck Surgery, 2017

Objective Laryngeal cysts may occur at any mucosa-lined location within the larynx and
account for 5% to 10% of nonmalignant laryngeal lesions. A number of proposed
classifications for laryngeal cysts exist; however, no previously published classification aims

CT Study of the Arytenoid Cartilage in Patients with Laryngeal Contact Granuloma

J Li, S Tian, S Zou, Q Wang, X Tai, X Chen - Otolaryngology–Head and Neck Surgery, 2017

Objective To explore high-resolution computed tomography (HRCT) characteristics of
arytenoid cartilage in patients with laryngeal contact granuloma (LCG). Setting Tertiary
hospitals. Study Design Individual case-control study. Methods HRCT scans were obtained

Low-dose succinylcholine to facilitate laryngeal mask airway insertion: A comparison of two doses

LR George, R Sahajanandan, S Ninan - 2017

Background and Aims: Around the world, the use of the laryngeal mask airway (LMA) is
becoming more common for different surgeries accounting for it being the dominant choice
of airway in numerous surgeries. Although propofol is known to blunt the laryngeal reflexes

Downregulation of miRNA-26b inhibits cancer proliferation of laryngeal carcinoma through autophagy by targeting ULK2 and inactivation of the PTEN/AKT pathway

S Wang, D Guo, C Li - Oncology Reports

Abstract Laryngeal carcinoma is one of the most common tumors of the head and neck
cancers, the pathogenesis of which remains yet unclear. It has been discovered through
research that microRNAs (miRNAs) play an important role during the genesis of laryngeal

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