Ιατρικά Άρθρα: 02/21/17

Τρίτη 21 Φεβρουαρίου 2017

Diagnosis and management of lentigo maligna: an observational study comparing 2005 with 2014 data in one institution

Summary

The incidence, clinical characteristics and management of lentigo maligna (LM) were assessed in a university hospital setting in 2005 and 2014. Multiple clinical variables were compared, and 28 and 43 cases, respectively were identified during the two time periods. The most common site of presentation was the cheek (50% vs. 44%), and an accurate clinical diagnosis of LM was made in 60% vs. 72%) of cases. Most of the patients received surgical treatment (75% in 2005 vs. 97% in 2014), with 47% and 33% of excisions, respectively, remaining involved at the peripheral surgical margin. During the 10-year follow-up for the 2005 cohort, 7 of the 28 patients had recurrence (3 of whom already had previously involved margins following surgery). This study shows that making an accurate clinical diagnosis of LM remains a significant challenge. Although surgery has become the preferred management option, achieving clear excision remains difficult, with involved margins increasing the risk of local recurrence and need for further intervention.

http://ift.tt/2kYf2Vm

Resolution of vocal fold leukoplakia during erlotinib treatment

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

The most commonly prescribed ear drops : Tobradex (brand), Cipro HC (brand), Ciprodex (brand), Vosol (brand),acetic acid (Vosol–generic), VosolHC (brand),acetic acid/aluminum acetate (Domeboro–generic), Cortisporin (brand),neomycin, polymyxin B sulfates, and hydrocortisone (Cortisporin–generic), ofloxacin (generic), sulfacetamide (generic)

http://otorhinolarygology.blogspot.com/2017/02/the-most-commonly-prescribed-ear-drops.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Gradual decrease in spermatogenesis caused by chronic stress

Publication date: Available online 21 February 2017
Source:Acta Histochemica
Author(s): Lizbeth Juárez-Rojas, Rosa María Vigueras-Villaseñor, Fahiel Casillas, Socorro Retana-Márquez
Chronic stress induces decreased sperm motility, viability and concentration in stressed males. Also, stress modifies oxidative status and causes apoptosis in testes, as well as a decrease in the epithelial area of seminiferous tubules. However, there are no studies that analyze the alterations caused by stress in testicular cells. Thus, in this study, alterations in the morphology of testicular germ cells caused by different days of chronic stress were assessed. Adult male rats were exposed to stress by immersion in cold water (ICW) daily for 3, 8, 20 or 50 consecutive days. Plasma testosterone and corticosterone were also assessed. Results showed that chronic stress causes loss of germ cells, and alteration of spermatogenesis. Seminiferous tubules from stressed males showed several degenerative signs, such as vacuoles in the basal epithelium, with picnotic indicia; moderate to severe exfoliation of degenerative germinal cells in the tubule lumen was also observed. These alterations were observed in all days of stress in a gradual way, from day 3–50. Testosterone levels were decreased at all those times, and corticosterone concentrations were increased on the same days. These results show that chronic stress causes severe damage to germ cells, which can account for infertility problems in males. These alterations are related to a decrease in testosterone as well as an increase in corticosterone caused by stress.

http://ift.tt/2kXZz7I

Comparative study of two models of combined pulmonary fibrosis and emphysema in mice

Publication date: Available online 21 February 2017
Source:Acta Histochemica
Author(s): Wan-Guang Zhang, Si-Si Wu, Li He, Qun Yang, Yi-Kuan Feng, Yue-Tao Chen, Guo-Hua Zhen, Yong-Jian Xu, Zhen-Xiang Zhang, Jian-Ping Zhao, Hui-Lan Zhang
Combined pulmonary fibrosis and emphysema (CPFE) is an "umbrella term" encompassing emphysema and pulmonary fibrosis, but its pathogenesis is not known. We established two models of CPFE in mice using tracheal instillation with bleomycin (BLM) or murine gammaherpesvirus 68 (MHV-68). Experimental mice were divided randomly into four groups: A (normal control, n=6), B (emphysema, n=6), C (emphysema+MHV-68, n=24), D (emphysema+BLM, n=6). Group C was subdivided into four groups: C1 (sacrificed on day 367, 7 days after tracheal instillation of MHV-68); C2 (day 374; 14days); C3 (day 381; 21days); C4 (day 388; 28days). Conspicuous emphysema and interstitial fibrosis were observed in BLM and MHV-68 CPFE mouse models. However, BLM induced diffuse pulmonary interstitial fibrosis with severely diffuse pulmonary inflammation; MHV-68 induced relatively modest inflammation and fibrosis, and the inflammation and fibrosis were not diffuse, but instead around bronchioles. Inflammation and fibrosis were detectable in the day-7 subgroup and reached a peak in the day-28 subgroup in the emphysema + MHV-68 group. Levels of macrophage chemoattractant protein-1, macrophage inflammatory protein-1α, interleukin-13, and transforming growth factor-β1 in bronchoalveolar lavage fluid were increased significantly in both models. Percentage of apoptotic type-2 lung epithelial cells was significantly higher; however, all four types of cytokine and number of macrophages were significantly lower in the emphysema+MHV-68 group compared with the emphysema +BLM group. The different changes in pathology between BLM and MHV-68 mice models demonstrated different pathology subtypes of CPFE: macrophage infiltration and apoptosis of type-II lung epithelial cells increased with increasing pathology score for pulmonary fibrosis.

http://ift.tt/2kY3zp1

Wnt-1 immunodetection in the regenerating tail of lizard suggests it is involved in the proliferation and distal growth of the blastema

Publication date: Available online 21 February 2017
Source:Acta Histochemica
Author(s): Lorenzo Alibardi
Lizard tail regeneration depends from growth of the apical tip and autonomous regeneration of a new spinal cord, cartilaginous tube and muscles. The presence of embryonic signaling pathways is likely involved and we have focused on immunolocalization of Wnt1 protein in regenerating tissues, a protein promoting proliferation and tumorigenesis. Western blot indicates some immunoreactive bands in the expected range at 46 and 33kDa in the regenerating tail. Immunolocalization indicates that Wnt1 is prevalently detected in the apical wound epidermis, blastema, and ependyma ampulla of the regenerating tail while it lowers in other tissues of more proximal regions close to the original tail stump. Although a gradient for Wnt1 was not detected, the higher immunofluorescence present in the apical region of the blastema and around the regenerating spinal cord indicates that the protein could be secreted from the apical wound epidermis and the ependyma and might influence cell proliferation in the blastema, the distal-most growing center of the new tail. The present observations suggest the involvement of the Wnt pathway to direct the process of tail regeneration in lizard. The stimulation of proliferation of epidermal and mesenchymal cells in the apical blastema by Wnt proteins remains to be experimentally validated.

http://ift.tt/2lm55EC

Neuronal differentiation in the early human retinogenesis

Publication date: Available online 20 February 2017
Source:Acta Histochemica
Author(s): Anita Rancic, Natalija Filipovic, Josipa Marin Lovric, Snjezana Mardesic, Mirna Saraga-Babic, Katarina Vukojevic
AimOur study investigates the differentiation of retinal stem cells towards different neuronal subtypes during the critical period of human eye development.MethodsExpression of the neuronal marker neurofilament 200 (NF200), tyrosine hydroxilase (TH) and choline acetyltransferase (ChAT) was seen by immunofluorescence in the 5th–12th – week stage of development in the human eye. Data was analysed by Mann–Whitney, Kruskal–Wallis and Dunn's post hoc tests.ResultsNF200, TH and ChAT cells appeared in the 5th/6th week and gradually increased during further development. The proportion of TH positive areas were distributed similarly to NF200, with a higher proportion in the outer neuroblastic layer. The proportion of a ChAT positive surface was highest in the 5th/6th – week whilst from the 7th week onwards, its proportion became higher in the optic nerve and inner neuroblastic layers than in the outer layer, where a decrease of ChAT positive areas were seen.ConclusionsOur study indicates a high differentiation potential of early retinal cells, which decreased with the advancement of development. The observed great variety of retinal phenotypic expressions results from a large scale of influences, taking place at different developmental stages.

http://ift.tt/2lmbJuT

Sonoelastomics for Breast Tumor Classification: A Radiomics Approach with Clustering-Based Feature Selection on Sonoelastography

Publication date: Available online 21 February 2017
Source:Ultrasound in Medicine & Biology
Author(s): Qi Zhang, Yang Xiao, Jingfeng Suo, Jun Shi, Jinhua Yu, Yi Guo, Yuanyuan Wang, Hairong Zheng
A radiomics approach to sonoelastography, called "sonoelastomics," is proposed for classification of benign and malignant breast tumors. From sonoelastograms of breast tumors, a high-throughput 364-dimensional feature set was calculated consisting of shape features, intensity statistics, gray-level co-occurrence matrix texture features and contourlet texture features, which quantified the shape, hardness and hardness heterogeneity of a tumor. The high-throughput features were then selected for feature reduction using hierarchical clustering and three-feature selection metrics. For a data set containing 42 malignant and 75 benign tumors from 117 patients, seven selected sonoelastomic features achieved an area under the receiver operating characteristic curve of 0.917, an accuracy of 88.0%, a sensitivity of 85.7% and a specificity of 89.3% in a validation set via the leave-one-out cross-validation, revealing superiority over the principal component analysis, deep polynomial networks and manually selected features. The sonoelastomic features are valuable in breast tumor differentiation.

http://ift.tt/2ltFqsk

Investigation of Ultrasound-Measured Flow Velocity, Flow Rate and Wall Shear Rate in Radial and Ulnar Arteries Using Simulation

Publication date: Available online 21 February 2017
Source:Ultrasound in Medicine & Biology
Author(s): Xiaowei Zhou, Chunming Xia, Gandy Stephen, Faisel Khan, George A. Corner, Peter R. Hoskins, Zhihong Huang
Parameters of blood flow measured by ultrasound in radial and ulnar arteries, such as flow velocity, flow rate and wall shear rate, are widely used in clinical practice and clinical research. Investigation of these measurements is useful for evaluating accuracy and providing knowledge of error sources. A method for simulating the spectral Doppler ultrasound measurement process was developed with computational fluid dynamics providing flow-field data. Specific scanning factors were adjusted to investigate their influence on estimation of the maximum velocity waveform, and flow rate and wall shear rate were derived using the Womersley equation. The overestimation in maximum velocity increases greatly (peak systolic from about 10% to 30%, time-averaged from about 30% to 50%) when the beam–vessel angle is changed from 30° to 70°. The Womersley equation was able to estimate flow rate in both arteries with less than 3% error, but performed better in the radial artery (2.3% overestimation) than the ulnar artery (15.4% underestimation) in estimating wall shear rate. It is concluded that measurements of flow parameters in the radial and ulnar arteries with clinical ultrasound scanners are prone to clinically significant errors.

http://ift.tt/2kKro8t

Mismatch field latency, but not power, may mark a shared autistic and schizotypal trait phenotype.

Publication date: Available online 21 February 2017
Source:International Journal of Psychophysiology
Author(s): Talitha C. Ford, Will Woods, David P. Crewther
The auditory mismatch negativity (MMN), a preattentive processing potential, and its magnetic counterpart (MMF) are consistently reported as reduced in schizophrenia and autism spectrum disorders. This study investigates whether MMF characteristics differ between subclinically high and low scorers on the recently discovered shared autism and schizophrenia phenotype, Social Disorganisation.A total of 18 low (10 female) and 19 high (9 female) Social Disorganisation scorers underwent magnetoencephalography (MEG) during a MMF paradigm of 50ms standard (1000Hz, 85%) and 100ms duration deviant tones. MMF was measured from the strongest active magnetometer over the right and left hemispheres (consistent across groups) after 100ms.No differences in MMF power were found, however there was a significant delay in the MMF peak (p= 0.007). The P3am (following the MMF) was significantly reduced across both hemispheres for the high Social Disorganisation group (p= 0.025), there were no specific hemispheric differences in P3am power or latency. Right MMF peak latency increased with higher scores on the schizotypal subscales Odd Speech, Odd Behaviour and Constricted Affect.Findings suggest that MMF peak latency delay marks a convergence of the autism and schizophrenia spectra at a subclinical. These findings have significant implications for future research methodology, as well as clinical practice.

http://ift.tt/2ltCz2t

A single injection of protein-loaded coacervate-gel significantly improves cardiac function post infarction

Publication date: May 2017
Source:Biomaterials, Volume 125
Author(s): H.K. Awada, D.W. Long, Z. Wang, M.P. Hwang, K. Kim, Y. Wang
After myocardial infarction (MI), the heart undergoes fibrotic pathological remodeling instead of repair and regeneration. With multiple pathologies developing after MI, treatment using several proteins is expected to address this range of pathologies more effectively than a single-agent therapy. A factorial design of experiments study guided us to combine three complementary factors in one injection: tissue inhibitor of metalloproteinases-3 (TIMP-3) was embedded in a fibrin gel for signaling in the initial phase of the treatment, while basic fibroblast growth factor (FGF-2) and stromal cell-derived factor 1-alpha (SDF-1α) were embedded in heparin-based coacervates for sustained release and distributed within the same fibrin gel to exert their effects over a longer period. The gel was then tested in a rat model of myocardial infarction. Contractility of rat hearts treated with the protein coacervate-gel composite stabilized and slightly improved after the first week while contractility continued to decrease in rats treated with free proteins or saline over the 8 week study period. Hearts receiving the protein coacervate-gel composite treatment also exhibited reduced ventricular dilation, inflammation, fibrosis, and extracellular matrix (ECM) degradation. Revascularization, cardiomyocyte preservation, stem cell homing, and increased myocardial strain likely all contributed to the repair. This study demonstrates the potential of a multifactorial therapeutic approach in MI, using three complementary proteins delivered sequentially for comprehensive healing. The study also shows the necessity of controlled delivery for growth factors and cytokines to be an effective treatment.

http://ift.tt/2kXMZ8F

Regulating dynamic signaling between hematopoietic stem cells and niche cells via a hydrogel matrix

Publication date: May 2017
Source:Biomaterials, Volume 125
Author(s): Bhushan P. Mahadik, Narayanan A.K. Bharadwaj, Randy H. Ewoldt, Brendan A.C. Harley
Hematopoietic stem cells (HSC) reside in unique bone marrow niches and are influenced by signals from surrounding cells, the extracellular matrix (ECM), ECM-bound or diffusible biomolecules. Here we describe the use of a three-dimensional hydrogel to alter the balance of HSC-generated autocrine feedback and paracrine signals generated by co-cultured niche-associated cells. We report shifts in HSC proliferation rate and fate specification in the presence of lineage positive (Lin⁺) niche cells. Hydrogels promoting autocrine feedback enhanced expansion of early hematopoietic progenitors while paracrine signals from Lin⁺ cells increased myeloid differentiation. We report thresholds where autocrine vs. paracrine cues alter HSC fate transitions, and were able to selectively abrogate the effects of matrix diffusivity and niche cell co-culture via the use of inhibitory cocktails of autocrine or paracrine signals. Together, these results suggest diffusive biotransport in three-dimensional biomaterials are a critical design element for the development of a synthetic stem cell niche.

http://ift.tt/2llW0fm

Lipopolyplex potentiates anti-tumor immunity of mRNA-based vaccination

Publication date: May 2017
Source:Biomaterials, Volume 125
Author(s): Stefano Persano, Maria L. Guevara, Zhaoqi Li, Junhua Mai, Mauro Ferrari, Pier Paolo Pompa, Haifa Shen
mRNA-based vaccines have the benefit of triggering robust anti-cancer immunity without the potential danger of genome integration from DNA vaccines or the limitation of antigen selection from peptide vaccines. Yet, a conventional mRNA vaccine comprising of condensed mRNA molecules in a positively charged protein core structure is not effectively internalized by the antigen-presenting cells. It cannot offer sufficient protection for mRNA molecules from degradation by plasma and tissue enzymes either. Here, we have developed a lipopolyplex mRNA vaccine that consists of a poly-(β-amino ester) polymer mRNA core encapsulated into a 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine/1,2-dioleoyl-sn-glycero-3-phosphatidyl-ethanolamine/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000 (EDOPC/DOPE/DSPE-PEG) lipid shell. This core-shell structured mRNA vaccine enters dendritic cells through macropinocytosis. It displayed intrinsic adjuvant activity by potently stimulating interferon-β and interleukin-12 expression in dendritic cells through Toll-like receptor 7/8 signaling. Dendritic cells treated with the mRNA vaccine displayed enhanced antigen presentation capability. Mice bearing lung metastatic B16-OVA tumors expressing the ovalbumin antigen were treated with the lipopolyplex mRNA, and over 90% reduction of tumor nodules was observed. Collectively, this core-shell structure offers a promising platform for mRNA vaccine development.

http://ift.tt/2llWO3E

Three cases of Gordon syndrome with dominant KLHL3 mutations

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

http://ift.tt/2kKjfkt

Non-HDL-cholesterol and C-reactive protein in children and adolescents with type 1 diabetes

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

http://ift.tt/2maCel3

Vascular risk factors are associated with retinal arteriolar narrowing and venular widening in children and adolescents with type 1 diabetes

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

http://ift.tt/2kKbQkW

Unexplained cyanosis caused by hepatopulmonary syndrome in a girl with APECED syndrome

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

http://ift.tt/2maz8gS

A retrospective analysis of longitudinal changes in bone mineral content in cystic fibrosis

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

http://ift.tt/2maFWvl

Nutritional status and metabolic profile in neurologically impaired pediatric surgical patients

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

http://ift.tt/2kKgoYI

Can the burden of disease due to food allergy be prevented?

http://ift.tt/2lEngGr

Regulating dynamic signaling between hematopoietic stem cells and niche cells via a hydrogel matrix

Erratum

http://ift.tt/2l6hQ3E

Lipopolyplex potentiates anti-tumor immunity of mRNA-based vaccination

Response to inhaled corticosteroids on serum CD28, quality of life, and peak expiratory flow rate in bronchial asthma

http://ift.tt/2lEi8lm

A single injection of protein-loaded coacervate-gel significantly improves cardiac function post infarction

Erratum

http://ift.tt/2lEnZXQ

Erratum

http://ift.tt/2l6nYsX

What accounts for the association between late preterm births and risk of asthma?

http://ift.tt/2lEes3d

For the Patient

http://ift.tt/2l6iwpT

The emotional, social, and financial burden of food allergies on children and their families

http://ift.tt/2l6l3Al

The National Institutes of Allergy and Infectious Diseases sponsored guidelines on preventing peanut allergy: A new paradigm in food allergy prevention

http://ift.tt/2lEo5id

Understanding alpha-1 antitrypsin deficiency: A review with an allergist's outlook

http://ift.tt/2l6h86z

State-of-the-art testing for alpha-1 antitrypsin deficiency

http://ift.tt/2lEqLwf

Allergen immunotherapy at university health services and allergist's reasons for guidelines nonadherence

http://ift.tt/2l6eu0x

American Academy of Asthma, Allergy & Immunology membership experience with venom immunotherapy in chronic medical conditions and pregnancy, and in young children

http://ift.tt/2lEf34T

Relation of indoor and outdoor airborne fungal spore levels in the Kansas City metropolitan area

http://ift.tt/2l61M20

The persistence of chronic spontaneous urticaria in childhood is associated with the urticaria activity score

http://ift.tt/2lEAOBx

Health-related quality of life with hereditary angioedema following prophylaxis with subcutaneous C1-inhibitor with recombinant hyaluronidase

http://ift.tt/2l68vcp

A randomized study of BI 671800, a CRTH2 antagonist, as add-on therapy in poorly controlled asthma

http://ift.tt/2l61Oa2

Ejection Fraction: Misunderstood and Overrated (Changing the Paradigm in Categorizing Heart Failure).

Author: Konstam, Marvin A. MD; Abboud, Francois M. MD

Page: 717-719

http://ift.tt/2marTWu

Prevalence, Incidence, and Mortality of Stroke in China: Results from a Nationwide Population-Based Survey of 480 687 Adults.

Author: Wang, Wenzhi MD; Jiang, Bin MD; Sun, Haixin MD, PhD; Ru, Xiaojuan PhD; Sun, Dongling PhD; Wang, Linhong MD; Wang, Limin MD; Jiang, Yong MD; Li, Yichong PhD; Wang, Yilong MD, PhD; Chen, Zhenghong PhD; Wu, Shengping MD; Zhang, Yazhuo MD; Wang, David DO; Wang, Yongjun MD; Feigin, Valery L. MD, PhD; for the NESS-China Investigators

Page: 759-771

http://ift.tt/2maAmcd

Looking Back at Look AHEAD Through the Lens of Recent Diabetes Outcome Trials.

Author: Belalcazar, L. Maria MD; Ballantyne, Christie M. MD

Page: 720-723

http://ift.tt/2kKhVOl

Clinical and Echocardiographic Characteristics and Cardiovascular Outcomes According to Diabetes Status in Patients With Heart Failure and Preserved Ejection Fraction: A Report From the I-Preserve Trial (Irbesartan in Heart Failure With Preserved Ejection Fraction).

Author: Kristensen, Soren L. MD, PhD; Mogensen, Ulrik M. MD, PhD; Jhund, Pardeep S. MBChB, MSc, PhD; Petrie, Mark C. MB ChB; Preiss, David MD, PhD; Win, Sithu MD; Kober, Lars MD, DMSc; McKelvie, Robert S. MD, PhD; Zile, Michael R. MD; Anand, Inder S. MD, DPhil (Oxon); Komajda, Michel MD; Gottdiener, John S. MD; Carson, Peter E. MD; McMurray, John J. V. MD

Page: 724-735

http://ift.tt/2maqcZa

The Diabetic Heart Failure With Preserved Ejection Fraction Phenotype: Is it Real and Is It Worth Targeting Therapeutically?.

Author: Lindman, Brian R. MD, MSc

Page: 736-740

http://ift.tt/2kKnXyu

Genetic Obesity and the Risk of Atrial Fibrillation: Causal Estimates from Mendelian Randomization.

Author: Chatterjee, Neal A. MD; Giulianini, Franco PhD; Geelhoed, Bastiaan PhD; Lunetta, Kathryn L. PhD; Misialek, Jeffrey R. MPH; Niemeijer, Maartje N. MD, MSc; Rienstra, Michiel MD, PhD; Rose, Lynda M. MS; Smith, Albert V. PhD; Arking, Dan E. PhD; Ellinor, Patrick T. MD, PhD; Heeringa, Jan MD, PhD; Lin, Honghuang PhD; Lubitz, Steven A. MD, MPH; Soliman, Elsayed Z. MD, MSc; Verweij, Niek PhD; Alonso, Alvaro MD, PhD; Benjamin, Emelia J. MD, ScM; Gudnason, Vilmundur MD, PhD; Stricker, Bruno H. C. MMed, PhD; Van Der Harst, Pim MD, PhD; Chasman, Daniel I. PhD; Albert, Christine M. MD, MPH

Page: 741-754

http://ift.tt/2mazPqO

Mendelian Randomization: Using Natural Genetic Variation to Assess the Causal Role of Modifiable Risk Factors in Observational Studies.

Author: Neeland, Ian J. MD; Kozlitina, Julia PhD

Page: 755-758

http://ift.tt/2kKmrg3

Risk Factors for Coarctation of the Aorta on Prenatal Ultrasound: A Systematic Review and Meta-Analysis.

Author: Familiari, Alessandra MD; Morlando, Maddalena MD; Khalil, Asma MD; Sonesson, Sven-Erik MD, PhD; Scala, Carolina MD; Rizzo, Giuseppe MD; Del Sordo, Gelsomina MD; Vassallo, Chiara MD; Elena Flacco, Maria MD; Manzoli, Lamberto MD; Lanzone, Antonio MD, PhD; Scambia, Giovanni MD, PhD; Acharya, Ganesh MD, PhD; D'Antonio, Francesco MD, PhD

Page: 772-785

http://ift.tt/2kKfYBM

Functional Definition of Progenitors Versus Mature Endothelial Cells Reveals Key SoxF-Dependent Differentiation Process.

Author: Patel, Jatin PhD; Seppanen, Elke J. PhD; Rodero, Mathieu P. PhD; Wong, Ho Yi BSc; Donovan, Prudence PhD; Neufeld, Zoltan PhD; Fisk, Nicholas M. MBBS, PhD; Francois, Mathias PhD; Khosrotehrani, Kiarash MD, PhD

Page: 786-805

http://ift.tt/2mahav0

Management of Pregnancy in Patients With Complex Congenital Heart Disease: A Scientific Statement for Healthcare Professionals From the American Heart Association.

Author: Canobbio, Mary M. RN, MN, FAHA, Chair; Warnes, Carole A. MD, FRCP, Co-Chair; Aboulhosn, Jamil MD; Connolly, Heidi M. MD; Khanna, Amber MD; Koos, Brian J. MD, DPhil; Mital, Seema MD, FAHA, FRCPC; Rose, Carl MD; Silversides, Candice MD, FRCPC; Stout, Karen MD, FAHA; On behalf of the American Heart Association Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Cardiovascular Disease in the Young; Council on Functional Genomics and Translational Biology; and Council on Quality of Care and Outcomes Research

Page: e50-e87

http://ift.tt/2mawKXz

Preventive Statin Use Recommended by US Task Force.

Author: Kuehn, Bridget M.

Page: 806-807

http://ift.tt/2kKiJ5K

What Is the Structural Abnormality in This Patient?.

Author: Miranda-Arboleda, Andres F. MD; Gandara-Ricardo, Jairo MD; Arevalo-Guerrero, Edwin F. MD; Munoz-Ortiz, Edison MD

Page: 808-811

http://ift.tt/2maPpm3

Assessment of Cardiac Arrhythmias at Extreme High Altitude Using an Implantable Cardiac Monitor: REVEAL HA Study (REVEAL High Altitude).

Author: Boos, Christopher John MBBS, MD; Holdsworth, David A. BM, BCh, MA; Woods, David Richard MB, ChB, MD; O'Hara, John BSc, MSc, PhD; Brooks, Naomi BSc; Macconnachie, Lee BSc; Bakker-Dyos, Josh BSc, MBChB; Paisey, John DM; Mellor, Adrian MB, ChB, MD

Page: 812-814

http://ift.tt/2kKnTie

Association Between Aortic Dissection and Systemic Exposure of Vascular Endothelial Growth Factor Pathway Inhibitors in the Japanese Adverse Drug Event Report Database.

Author: Oshima, Yasuo MD, PhD; Tanimoto, Tetsuya MD; Yuji, Koichiro MD, PhD; Tojo, Arinobu MD, PhD

Page: 815-817

http://ift.tt/2maxRqs

Letter by Cerit et al Regarding Article, "Thyroid Function and Sudden Cardiac Death: A Prospective Population-Based Cohort Study".

Author: Cerit, Levent MD; Kemal, Hatice S. MD; Duygu, Hamza MD

Page: e88-e89

http://ift.tt/2kKly78

Response by Chaker et al to Letter Regarding Article, "Thyroid Function and Sudden Cardiac Death: A Prospective Population-Based Cohort Study".

Author: Chaker, Layal MD, MSc; van den Berg, Marten MD, MSc; Stricker, Bruno H.C. MMed, PhD; Peeters, Robin P. MD, PhD

Page: e90-e91

http://ift.tt/2mapj2N

Taking the vehicle out of drug delivery

Publication date: Available online 20 February 2017
Source:Materials Today
Author(s): Jianliang Shen, Joy Wolfram, Mauro Ferrari, Haifa Shen

http://ift.tt/2lK1TUi

Letter by Ma et al Regarding Article, "Induction of Therapeutic Hypothermia During Out-of-Hospital Cardiac Arrest Using a Rapid Infusion of Cold Saline: The RINSE Trial (Rapid Infusion of Cold Normal Saline)".

Author: Ma, Lei-Lei MD; Ge, Jun-Bo MD; Sun, Ai-Jun MD

Page: e92-e93

http://ift.tt/2kKi6t8

Letter by Kohlhauer et al Regarding Article, "Induction of Therapeutic Hypothermia During Out-of-Hospital Cardiac Arrest Using a Rapid Infusion of Cold Saline: The RINSE Trial (Rapid Infusion of Cold Normal Saline)".

Author: Kohlhauer, Matthias DVM, PhD; Mongardon, Nicolas MD, PhD; Tissier, Renaud DVM, PhD

Page: e94-e95

http://ift.tt/2mavweQ

Application of the Balanced Scorecard for Faculty Development

Publication date: Available online 21 February 2017
Source:Academic Radiology
Author(s): Jacob Smith, Somnath J. Prabhu, Puneet Bhargava

http://ift.tt/2maE59R

Generation of thermosensitive male-sterile maize by targeted knockout of the ZmTMS5 gene

Publication date: Available online 21 February 2017
Source:Journal of Genetics and Genomics
Author(s): Jun Li, Huawei Zhang, Xiaomin Si, Youhui Tian, Kunling Chen, Jinxing Liu, Huabang Chen, Caixia Gao

http://ift.tt/2mat8Vv

Dipeptide HCH6-1 inhibits neutrophil activation and protects against acute lung injury by blocking FPR1

Publication date: Available online 21 February 2017
Source:Free Radical Biology and Medicine
Author(s): Shun-Chin Yang, Shih-Hsin Chang, Pei-Wen Hsieh, Yin-Ting Huang, Chiu-Ming Ho, Yung-Fong Tsai, Tsong-Long Hwang
Formyl peptide receptor 1 (FPR1) is an emerging therapeutic target for the discovery of drugs to treat neutrophilic inflammatory diseases. However, development of FPR1 antagonists for clinical use is still inadequate. The purpose of this study was to identify a synthetic dipeptide N-(N-benzoyl-L-tryptophanyl)-D-phenylanlanine methyl ester (HCH6-1) as a FPR1 inhibitor and to investigate its protective effects against acute lung injury (ALI). HCH6-1 inhibited superoxide anion generation, elastase release, and chemotaxis in human neutrophils specifically activated by formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLF), an FPR1 agonist. HCH6-1 produced right shifts in the concentration-response curves of fMLF, suggesting that HCH6-1 was a competitive antagonist of FPR1. Indeed, HCH6-1 bound to FPR1 in human neutrophils and neutrophil-like THP-1 as well as hFPR1-transfected HEK293 cells. Also, the FPR1 downstream signaling pathways were competitively inhibited by HCH6-1. Furthermore, HCH6-1 prevented pulmonary neutrophil infiltration and edema along with alveolar damage in LPS-induced ALI in mice. Our findings suggest that HCH6-1, a FPR1 antagonist, may have potential as a new therapeutic agent for treating FPR1-involved inflammatory lung diseases.

Graphical abstract

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Interaction of plasmenylcholine with free radicals in selected model systems

Publication date: Available online 21 February 2017
Source:Free Radical Biology and Medicine
Author(s): A. Broniec, A. Żądło, A. Pawlak, B. Fuchs, R. Kłosiński, D. Thompson, T. Sarna
Plasmalogens (Plg) - naturally occurring glycerophospholipids with the vinyl-ether group in the sn-1 position are generally viewed as physiological antioxidants. Although there are numerous examples of antioxidant action of plasmalogen in cell cultures and in experimental animals, this hypothesis is far from being satisfactorily proven due to substantial limitations of such studies. Thus, plasmalogen reactivity in cells results in the accumulation of toxic byproducts and the experimental design is usually too complicated to evaluate the protective function of solely one type of lipid molecular species. In this study, experiments were performed in homogenous and heterogeneous model systems consisting of solutions in organic solvents as well as micelles and liposomes containing pure synthetic plasmenylcholines. Under the experimental conditions used, chemical reactivity of plasmalogens could be attributed to specific fatty acid esterification pattern. This is important because the chemical reactivity cannot be separated from physico-chemical properties of the lipids. Time-dependent formation of phospholipid and cholesterol hydroperoxides were determined by iodometric assay and HPLC-EC. EPR oximetry and Clark electrode were employed to detect the accompanying changes in oxygen concentration. Oxidation of the studied lipids was monitored by standard colorimetric TBARS method as well as MALDI-TOF mass spectrometry. Our data indicate that the reactivity of sn-2 monounsaturated vinyl ether lipids in peroxyl radical-induced or iron-catalyzed peroxidation reactions is comparable with that of their diacyl analogs. In samples containing cholesterol and plasmalogens, oxidative processes lead to accumulation of the radical oxidation product of cholesterol. It can be concluded that the antioxidant action of plasmalogens takes place intramolecularly rather than intermolecularly and depends on the degree of unsaturation of esterified fatty acids. Thus, it is questionable if plasmalogens can really be viewed as "endogenous antioxidant", even though they may exhibit, under special conditions, protective effect.

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Homozygous mutation in TXNRD1 is associated with genetic generalized epilepsy

Publication date: Available online 21 February 2017
Source:Free Radical Biology and Medicine
Author(s): Alexei P Kudin, Gregor Baron, Gábor Zsurka, Kevin G Hampel, Christian E Elger, Alexander Grote, Yvonne Weber, Holger Lerche, Holger Thiele, Peter Nürnberg, Herbert Schulz, Ann-Kathrin Ruppert, Thomas Sander, Qing Cheng, Elias SJ Arnér, Lutz Schomburg, Sandra Seeher, Noelia Fradejas-Villar, Ulrich Schweizer, Wolfram S Kunz
Increased oxidative stress has been widely implicated in the pathogenesis in various forms of human epilepsy. Here, we report a homozygous mutation in TXNRD1 (thioredoxin reductase 1) in a family with genetic generalized epilepsy. TXNRD1 is an essential selenium-containing enzyme involved in detoxification of reactive oxygen species (ROS) and redox signaling. The TXNRD1 mutation p.Pro190Leu affecting a highly conserved amino acid residue was identified by whole-exome sequencing of blood DNA from the index patient. The detected mutation and its segregation within the family – all siblings of the index patient were homozygous and the parents heterozygous – were confirmed by Sanger sequencing. TXNRD1 activity was determined in subcellular fractions from a skeletal muscle biopsy and skin fibroblasts of the index patient and the expression levels of the mutated protein were assessed by ⁷⁵Se labeling and Western blot analysis. As result of the mutation, the activity of TXNRD1 was reduced in the patient's fibroblasts and skeletal muscle (to 34 ± 3% and 16 ± 8% of controls, respectively). In fibroblasts, we detected reduced ⁷⁵Se-labeling of the enzyme (41 ± 3% of controls). An in-depth in vitro kinetic analysis of the recombinant mutated TXNRD1 indicated 30–40% lowered kcat/Se values. Therefore, a reduced activity of the enzyme in the patient's tissue samples is explained by (i) lower enzyme turnover and (ii) reduced abundance of the mutated enzyme as confirmed by Western blotting and ⁷⁵Se labeling. The mutant fibroblasts were also found to be less resistant to a hydrogen peroxide challenge. Our data agree with a potential role of insufficient ROS detoxification for disease manifestation in genetic generalized epilepsy.

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The effect of oxidized phospholipids on phenotypic polarization and function of macrophages

Publication date: Available online 21 February 2017
Source:Free Radical Biology and Medicine
Author(s): Vlad Serbulea, Dory DeWeese, Norbert Leitinger
Oxidized phospholipids are products of lipid oxidation that are found on oxidized low-density lipoproteins and apoptotic cell membranes. These biologically active lipids were shown to affect a variety of cell types and attributed pro-as well as anti-inflammatory effects. In particular, macrophages exposed to oxidized phospholipids drastically change their gene expression pattern and function. These 'Mox,'macrophages were identified in atherosclerotic lesions, however, it remains unclear how lipid oxidation products are sensed by macrophages and how they influence their biological function. Here, we review recent developments in the field that provide insight into the structure, recognition, and downstream signaling of oxidized phospholipids in macrophages.

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Regulation of STAT3 and NF-κB Activations by S-Nitrosylation in Multiple Myeloma

Publication date: Available online 21 February 2017
Source:Free Radical Biology and Medicine
Author(s): Jinsu Kim, Seungho Choi, Nishant Saxena, Avtar K. Singh, Inderjit Singh, Je-Seong Won
Numerous reports suggest that aberrant activations of STAT3 and NF-κB promote survival and proliferation of multiple myeloma (MM) cells. In the present report, we demonstrate that a synthetic S-nitrosothiol compound, S-nitroso-N-acetylcysteine (SNAC), inhibits proliferation and survival of multiple MM cells via S-nitrosylation-dependent inhibition of STAT3 and NF-κB. In human MM cells (e.g. U266, H929, and IM-9 cells), SNAC treatment increased S-nitrosylation of STAT3 and NF-κB and inhibited their activities. Consequently, SNAC treatment resulted in MM cell cycle arrest at G1/S check point and inhibited their proliferation. SNAC also decreased the expression of cell survival factors and increased the activities of caspases, thus increased sensitivity of MM cells to melphalan, a chemotherapeutic agent for MM. In U266 xenografted mice, SNAC treatment decreased the activity of STAT3 and reduced the growth of human CD138 positive cells (U266 cells) in the bone marrow and also reduced their production of human IgE into the serum. Taken together, these data document the S-nitrosylation mediated inhibition of MM cell proliferation and cell survival via inhibition of STAT3 and NF-κB pathways and its efficacy in animal model of MM.

Graphical abstract

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Progress and challenges in electrochemiluminescent aptasensors

Publication date: 15 June 2017
Source:Biosensors and Bioelectronics, Volume 92
Author(s): Kateryna Muzyka, Muhammad Saqib, Zhongyuan Liu, Wei Zhang, Guobao Xu
The importance of developing new diagnostic and detection technologies for the growing number of sensing challenges is rising each year. Here, we present a comprehensive and concise review on electrochemiluminescent (ECL) aptasensors by putting special emphasis on its characteristic features, advances, challenges, and applications of ECL based aptasensors. ECL is an ideal tool for constructing such sensors because of its inherent characteristics and can be easily integrated into aptamer based sensing platforms. This review summarizes the "synergistic benefits" of ECL aptamer-based sensors; classifications of ECL aptamer-based assay designs, and signal amplification strategies. This critical review highlights the effects of integration of nanomaterials, immobilization techniques, and amplification/detection strategies on the analytical performance of ECL based aptasensors. Moreover, several proof-of-concepts with appropriate figures and explanations have been shown to provide a general guide for the design of ECL aptasensors, and to stimulate further application of these ECL aptasensors. Finally, we conclude with the remaining challenges and opportunities to inspire further developments in ECL aptasensors.

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A reusable aptasensor of thrombin based on DNA machine employing resonance light scattering technique

Publication date: 15 June 2017
Source:Biosensors and Bioelectronics, Volume 92
Author(s): Yining Hou, Jifeng Liu, Min Hong, Xia Li, Yanhua Ma, Qiaoli Yue, Chen-Zhong Li
The design of molecular nanodevices attracted great interest in these years. Herein, a reusable, sensitive and specific aptasensor was constructed based on an extension-contraction movement of DNA interconversion for the application of human thrombin detection. The present biosensor was based on resonance light scattering (RLS) using magnetic nanoparticles (MNPs) as the RLS probe. MNPs coated with streptavidin can combine with biotin labeled thrombin aptamers. The combined nanoparticles composite is monodispersed in aqueous medium. When thrombin was added a sandwich structure can form on the surface of MNPs, which induced MNPs aggregation. RLS signal was therefore enhanced, and there is a linear relationship between RLS increment and thrombin concentration in the range of 60pM–6.0nM with a limit of detection at 3.5pM (3.29SB/m, according to the recent recommendation of IUPAC). The present aptasensor can be repeatedly used for at least 6 cycling times by heat to transfer G-quadruplex conformation to single strand of DNA sequence and release thrombin. MNPs can be captured by applying the external magnetic field. Furthermore, the proposed biosensor was successfully applied to detect thrombin in human plasma.

http://ift.tt/2kXySQy

Design of elution strategy for simultaneous detection of chloramphenicol and gentamicin in complex samples using surface plasmon resonance

Publication date: 15 June 2017
Source:Biosensors and Bioelectronics, Volume 92
Author(s): Yinqiang Xia, Rongxin Su, Renliang Huang, Li Ding, Libing Wang, Wei Qi, Zhimin He
For the analysis of massive samples containing multiple analytes, the enhancement of detection efficiency is crucial. In this study, a facile method was developed for sequential detection of chloramphenicol (CAP) and gentamicin (GEN) in complex samples, e.g. milk, using a surface plasmon resonance (SPR)-based biosensor. Based on the immune inhibition format, two conjugates of antigen and bovine serum albumin (BSA)—denoted as CAP–BSA and GEN–BSA—were grafted on the same channel of the SPR sensor chip. Two standard curves for CAP and GEN were separately obtained by first mixing a single antibody with different concentrations of the relevant antigen. Moreover, different regeneration solutions were screened for sequential analysis. An alkaline solution was found to completely remove the antibody against GEN (AbGEN) from the chip, but it exhibited limited ability to dissociate the antibody against CAP (AbCAP). Therefore, alkaline solution and Gly-HCl solutions are successively applied to elute AbGEN and AbCAP, respectively. By gradual elutions, CAP and GEN concentrations were simultaneously calculated with limit of detection values of 5.28ng/mL and 2.26ng/mL, respectively. Furthermore, the spiking milk samples with CAP and GEN validated the assay with recoveries of 77.6–101.1%. Therefore, this method is expected to improve the detection efficiency of SPR biosensors.

http://ift.tt/2kK1amp

Source apportionment of ambient PM10 and PM2.5 in Haikou, China

Publication date: 1 July 2017
Source:Atmospheric Research, Volume 190
Author(s): Xiaozhen Fang, Xiaohui Bi, Hong Xu, Jianhui Wu, Yufen Zhang, Yinchang Feng
In order to identify the sources of PM10 and PM2.5 in Haikou, 60 ambient air samples were collected in winter and spring, respectively. Fifteen elements (Na, Mg, Al, Si, K, Ca, Ti, V, Cr, Mn, Fe, Ni, Cu, Zn and Pb), water-soluble ions (SO4²⁻ and NO3⁻), and organic carbon (OC) and elemental carbon (EC) were analyzed. It was clear that the concentration of particulate matter was higher in winter than in spring. The value of PM2.5/PM10 was >0.6. Moreover, the proportions of TC, ions, Na, Al, Si and Ca were more high in PM10 and PM2.5. The SOC concentration was estimated by the minimum OC/EC ratio method, and deducted from particulate matter compositions when running CMB model. According to the results of CMB model, the resuspended dust (17.5–35.0%), vehicle exhaust (14.9–23.6%) and secondary particulates (20.4–28.8%) were the major source categories of ambient particulate matter. Additionally, sea salt also had partial contribution (3–8%). And back trajectory analysis results showed that particulate matter was greatly affected by regional sources in winter, while less affected in spring. So particulate matter was not only affected by local sources, but also affected by sea salt and regional sources in coastal cities. Further research could focuses on establishing the actual secondary particles profiles and identifying the local and regional sources of PM at once by one model or analysis method.

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The rise of inorganic nanomaterial implementation in food applications

Publication date: July 2017
Source:Food Control, Volume 77
Author(s): Isuru R. Ariyarathna, R.M.P.I. Rajakaruna, D. Nedra Karunaratne
The amalgamation of nanoparticles (NPs) with food industry has improved the quality of our lives despite the discovery of some plausible health concerns arising from the inclusion of NPs. Certain physical properties such as fine particle size, high surface area, and high reactivity are the preeminent reasons for the frequent application of NPs in a diversified range of industrial applications. The contribution of inorganic nanomaterials (INMs) is of great significance considering its potential for development of the food industry. Therefore, the toxicological impact on human health causes by INM-associated food applications is an issue currently being addressed. Albeit there being plenteous associations with nanomaterials in the food industry, inclusion of INMs is chiefly found in food packaging. INMs are also used to encapsulate sustenance supplements, develop sensors, or detectors that are utilizable in food applications and to boost the growth of crops. Only a limited number of elements such as Zn, Al, Ti, Au, Ag, Si, Cu, Co, and Fe and/or their derivatives have been documented as possible INMs befitting food applications. Implementation of most INMs is still in the research and development stage, and applications in the food industry are yet to find approval owing to health concerns. In this review recent findings, benefits, detriments, conveniences, and risks that are associated with INMs in food applications are discussed.

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Distinct inflammatory gene expression in extraocular muscle and fat from patients with Graves orbitopathy

Objective

This study sought to compare patients with thyroid eye disease (TED) and normal controls with respect to the expression of the NR3C1, CHUK, IKBKB, FOS, NFKB and HSD11B1 genes in orbital fat (OF) and extraocular muscle (EOM).

Design and methods

A prospective study design was used to evaluate 34 TED patients and 38 healthy controls. OF was harvested from 33 TED patients and 27 controls. EOM biopsies were obtained from 32 TED patients and 18 controls. Samples were examined by real-time PCR and evaluated using appropriate statistical analyses with a significance cut-off of P < 0.05.

Results

NR3C1 mRNA levels were higher in TED EOM (median 213 (96–376)) than those in control EOM (78 (34–138)) (P < 0.001), and NFKB expression was elevated in TED muscle (223 (31–520)) relative to that in control muscle (8 (6–31)) (P < 0.001). HSD11B1 expression was higher in TED EOM (0.78 (0.47–2.01)) than that in control EOM (0.22 (0.09–0.51)) (P < 0.001). Levels of CHUK, IKBKB, and FOS were higher in TED EOM (115 (20–223), 111 (54–299) and 0.11 (0.03–0.19), respectively) than those in control EOM (5.8 (2–13), 21 (5–52) and 0.05 (0.001–0.03) respectively) (P < 0.001).

Conclusion

Tissues involved in GO exhibited different mRNA levels of NR3C1, CHUK, IKBKB, FOS, NFKB and HSD11B1. Gene expression in OF was similar for TED patients and controls. CHUK, IKBKB, FOS, NFKB, and HSD11B1 mRNA levels were higher in TED EOM than those in control EOM. NFKB was disproportionally elevated compared with NR3C1; this finding was indicative of a local proinflammatory profile.

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MANAGEMENT OF ENDOCRINE DISEASE: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: update on the management of adult patients and prenatal treatment

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is characterized by cortisol and in some cases aldosterone deficiency associated with androgen excess. Goals of treatment are to replace deficient hormones and control androgen excess, while avoiding the adverse effects of exogenous glucocorticoid. Over the last 5 years, cohorts of adults with CAH due to 21-hydroxylase deficiency from Europe and the United States have been described, allowing us to have a better knowledge of long-term complications of the disease and its treatment. Patients with CAH have increased mortality, morbidity and risk for infertility and metabolic disorders. These comorbidities are due in part to the drawbacks of the currently available glucocorticoid therapy. Consequently, novel therapies are being developed and studied in an attempt to improve patient outcomes. New management strategies in the care of pregnancies at risk for congenital adrenal hyperplasia using fetal sex determination and dexamethasone have also been described, but remain a subject of debate. We focused the present overview on the data published in the last 5 years, concentrating on studies dealing with cardiovascular risk, fertility, treatment and prenatal management in adults with classic CAH to provide the reader with an updated review on this rapidly evolving field of knowledge.

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Testosterone prevents protein loss via the hepatic urea cycle in human

Context

The urea cycle is a rate-limiting step for amino acid nitrogen elimination. The rate of urea synthesis is a true indicator of whole-body protein catabolism. Testosterone reduces protein and nitrogen loss. The effect of testosterone on hepatic urea synthesis in humans has not been studied.

Objective

To determine whether testosterone reduces hepatic urea production.

Design

An open-label study.

Patients and intervention

Eight hypogonadal men were studied at baseline, and after two weeks of transdermal testosterone replacement (Testogel, 100 mg/day).

Main outcomes measures

The rate of hepatic urea synthesis was measured by the urea turnover technique using stable isotope methodology, with ¹⁵N₂-urea as tracer. Whole-body leucine turnover was measured, from which leucine rate of appearance (LRa), an index of protein breakdown and leucine oxidation (Lox), a measure of irreversible protein loss, were calculated.

Results

Testosterone administration significantly reduced the rate of hepatic urea production (from 544.4 ± 71.8 to 431.7 ± 68.3 µmol/min; P < 0.01), which was paralleled by a significant reduction in serum urea concentration. Testosterone treatment significantly reduced net protein loss, as measured by percent Lox/LRa, by 19.3 ± 5.8% (P < 0.05). There was a positive association between Lox and hepatic urea production at baseline (r² = 0.60, P < 0.05) and after testosterone administration (r² = 0.59, P < 0.05).

Conclusion

Testosterone replacement reduces protein loss and hepatic urea synthesis. We conclude that testosterone regulates whole-body protein metabolism by suppressing the urea cycle.

http://ift.tt/2magczb

Primary adrenal insufficiency is associated with impaired natural killer cell function: a potential link to increased mortality

Objective

Mortality in patients with primary adrenal insufficiency (PAI) is significantly increased, with respiratory infections as a major cause of death. Moreover, patients with PAI report an increased rate of non-fatal infections. Neutrophils and natural killer (NK) cells are innate immune cells that provide frontline protection against invading pathogens. Thus, we compared the function and phenotype of NK cells and neutrophils isolated from PAI patients and healthy controls to ascertain whether altered innate immune responses could be a contributory factor for the increased susceptibility of PAI patients to infection.

Design and methods

We undertook a cross-sectional study of 42 patients with PAI due to autoimmune adrenalitis (n = 37) or bilateral adrenalectomy (n = 5) and 58 sex- and age-matched controls. A comprehensive screen of innate immune function, consisting of measurements of neutrophil phagocytosis, reactive oxygen species production, NK cell cytotoxicity (NKCC) and NK cell surface receptor expression, was performed on all subjects.

Results

Neutrophil function did not differ between PAI and controls. However, NKCC was significantly reduced in PAI (12.0 ± 1.5% vs 21.1 ± 2.6%, P < 0.0001). Phenotypically, the percentage of NK cells expressing the activating receptors NKG2D and NKp46 was significantly lower in PAI, as was the surface density of NKG2D (all P < 0.0001). Intracellular granzyme B expression was significantly increased in NK cells from PAI patients (P < 0.01).

Conclusions

Adrenal insufficiency is associated with significantly decreased NKCC, thereby potentially compromising early recognition and elimination of virally infected cells. This potential impairment in anti-viral immune defense may contribute to the increased rate of respiratory infections and ultimately mortality in PAI.

http://ift.tt/2kJQxA6

Folgen kritischer Erkrankung und mögliche Interventionen

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 137-144
DOI: 10.1055/s-0042-103263

Nach überlebter kritischer Erkrankung leiden Patienten häufig unter einer persistierenden körperlichen und mentalen Morbidität, die nicht allein auf die Grunderkrankungen zurückzuführen ist. Eine häufig zu findende Kombination aus physischen, psychischen und kognitiven Defiziten wird als Post-intensive Care Syndrome (PICS) bezeichnet. Der nachfolgende Artikel beleuchtet die Epidemiologie dieser Beeinträchtigungen und stellt post-intensivmedizinische Interventionen mit dem Ziel der Prävention und Therapie vor.
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