Publication date: Available online 17 April 2017
Source:Practical Radiation Oncology
Author(s): David J. Sher, David J. Adelstein, Gopal K. Bajaj, David M. Brizel, Ezra E.W. Cohen, Aditya Halthore, Louis B. Harrison, Charles Lu, Benjamin J. Moeller, Harry Quon, James W. Rocco, Erich M. Sturgis, Roy B. Tishler, Andy Trotti, John Waldron, Avraham Eisbruch
PurposeTo present evidence-based guidelines for the treatment of oropharyngeal squamous cell carcinoma (OPSCC) with definitive or adjuvant radiation therapy (RT).Methods and materialsThe American Society for Radiation Oncology convened the OPSCC Guideline Panel to perform a systematic literature review investigating the following key questions: (1) When is it appropriate to add systemic therapy to definitive RT in the treatment of OPSCC? (2) When is it appropriate to deliver postoperative RT with and without systemic therapy following primary surgery for OPSCC? (3) When is it appropriate to use induction chemotherapy in the treatment of OPSCC? (4) What are the appropriate dose, fractionation, and volume regimens with and without systemic therapy in the treatment of OPSCC?ResultsPatients with stage IV and stage T3 N0-1 OPSCC treated with definitive RT should receive concurrent high-dose intermittent cisplatin. Patients receiving adjuvant RT following surgical resection for positive surgical margins or extracapsular extension should be treated with concurrent high-dose intermittent cisplatin, and individuals with these risk factors who are intolerant of cisplatin should not routinely receive adjuvant concurrent systemic therapy. Induction chemotherapy should not be routinely delivered to patients with OPSCC. For patients with stage IV and stage T3 N0-1 OPSCC ineligible for concurrent chemoradiation therapy, altered fractionation RT should be used.ConclusionThe successful management of OPSCC requires the collaboration of radiation, medical, and surgical oncologists. When high-level data are absent for clinical decision-making, treatment recommendations should incorporate patient values and preferences to arrive at the optimal therapeutic approach.
http://ift.tt/2oGGfja
Δευτέρα 17 Απριλίου 2017
Radiation therapy for oropharyngeal squamous cell carcinoma: Executive summary of an ASTRO Evidence-Based Clinical Practice Guideline
Nasal ala reconstruction: Tunnelled island pedicle melolabial flap; jigsaw puzzle advancement flap; spiral flap; dog-ear island pedicle flap and banner melolabial transposition flap.
Skin tumours of the nasal ala are common and surgery is the treatment
of choice. Nasal ala reconstruction is challenging due to the reduced
mobility and unique features of its thick and sebaceous skin. The
natural arc of the ala and its boundary with the cheek are difficult
features to reproduce. One should bear in mind the functional and
cosmetic risks of nasal ala reconstruction. A distorted nasal contour
may impair the nasal valve; the alar rim may notch or elevate; facial
symmetry may be disrupted by blunting of the alar crease, trapdooring,
bridging of the nasofacial sulcus and poor colour and texture match.
Our aim is to review and compare the functional and cosmetic results
of different local flaps used to correct intermediate-thickness
defects on the nasal ala after surgical excision of cutaneous tumours.
We present representative patients who were treated at our
Dermatological Surgery Unit from June 2015 to September 2016.
The choice of the flap was adapted to the patients' physiognomy and
the defects' size: tunnelled island pedicle melolabial flap [Figure
1]; jigsaw puzzle advancement flap [Figure 2]; spiral flap [Figure 3];
dog-ear island pedicle flap [Figure 4] and banner melolabial
transposition flap [Figure 5]. Surgery was performed under
loco-regional anaesthesia, in an outpatient basis, followed by
prophylactic antibiotic therapy. There were neither immediate
complications nor subsequent flap necrosis. The tumours were
completely excised.
Figure 1: Female, 86-year-old, nodular ulcerated basal cell carcinoma
in the nasal ala: tunnelled island pedicle melolabial flap. (a)
Surgical plan, (b) primary defect, (c) secondary defect after
tunnelling of the flap, (d) immediate post-operative, (e and f) result
after healing (10 months after surgery).
Click here to view
Figure 2: Male, 76-year-old, nodular basal cell carcinoma on the nasal
ala: jigsaw puzzle advancement flap. (a) surgical plan, (b) primary
and secondary defects, (c) anchoring sutures secure the flap in place;
(d) immediate post-operative, (e) result after healing (3 months after
surgery).
Click here to view
Figure 3: Female, 76-year-old, nodular basal cell carcinoma on the
nasal ala: spiral flap, a combination of advancement and rotation. (a)
Surgical plan, (b) immediate post-operative, (c) result after healing
(2 months after surgery).
Click here to view
Figure 4: Female, 76-year-old, basal cell carcinoma on the nasal ala:
dog-ear island flap, combining two flaps: cheek advancement and
rotated island pedicle. (a) Surgical plan, (b) primary defect, (c)
immediate post-operative, (d) day 7 post-operative, (e) result after
healing (1 month after surgery).
Click here to view
Figure 5: Male, 83-year-old, two nodular basal cell carcinomas on the
nasal ala and dorsum: Banner's melolabial transposition flap. (a)
Surgical plan, (b) primary defect, (c) immediate post-operative, (d)
result after healing (7 months after surgery)
Click here to view
Facial symmetry was well preserved by the spiral and jigsaw puzzle
flaps [Figure 2] and [Figure 3]. The nasal sulcus was left intact by
the spiral flap as well as the tunnelled melolabial island flap
[Figure 1] and [Figure 3]. The melolabial flaps and the dog-ear island
flap allowed for the correction of larger defects on the nasal ala
[Figure 1], [Figure 4] and [Figure 5]. The dog-ear island flap [Figure
4] obtained a good result despite the large size of the primary
defect. Banner's melolabial transposition flap [Figure 5] was used to
correct a complex defect involving not only the nasal ala but also the
nasal dorsum and resulted in facial asymmetry due to trapdooring.
The small size of the defects that can be addressed by the spiral and
puzzle flaps may explain their superior cosmetic results.[1],[2] The
tunnelled melolabial island flap, although technically demanding, may
produce excellent results; compared to the cheek-to-nose interpolation
flap, the tunnelling technique offers the advantage of being one-stage
procedure. The dog-ear island flap is an adaptation of the cheek
advancement flap; despite its apparent complexity, it offers a viable
alternative to the melolabial flaps,[3] with a lower risk of trapdoor
effect and with proper preservation of the alar contour. The discussed
flaps are useful alternatives to the bilobed transposition flap and
the skin graft for the surgical reconstruction of the nasal ala.
When planning the surgery, it is important to assess the primary
defect on the nasal ala: size and location (medial or lateral), depth,
involvement of other cosmetic units/subunits and extension to the alar
rim, nasal tip or adjacent cheek. Several techniques have been
developed that are useful for the reconstruction of defects of the
nasal ala. Based on our experience and a review of the literature, we
present an algorithm [Table 1] to optimise the choices in the
reconstruction of intermediate-thickness defects in nasal ala. In
[Table 2], we review the main advantages and caveats of some of the
most useful surgical techniques for nasal ala
reconstruction.[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14]
Table 1: Nasal ala reconstruction: What is the optimal approach
according to the defects' size and location?
Click here to view
Table 2: Nasal ala reconstruction: major advantages and potential
caveats of different surgical techniques
Click here to view
In the nasal ala, given the paucity of surrounding skin and the
importance of minimising nasal ala distortion, flaps that recruit skin
from a distant site should be considered. Mastering different
techniques is essential for a surgeon to optimise treatment for each
patient. At the end of the day, the best choice depends on many
factors and should be adapted on a case-by-case basis and to the
surgeon's expertise.
--
Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480
alsfakia@gmail.com
Paediatric traumatic pneumomediastinum: the spinnaker sail sign
Description
A 20-month-old female infant was admitted to the emergency room after being run over by a car. She presented with pallor and signs of impaired peripheral perfusion, despite being conscious and alert. Signs of respiratory distress were recognised. There was a bilateral decrease of respiratory murmurs at pulmonary auscultation and her heart sounds were also diminished. Her peripheral oxygen saturation was 94% and her respiratory rate was 54 breaths per minute. A cervical and thoracic crepitus were present. There were no alterations at abdominal examination. Her blood pressure was 142/58 mmHg.
She presented with a Glasgow Coma Scale score of 15 and had normal reactive pupils. Facial oedema was observed and an epicranial haematoma was also detected. Haematological workup revealed a haemoglobin value of 12.9 g/dL.
A supine chest radiograph showed left hydropneumothorax, right pneumothorax and pulmonary contusion. This exam also showed significant pneumomediastinum revealing the spinnaker sail sign,...
http://ift.tt/2oH22ao
CAD/CAM Removable Dental Prostheses: a Review of Digital Impression Techniques for Edentulous Arches and Advancements on Design and Manufacturing Systems
Abstract
Purpose of Review
The aim of this article is to provide an overview of CAD/CAM removable dental prostheses in the treatment of completely edentulous patients.
Recent Findings
Computer-aided design/computer-aided manufacturing protocols continue to evolve in many areas in dentistry including removable complete dentures. Current protocols are advantageous in decreasing the number of clinical appointments needed, which may reduce the distress in elderly with limited access to care. In addition, CAD/CAM complete dentures are fabricated using standardized techniques using high-value quality controlled materials. Laboratory tabletop scanners are being used predominantly for the digitization of conventional impressions or dental casts. Further research is needed to further advance existing intra-oral scanners in digital impressioning of the completely edentulous jaws.
Summary
Use of digital technology in complete denture manufacturing provides prostheses with improved quality such as reduced porosity, polymerization shrinkage, and improved retention. Presence of digital depository data allows replacement dentures to be fabricated in case they are lost or damaged.
http://ift.tt/2omQ4AF
Taste Sensing Systems Influencing Metabolic Consequences
Abstract
Recent Findings
The taste information contributes to evaluate the quality and nutritional value of food before it is ingested, and thus, is essential for maintaining nutritive homeostasis within the body. Recent studies revealed that taste sensitivity is modulated by humoral factors such as hormones. Angiotensin II is a key hormone regulating sodium and water balance. Investigations of its involvement in the taste system revealed that angiotensin II suppresses the gustatory NaCl responses (amiloride-sensitive component) and enhances sweet taste sensitivity without affecting umami, sour, and bitter responses in mice.
Summary
These results suggest that taste modulation by angiotensin II may play important roles in maintaining electrolyte and glucose homeostasis.
Purpose of Review
This review focuses on the molecular mechanisms of salty taste perception and its modulation through the angiotensin II signaling to work out novel strategies to control food intake influencing metabolic consequences.
http://ift.tt/2nUUOlQ
Root Coverage Procedures for Multiple Recession Defects
Abstract
Purpose of Review
The demand for root coverage in multiple gingival recession defects has increased in recent years. Compared to isolated recession, multiple gingival recession defects are much more challenging due to various limiting factors and require more sophisticated surgical techniques. This review aims to address recent progress in the management of multiple recession defects.
Recent Findings
The subepithelial connective tissue graft (SCTG) procedure, while effective, is limited due to tissue availability and patient preference to avoid a donor harvest site. Different surgical techniques and biological materials have been studied in an attempt to find ideal alternatives.
Summary
Based on the studies reviewed, the SCTG procedure still remains the gold standard in terms of percent root coverage. Acellular dermal matrix allograft in conjunction with different flap designs has shown comparable, satisfactory results up to 1 year postoperatively. Other materials such as porcine collagen matrix and enamel matrix derivative also show some promise. Well-designed studies with long-term outcomes are still needed.
http://ift.tt/2omQjMi
Well-Differentiated Neuroendocrine Tumors in Skin: Terminology and Diagnostic Utility of Cytokeratin 5/6 and p63
Abstract
Background
Well-differentiated neuroendocrine tumors (WDNETs) in skin include metastases from visceral primary sites and very uncommonly, primary cutaneous carcinoid tumors. Cutaneous WDNET may present a diagnostic challenge and in particular can be mistaken for a benign skin adnexal tumor. In contrast to cutaneous adnexal tumors, metastatic adenocarcinomas to the skin are cytokeratin 5/6 (CK 5/6) and p63 negative in the majority of cases. It is unclear if failure to stain with CK 5/6 and p63 would be helpful in differentiating WDNETs from cutaneous adnexal neoplasms.
Methods
We reviewed ten cases of cutaneous WDNETs (8 cases of metastatic disease and 2 presumed primary carcinoid tumors of the skin) and performed immunohistochemical stains for CK 5/6 and p63 on all cases.
Results
All ten cases were negative with both CK 5/6 and p63.
Conclusion
Negative staining for cytokeratin 5/6 and p63 can be helpful to distinguish WDNETs from cutaneous adnexal neoplasms. It is important to consider WDNETs in the differential diagnosis of cutaneous adnexal neoplasms as low grade tumors may be first sign of aggressive metastatic disease.
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Serum Toll-Like Receptor-2, Toll-Like Receptor-4 Levels in Patients with HBeAg-Negative Chronic Viral Hepatitis B
Viral Immunology , Vol. 0, No. 0.
http://ift.tt/2ooc3qU
Detection of the Canine Parvovirus 2c Subtype in Australian Dogs
Viral Immunology , Vol. 0, No. 0.
http://ift.tt/2pbZZOH
Development and Validation of Monoclonal Antibody-Based Antigen Capture ELISA for Detection of Group A Porcine Rotavirus
Viral Immunology , Vol. 0, No. 0.
http://ift.tt/2oohs1g
The multiple genetic causes of central hypothyroidism
Publication date: Available online 17 April 2017
Source:Best Practice & Research Clinical Endocrinology & Metabolism
Author(s): Luca Persani, Marco Bonomi
An insufficient stimulation by thyrotropin (TSH) of an otherwise normal thyroid gland represents the cause of Central Hypothyrodism (CeH). CeH is about 1,000-folds rarer than Primary Hypothyroidism and often represents a real challenge for the clinicians, mainly because they cannot rely on adequately sensitive parameters for diagnosis or management, as it occurs with circulating TSH in PH. Therefore, CeH diagnosis can be frequently missed or delayed in patients with a previously unknown pituitary involvement. A series of genetic defects have been described to account for isolated CeH or combined pituitary hormone defects (CPHDs) with variable clinical characteristics and degrees of severity. The recently identified candidate gene IGSF1 appears frequently involved. This review provides an updated illustration of the different genetic defects accounting for CeH.
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Hormonal and reproductive risk factors of papillary thyroid cancer: A population-based case-control study in France
Source:Cancer Epidemiology, Volume 48
Author(s): Emilie Cordina-Duverger, Christophe Leux, Monica Neri, Catherine Tcheandjieu, Anne-Valérie Guizard, Claire Schvartz, Thérèse Truong, Pascal Guénel
The three times higher incidence of thyroid cancer in women compared to men points to a role of female sex hormones in its etiology. However the effects of these factors are poorly understood. We analyzed the association between thyroid cancer and hormonal and reproductive factors among women enrolled in CATHY, a population-based case-control study conducted in France. The study included 430 cases of papillary thyroid cancer and 505 controls frequency-matched on age and area of residence. The odds ratios for thyroid cancer increased with age at menarche (p trend 0.05). Postmenopausal women were at increased risk, as compared to premenopausal women, particularly if menopause followed an ovariectomy, and for women with age at menopause <55years. In addition, use of oral contraceptives and menopausal hormone therapy reduced the association with thyroid cancer by about one third, and breastfeeding by 27%. Overall, these findings provide evidence that the risk of thyroid cancer increases with later age at menarche and after menopause, and decreases with use of oral contraceptives and menopausal hormone therapy. These findings confirm an implication of hormonal factors in papillary thyroid cancer risk, whose mechanisms need to be elucidated.
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Overall survival in elderly patients with colorectal cancer: A population-based study in the Caribbean
Source:Cancer Epidemiology, Volume 48
Author(s): Clarisse Joachim, Lidvine Godaert, Moustapha Dramé, Jacqueline Véronique-Baudin, Jonathan Macni, Juliette Smith-Ravin, Jean-Luc Novella, Rachid Mahmoudi
BackgroundPopulation-based Cancer registries (PBCR) play an important role in cancer surveillance and research. The aim of this study was to examine overall survival in elderly patients with colorectal cancer (CRC) by analysing data from the Martinique PBCR between 1993 and 2012.MethodsThe log-rank test was used to assess the statistical differences of the survival curves by each categorical variable: age at diagnosis, sex, histology, zone of residence, subsite, stage at diagnosis, and chemotherapy. A multivariable Cox model was performed to identify independent prognostic factors for overall survival in elderly patients with colorectal cancer.ResultsAmong 2230 patients included in the study, 60.8% were aged≥65years; mean age at diagnosis of these patients was 75.7±7.2years. For the period 2008–2012, 532 elderly patients were analysed; mean age of those receiving chemotherapy was 73.0±0.4 versus 77.9±0.4years for those not receiving chemotherapy (p<0.0001). Stage at diagnosis was evaluated in 87.8% (467/532) of patients; 63.0% (294/467) had stage III–IV and 49.3% of these patients (145/294) received chemotherapy. Chemotherapy was less frequently prescribed in patients aged 75–84 and ≥85 years as compared to those aged 65–74 years (41.1% and 15.0% versus 64.6% respectively; p<0.0001). Stage III–IV at diagnosis (HR=5.25; 3.70–7.45; p<0.0001), and not receiving chemotherapy (HR=3.05; 2.23–4.16; p<0.0001), were independent prognostic factors for overall survival.ConclusionOur study highlights the role of PBCR in evaluating cancer survival and patterns of care in elderly people of the French West- Indies. Chemotherapy was less frequently prescribed among the elderly
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A modification on Brook formula in calculating the misfit of Ni-based superalloys
Publication date: 15 July 2017
Source:Materials & Design, Volume 126
Author(s): Haibo Long, Shengcheng Mao, Sisi Xiang, Yanhui Chen, Hua Wei, Yizhou Zhou, JinLai Liu, Yinong Liu
The validity of the Brooke formula in estimating the lattice misfit based on dislocation network structure in Ni-based superalloys is investigated. The misfit value of a sample subjected to prolonged thermal exposure as derived from the popular Brooke formula is below that determined by X-ray diffraction (XRD) method, whereas the misfit estimated using the Brooke formula for a sample subjected to creep is greater than that determined by XRD method. These discrepancies imply the invalidity of the popular Brooke formula in two aspects: that a dislocation network is not always mature to fully relax the lattice misfit leading underestimate the misfit and that using the full magnitude of the Burgers vector overestimates the misfit. To overcome this problem, a modified Brook formula using the {100} projection of the edge component of a Burgers vector as the effective magnitude to relieve the misfit is proposed. The misfit derived from the modified Brook formula is in good agreement with the values determined by XRD method for a number of Ni-based superalloys studied.
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Time in the Therapeutic Range for Patients Taking Warfarin in Clinical Trials: Useful, but Also Misleading, Misused, and Overinterpreted.
http://ift.tt/2ptcbdE
Prioritizing Functional Capacity as a Principal End Point for Therapies Oriented to Older Adults With Cardiovascular Disease: A Scientific Statement for Healthcare Professionals From the American Heart Association.
http://ift.tt/2oGoosh
Treatment of Patients With Atrial Fibrillation and Heart Failure With Reduced Ejection Fraction.
http://ift.tt/2ptc2a6
Engagement, Research, and Evidence: Leveraging the National Patient-Centered Clinical Research Network for Better Cardiovascular Health.
http://ift.tt/2oGkQGP
Nicotinamide Phosphoribosyltransferase Promotes Pulmonary Vascular Remodeling and Is a Therapeutic Target in Pulmonary Arterial Hypertension.
http://ift.tt/2oGpx3e
Medical Therapy for Secondary Prevention and Long-Term Outcome in Patients With Myocardial Infarction With Nonobstructive Coronary Artery Disease.
http://ift.tt/2pt7U9Z
Myocardial Infarction With Nonobstructive Coronary Arteries (MINOCA): The Past, Present, and Future Management.
http://ift.tt/2oGpBQw
High-Sensitive Cardiac Troponin T as an Early Biochemical Signature for Clinical and Subclinical Heart Failure: MESA (Multi-Ethnic Study of Atherosclerosis).
http://ift.tt/2psPExC
High-Sensitive Cardiac Troponin for Prediction of Clinical Heart Failure: Are We Ready for Prime Time?.
http://ift.tt/2oGr9Kq
Impact of Practice-Based Management of Pulmonary Artery Pressures in 2000 Patients Implanted With the CardioMEMS Sensor.
http://ift.tt/2pt3ujm
Measuring Pulmonary Artery Pressures in Heart Failure: A New Useful Diagnostic Tool?.
http://ift.tt/2oGtYLe
Range of Risk Factor Levels: Control, Mortality, and Cardiovascular Outcomes in Type 1 Diabetes Mellitus.
http://ift.tt/2pt1sjc
Some Common Ground Emerges in Debate Over ECGs for Athletes.
http://ift.tt/2pt2GLz
Physical Activity Guided by Pulse Pressure in Patients With Continuous Flow Left Ventricular Assist Devices: A Pilot Study.
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Letter by Irfan Regarding Article, "Assessment of the European Society of Cardiology 0-Hour/1-Hour Algorithm to Rule-Out and Rule-In Acute Myocardial Infarction".
http://ift.tt/2psTWVv
Letter by Mueller and Roffi Regarding Article, "Assessment of the European Society of Cardiology 0-Hour/1-Hour Algorithm to Rule-Out and Rule-In Acute Myocardial Infarction".
http://ift.tt/2oG5QJ2
Response by Than et al to Letter Regarding Article, "Assessment of the European Society of Cardiology 0-Hour/1-Hour Algorithm to Rule-Out and Rule-In Acute Myocardial Infarction".
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Letter by Hermida et al Regarding Article, "The Heart's Circadian Rhythms Point to Potential Treatment Strategies".
http://ift.tt/2ptbmkO
Determination of veterinary penicillin antibiotics by fast high-resolution liquid chromatography and luminescence detection
Publication date: 1 August 2017
Source:Talanta, Volume 170
Author(s): M.L. Castillo-García, M.P. Aguilar-Caballos, A. Gómez-Hens
A chromatographic method based on the use of a fused-core column and luminescence detection is described for the determination of six penicillin antibiotics used in veterinary practice, namely amoxicillin, ampicillin, penicillin G, oxacillin, cloxacillin and nafcillin. The use of this column provides the separation of these antibiotics with retention times lower than 4.5min. The tris(2,2′-bipyridyl)ruthenium(II) [Ru(bpy)32+] – Ce(IV) system has been used as post-column derivatization reagent, obtaining a luminescence signal (λem 610nm) proportional to the analyte concentration when the system is excited at 450nm.The dynamic ranges of the calibration graphs are 100–10,000ngmL−1 for all the antibiotics assayed and the limits of detection are in the range of 44–51ngmL−1. The precision, established at two concentration levels of each analyte and expressed as the percentage of the relative standard deviation is in the range of 6.9–9.8%. The method has been satisfactorily applied to the analysis of water and pharmaceutical samples, with recoveries ranging from 88.6% to 108.5%.
Graphical abstract
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In-line moisture monitoring in fluidized bed granulation using a novel multi-resonance microwave sensor
Publication date: 1 August 2017
Source:Talanta, Volume 170
Author(s): Johanna Peters, Kathrin Bartscher, Claas Döscher, Wolfgang Taute, Michael Höft, Reinhard Knöchel, Jörg Breitkreutz
Microwave resonance technology (MRT) is known as a process analytical technology (PAT) tool for moisture measurements in fluid-bed granulation. It offers a great potential for wet granulation processes even where the suitability of near-infrared (NIR) spectroscopy is limited, e.g. colored granules, large variations in bulk density. However, previous sensor systems operating around a single resonance frequency showed limitations above approx. 7.5% granule moisture. This paper describes the application of a novel sensor working with four resonance frequencies. In-line data of all four resonance frequencies were collected and further processed. Based on calculation of density-independent microwave moisture values multiple linear regression (MLR) models using Karl-Fischer titration (KF) as well as loss on drying (LOD) as reference methods were build. Rapid, reliable in-process moisture control (RMSEP≤0.5%) even at higher moisture contents was achieved.
Graphical abstract
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Determination of stability characteristics for electrochemical biosensors via thermally accelerated ageing
Publication date: 1 August 2017
Source:Talanta, Volume 170
Author(s): Peter Panjan, Vesa Virtanen, Adama Marie Sesay
Biosensors are devices that are prone to ageing; this phenomenon can be characterized as a decrease in signal over time. Biosensor stability is of a crucial importance for commercial success and as biosensors are presently being applied to an increasing and variety of applications. Stability characteristics related to shelf life, reusability and/or continuous use stability are often poorly investigated or unreported in literature, yet are important factors. Instability or ageing can be accelerated at an elevated temperature; Arrhenius (exponential) and linear models were investigated in order to propose a novel method for rapid ageing characteristics determination. Linear correlation proved more suitable with higher coefficients of determination than exponential correlation. Degradation rate is linearly dependent on temperature and by utilizing the proposed models, long term shelf life of a biosensor can be determined in 4 days and continuous use stability in less than 24h. Reusability studies are found to correlate poorly due to the unpredictable nature of biosensor handling. Basic constructed screen printed electrode glucose oxidase biosensors were used as a model biosensor in order to propose models for shelf life, reusability and continuous use stability.
Graphical abstract
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A voltammetry sensor platform for baicalein and baicalin simultaneous detection in vivo based on Ta2O5-Nb2O5@CTS composite
Publication date: 1 August 2017
Source:Talanta, Volume 170
Author(s): Zhengkun Xie, Wang Lu, Lingxi Yang, Gaiping Li, Baoxian Ye
Baicalein and baicalin are the major flavonoids found in Scutellariae Radix, an essential herb which has had a presence in traditional Chinese medicine (TCMs) for more than two thousands of years. Owing to their similar characteristics and physiochemical properties, sensitive, it is a great challenge to detect both of them simultaneously. In this work, a novel, facile and sensitive electrochemical method was proposed based on tantalum oxide (Ta2O5), niobium oxide (Nb2O5) particles and antiseptic chitosan modified carbon paste electrode (Ta2O5-Nb2O5@CTS-CPE). Scanning electron microscope (SEM), X-ray diffraction spectroscopy (XRD), Fourier transform infrared spectroscopy (FTIR), cyclic voltammetry (CV) and electrochemical impedance spectrum (EIS) were used to characterize the properties and investigate the electrochemical response of the sensor. The electrochemical behaviors and redox mechanisms of two analytes were investigated at the target electrode. Under the optimum conditions, the highly sensitive and simultaneous determination of baicalein and baicalin was successfully achieved with a linear response range of 0.08–8.0μM for both of them. The obtained detection limits for baicalein and baicalin were of 0.05 and 0.03μM (S/N=3), respectively. Furthermore, the proposed sensor displayed high sensitivity, excellent stability and satisfactory results in Scutellariae Radix samples analysis and hydrolysis process analysis of baicalin in vivo.
Graphical abstract
http://ift.tt/2nXnKKb
Electrochemically deposited conductive composite sorbent for highly efficient online solid-phase microextraction of jasmonates in plant samples
Publication date: 1 August 2017
Source:Talanta, Volume 170
Author(s): Xu Ling, Zilin Chen
Conductive composite films composed of poly (3, 4-ethylenedioxythiophene) (PEDOT) and sulfonated graphene were electrochemically deposited on carbon fiber bundle in aqueous solutions for solid phase microextraction (SPME). During the electro-polymerization process, negatively charged sulfonated graphene were doped in PEDOT layer and uniformly dispersed in the composite. The modified carbon fiber bundle worked as sorbent was then successfully applied to online SPME-HPLC-UV analysis of jasmonates in wintersweet flowers. High extraction efficiency (over 420-fold), low limits of detection (0.1ngmL−1 for jasmonic acid and 0.01ngmL−1 for methyl jasmonate) and wide linear ranges (0.5–5000 and 0.05–5000ngmL−1, R>0.9997) have been obtained. It has been demonstrated that this method can be well used for jasmonates analysis in fresh wintersweet flowers with good recoveries (92.4–98.9%). The results were confirmed by HPLC-MS method.
Graphical abstract
http://ift.tt/2nXfbPo
Detection of Aβ oligomers based on magnetic-field-assisted separation of aptamer-functionalized Fe3O4 magnetic nanoparticles and BaYF5:Yb,Er nanoparticles as upconversion fluorescence labels
Publication date: 1 August 2017
Source:Talanta, Volume 170
Author(s): Ling-Feng Jiang, Bo-Cheng Chen, Ben Chen, Xue-Jian Li, Hai-Lin Liao, Hong-Miao Huang, Zhan-Jing Guo, Wen-Yan Zhang, Lin Wu
A sensitive and stable bioassay for the detection of Aβ oligomer (Aβo), a potentially promising candidate biomarker for Alzheimer's disease (AD) diagnosis, was developed using Fe3O4 magnetic nanoparticles (MNPs) as the recognition and concentration elements and BaYF5:Yb,Er upconversion nanoparticles (UCNPs) as highly sensitive labels, conjugated with the Aβo aptamer (DNA1) and the complementary oligonucleotide of the Aβo aptamer (DNA2), respectively. The DNA1 hybridized with DNA2 to form the duplex structure on the surface of the MNPs/UCNPs nanocomposites probe. When the target Aβo was introduced, the aptamer DNA1 preferentially bound with Aβo and caused the dissociation of some complementary DNA2, liberating some UCNP-labeled complementary DNA2 and leading to a decreased upconversion fluorescent intensity on the surface of MNPs. The decreased fluorescence intensity of UCNPs was related to the concentration of Aβo in the range of 0.2–15nM with a detection limit of 36 pM. The developed method then was successfully applied to measure Aβo in artificial cerebrospinal fluid. Benefiting from the magnetic separation and concentration effect of MNPs, the high sensitivity of UCNPs, as well as the selectivity and stability of the aptamer, the present strategy offered valuable information related to early diagnosis of AD process.
Graphical abstract
http://ift.tt/2pvB9Gs
Motivation to change, coping, and self-esteem in adolescent anorexia nervosa: a validation study of the Anorexia Nervosa Stages of Change Questionnaire (ANSOCQ)
Abstract
Background
Understanding motivation to change is a key issue in both the assessment and the treatment of eating disorders. Therefore, sound instruments assessing this construct are of great help to clinicians. Accordingly, the present study analysed the psychometric properties of the Anorexia Nervosa Stages of Change Questionnaire (ANSOCQ), including its relation to coping style and self-esteem.
Methods
N = 92 adolescents referred to an eating disorders outpatient clinic meeting criteria for anorexia nervosa gave written informed consent to participate in this study and completed the ANSOCQ, the Eating Disorder Inventory, the Eating Attitudes Test, the Body Image Questionnaire, two questionnaires measuring Self-Related Cognitions and the Coping Across Situations Questionnaire. After a treatment period of nine months, clinical anorexia nervosa diagnosis and the body mass index were re-assessed. In addition to exploratory factor analysis, correlational analysis was used to test for the convergent validity of the ANSOCQ and logistic regression analysis was used to test its predictive validity.
Results
The ANSOCQ had good psychometric properties. Factor analysis yielded two meaningful factors labelled as 'weight gain and control' and 'attitudes and feelings'. Internal consistencies of the two factors amounted to Cronbach's alpha = .87 and .76, respectively. Significant correlations with other scales measuring eating disorder psychopathology were indicative of meaningful construct validity. Higher motivation to change was related to higher self-esteem and a more active coping style. Higher (positive) ANSOCQ total scores predicted remission of anorexia nervosa after nine months of treatment. A higher score on 'attitudes and feelings' was a protective factor against drop-out from intervention.
Conclusions
The ANSOCQ is a clinically useful instrument for measuring motivation to change in adolescents with AN. Two factorial dimensions explain most of the variation. Self-esteem and coping style are relevant additional constructs for the understanding of the motivation to change in anorexia nervosa.
Trial registration
NCT02828956. Retrospectively registered July 2016
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Simulation-based instruction for pharmacy practice skill development: A review of the literature
Archives of Pharmacy Practice 2017 8(2):43-50
Background: Simulation is attractive for its potential for applying a control over learning environment, content complexity, teacher time, costs and risk. Simulation-based instruction (SBI) is poised to expand in pharmacy practice and education. This systematic review synthesises published, SBI in first-degree pharmacy programmes, especially those pertaining to psychomotor or cognitive skill development. Materials and Methods: MEDLINE, Cumulative Index to Nursing and Allied Health Literature, and some education journals were searched for relevant articles published between January 2000 and December 2015. Results: Of 108 articles identified, 12 were included, which were covering four major simulation-based interventions. These simulation-based interventions were diverse, and they covered a range of competencies and outcome measures. Nine studies included medication, and five studies included physical examination/procedure-related competencies as outcome measures. The evidence from nine studies suggested that skills could be improved through interventions involving human patient simulation. Conclusion: Despite improvements in students' ability to perform, there is a lack of evidence on how this translates to real settings and to patient satisfaction.
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Awareness, perception, attitude, and knowledge regarding complementary and alternative medicines (cams) among the pharmacy and medical students of a public university in Saudi Arabia
Archives of Pharmacy Practice 2017 8(2):51-63
Introduction: The use of natural products, that is, herbs for clinical and domestic purposes, is quite common in Saudi Arabia. Studies have reported an increasing use of complementary and alternative medicines (CAMs). This study aims to investigate the perception, attitude, and knowledge of the students regarding CAMs and their use. Materials and Methods: A quantitative, cross-sectional study targeting the students of the pharmacy and medical colleges at the University of Dammam, Saudi Arabia was conducted for a 6-month duration. It employed a survey questionnaire termed as CAMs inventory. Results: The majority of the respondents were females (N = 180, 60.8%), and a major segment (N = 170, 57.4%) belonged to the age group between 21 and 23 years. Nearly half of the students (N = 121, 40.9%) strongly agreed on the need for integration of CAMs-related courses in medical and allied health education, and a similar proportion (N = 129, 43.6%) of the target population acknowledged using CAMs, based on family recommendations (N = 134, 45.3%). Half of the students (N = 142, 48%) had no knowledge about CAMs. Some of the CAMs were more prevalent in males and vice versa (P value <0.05). Conclusion: A positive perception and attitude toward CAMs was observed. It is influenced by their traditional use and partly by the recent induction of CAMs-related education in pharmacy. The majority of the students agreed on integrating CAMs-related courses in their curriculum. It was also observed that the knowledge regarding the subject was inadequate. Lastly, gender has the potential to influence the use of particular CAMs.
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Unusual case of lamivudine-associated skin rashes in an HIV/AIDS patient: a case presentation
Archives of Pharmacy Practice 2017 8(2):82-83
In patients with human immunodeficiency virus (HIV) infection, lamivudine is used as a first-line drug for antiretroviral therapy. Lamivudine is relatively nontoxic in nature, and it can also be used during pregnancy. Herein, we describe a 43-year-old, HIV-positive female hospitalized with maculopapular, pruritic rash that appeared first on the extremities and gradually spread with systemic symptoms such as fever and myalgia after lamivudine therapy.
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Translation and psychometric analysis of the Malaysian version of medication understanding and use self-efficacy scale (m-muse) for diabetes mellitus
Archives of Pharmacy Practice 2017 8(2):64-69
Introduction: Enhancing diabetes self-efficacy (SE) level can improve the self-management behaviour in patients living with diabetes mellitus (DM). This study aimed to translate and assess the psychometric properties of Malaysian version of diabetes Medication Understanding and Use Self-Efficacy Scale (M-MUSE). Methods: Following the translation of English version of MUSE to Malay language using established international standard translation guidelines, 252 adult diabetics (≥ 18 years old; DM type 1 or 2) attending the Endocrine Clinic at Hospital Kuala Lumpur, Malaysia, were recruited in this cross-sectional study. After testing the face and content validity, the psychometric properties of the final M-MUSE were evaluated using the Classical Test Theory (CTT) for reliability (Cronbach's alpha (α) and intra-class correlation coefficient (ICC)) and construct validity (factor analysis (FA)). Results: The semantic and conceptual problems in M-MUSE were identified and modified by a qualified professional translation committee. The final version showed good reliability values for internal consistency (Cronbach's α = 0.89) and one month test-retest reliability (ICC = 0.72). The Bartlett's test of sphericity and the Kaiser-Meyer-Olkin tests proved the suitability of M-MUSE for factor analysis. The extracted single component M-MUSE (eigenvalue > 1) explained a total variance of 57.58% with an eigenvalue of 4.60. The two factor structures; namely taking medication (item # 1, 6, 7 and 8) and learning about medication (item # 2, 3, 4 and 5) explained a total variance of 59.25% with good factor loading values (ranged from 0.63 to 0.89 for taking medication, and 0.66 to 0.83 for learning about medication). Conclusion: The M-MUSE appears to be a linguistically reliable and valid measure that is conceptually equivalent to the original version. The M-MUSE can be used in Malaysian healthcare settings to evaluate the SE in understanding and using prescribed diabetes medications.
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Quality of methodological reporting of randomized clinical trials of sodium-glucose cotransporter-2 (sglt2) inhibitors
Archives of Pharmacy Practice 2017 8(2):78-81
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a new class of medicines approved recently for the treatment of type 2 diabetes. To improve the quality of randomized clinical trial (RCT) reports, the Consolidated Standards of Reporting Trials (CONSORT) statement for methodological features was created. For achieving our objective in this study, we assessed the quality of methodological reporting of RCTs of SGLT2 inhibitors according to the 2010 CONSORT statement. We reviewed and analyzed the methodology of SGLT2 inhibitors RCTs that were approved by the Food & Drug Administration (FDA). Of the 27 trials, participants, eligibility criteria, and additional analyses were reported in 100% of the trials. In addition, trial design, interventions, and statistical methods were reported in 96.3% of the trials. Outcomes were reported in 93.6% of the trials. Settings were reported in 85.2% of the trials. Blinding and sample size were reported in 66.7 and 59.3% of the trials, respectively. Sequence allocation and the type of randomization were reported in 63 and 74.1% of the trials, respectively. Besides those, a few methodological items were inadequate in the trials. Allocation concealment was inadequate in most of the trials. It was reported only in 11.1% of the trials. The majority of RCTs have high percentage adherence for more than half of the methodological items of the 2010 CONSORT statement.
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The impact of risk factors on ECG parameters and quality of life in post-myocardial infarct patients
Archives of Pharmacy Practice 2017 8(2):70-77
Introduction: Many epidemiological studies have shown that there are numerous risk factors for acute coronary disease. The aim is to determine the effect of risk factors on the echocardiographic changes and quality of life in patients treated with different methods 1 year after myocardial infarction. Methods: The research was a prospective–retrospective, clinical, epidemiological study and was conducted at the Clinic of Cardiology, University Clinical Center Sarajevo. Patients were divided into four groups based on the therapy treatment they got. The patients were divided into four groups based on the therapy treatment they received. The first group consisted of 40 patients who had had myocardial infarction and were treated with medications. The patients in the groups II and III were treated with percutaneous coronary intervention (PCI) [who immediately after incident underwent primary PCI or delayed PCI], and each group consisted of 40 patients. The group IV consisted of 40 patients, who underwent surgical revascularization (coronary artery bypass surgery). After the treatments have finished, an echocardiogram was performed on every patient. The Short Form (SF)-36 health survey was used for testing the life quality. Echocardiogram and the quality of life (QoL) testing were repeated a year after the treatment. Results: The study included 160 patients with a history of myocardial infarction, of which 130 (81.3%) were men, and 30 (18.8%) were women. The average age in the total sample was 54.9 ± 8.8 years. The review of risk factors' presence showed that in the total sample, most present was hypertension with 134 (83.8%), smoking with 120 (75.0%), and hypercholesterolemia with 110 or 68.8% of patients. Hypertension showed a statistically significant negative effect on the SF-scales only in the group III according to the mental health (P = 0.020), social functioning (P = 0.013), and pain (P = 0.011). A statistically significant effect of smoking was observed in the group III according to left ventricular internal dimension in end-diastole (P = 0.000) and left ventricular internal dimension in end-systole (P = 0.001) in the sense that smokers have the higher values of these parameters, and negative to ejection fraction (EF) (P = 0.001) in the sense that smokers have lower EF. In the group IV, positive correlation was observed to EF (P = 0.038), and negative toward the mitral regurgitation (P = 0.032). Conclusion: High blood pressure negatively affected the QoL. Smoking is negatively associated with all observed echocardiographic parameters in all the groups except with the size of the left atrium.
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Pharmacy without pharmacist: Body without soul
Archives of Pharmacy Practice 2017 8(2):84-84
http://ift.tt/2nX6nct
Metabolic reprograming of anti-tumor immunity
Madhusudhanan Sukumar | Rigel J Kishton | Nicholas P Restifo
http://ift.tt/2oQlELl
How Should Physicians Respond to Latest Alopecia Research?
Dr Lipper discusses evidence and strategy for treating patients with alopecia areata.
Medscape Dermatology
http://ift.tt/2nWZisk
Movie Villains With Scars May Haunt Those With Skin Conditions
The scars and facial features of some of cinema's most terrifying villains may end up haunting people who share those traits, suggests a new study.
Reuters Health Information
http://ift.tt/2nNhDb5
Extreme lightweight structures: avian feathers and bones
Publication date: Available online 17 April 2017
Source:Materials Today
Author(s): Tarah N. Sullivan, Bin Wang, Horacio D. Espinosa, Marc A. Meyers
Flight is not the exclusive domain of birds; mammals (bats), insects, and some fish have independently developed this ability by the process of convergent evolution. Birds, however, greatly outperform other flying animals in efficiency and duration; for example the common swift (Apus apus) has recently been reported to regularly fly for periods of 10 months during migration. Birds owe this extraordinary capability to feathers and bones, which are extreme lightweight biological materials. They achieve this crucial function through their efficient design spanning multiple length scales. Both feathers and bones have unusual combinations of structural features organized hierarchically from nano- to macroscale and enable a balance between lightweight and bending/torsional stiffness and strength. The complementary features between the avian bone and feather are reviewed here, for the first time, and provide insights into nature's approach at creating structures optimized for flight. We reveal a novel aspect of the feather vane, showing that its barbule spacing is consistently within the range 8–16μm for birds of hugely different masses such as Anna's Hummingbird (Calypte anna) (4g) and the Andean Condor (Vultur gryphus) (11,000g). Features of the feather and bone are examined using the structure-property relationships that define Materials Science. We elucidate the role of aerodynamic loading on observed reinforced macrostructural features and efficiently tailored shapes adapted for specialized applications, as well as composite material utilization. These unique features will inspire synthetic structures with maximized performance/weight for potential use in future transportation systems.
http://ift.tt/2oj4FOm
The feasibility of contralateral lower neck sparing intensity modulation radiated therapy for nasopharyngeal carcinoma patients with unilateral cervical lymph node involvement
Nasopharyngeal carcinoma (NPC) is a malignant tumor type with a reported yearly incidence of 30–80 per 100,000 in southern China [1]. The nasopharynx contains a well-developed lymphatic network, and NPC has a higher incidence of cervical lymph node (LN) metastasis compared to other head and neck cancers [2]. Radiotherapy is the mainstay treatment for non-disseminated NPC. Currently, most protocols recommended by various research bodies, such as the Radiation Therapy Oncology Group, require routine prophylactic irradiation of the retropharyngeal area, Levels II–V and supraclavicular LN areas, regardless of nodal status [3–5].
http://ift.tt/2onDNvY
Improving accuracy of RNA-based diagnosis and prognosis of oral cancer by using noninvasive methods
Well over a decade ago the first studies were published that attempted to allow the identification of head and neck and, more narrowly, oral squamous cell carcinoma (OSCC) based on gene expression [1–3]. These studies relied on surgical biopsy to obtain tissue from which RNA was purified then analyzed. Unfortunately, for a number of reasons, this work did not lead to a method of tumor detection superior to that of histopathology of surgically obtained tissue by single biopsy, which is accurate 90% of the time [4].
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LALF 32-51 -E7 therapeutic vaccine induces antitumor immunity against human papillomavirus type 16 E7-expressing murine tumor metastases in the lungs
Abstract
One important goal of cancer immunotherapy is to prevent and treat tumor metastasis. We have previously reported the significant antitumor effect induced by the immunization with our human papillomavirus therapeutic protein-based vaccine (LALF32-51-E7) without adjuvant and admixed with clinically relevant adjuvants in the subcutaneous TC-1 tumor challenge model. In the present study, we evaluated the efficacy of the above mentioned vaccine formulations in controlling the hematogenous spread of TC-1 tumor cells using a more tumourigenic clone named TC-1* and other intravenous injection site less stressful than the tail vein. We generated a lung metastasis model by injecting TC-1* cells into the retro-orbital venous sinus and this is the first study describing it. Also, this is the first study that demonstrates the efficacy of the immunization with LALF32-51-E7 without adjuvant and admixed with VSSP or Al(OH)3 in controlling metastatic tumors increasing the survival of the mice. Our TC-1 lung metastasis model can be used to test the efficacy of other immunotherapeutic strategies based on E6/E7 antigens.
http://ift.tt/2pLlbqJ
Genetic alterations in mesiodens as revealed by targeted NGS and gene co-occurrence network analysis
Abstract
Objective
Mesiodens is the most common type of supernumerary tooth which includes a population prevalence of 0.15-1.9%. Alongside evidence that the condition is heritable, mutations in single genes have been reported in few human supernumerary tooth cases. Gene sequencing methods in tradition way are time-consuming and labor-intensive, whereas next generation sequencing and bioinformatics are cost-effective for large samples and target sizes.
Materials and Methods
We describe the application of a targeted next generation sequencing (NGS) and bioinformatics approach to samples from 17 mesiodens patients. Subjects were diagnosed on the basis of panoramic radiograph. 101 candidate genes which were captured custom gene were sequenced on the Illumina HiSeq2500. Multistep bioinformatics processing was performed including variant identification, base calling, and in silico analysis of putative disease-causing variants.
Results
Targeted capture identified 88 non-synonymous, rare, exonic variants involving 42 of the 101 candidate genes. Moreover, we investigated gene co-occurrence relationships between the genomic alterations and identified 88 significant relationships among 18 most recurrent driver alterations.
Conclusion
Our search for co-occurring genetic alterations revealed that such alterations interact cooperatively to drive mesiodens. We discovered a gene co-occurrence network in mesiodens patients with functionally enriched gene groups in the sonic hedgehog (SHH), bone morphogenetic proteins (BMP), and wingless integrated (WNT) signaling pathways.
This article is protected by copyright. All rights reserved.
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Oral Candida Colonization and Oral Lichen Planus
Abstract
In a well-designed clinical trial, Marable et al. has reported on the incidence of oral candidiasis in patients treated with topical steroids for oral lichen planus (OLP). (Marable et al, 2016) It has been observed that "There was no significant difference in the incidence of oral fungal infection between OLP patients treated with a preventive antimycotic therapy and those not treated prophylactically". (Marable et al, 2016)
This article is protected by copyright. All rights reserved.
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Biochemical alteration in children with idiopathic nephrotic syndrome associated with an increased risk of sensorineural hearing loss; additional insights in cochlear renal relationship
Children with Idiopathic Nephrotic Syndrome (INS) are at risk of hearing loss due to the adverse impact of medications and related immunological and genetic factors on both cochlea and kidney. So this work was planned to evaluate hearing status in children with INS and to clarify the possible associated risk factors by interpreting the clinical and laboratory profiles of those children.
http://ift.tt/2pLmbeN
Comprehensive management of congenital choanal atresia
To present results of a one-stage minimally invasive surgical procedure for congenital choanal atresia (CCA). Seven outcome measures were applied.
http://ift.tt/2psrPWt
Left and right reaction time differences to the sound intensity in normal and AD/HD children
Right hemisphere, which is attributed to the sound intensity discrimination, has abnormality in people with attention deficit/hyperactivity disorder (AD/HD). However, it is not studied whether the defect in the right hemisphere has influenced on the intensity sensation of AD/HD subjects or not. In this study, the sensitivity of normal and AD/HD children to the sound intensity was investigated.
http://ift.tt/2pLAhfQ
Comparison of First Year of Life Acute Otitis Media Admissions Before and After the 13-Valent Pneumococcal Conjugate Vaccine
Acute otitis media (AOM) is a common childhood infection, which is usually managed in the outpatient setting. Yet, the more severe cases are referred for inpatient treatment. We hypothesized that pneumococcal conjugate vaccines (PCVs), administered during the first year of life, would decrease AOM admissions rate in this age group. We studied the characteristics of infants admitted with AOM and acute mastoiditis (AM) in the PCV13 era, routinely given from November 2010 to all infants.
http://ift.tt/2pssGq1
Cochlear implantation and clinical features in patients with Noonan syndrome and Noonan syndrome with multiple lentigines caused by a mutation in PTPN11
Existing literature only reports a few patients with Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML) who underwent cochlear implantation (CI). The present study describes four NS patients and one NSML patient with a PTPN11 mutation. They all had severe to profound hearing loss, and they received a CI. The age at which the CI surgery occurred ranged from 1-13 years old, and the audiological results in all five patients improved after the CI. Otological and audiological examinations in NS and NSML are important, and for those with severe hearing loss, the CI surgery improved the audiological outcome regardless of age.
http://ift.tt/2pLwpvq
Management of non-organic hearing loss in children – a case study
A 10 year-old girl was admitted due to the claim of progressively developing hearing loss. The impedance audiometry showed no abnormalities but it was impossible to obtain reliable outcomes during pure tone audiometry assessment. The girl was additionally sent for speech audiometry, indicating a bilateral hearing loss and objective evaluations such as distortion product otoacoustic emissions, and auditory brainstem responses, which results indicated a normal hearing. On the second day, repeated subjective audiometric tests showed also normal hearing, despite constantly reported hearing loss.
http://ift.tt/2psqnDG
The watch-pat in pediatrics sleep disordered breathing: Pilot study on children with negative nocturnal pulse oximetry
The main purpose of this study was to determine the efficacy of Watch-PAT in Pediatric Sleep Disordered Breathing (PSDB) diagnosis in children with symptoms suggestive of PSDB, in which the nocturnal pulse oximetry was negative according to the Brouilette criteria.
http://ift.tt/2pLrRW1
Nasal ala reconstruction: Surgical conundrum
Journal of Cutaneous and Aesthetic Surgery 2017 10(1):55-58
http://ift.tt/2nWO3jw
Should advertising by aesthetic surgeons be permitted?
Journal of Cutaneous and Aesthetic Surgery 2017 10(1):48-48
http://ift.tt/2nWK2LK
Autologous platelet-rich fibrin matrix in non-healing trophic ulcers in patients with Hansen's disease
Journal of Cutaneous and Aesthetic Surgery 2017 10(1):3-7
Background: Non-healing trophic ulcers in Hansen's disease patients is one of the major causes for disability. It has been shown that autologous platelet-rich fibrin matrix (PRFM) is effective in healing chronic non-healing leg ulcers. Aim: The objective of this study is to demonstrate the efficacy of autologous platelet-rich fibrin matrix (PRFM) in non-healing trophic ulcers in patients treated for Hansen's disease. Design: A prospective study. Setting: An institution-based clinic. Participants: Seven treated patients with Hansen's disease, with a mean age of 38.33 years, with nine non-healing trophic ulcer of more than 6 weeks duration. Measurements: Photographs were taken before treatment and at every subsequent sitting. Area and volume were calculated at baseline and every subsequent sitting till the closure was achieved. Materials and Methods: The healthy ulcers were treated with PRFM at weekly intervals, repeated once a week for a maximum of five sittings as per requirement. Results: The mean percentage improvement in the area was 93.52%, and volume was 97.74% at the end of the second sitting. All ulcers closed by a maximum of five sittings. No adverse events were noted. Conclusion: PRFM for the treatment of trophic ulcers in treated patients with Hansen's disease is a feasible, safe, simple and inexpensive method.
http://ift.tt/2nWK2ve
Should advertising by aesthetic surgeons be permitted?
Journal of Cutaneous and Aesthetic Surgery 2017 10(1):45-47
Cosmetic, aesthetic and cutaneous surgical procedures require qualified specialists trained in the various procedures and competent to handle complications. However, it also requires huge investments in terms of infrastructure, trained staff and equipment. To be viable advertising is essential to any establishment which provides cosmetic and aesthetic procedures. Business men with deep pockets establish beauty chains which also provide these services and advertise heavily to sway public opinion in their favour. However, these saloons and spas lack basic medical facilities in terms of staff or equipment to handle any complication or medical emergency. To have a level playing field ethical advertising should be permitted to qualified aesthetic surgeons as is permitted in the US and UK by their respective organisations.
http://ift.tt/2nWBzbG
Accelerated wound healing: Harnessing the power of platelets, biomaterials, stem cells and gene therapy
Journal of Cutaneous and Aesthetic Surgery 2017 10(1):1-2
http://ift.tt/2pLl26R
Comparison of efficacy of autologous platelet-rich fibrin versus saline dressing in chronic venous leg ulcers: A randomised controlled trial
Journal of Cutaneous and Aesthetic Surgery 2017 10(1):8-12
Background: Venous leg ulcer is a chronic condition, and various treatment modalities are available. Platelet-rich fibrin (PRF) is one of the newer modalities and it contains fibroblast growth factor (GF), vascular endothelial GF, angiopoitin and platelet-derived GF which enhances the wound healing. Hence, we conducted a randomised controlled trial to compare the efficacy of PRF versus saline dressing in chronic venous leg ulcers. Aim: This study aims to compare the efficacy of autologous PRF with saline dressing in patients with chronic venous leg ulcer and to compare the mean reduction in ulcer area at the end of 4 weeks. Materials and Methods: Fifteen patients with chronic venous leg ulcers of >6 months duration having an ulcer area of 1 cm × 1 cm to 5 cm × 5 cm were taken into the study and were randomly divided into two groups. Group 1: Patients received PRF dressing. Ten millilitres of patient's blood was taken and centrifuged at 3000 rpm for 15 min. A fibrin clot obtained in the middle of the tube was removed and used for dressing over the wound surface. It was repeated every week for 4 weeks. Group 2: Patients received saline dressings once a week for 4 weeks. The assessment of the ulcer size was done with the help of photographs, and ulcer area was measured. Results: The mean reduction in the area of the ulcer size in PRF group was 85.51%, and the mean reduction in the area of the ulcer size in Saline group was 42.74% which was statistically significant with a P< 0.001 and t = 4.11. Conclusion: We conclude that PRF dressing can be used as it is effective, inexpensive, safe and an outpatient procedure.
http://ift.tt/2nWNOoJ
Plaque like giant dermatofibroma: A case report
Journal of Cutaneous and Aesthetic Surgery 2017 10(1):51-53
Dermatofibroma, also known as benign fibrous histiocytoma, is a soft-tissue tumour that usually occurs in the mid-adult life and shows a slight female predominance. Giant dermatofibroma, a very rare clinical variant, is characterised by its unusually large size, benign biological behaviour despite its large size and same histopathological characteristics as conventional dermatofibroma. We report a 63-year-old woman who presented with a large tumour on the scapular region which showed histopathological features of benign dermatofibroma.
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Using amniotic membrane as a novel method to reduce post-burn hypertrophic scar formation: A prospective follow-up study
Journal of Cutaneous and Aesthetic Surgery 2017 10(1):13-17
Background: Several studies have shown that the application of amniotic membrane as a biological dressing in the management of burns is accompanied by rapid re-epithelialisation. In this follow-up study, we aimed to evaluate the possible role of amniotic membrane as an adjunct to split thickness skin grafting on reducing itching and severity of hypertrophic scar formation. Materials and Methods: From October 2013 to January 2015, in a prospective follow-up study, 54 patients (108 limbs) with second and third degree burns, covering 4%–15% of total body surface area (TBSA), were included in the study. All patients needed split-thickness skin grafts for burn-wound coverage. Selected patients had symmetric burns on two (upper or lower) extremities. Then, in every patient, the extremities were randomly divided into two groups: In one limb, the skin graft was traditionally fixed with skin staples (control group) and in the other limb, the skin graft was covered with an amniotic membrane (amnion group). Therefore, in every patient, the graft was covered with an amniotic membrane in one extremity and fixed with skin staples in the other extremity. Finally, after 6 months, the degree of itching and hypertrophic scar formation was compared between the two groups. Results: The study group was composed of 108 limbs in 54 patients (27 males and 27 females) with a mean age of 23.54 % 4.9 years and burn 9.03 % 2.69% TBSA. The patients were divided into two groups: 54 limbs in amnion group and 54 limbs in control group. In 59.25% of the cases, patient had less itching in the extremity covered with amniotic membrane. Furthermore, in 64.81% of the cases, patients had less hypertrophic scar formation in the extremity covered with amniotic membrane. These differences were statistically significant (P < 0.001). Conclusions: Amniotic membrane used as an adjunct in split thickness skin grafting is a novel modality which significantly reduces scar formation and itching that can be greatly distressing to burn patients. However, still more prospective well designed studies are needed to prove it.
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Successful management of dowling-degos disease with combination of Q-switched Nd: YAG and fractional carbon dioxide laser
Journal of Cutaneous and Aesthetic Surgery 2017 10(1):60-62
http://ift.tt/2pLchK2
A comparative study of collagen dressing versus petrolatum gauze dressing in reducing pain at the donor area
Journal of Cutaneous and Aesthetic Surgery 2017 10(1):18-21
Background: Skin graft is one of the commonly done procedures by plastic surgeons, dermato surgeons and general surgeons. Pain at the donor area is a common complaint by the patient. The skin graft donor site area is usually covered with petrolatum dressing dermatosurgeons. Aim: This study was done to compare collagen dressing with petroleum gauze dressing in control of post-operative pain on skin graft donor area. Materials and Methods: The study was done on forty patients, twenty as study group who received collagen dressing and twenty as control group who received petroleum gauze dressing. The procedure was randomly selected by permutated block size of four. The post-operative pain was assessed with numerical pain rating scale 0 to 10. Nursing staff did the recording of pain scale. The nursing staff was not aware whether patient had collagen or petroleum gauze dressing. Statistics: Statistical analysis used was independent 't'-test (two-sample test) and Levene's test. Results: Statistics proved that study group (collagen dressing) had lesser pain than control group (petroleum gauze dressing). Conclusion: The collagen sheet dressing on skin graft donor area reduces pain in post-operative period.
http://ift.tt/2pLelBz
Nasolabial perforator flap for one-stage reconstruction of nasal defects
Journal of Cutaneous and Aesthetic Surgery 2017 10(1):22-27
Background: The excellent freedom of movement and range of this flap when based on a the nasolabial perforator flap have not been sufficiently explored. In this study, along with demonstrating the other key advantages of this flap over its traditional counterpart, we will endeavour to fill these lacunae in the available literature. Materials and Methods: From February 2009 to February 2012, twenty patients with nasal defects were repaired with a nasolabial perforator flap in the Department of Plastic and Cosmetic Surgery at Sir Ganga Ram Hospital, New Delhi. Of these, two patients (10%) underwent the procedure bilaterally. Thus, a total of 22 nasolabial perforator flap procedures were carried out. Prospectively, collected clinical records and data of each patient were retrospectively retrieved and reviewed to study the nasal defect and surgery done. Results: All the twenty (100%) patients had good functional and aesthetic outcome. All patients who had nasal stenosis preoperatively had very good improvement in the patency of the nasal passages, breathing and nasal blockage with complete recovery of symptoms. The patients were entirely satisfied with the functional recovery. Conclusions: The reliability and versatility of the nasolabial perforator flap exceed its recognised application in reconstruction of nasal defects and it must form a part of every plastic surgeon's armamentarium.
http://ift.tt/2pL9OiS
Spring-loaded syringe for multiple rapid injections
Journal of Cutaneous and Aesthetic Surgery 2017 10(1):49-50
Mesotherapy refers to multiple injections of small quantity of the drug over a large area. The mesoguns available are expensive and the motor-driven models tends to waste the expensive material to be injected since the plunger stops after injecting without recoil. We searched for a less expensive device which would inject like the mesogun and still not waste the solution. On searching the web, we identified a spring-loaded syringe. We describe the assembly and use of this inexpensive syringe for delivering multiple injections with minimal wastage.
http://ift.tt/2nWKxG0
Intra-individual right-left comparative study of medium depth peels in superficial nail abnormalities
Journal of Cutaneous and Aesthetic Surgery 2017 10(1):28-32
Background: Superficial nail abnormalities include conditions which produce nail surface changes such as trachyonychia, pitting and ridging. Mostly, this is a neglected area due to the dearth of treatment options. Glycolic acid peeling has been reported to be effective in such cases. Aim: This study aims to assess the safety and efficacy of medium depth peels (70% glycolic acid versus phenol combination peel [8% phenol with 15% trichloroacetic acid]) in patients with superficial nail abnormalities. Materials and Methods: A right-left comparative study in patients with superficial nail abnormalities was done. On the right finger or toenails phenol combination peels and on the left side 70% glycolic acid was used in a predefined protocol over 12 weeks. The severity was assessed objectively by a new devised index (Nail Surface abnormality Index (NSI]). Patient's subjective perception of severity was assessed by Visual Analogue Scale (VAS), and that of the physician was assessed by Physician's Global Assessment (PGA) scores. Results: A total of 17 patients were enrolled, two dropped out and 15 patients were included in the final analysis (mean age 19.2 years, total 120 nails treated). The mean NSI score declined from 7.88 % 0.45 to 4.02 % 0.45 on the right side; and from 8.0 % 0.45 to 4.32 % 0.44 on left side, at the end of 12 weeks. The VAS declined from 6.57 % 0.26 to 3.87 % 0.33 on right side and from 6.32 % 0.28 to 3.78 % 0.32 on left side. According to PGA score, five patients showed good improvement, seven showed moderate improvement and three responded poorly. Conclusion: Both the medium depth peels were found to be safe and equally efficacious modalities for treatment of superficial nail abnormalities.
http://ift.tt/2pLfvgD
Reconstruction with dorsal nasal flap after excision of basal cell carcinoma of the nose
Journal of Cutaneous and Aesthetic Surgery 2017 10(1):54-55
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Comparative study of efficacy and safety of botulinum toxin a injections and subcutaneous curettage in the treatment of axillary hyperhidrosis
Journal of Cutaneous and Aesthetic Surgery 2017 10(1):33-39
Background: Primary focal axillary hyperhidrosis is a chronic distressing disorder affecting both the sexes. When the condition is refractory to conservative management, we should go for more promising therapies like intradermal botulinum toxin A (BtxA) injections in the axilla, and surgical therapies like subcutaneous curettage of sweat glands. Aims and Objectives: The aim of this study is to compare the efficacy, safety and duration of action of intradermal BtxA injections in one axilla and subcutaneous curettage of sweat glands in the other axilla of the same patient with axillary hyperhidrosis. Materials and Methods: Twenty patients (40 axillae) received intradermal BtxA injections on the right side (20 axillae) and underwent tumescent subcutaneous curettage of sweat glands on the left side (20 axillae). Sweat production rate was measured using gravimetry analyses at baseline and at 3 months after the procedure. Subjective analyses were done using hyperhidrosis disease severity scale (HDSS) score at baseline, at 3rd and 6th month after the procedure. Results: At 3 months post-treatment, the resting sweat rate in the toxin group improved by 80.32% versus 79.79% in the subcutaneous curettage method (P = 0.21). Exercise-induced sweat rate in the toxin group improved by 88.76% versus 88.8% in the subcutaneous curettage group (P = 0.9). There was a significant difference in the HDSS score after treatment with both the modalities. There were no adverse events with BtxA treatment compared to very minor adverse events with the surgical method. Conclusion: Both intradermal BtxA injections and tumescent subcutaneous curettage of sweat glands had a significant decrease in the sweat rates with no significant difference between the two modalities. Hence, in resource poor settings where affordability of BtxA injection is a constraint, subcutaneous curettage of sweat glands can be preferred which has been found equally effective with no or minimal adverse events.
http://ift.tt/2nWRQgC
Squamous cell carcinoma of the nail bed: The great mimicker
Journal of Cutaneous and Aesthetic Surgery 2017 10(1):59-60
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Long-pulsed Nd: YAG laser and intense pulse light-755 nm for idiopathic facial hirsutism: A comparative study
Journal of Cutaneous and Aesthetic Surgery 2017 10(1):40-44
Background: Hirsutism means excessive terminal hair growth in a female in male pattern distribution. Perception of hirsutism is subjective. Permanent laser hair reduction is a slow process taking many sessions and tracking of improvement parameters is tedious. Hence, a lot of confusion still exists regarding the type of laser most beneficial for treatment. Aim: The aim of this study was to compare the effectiveness and safety profile of long-pulsed Nd: YAG laser (1064 nm) and intense pulse light (IPL)-755 nm in management of idiopathic facial hirsutism. Settings and Design: Open-labelled, randomly allocated experimental study. Subjects and Methods: The study included 33 cases of idiopathic facial hirsutism. Patients were randomly divided into Group A, treated with long-pulsed Nd: YAG laser and Group B, treated with IPL-755 for a total of six sessions at 1 month interval. Statistical Analysis: Chi-square test was used in Medcalc® version 9.0 and the test of significance was taken to be P< 0.05. Results: Average percentage of improvement in Group A, according to patients at each sessions were 46.33%, 70.66%, 81.66%, 84.67%, 85.33%, 87.33% and that in Group B were 28.06%, 39.72%, 52.22%, 64.72%, 67.78%, 71.11%, respectively. Excellent response (>75% reduction in hair) after six sessions in Group A was seen in fourteen (93.33%) out of fifteen patients, whereas in Group B, it was seen only in three (16.66%) out of eighteen patients. In Group A, erythema was seen in 26.67%, perifollicular edema and hyperpigmentation in 13.33% each. In Group B, erythema was seen in 50% patients, perifollicular edema in 16.67% and hyperpigmentation in 38.89% patients. Conclusions: Long-pulsed Nd: YAG Laser (1064 nm) is better than IPL-755 nm in terms of safety and effectiveness in the management of idiopathic facial hirsutism.
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Erratum: Recurrent adult nasal dermoid cyst
Journal of Cutaneous and Aesthetic Surgery 2017 10(1):63-63
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The protective effects of dexmedetomidine on ischemic brain injury: A meta-analysis
Intracranial lesions, trauma or surgery-related damage activate immune inflammation and neuroendocrine responses, causing ischemic brain injury. Studies have shown that inflammatory cascade mediated by neuroendocrine hormones and proinflammatory mediators is implicated in the pathophysiology of ischemic brain injury. Alpha2-adrenoceptor agonists, dexmedetomidine, is widely used as neuroprotectants in anesthesia practice. However, it is still lack of a comprehensive meta-analysis to evaluate the neuroprotection of dexmedetomidine against ischemic brain injury via suppressing these two physiological responses.
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Multidisciplinary management of head and neck cancer: First expert consensus using Delphi methodology from the Spanish Society for Head and Neck Cancer (part 2)
Introduction and Methodology has been described in the first part of this article.
http://ift.tt/2oiM4lF
Sodium oxybate treatment in narcolepsy and its effect on muscle tone
To estimate the effect of the compound sodium oxybate (SO) on chin muscle tone in sleep, a re-analysis of the results of the international multicenter study SXB-15 was performed, applying a validated semi-automatic analysis of muscle tone. This analysis distinguishes short (<0.5 sec) and long (>0.5 sec) muscle activity indices per hour (SMI, LMI) in 116 patients with narcolepsy-cataplexy. While stable stimulant medication was permitted, tricyclics and SSRIs were withdrawn. Polysomnographies were performed at baseline (V5), four weeks after titration of SO to 4.5g, 6g, or 9g or placebo (V6) and after another four weeks on stable SO dose (V7).
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Multidisciplinary management of head and neck cancer: First expert consensus using Delphi methodology from the Spanish Society for Head and Neck Cancer (part 1)
HNSCC is the fifth most common malignancy worldwide and the eighth most common cause of cancer-related mortality [1,2]. Tobacco and alcohol abuse are the main risk factors, but in the past few years HPV infection has emerged as a new risk factor for a substantial percentage of HNSCC-especially in oropharyngeal cancer (OPC) [3]. Only one third of the patients present with early stage disease, while most of them will have locally advanced (LA) disease by the time of diagnosis [4]. In these patients, 5-year survival has remained invariable in the last decades [5].
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The reliability and criterion validity of 2D video assessment of single leg squat and hop landing
Publication date: Available online 17 April 2017
Source:Journal of Electromyography and Kinesiology
Author(s): Lee Herrington, Faisal Alenezi, Msaad Alzhrani, Hasan Alrayani, Richard Jones
The objective was to assess the intra-tester, within and between day reliability of measurement of hip adduction (HADD) and frontal plane projection angles (FPPA) during single leg squat (SLS) and single leg landing (SLL) using 2D video and the validity of these measurements against those found during 3D motion capture. 15 healthy subjects had their SLS and SLL assessed using 3D motion capture and video analysis. Inter-tester reliability for both SLS and SLL when measuring FPPA and HADD show excellent correlations (ICC2,1 0.97-0.99). Within and between day assessment of SLS and SLL showed good to excellent correlations for both variables (ICC3,1 0.72-91). 2D FPPA measures were found to have good correlation with knee abduction angle in 3-D (r = 0.79, p = 0.008) during SLS, and also to knee abduction moment (r = 0.65, p =0.009). 2D HADD showed very good correlation with 3D HADD during SLS (r = 0.81, p = 0.001), and a good correlation during SLL (r = 0.62, p =0.013). All other associations were weak (r<0.4). This study suggests that 2D video kinematics have a reasonable association to what is being measured with 3D motion capture.
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The effect of handedness and laterality in a microlaryngeal surgery simulator
There are no controlled prospective studies evaluating the effect of dominant handedness in left- and right-sided surgery in otolaryngology. Endoscopic microlaryngeal phonosurgery is an ideal procedure to assess technical aspects of handedness and laterality, due to anatomic symmetry. In this study, we analyzed (1) choice of surgical approach and (2) outcomes based on handedness and laterality in a microlaryngeal simulator.
http://ift.tt/2pscOUD
The effect of handedness and laterality in a microlaryngeal surgery simulator
There are no controlled prospective studies evaluating the effect of dominant handedness in left- and right-sided surgery in otolaryngology. Endoscopic microlaryngeal phonosurgery is an ideal procedure to assess technical aspects of handedness and laterality, due to anatomic symmetry. In this study, we analyzed (1) choice of surgical approach and (2) outcomes based on handedness and laterality in a microlaryngeal simulator.
http://ift.tt/2pscOUD
Prevalence and Descriptive Epidemiology of Atopic Dermatitis and Its Impact on Quality of Life in Singapore
Abstract
Atopic dermatitis (AD) is a common, chronic, pruritic skin condition that is known to negatively impact the quality of life (QOL) of patients1,2. Due to its increasing prevalence, AD can impose a substantial economic burden on a country's healthcare system.3 A study in 2002 found a prevalence of 20.8% of AD in Singapore schoolchildren aged between 7 and 12 years4.
This article is protected by copyright. All rights reserved.
http://ift.tt/2oFK9se
Prevalence and Descriptive Epidemiology of Atopic Dermatitis and Its Impact on Quality of Life in Singapore
Abstract
Atopic dermatitis (AD) is a common, chronic, pruritic skin condition that is known to negatively impact the quality of life (QOL) of patients1,2. Due to its increasing prevalence, AD can impose a substantial economic burden on a country's healthcare system.3 A study in 2002 found a prevalence of 20.8% of AD in Singapore schoolchildren aged between 7 and 12 years4.
This article is protected by copyright. All rights reserved.
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Serum Endocan Levels in Children with Community-Acquired Pneumonia
Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.
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Serum Endocan Levels in Children with Community-Acquired Pneumonia
Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.
http://ift.tt/2oFrywr
Azacitidine Mitigates Graft-versus-Host Disease via Differential Effects on the Proliferation of T Effectors and Natural Regulatory T Cells In Vivo [TRANSPLANTATION]
Azacitidine (AzaC) mitigates graft-versus-host disease (GvHD) in both murine preclinical transplant models and in human clinical trials while maintaining a robust graft-versus-leukemia effect. Previous studies have failed to investigate the role of natural regulatory T cells (nTregs) on the mitigation of GvHD by AzaC, instead focusing on the generation of suppressive Tregs (CD4+CD25+FOXP3+) through the in vivo conversion of alloreactive donor T effectors (Teffs; CD4+CD25–FOXP3–) and the direct antiproliferative effects of AzaC on allogeneic T cells. Using B6.Foxp3DTR/GFP mice in which Tregs can be specifically ablated through administration of diphtheria toxin, we demonstrate that natural Tregs are required in the donor graft for AzaC to optimally protect against GvHD and that nTregs, unlike Teffs (CD3+FOXP3–), are resistant to the antiproliferative effects of AzaC. Gene expression analysis identified the potent cell cycle inhibitor, p21, was significantly upregulated in Teffs but not nTregs after treatment with AzaC. Furthermore, we demonstrate that Teffs deficient in p21 are less sensitive to the antiproliferative effects of AzaC. These results demonstrate that nTregs are essential for AzaC to fully protect against GvHD and have important clinical implications for future clinical trials testing AzaC as a novel method of GvHD prophylaxis in man.
http://ift.tt/2onyCMC
Identification of Novel STAT6-Regulated Proteins in Mouse B Cells by Comparative Transcriptome and Proteome Analysis [SYSTEMS IMMUNOLOGY]
The transcription factor STAT6 plays a key role in mediating signaling downstream of the receptors for IL-4 and IL-13. In B cells, STAT6 is required for class switch recombination to IgE and for germinal center formation during type 2 immune responses directed against allergens or helminths. In this study, we compared the transcriptomes and proteomes of primary mouse B cells from wild-type and STAT6-deficient mice cultured for 4 d in the presence or absence of IL-4. Microarray analysis revealed that 214 mRNAs were upregulated and 149 were downregulated >3-fold by IL-4 in a STAT6-dependent manner. Across all samples, ~5000 proteins were identified by label-free quantitative liquid chromatography/mass spectrometry. A total of 149 proteins was found to be differentially expressed >3-fold between IL-4–stimulated wild-type and STAT6–/– B cells (75 upregulated and 74 downregulated). Comparative analysis of the proteome and transcriptome revealed that expression of these proteins was mainly regulated at the transcriptional level, which argues against a major role for posttranscriptional mechanisms that modulate the STAT6-dependent proteome. Nine proteins were selected for confirmation by flow cytometry or Western blot. We show that CD30, CD79b, SLP-76, DEC205, IL-5Rα, STAT5, and Thy1 are induced by IL-4 in a STAT6-dependent manner. In contrast, Syk and Fc receptor–like 1 were downregulated. This dataset provides a framework for further functional analysis of newly identified IL-4–regulated proteins in B cells that may contribute to germinal center formation and IgE switching in type 2 immunity.
http://ift.tt/2oGqASA
Rip2 Is Required for Nod2-Mediated Lysozyme Sorting in Paneth Cells [MUCOSAL IMMUNOLOGY]
Paneth cells play an important role in maintaining intestinal homeostasis by secreting a large number of antimicrobial peptides into the intestinal lumen. In this study, we found that Rip2 is required for lysozyme sorting in Paneth cells in a manner that is dependent on Nod2, LRRK2, and Rab2a. Rip2 deficiency in mouse led to lysosomal degradation of lysozyme in Paneth cells and prevented the recruitment of Rab2a onto dense core vesicles (DCVs). Like Nod2 and LRRK2, Rip2 localizes to DCVs in Paneth cells, and its DCV localization depends on Nod2 and LRRK2. Thus, we delineated a genetic pathway, consisting of Nod2–LRRK2–Rip2–Rab2a, which is required for lysozyme sorting. Taken together, our results indicate that the lysozyme-sorting process in Paneth cells is orchestrated by a number of host factors and highlight the importance of Paneth cell function in intestinal homeostasis.
http://ift.tt/2oGxZBf
Vigilin Regulates the Expression of the Stress-Induced Ligand MICB by Interacting with Its 5' Untranslated Region [INNATE IMMUNITY AND INFLAMMATION]
NK cells are part of the innate immune system, and are able to identify and kill hazardous cells. The discrimination between normal and hazardous cells is possible due to an array of inhibitory and activating receptors. NKG2D is one of the prominent activating receptors expressed by all human NK cells. This receptor binds stress-induced ligands, including human MICA, MICB, and UL16-binding proteins 1-6. The interaction between NKG2D and its ligands facilitates the elimination of cells under cellular stress, such as tumor transformation. However, the mechanisms regulating the expression of these ligands are still not well understood. Under normal conditions, the NKG2D ligands were shown to be posttranscriptionally regulated by cellular microRNAs and RNA-binding proteins (RBPs). Thus far, only the 3' untranslated regions (UTRs) of MICA, MICB, and UL16-binding protein 2 were shown to be regulated by RBPs and microRNAs, usually resulting in their downregulation. In this study we investigated whether MICB expression is controlled by RBPs through its 5'UTR. We used an RNA pull-down assay followed by mass spectrometry and identified vigilin, a ubiquitously expressed multifunctional RNA-binding protein. We demonstrated that vigilin binds and negatively regulates MICB expression through its 5'UTR. Additionally, vigilin downregulation in target cells led to a significant increase in NK cell activation against said target cells. Taken together, we have discovered a novel mode of MICB regulation.
http://ift.tt/2oGpSVf
Characterization of the B Cell Receptor Repertoire in the Intestinal Mucosa and of Tumor-Infiltrating Lymphocytes in Colorectal Adenoma and Carcinoma [MUCOSAL IMMUNOLOGY]
The B cells inhabited in mucosa play a vital role in mediating homeostasis with autoantigens and external Ags. Tumor-infiltrating lymphocytes are potential prognostic markers and therapeutic agents for cancer. However, the spatial heterogeneity of the B cell repertoire in intestinal mucosa and the tumor-infiltrating lymphocytes in colorectal cancer (CRC) remain poorly understood. In this study, we developed an unbiased method to amplify the IgH repertoire, as well as a bioinformatic pipeline to process these high-throughput sequencing data. With biopsies from seven intestinal mucosal segments, we uncovered their strong spatial homogeneity among the large intestine, where the clone overlap rate was up to 62.21%. The heterogeneity between terminal ileum and large intestine was also observed, including discrepant isotype distribution and low clone overlap rate. With tumor and adjacent normal mucosal tissues from CRC and colorectal advanced adenoma (AD) patients, we observed a similar IgH profile between tumor and adjacent normal mucosal tissues in AD, as well as a slight difference in CRC. Interestingly, we found distinct repertoire properties in the CRC tumor from AD and normal mucosa. Finally, we identified 1445 public clones for the normal mucosa, and 22 public clones for the CRC tumor with characteristic features. These data may be of potential use in clinical prognosis, diagnosis, and treatment of CRC.
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Inducible TAP1 Negatively Regulates the Antiviral Innate Immune Response by Targeting the TAK1 Complex [INNATE IMMUNITY AND INFLAMMATION]
The innate immune response is critical for host defense and must be tightly controlled, but the molecular mechanisms responsible for its negative regulation are not yet completely understood. In this study, we report that transporter 1, ATP-binding cassette, subfamily B (TAP1), a virus-inducible endoplasmic reticulum–associated protein, negatively regulated the virus-triggered immune response. In this study, we observed upregulated expression of TAP1 following virus infection in human lung epithelial cells (A549), THP-1 monocytes, HeLa cells, and Vero cells. The overexpression of TAP1 enhanced virus replication by inhibiting the virus-triggered activation of NF-B signaling and the production of IFNs, IFN-stimulated genes, and proinflammatory cytokines. TAP1 depletion had the opposite effect. In response to virus infection, TAP1 interacted with the TGF-β–activated kinase (TAK)1 complex and impaired the phosphorylation of TAK1, subsequently suppressing the phosphorylation of the IB kinase complex and NF-B inhibitor α (IBα) as well as NF-B nuclear translocation. Our findings collectively suggest that TAP1 plays a novel role in the negative regulation of virus-triggered NF-B signaling and the innate immune response by targeting the TAK1 complex.
http://ift.tt/2onBKrF
Hydrogen Peroxide Triggers a Dual Signaling Axis To Selectively Suppress Activated Human T Lymphocyte Migration [INNATE IMMUNITY AND INFLAMMATION]
H2O2 is an early danger cue required for innate immune cell recruitment to wounds. To date, little is known about whether H2O2 is required for the migration of human adaptive immune cells to sites of inflammation. However, oxidative stress is known to impair T cell activity, induce actin stiffness, and inhibit cell polarization. In this study, we show that low oxidative concentrations of H2O2 also impede chemokinesis and chemotaxis of previously activated human T cells to CXCL11, but not CXCL10 or CXCL12. We show that this deficiency in migration is due to a reduction in inflammatory chemokine receptor CXCR3 surface expression and cellular activation of lipid phosphatase SHIP-1. We demonstrate that H2O2 acts through an Src kinase to activate a negative regulator of PI3K signaling, SHIP-1 via phosphorylation, providing a molecular mechanism for H2O2-induced chemotaxis deficiency. We hypothesize that although H2O2 serves as an early recruitment trigger for innate immune cells, it appears to operate as an inhibitor of T lymphocyte immune adaptive responses that are not required until later in the repair process.
http://ift.tt/2oGuN8G
Identification of C3b-Binding Small-Molecule Complement Inhibitors Using Cheminformatics [MOLECULAR AND STRUCTURAL IMMUNOLOGY]
The complement system is an elegantly regulated biochemical cascade formed by the collective molecular recognition properties and proteolytic activities of more than two dozen membrane-bound or serum proteins. Complement plays diverse roles in human physiology, such as acting as a sentry against invading microorganisms, priming of the adaptive immune response, and removal of immune complexes. However, dysregulation of complement can serve as a trigger for a wide range of human diseases, which include autoimmune, inflammatory, and degenerative conditions. Despite several potential advantages of modulating complement with small-molecule inhibitors, small-molecule drugs are highly underrepresented in the current complement-directed therapeutics pipeline. In this study, we have employed a cheminformatics drug discovery approach based on the extensive structural and functional knowledge available for the central proteolytic fragment of the cascade, C3b. Using parallel in silico screening methodologies, we identified 45 small molecules that putatively bind C3b near ligand-guided functional hot spots. Surface plasmon resonance experiments resulted in the validation of seven dose-dependent C3b-binding compounds. Competition-based biochemical assays demonstrated the ability of several C3b-binding compounds to interfere with binding of the original C3b ligand that guided their discovery. In vitro assays of complement function identified a single complement inhibitory compound, termed cmp-5, and mechanistic studies of the cmp-5 inhibitory mode revealed it acts at the level of C5 activation. This study has led to the identification of a promising new class of C3b-binding small-molecule complement inhibitors and, to our knowledge, provides the first demonstration of cheminformatics-based, complement-directed drug discovery.
http://ift.tt/2onwtRc
IL-26 Confers Proinflammatory Properties to Extracellular DNA [INNATE IMMUNITY AND INFLAMMATION]
In physiological conditions, self-DNA released by dying cells is not detected by intracellular DNA sensors. In chronic inflammatory disorders, unabated inflammation has been associated with a break in innate immune tolerance to self-DNA. However, extracellular DNA has to complex with DNA-binding molecules to gain access to intracellular DNA sensors. IL-26 is a member of the IL-10 cytokine family, overexpressed in numerous chronic inflammatory diseases, in which biological activity remains unclear. We demonstrate in this study that IL-26 binds to genomic DNA, mitochondrial DNA, and neutrophil extracellular traps, and shuttles them in the cytosol of human myeloid cells. As a consequence, IL-26 allows extracellular DNA to trigger proinflammatory cytokine secretion by monocytes, in a STING- and inflammasome-dependent manner. Supporting these biological properties, IL-10–based modeling predicts two DNA-binding domains, two amphipathic helices, and an in-plane membrane anchor in IL-26, which are structural features of cationic amphipathic cell-penetrating peptides. In line with these properties, patients with active autoantibody-associated vasculitis, a chronic relapsing autoimmune inflammatory disease associated with extensive cell death, exhibit high levels of both circulating IL-26 and IL-26–DNA complexes. Moreover, in patients with crescentic glomerulonephritis, IL-26 is expressed by renal arterial smooth muscle cells and deposits in necrotizing lesions. Accordingly, human primary smooth cells secrete IL-26 in response to proinflammatory cytokines. In conclusion, IL-26 is a unique cationic protein more similar to a soluble pattern recognition receptor than to conventional cytokines. IL-26 expressed in inflammatory lesions confers proinflammatory properties to DNA released by dying cells, setting up a positive amplification loop between extensive cell death and unabated inflammation.
http://ift.tt/2onmew2
Limited Presence of IL-22 Binding Protein, a Natural IL-22 Inhibitor, Strengthens Psoriatic Skin Inflammation [INNATE IMMUNITY AND INFLAMMATION]
Psoriasis is a chronic inflammatory disease resulting from dysregulated immune activation associated with a large local secretion of cytokines. Among them, IL-22 largely contributes to epithelial remodeling and inflammation through inhibiting the terminal differentiation of keratinocytes and inducing antimicrobial peptides and selected chemokines. The activity of IL-22 is regulated by IL-22 binding protein (IL-22BP); however, the expression and role of IL-22BP in psoriatic skin has remained unknown so far. Here we showed that nonaffected skin of psoriasis patients displayed lower expression of IL-22BP than skin of healthy controls. Furthermore, the strong IL-22 increase in lesional psoriatic skin was accompanied by a moderate induction of IL-22BP. To investigate the role of IL-22BP in controlling IL-22 during skin inflammation, we used imiquimod-induced skin disease in rodents and showed that rats with genetic IL-22BP deficiency (Il22ra2–/–) displayed exacerbated disease that associated with enhanced expression of IL-22–inducible antimicrobial peptides. We further recapitulated these findings in mice injected with an anti–IL-22BP neutralizing Ab. Hypothesizing that the IL-22/IL-22BP expression ratio reflects the level of bioactive IL-22 in psoriasis skin, we found positive correlations with the expression of IL-22–inducible molecules (IL-20, IL-24, IL-36, CXCL1, and BD2) in keratinocytes. Finally, we observed that serum IL-22/IL-22BP protein ratio strongly correlated with psoriasis severity. In conclusion, we propose that although IL-22BP can control deleterious actions of IL-22 in the skin, its limited production prevents a sufficient neutralization of IL-22 and contributes to the development and maintenance of epidermal alterations in psoriasis.
http://ift.tt/2oGonX0