Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Τρίτη 26 Δεκεμβρίου 2017
Effect of glucocorticoid treatment on BAFF and APRIL expression in patients with immune thrombocytopenia (ITP)
Publication date: Available online 26 December 2017
Source:Clinical Immunology
Author(s): Julian Kamhieh-Milz, Nuha Ghosoun, Viktor Sterzer, Abdulgabar Salama
Immune thrombocytopenic purpura (ITP) is an idiopathic bleeding disorder. B cell activating factor (BAFF) and 'A proliferation-inducing ligand' (APRIL) have regulatory effects on B and T cells and may represent relevant factors in the pathogenesis of ITP. Serum levels and gene expression were investigated in ITP patients. Both BAFF and APRIL serum levels were significantly elevated in active ITP. However, gene expression analysis revealed both factors to have a tendency toward downregulation. Glucocorticoid treatment significantly reduced BAFF but not APRIL serum levels, which may be mediated by differences in transcription factor binding sites. The glucocorticoid receptor binding site is present in the BAFF promotor region, but not in the APRIL promotor region. Prednisolone in combination with vitamin D3 may be effective in reducing APRIL serum levels. In conclusion, glucocorticoid treatment exerts different regulatory effects on both BAFF and APRIL, whereas antioxidant supplementation may also be beneficial in reducing serum levels.
http://ift.tt/2pFXjtB
Hypopharyngeal Evaluation in Obstructive Sleep Apnea with Awake Flexible Laryngoscopy: Validation and Updates to Cormack-Lehane and Modified Cormack-Lehane Scoring Systems
Abstract
Objective
To validate the use of Cormack-Lehane and Modified Cormack-Lehane scoring systems to classify patterns of hypopharyngeal airway visualization seen during awake flexible laryngoscopy among patients with obstructive sleep apnea.
Study Design
Validation study using samples collected from a prospective database.
Setting
University Medical Center.
Participants
Data was obtained from a retrospective review of a prospective database of flexible fiberoptic examination recordings in 274 consecutive OSA subjects (Stanford Sleep Medicine/Surgery Clinic).
Main Outcome Measures
Single still images from awake fiberoptic laryngoscopy examinations of the vocal cords from 90 different patients were presented to 2 experts and 4 novice raters. Raters used two grading systems (Cormack-Lehane scale and Modified Cormack-Lehane) to rate vocal cord visualization. Percent agreement and Cohen's kappa statistical analysis were used to evaluate inter-rater reliability and intra-rater reliability for each grading system. Feedback from the participants was then used to propose updates to further improve upon the existing grading scales for their applicability to awake flexible endoscopy.
Results
The Cormack-Lehane and Modified Cormack-Lehane scale both communicate un-obstructed and restricted views of the vocal cords reliably. Compared to the 4-grade scale, however, a modified 5-grade Vocal Cord Grading System allows for better objective communication of common variations in hypopharyngeal airway visualization.
Conclusion
We propose a 5-Grade Vocal Cord Grading System that builds upon existing grading systems to allow for efficient and reliable communication of hypopharyngeal airway examination during awake fiberoptic laryngoscopy.
This article is protected by copyright. All rights reserved.
http://ift.tt/2DXz5xS
Itching for answers: Prevalence and severity of pruritus in psoriasis
Abstract
Background/Objectives
Pruritus is the most frequently reported complaint or symptom for psoriasis patients. Despite the morbidity associated with pruritus in psoriasis few studies have evaluated the prevalence of itch in psoriasis with the current use of biological agents.
Method
This was a multi-site cross-sectional observational study conducted in New South Wales, Australia. Psoriasis patients were approached during their outpatient clinic, phototherapy or private consultations. Data on psoriasis characteristics, severity and treatment were collected. The patients were then asked to complete a survey regarding the frequency, severity and aggravators of their psoriasis.
Results
Data were collected from 179 patients with a mean age of 52.3 years, of whom 55% were male. Altogether 63 (35%) had a psoriasis area severity index (PASI) > 10, 42 (24%) were on biological agents and 84 (47%) were receiving phototherapy. The number of patients who reported itch all the time was 40 (22%), most of the time 48 (27%), and never 19 (11%). Patients with nail psoriasis were significantly less likely to have itch all or most of the time (P = 0.01). Itch all or most of the time was significantly more likely in patients with PASI > 10 (P = 0.013). No treatment was associated with reduced itch. Itch was reported to be most frequent in the winter season.
Conclusion
Few patients with psoriasis do not suffer from pruritus. Despite their promise, biological agents are not associated with reduced itch.
http://ift.tt/2pD0UIJ
Mycosis fungoides occurring at the site of previous herpes zoster eruption
Abstract
Numerous clinicopathological variants of mycosis fungoides have been described in the literature. Dermatomal or zosteriform mycosis fungoides is one reported variant but a clear aetiology has never been documented. We report a case of mycosis fungoides proved by biopsy and immunohistochemistry that developed in a 55-year-old man at the site of previous herpes zoster eruption. We also present a review of the relevant literature to add to the understanding of rare variants of mycosis fungoides and aid in the clinical recognition of zosteriform mycosis fungoides.
http://ift.tt/2DUFjib
Hemitransdomal versus Dome-Binding Suture
Facial plast Surg
DOI: 10.1055/s-0036-1598014
The dome-binding suture (DBS) and hemitransdomal suture (HTS) are suture techniques used to narrow and define the nasal tip. The DBS can create a pinched, unnatural appearance, while the HTS puts the lateral crus in a more favorable orientation. This allows a natural contour between the nasal tip and alar lobule while maintaining alar margin support. Objective measurement of the rotational axis of the lateral crus between the DBS and the HTS has not been reported in the literature. To determine whether the DBS or HTS technique results in a more favorable rotational axis of the lateral crus as measured by the alar surface septal angle (ASSA). Open rhinoplasty with cephalic trim and placement of a DBS or HTS was performed in 6 cadaveric heads, for a total of 12 lower lateral cartilages at the VirtuOHSU Simulation and Surgical Training Center at Oregon Health and Science University (OHSU). ASSA measurements were taken at baseline and after placement of either a DBS or HTS. A total of 36 ASSA measurements were obtained. The median baseline ASSA prior to suture placement was 142 degrees (interquartile range [IQR]: 131.5–145 degrees), following DBS placement was 141 degrees (IQR: 33–150.5 degrees), and following HTS placement was 112 degrees (IQR: 108–117 degrees). There was no statistically significant difference of ASSA measurements between baseline and DBS placement (p = 0.24), but there was a statistically significant difference between baseline and HTS (p < 0.0001) and between DBS and HTS (p < 0.0001). The HTS technique creates a more favorable rotational axis of the lateral crus as compared with the DBS, as measured by the ASSA. This study provides objective data to support the use of the HTS for nasal tip contouring.
[...]
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Article in Thieme eJournals:
Table of contents | Abstract | Full text
http://ift.tt/2DhaqTR
Frontal Fibrosing Alopecia: A Retrospective Analysis of 72 Patients from a German Academic Center
Facial plast Surg
DOI: 10.1055/s-0037-1615281
Frontal fibrosing alopecia (FFA) describes the scarring, band-like recession of the frontotemporal hairline. Treatment is difficult, and currently, no evidence-based therapy exists. The purpose of this study is to report clinical features and treatment responses in a large cohort of patients with FFA. The authors analyzed a series of 72 patients with a clinical or histologic diagnosis of FFA. A total of 70 patients were female (97.2%), and 2 were male (2.8%). In females, the first onset of FFA was postmenopausal in 81.4% (n = 57). Documented eyebrow loss was present in 61.1% (n = 44), whereas involvement of eyelashes and body hair was reported in only 4.2% (n = 3) and 5.6% (n = 4), respectively. Clinical symptoms were itching (40.3%, n = 29) and trichodynia (4.2%, n = 3) in the alopecic area. Virtually all patients were treated with topical high-potency steroids. Additional treatments were topical tacrolimus, systemic retinoids, and hydroxychloroquine. A total of 48 patients (66.7%) received a combination of high-potency steroids with topical pimecrolimus. In this subgroup, subjective improvement or disease stabilization was reported by 64.6% (n = 31), and the hairline was stabilized on average after 9 to 12 months of therapy. The combination therapy of topical high-potency steroids with pimecrolimus may be an effective and steroid-saving treatment for FFA.
[...]
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Article in Thieme eJournals:
Table of contents | Abstract | Full text
http://ift.tt/2C9qoAc
Otoplasty Online Information: A Comprehensive Analysis of the Websites and Videos that Patients View Regarding Cosmetic Ear Surgery
Facial plast Surg
DOI: 10.1055/s-0037-1615280
Physicians should be aware of both websites and videos available online regarding the otoplasty procedure to provide quality care. This study systematically analyzes the authorships, reliability, quality, and readability of the websites, as well as the authorships and primary objectives of the videos regarding otoplasty. Validated instruments were used to analyze the reliability, quality, and readability of websites, and videos were systematically categorized and analyzed. A Google search was conducted, and the first five pages of results were included in this study. After excluding unrelated websites, the remaining 44 websites were categorized by authorship (physician, patient, academic, or unaffiliated) and were analyzed using the validated DISCERN instrument for reliability and quality, as well as various other validated instruments to measure readability. A YouTube search was also conducted, and the first 50 relevant videos were included in the study. These videos were categorized by authorship and their primary objective. Website authorships were physician-dominated. Reliability, quality, and overall DISCERN score differ between the four authorship groups by a statistically significant margin (Kruskall–Wallis test, p < 0.05). Unaffiliated websites were the most reliable, and physician websites were the least reliable. Academic websites were of the highest quality, and patient websites were of the lowest quality. Readability did not differ significantly between the groups, though the readability measurements made showed a general lack of material easily readable by the general public. YouTube was likewise dominated by physician-authored videos. While the physician-authored videos sought mainly to inform and to advertise, patient-authored videos sought mainly to provide the patient's perspective. Academic organizations showed very little representation on YouTube, and the YouTube views on otoplasty videos were dominated by the top 20 videos, which represented over 93% of the total views of videos included in this study.
[...]
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Article in Thieme eJournals:
Table of contents | Abstract | Full text
http://ift.tt/2DhXOvN
Diagnosis and management of peristomal pyoderma gangrenosum: A systematic review
Peristomal pyoderma gangrenosum (PPG) is an uncommon subtype of pyoderma gangrenosum. PPG is a challenging condition to diagnose and treat; no evidence-based guidelines exist.
http://ift.tt/2BVtKd4
Comorbidity scores associated with limited life expectancy in the very elderly with nonmelanoma skin cancer
There is controversy regarding nonmelanoma skin cancer (NMSC) treatment in the very elderly, with some suggesting that this population may not live long enough to benefit from invasive treatments. Tools to assess limited life expectancy (LLE) exist, but performance in the very elderly NMSC population has not been well-defined.
http://ift.tt/2zxOSQB
A Split-Face, Single-Blinded, Randomized Controlled Comparison of Alexandrite 755 nm Picosecond Laser vs. Alexandrite 755 nm Nanosecond Laser in the Treatment of Acquired Bilateral Nevus of Ota-like Macules (ABNOM)
Q-switched alexandrite lasers (QSAL) have been used for the treatment of acquired bilateral nevus of Ota-like macules (ABNOM). Currently, picosecond alexandrite laser (PSAL) pulses have become available for pigmentary disorders. However, no studies have compared PSAL and QSAL in the treatment of ABNOM.
http://ift.tt/2BSZgZk
Immune Mechanisms of Oral Immunotherapy
Source:Journal of Allergy and Clinical Immunology
Author(s): Michael D. Kulis, Sarita U. Patil, Erik Wambre, Brian P. Vickery
Oral immunotherapy (OIT) has reproducibly demonstrated successful desensitization in food-allergic subjects completing clinical trials and, in some studies, sustained unresponsiveness. These clinical outcomes have been associated with characteristic modifications in the allergen-specific immune response, but a detailed synthesis of OIT's mechanisms of action is lacking. In this Rostrum, we review the current evidence regarding the human immune response to OIT, explore possible mechanisms, and identify knowledge gaps for future research.
http://ift.tt/2DRedbD
Resource limitation prevents the emergence of drug resistance by intensifying within-host competition [Evolution]
Slowing the evolution of antimicrobial resistance is essential if we are to continue to successfully treat infectious diseases. Whether a drug-resistant mutant grows to high densities, and so sickens the patient and spreads to new hosts, is determined by the competitive interactions it has with drug-susceptible pathogens within the host....
http://ift.tt/2l19i06
Architecture of the human PI4KIII{alpha} lipid kinase complex [Cell Biology]
Plasma membrane (PM) phosphoinositides play essential roles in cell physiology, serving as both markers of membrane identity and signaling molecules central to the cell's interaction with its environment. The first step in PM phosphoinositide synthesis is the conversion of phosphatidylinositol (PI) to PI4P, the precursor of PI(4,5)P2 and PI(3,4,5)P3. This...
http://ift.tt/2l1Dw3c
In This Issue [This Week in PNAS]
Water management system in ancient China Map of the Liangzhu city and hydraulic system, lower Yangtze River, China. The ancient Liangzhu culture of China represents a peak of early social and cultural development that preceded the Chinese dynasties of the historical record. The Liangzhu were an agrarian society and strongly...
http://ift.tt/2zziLQB
Correction for Possner and Caldeira, Geophysical potential for wind energy over the open oceans [Correction]
ENVIRONMENTAL SCIENCES, SUSTAINABILITY SCIENCE Correction for "Geophysical potential for wind energy over the open oceans," by Anna Possner and Ken Caldeira, which was first published October 9, 2017; 10.1073/pnas.1705710114 (Proc Natl Acad Sci USA 114:11338–11343). The authors note that Fig. 6 appeared incorrectly. The corrected figure and its legend appear...
http://ift.tt/2C7Q7eW
Intercellular competition and levels of development: The plasticity of inevitability [Biological Sciences]
Nelson and Masel (1) present a general mathematical model that describes effects of somatic cell changes on aging bounded by juxtaposed loss of cellular vigor and uncontrolled cell growth. The formulation reflects observations on a wide range of multicellular organisms, from Caenorhabditis elegans to Homo sapiens, incorporating the Picard–Lindelöf and...
http://ift.tt/2BTbPnz
Machine learning shows association between genetic variability in PPARG and cerebral connectivity in preterm infants [Developmental Biology]
Preterm infants show abnormal structural and functional brain development, and have a high risk of long-term neurocognitive problems. The molecular and cellular mechanisms involved are poorly understood, but novel methods now make it possible to address them by examining the relationship between common genetic variability and brain endophenotype. We addressed...
http://ift.tt/2BHInNb
NO and COX2: Dual targeting for aggressive cancers [Pharmacology]
A number of tumor-specific characteristics are known to associate with a cancer's growth, metastatic potential, and response to therapy. Among these are mutational load and gene-expression patterns in the tumor cells and the interaction of the tumor cells with the many cellular and noncellular components that comprise the microenvironment of...
http://ift.tt/2zycpRF
De novo reconstitution reveals the proteins required for skeletal muscle voltage-induced Ca2+ release [Physiology]
Skeletal muscle contraction is triggered by Ca2+ release from the sarcoplasmic reticulum (SR) in response to plasma membrane (PM) excitation. In vertebrates, this depends on activation of the RyR1 Ca2+ pore in the SR, under control of conformational changes of CaV1.1, located ∼12 nm away in the PM. Over the...
http://ift.tt/2Cbo8eo
Photochemistry of highly excited states [Chemistry]
These days on earth we are photochemically reasonably well shielded. The far UV radiation is filtered by the ozone and other components of the atmosphere. In the ionosphere and beyond there is much challenging chemistry induced by such higher-energy photons. The shielding by the atmosphere also makes demands on such...
http://ift.tt/2BTbMYV
Predicting glycosaminoglycan surface protein interactions and implications for studying axonal growth [Biophysics and Computational Biology]
Cell-surface carbohydrates play important roles in numerous biological processes through their interactions with various protein-binding partners. These interactions are made possible by the vast structural diversity of carbohydrates and the diverse array of carbohydrate presentations on the cell surface. Among the most complex and important carbohydrates are glycosaminoglycans (GAGs), which...
http://ift.tt/2BU50SN
Dopamine prediction error responses update demand [Neuroscience]
According to the law of demand, the quantity demanded for a reward is dependent upon the price; as the price of the reward increases, the quantity demanded decreases (1). Conversely, when the price decreases, the quantity demanded increases. This relationship can be observed at any local bar during "happy hour,"...
http://ift.tt/2zxZKOn
Ultrafast rotation in an amphidynamic crystalline metal organic framework [Chemistry]
Amphidynamic crystals are an emergent class of condensed phase matter designed with a combination of lattice-forming elements linked to components that display engineered dynamics in the solid state. Here, we address the design of a crystalline array of molecular rotors with inertial diffusional rotation at the nanoscale, characterized by the...
http://ift.tt/2BFb8Kc
The hydraulic lift of early states societies [Anthropology]
The trajectory of social complexity is hardly a linear progression, with twists and turns precipitated by unintended consequences, consequences that can be advantageous or deleterious to a society and the biophysical environment that society inhabits. The article by Liu et al. (1) provides clear evidence for a complex set of...
http://ift.tt/2BTbJMJ
Single-cell analysis resolves the cell state transition and signaling dynamics associated with melanoma drug-induced resistance [Engineering]
Continuous BRAF inhibition of BRAF mutant melanomas triggers a series of cell state changes that lead to therapy resistance and escape from immune control before establishing acquired resistance genetically. We used genome-wide transcriptomics and single-cell phenotyping to explore the response kinetics to BRAF inhibition for a panel of patient-derived BRAFV600-mutant...
http://ift.tt/2zyJCwi
How reduced excitonic coupling enhances light harvesting in the main photosynthetic antennae of diatoms [Biophysics and Computational Biology]
Strong excitonic interactions are a key design strategy in photosynthetic light harvesting, expanding the spectral cross-section for light absorption and creating considerably faster and more robust excitation energy transfer. These molecular excitons are a direct result of exceptionally densely packed pigments in photosynthetic proteins. The main light-harvesting complexes of diatoms,...
http://ift.tt/2zyg0iE
Early endosome as a pathogenic target for antiphosphatidylethanolamine antibodies [Medical Sciences]
Phosphatidylethanolamine (PE) is a major phospholipid species with important roles in membrane trafficking and reorganization. Accumulating clinical data indicate that the presence of circulating antibodies against PE is positively correlated with the symptoms of antiphospholipid syndromes (APS), including thrombosis and repeated pregnancy loss. However, PE is generally sequestered inside a...
http://ift.tt/2C6uGLh
Ultrafast 25-fs relaxation in highly excited states of methyl azide mediated by strong nonadiabatic coupling [Chemistry]
Highly excited electronic states are challenging to explore experimentally and theoretically—due to the large density of states and the fact that small structural changes lead to large changes in electronic character with associated strong nonadiabatic dynamics. They can play a key role in astrophysical and ionospheric chemistry, as well as...
http://ift.tt/2zyLDbQ
Default neglect in attempts at social influence [Psychological and Cognitive Sciences]
Current theories suggest that people understand how to exploit common biases to influence others. However, these predictions have received little empirical attention. We consider a widely studied bias with special policy relevance: the default effect, which is the tendency to choose whichever option is the status quo. We asked participants...
http://ift.tt/2BGJGvW
Designing flexible 2D transition metal carbides with strain-controllable lithium storage [Chemistry]
Efficient flexible energy storage systems have received tremendous attention due to their enormous potential applications in self-powering portable electronic devices, including roll-up displays, electronic paper, and "smart" garments outfitted with piezoelectric patches to harvest energy from body movement. Unfortunately, the further development of these technologies faces great challenges due to...
http://ift.tt/2BSNiil
Structure-based prediction of ligand-protein interactions on a genome-wide scale [Biophysics and Computational Biology]
We report a template-based method, LT-scanner, which scans the human proteome using protein structural alignment to identify proteins that are likely to bind ligands that are present in experimentally determined complexes. A scoring function that rapidly accounts for binding site similarities between the template and the proteins being scanned is...
http://ift.tt/2BU51WR
The sinonasal microbiota, neural signaling, and depression in chronic rhinosinusitis
Background
The complex relationships between the human microbiota, the immune system, and the brain play important roles in both health and disease, and have been of increasing interest in the study of chronic inflammatory mucosal conditions. We hypothesized that the sinonasal microbiota may act as a modifier of interkingdom neural signaling and, subsequently, mental health, in the upper respiratory inflammatory condition chronic rhinosinusitis (CRS). In this study we investigated associations between the sinonasal microbiota; local concentrations of the neurotransmitters serotonin, dopamine, and γ-aminobutyric acid (GABA); and depression severity in a cohort of 14 CRS patients and 12 healthy controls.
Methods
Subject demographics, clinical severity scores, depression index scores, and sinonasal swab and mucus samples were collected at the time of surgery. Bacterial communities were characterized from swabs by 16S rRNA gene-targeted sequencing and quantified by quantitative polymerase chain reaction. Mucus concentrations of the neurotransmitters serotonin, dopamine, and GABA were quantified by enzyme-linked immunosorbent assay.
Results
Several commonly "health-associated" sinonasal bacterial taxa were positively associated with higher neurotransmitter concentrations and negatively associated with depression severity. In contrast, several taxa commonly associated with an imbalanced sinonasal microbiota negatively associated with neurotransmitters and positively with depression severity. Few significant differences were identified when comparing between control and CRS subject groups, including neurotransmitter concentrations, depression scores, or sinonasal microbiota composition or abundance.
Conclusion
The findings obtained lend support to the potential for downstream effects of the sinonasal microbiota on neural signaling and, subsequently, brain function and behavior.
http://ift.tt/2C8Qvau
Osteologic analysis of ethnic differences in supernumerary ethmoidal foramina: implications for endoscopic sinus and orbit surgery
Background
Knowledge of the position of the ethmoidal arteries is critical to enable safe endoscopic sinus and orbital surgery. The presence of a third or "middle" ethmoid variant has recently become more relevant as endoscopic intraconal surgery continues to advance. The purpose of this study was to quantify the presence of supernumerary (ie, over 2) ethmoid foramina in different ethnicities and genders.
Methods
Morphometric osteologic measurements were performed in 273 orbits. Prevalence of supernumerary ethmoid foramina and orbital length data were obtained from human skulls of Asian (n = 54), Caucasian (n = 70), African (n = 39), Hispanic (n = 49), and Middle Eastern (n = 61) derivation. Correlations between gender, ethnicity, symmetry, orbital floor, and lamina papyracea length were assessed by analysis of variance, paired t test, and χ2 test.
Results
Supernumerary foramina were identified in 95 of 273 orbits (34.79%). A significantly higher prevalence was seen in Asian (42.59%), African (41.02%), and Hispanic (41.00%) skulls as compared with Caucasian (25.71%) and Middle Eastern (22.95%) skulls (p < 0.05 for all). The length of the orbital floor was significantly shorter in the Asian (3.35 ± 1.52 cm) specimens (p < 0.01). Asians were found to have the highest risk of ethmoid artery injury compared with the other ethnic groups (ratio of number of supernumerary foramina to orbital floor length = 0.72).
Conclusion
Supernumerary ethmoidal foramina were common among all orbits studied. Orbits of Asian and African derivation had significantly greater numbers of ethmoidal foramina, both unilaterally and symmetrically and within a shorter orbital length, suggesting a greater proximity between the ethmoidal vessels. Surgeons should be alert to the possible presence of middle ethmoidal vessels during endoscopic sinus and orbital approaches.
http://ift.tt/2lcfPEm
Isolated unilateral adrenal gland hemorrhage following motor vehicle collision: a case report and review of the literature
Adrenal gland trauma is a rare condition that typically stems from blunt force trauma, and is associated with multiple organ injuries. Alternatively, isolated adrenal gland trauma is extremely rare, accounting...
http://ift.tt/2DguEgu
A novel lateral flow immunoassay for the rapid detection of anti-Dsg3 IgG serum autoantibodies in pemphigus vulgaris
Abstract
Pemphigus vulgaris (PV) is a severe autoimmune blistering disease of the skin and mucous membranes. As autoantibodies play an essential role in the disease pathogenesis, the serological detection of anti-desmoglein 3 IgG represents a central tool in the diagnosis of the disease. In this study, we show the validation of a novel lateral flow immunoassay (LFIA) which rapidly detects anti-desmoglein 3 (Dsg3) IgG in human serum. In contrast to other diagnostic procedures, the assay is compact and simple to perform and delivers a fast "yes" or "no" answer within 10 min without additional hardware requirements for test evaluation. For validation a blinded collection of 200 sera including 100 sera from 14 PV patients, 75 sera from 24 bullous pemphigoid patients, and 25 sera from 6 patients with pemphigus foliaceus collected at different time points during disease was used. Presence or non-presence of anti-Dsg3 IgG within sera was confirmed using a commercially available Dsg3-ELISA. For qualitative evaluation Dsg3-LFIA test results were assessed by two independent groups of human observers. Furthermore quantitative evaluation using POCScan reader was applied. The Dsg3-LFIA demonstrated reliable test results with a sensitivity and specificity of 78.1% and 97.1%, respectively. Test results from POCScan and human observers showed a substantial agreement. The Dsg3-LFIA represents a new diagnostic tool for the immediate and reliable detection of anti-desmoglein 3 serum IgG autoantibodies that does not require additional hardware. Further prospective trials are warranted to validate the Dsg3 LFIA in pemphigus.
This article is protected by copyright. All rights reserved.
http://ift.tt/2zyNnBL
Chemoradiation vs Immunotherapy and Radiation for Head and Neck Cancer
Condition: Head and Neck Squamous Cell Carcinoma
Interventions: Drug: Pembrolizumab; Radiation: Radiation therapy; Drug: Cisplatin
Sponsors: Loren Mell, MD; Merck Sharp & Dohme Corp.
Not yet recruiting
http://ift.tt/2CaA53C
Interventions: Drug: Pembrolizumab; Radiation: Radiation therapy; Drug: Cisplatin
Sponsors: Loren Mell, MD; Merck Sharp & Dohme Corp.
Not yet recruiting
http://ift.tt/2CaA53C
An insertion mutation in HOXC13 underlies pure hair and nail ectodermal dysplasia with lacrimal duct obstruction
Abstract
Pure hair and nail ectodermal dysplasia (PHNED; MIM 602032, 614929, and 614931) is an autosomal recessive ED that is characterized by hypotrichosis and nail dystrophy only, without further ectodermal or non-ectodermal alterations. To date, homozygous mutations in three genes have been reported to cause PHNED: KRT85 (MIM 602767), encoding keratin, type II cuticular Hb5 like; KRT74 (MIM 608248), encoding keratin, type II cytoskeletal 74; and HOXC13 (MIM 142976), encoding Homeobox C13. Here, we studied the genetic basis of PHNED in an Iranian kindred, displaying double consanguinity (Fig. 1a-g).
http://ift.tt/2Dhs3mr
Response to: ‘Human orf complicated by epidermolysis acquisita’
Abstract
Dear editor, we read with great interest the article 'Human orf complicated by epidermolysis bullosa acquisita' by Zeulgaray and colleagues.1 Recently, a Moroccan patient who contracted orf (fig. 1a) after slaughtering a sheep during Eid Al-Adha was admitted to our hospital and developed a similar pruritic vesiculobullous eruption predominantly on the hands and forearms (fig. 1b). Hematoxylin and eosin staining of punch biopsies from areas of the vesicullobullous eruption showed spongiotic dermatitis with eosinophilia, most consistent with an id reaction.
This article is protected by copyright. All rights reserved.
http://ift.tt/2C6OmvO
Aberrant DNA methylation is associated with aggressive clinicopathological features and poor survival in cutaneous melanoma
Abstract
Background
Promoter methylation of tumor suppressor genes (TSGs) has recently been implicated in the pathogenesis of several types of cancer. Regarding melanoma, over a hundred genes that contribute to its pathogenesis have been identified to be aberrantly hypermethylated. This is a retrospective observational study that aims to analyze the prevalence of CpG island methylation in a series of primary melanoma, to identify the associations with the main clinicopathological features, and to explore the prognostic significance of methylation in melanoma survival.
Materials and Methods
DNA methylation was analyzed using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) in a series of 170 melanoma formalin-fixed paraffin embedded (FFPE) tumor samples. The relationship between the methylation status, known somatic mutations and clinicopathological features was evaluated. Disease-free survival (DFS) and overall survival (OS) were displayed by the Kaplan-Meier method.
Results
In the entire cohort, one or more genes were detected to be methylated in 55% of the patients. The most prevalent methylated genes were RARB 31%, PTEN 24%, APC 16%, CDH13 16%, ESR1 14%, CDKN2A 6%, and RASSF1 5%. An association between aberrant methylation and aggressive clinicopathological features was observed (older age, increased Breslow, presence of mitosis and ulceration, fast-growing melanomas, advancing stage, and TERT mutations). Furthermore, Kaplan-Meier survival analysis showed a correlation of methylation and poorer DFS and overall survival OS.
Conclusions
Aberrant methylation of TSGs is a frequent event in melanoma. It is associated to aggressive clinicopathological features and poorer survival. Epigenetic alterations may represent a significant prognostic marker with utility in routine practice.
This article is protected by copyright. All rights reserved.
http://ift.tt/2DewChx
A possible association between BP230-type bullous pemphigoid and dementia: report of two elderly cases
Bullous pemphigoid (BP) is the most common autoimmune blistering disease, and it features itchy oedematous erythemas and tense bullae on the whole body most commonly in the elderly. BP180 is the most common autoantigens of BP, and BP230 is the only target of autoantibodies in approximately 8% of patients with BP1. It has been reported that elderly patients with BP sometimes have comorbidities associated with neurological disease (ND) including dementia2. BP antigens and their isoforms can be identified in skin as well as in neuronal tissues, suggesting that exposure of the neuronal antigen may lead to an immune reaction against the epithelial isoform3. Here, we describe two elderly cases of BP with dementia in which the autoantibodies reacted to BP230 but not to BP180 (BP230-BP).
This article is protected by copyright. All rights reserved.
http://ift.tt/2C6OgEs
Point mutation in p14ARF-specific exon 1β of CDKN2A causing familial melanoma and astrocytoma
Abstract
Rarely, melanoma is dominantly inherited, with CDKN2A mutations accounting for >85% of mutation-positive families (1). CDKN2A encodes two, non-homologous proteins, p16 and p14ARF, with individually unique first exons (1α and 1β, respectively) and alternative reading frames. Over 95% of the CDKN2A mutations in familial melanoma occur in the p16 transcript (1).
http://ift.tt/2Dewr5R
Postoperative mortality and morbidity following non-cardiac surgery in a healthy patient population
Abstract
Purpose
Perioperative mortality ranges from 0.4% to as high as nearly 12%. Currently, there are no large-scale studies looking specifically at the healthy surgical population alone. The primary objective of this study was to report 30-day mortality and morbidity in healthy patients and define any risk factors.
Methods
Using the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) dataset, all patients assigned an American Society of Anesthesiologists physical status (ASA PS) classification score of 1 or 2 were included. Further patients were excluded if they had a comorbidity or underwent a procedure not likely to classify them as ASA PS 1 or 2. Multivariable logistic regression was performed to identify predictors of the outcomes, in which odds ratios (OR) and 95% confidence intervals (95% CI) were reported.
Results
There were 687,552 healthy patients included in the final analysis. Following surgery, 0.7, 7.0, and 0.7 per 1000 persons experienced 30-day mortality, sepsis, and stroke or myocardial infarction, respectively. Healthy patients greater than 80 years of age had the highest odds for mortality (OR 17.7, 95% CI 12.4–25.1, p < 0.001). Case duration was associated with increased mortality, especially in cases greater than or equal to 6 h (OR 3.0, 95% CI 2.0–4.5, p < 0.001).
Conclusions
Thirty-day mortality and morbidity is, as expected, lower in the healthy surgical population. Age may be an indication to further risk stratify patients that are ASA PS 1 or 2 to better reflect perioperative risk.
http://ift.tt/2De9wYn
Re-irradiation with curative intent in patients with squamous cell carcinoma of the head and neck: a national survey of usual practice on behalf of the Italian Association of Radiation Oncology (AIRO)
Abstract
Objective
To report the results of a national survey investigating the pattern of practice of curative re-irradiation (ReRT) for recurrent squamous cell carcinoma of the head and neck.
Methods
In March 2016, a 22-item, 4-section questionnaire was sent to all Italian Radiation Oncology centers. Sections were focused on assessing the expertise level of each center and collecting specific information on reRT prescription modalities in the adjuvant and definitive settings.
Results
Overall, 77 centers completed the survey. The majority (50/77, 64.9%) of participating radiation oncologists were senior consultants (> 10 years of experience). Of the responding centers, 63 (81.8%) performed curative ReRT, while 14 (18.1%) did not, mainly (5/14, 35.7%) due to the avoidance of severe toxicity. The use of adjuvant ReRT was reported by less than half of the interviewed radiation oncologists (36/77, 46.7%). In case of unresectable local recurrence, definitive ReRT was claimed to be adopted in 55/77 (71.4%) for non-nasopharyngeal and 47/77 (61%) for nasopharyngeal cancer. The preferred treatment technique was Intensity Modulated Radiation Therapy (IMRT) followed by Stereotactic Body Radiation Therapy (SBRT). When IMRT was applied, the most common (19/55 responders, 34.5%) selection of treatment volume consisted of the Gross Tumor Volume (GTV) + 0.5 cm margin to account for microscopic disease.
Conclusion
Despite the absence of definitive evidence-based recommendations, a possible consideration for ReRT in case of unresectable recurrent head and neck cancer was reported by over 80% of radiation oncologists taking part in the national survey.
http://ift.tt/2BDdEkg
Legionella feeleii: an unusual organism associated with cutaneous infection in an immunocompromised patient
Summary
We report a 23-year-old immunocompromised woman who, following cardiac transplantation, presented with an unusual cutaneous eruption. She developed a widespread pustular rash, systemic symptoms and a high temperature with raised inflammatory markers. The diagnosis was reached when a skin biopsy was cultured onto Legionella agar (buffered charcoal yeast extract) and Legionella feeleii was isolated. The patient was treated with 6 weeks of moxifloxacin and her cutaneous lesions gradually resolved. Cutaneous Legionella infections are uncommon and usually affect immunocompromised patients.
http://ift.tt/2C89Mv6
Morphoea profunda and its relationship to eosinophilic fasciitis
Summary
In this small case series, all eight patients were women in their fifth and sixth decades. This is similar to the female predominance in morphoea and less in keeping with eosinophilic fasciitis (EF). All cases had diffuse induration of their limbs with both proximal and distal patterns of distribution, and five of the patients exhibited peau d'orange skin. All patients had diffuse induration of the lower limbs and half had restricted ankle movements. Six patients had concomitant superficial morphoea. This group of patients demonstrated a unique subtype of the morphoea spectrum with some features overlapping with EF. However, there appear to be points of distinction, and we propose that some previously reported cases labelled as EF would be better described as having morphoea profunda (MP). Methotrexate may be a useful treatment for MP, hence it is important to distinguish this from EF, as management may differ.
http://ift.tt/2BEbtwK
Recessive epidermolytic ichthyosis results from loss of keratin 10 expression, regardless of the mutation location
Summary
Epidermolytic ichthyosis (EI) is a rare skin disorder caused by mutations in the genes KRT1 and KRT10, and is usually inherited in an autosomal dominant fashion. Only five recessive mutations causing EI have been described, all of which are located in the central region of the KRT10 gene. In the current study, we aimed to identify the genetic defect underlying EI in a 12-year-old patient. Direct sequencing of the patient's genomic DNA revealed a novel homozygous nonsense mutation residing within the proximal part KRT10 first exon. The mutation was found to co-segregate with the disease phenotype in an autosomal recessive fashion. Using real-time quantitative PCR, we found an almost two-fold decrease in KRT10 expression in the patient's skin compared with the skin of healthy controls. Western blot analysis showed complete absence of keratin 10 protein in the patient's skin, suggesting early protein degradation.
http://ift.tt/2BDc9CE
A protective role for FADD dominant negative (FADD-DN) mutant in trinitrochlorobenzene (TNCB)-induced murine contact hypersensitivity reactions
Summary
Background
Fas-associated protein with death domain (FADD) is a classic adaptor protein in apoptosis. Increasing evidence has shown that FADD is also implicated in T-cell development, activation and proliferation. The role of FADD in inflammatory disorders remains largely unexplored.
Aim
To assess the role of FADD in inflammatory disorders.
Methods
We established an experimental model of contact hypersensitivity (CHS) by using 2,4,6-trinitrochlorobenzene (TNCB) on transgenic mice expressing a dominant negative mutant of FADD (FADD-DN),
Results
CHS responses were clearly attenuated in FADD-DN mice compared with control mice. In the retroauricular lymph nodes, the ratio of CD8+ T cells was also decreased.
Conclusion
FADD-DN appears to play a protective role in TNCB-induced CHS reactions.
http://ift.tt/2Ca1WRS
Εγγραφή σε:
Αναρτήσεις (Atom)