Health Cards by Google: dermatologist review of inclusivity and utility of the medical search application

Abstract

One in twenty Google web searches are related to medical conditions¹ indicating the prominent role of the internet as a resource for medical information. Indeed, 72% of internet users report searching online for medical conditions; 77% began with Google, Bing, or Yahoo.² While 53% additionally sought physician consultation, 46% did not.³ Responding to its place in the medical community, in 2015 Google partnered with academic, government, and business-based ventures to develop "health cards" for searched disorders, and, in summer 2016, debuted a "related conditions" generator, suggesting diagnoses related to input disorders or symptoms.

This article is protected by copyright. All rights reserved.

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An evaluation of high-stage cutaneous squamous cell carcinoma outcomes by gender

Abstract

Data from the World Health Organization indicate that global overall age-adjusted cancer incidence and mortality rates are 1.2- and 1.5-fold higher in men as compared to women, respectively.¹ Non-melanoma skin cancer (NMSC) is the most common cancer among white populations, yet the prognostic significance of gender remains unclear.² A possible relationship may exist given that in melanoma, women have a lower mortality risk as compared to men.^3,4

This article is protected by copyright. All rights reserved.

http://ift.tt/2gCbxna

Not every patient needs triglyceride check, but all can get pancreatitis: A systematic review and clinical characterization of Isotretinoin associated Pancreatitis

Abstract

Isotretinoin is a medication to treat primarily nodulocystic acne vulgaris. A serious complication is pancreatitis, either idiosyncratic, and not preventable or predictable; or due to elevated triglycerides. Triglyceride are elevated in practically all patients on isotretinoin, but may not be abnormal, or too minimally elevated to pose a pancreatitis risk.¹ Elevated triglycerides are not a cause of arteriosclerotic risk. but can be a marker.^2,3 Objective of this review was to clinically characterize patients with isotretinoin induced pancreatitis particularly due to hypertriglyceridemia to evaluate what monitoring is sensible.

This article is protected by copyright. All rights reserved.

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Reply to ‘A phase II randomized controlled trial of nicotinamide for skin cancer chemoprevention in renal transplant recipients’: reply from the authors

Abstract

We thank Yélamos et al. for their interest in our nicotinamide chemoprevention studies.¹ Some of their comments are pertinent, while others are based on a flawed interpretation of our data.

Zhao² previously commented on (nonsignificant) numerical differences in the frequency of adverse-event term groupings (mucocutaneous infections) between the placebo and nicotinamide groups in our ONTRAC chemoprevention study (Oral Nicotinamide To Reduce Actinic Cancer).³ As stated previously, chance remains a highly plausible explanation for the numerically higher mucocutaneous infections in the nicotinamide arm and also, for example, for the numerically lower respiratory infections observed in the nicotinamide arm.⁴

This article is protected by copyright. All rights reserved.

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Age assessment based on third molar mineralisation

Abstract

Purpose

The method published in 1973 by Demirjian et al. to assess age based on the mineralisation stage of permanent teeth is standard practice in forensic and orthodontic diagnostics. From age 14 onwards, however, this method is only applicable to third molars. No current epidemiological data on third molar mineralisation are available for Caucasian Central-Europeans. Thus, a method for assessing age in this population based on third molar mineralisation is presented, taking into account possible topographic and gender-specific differences.

Methods

The study included 486 Caucasian Central-European orthodontic patients (9–24 years) with unaffected dental development. In an anonymized, randomized, and blinded manner, one orthopantomogram of each patient at either start, mid or end of treatment was visually analysed regarding the mineralisation stage of the third molars according to the method by Demirjian et al. Corresponding topographic and gender-specific point scores were determined and added to form a dental maturity score. Prediction equations for age assessment were derived by linear regression analysis with chronological age and checked for reliability within the study population.

Results

Mineralisation of the lower third molars was slower than mineralisation of the upper third molars, whereas no jaw-side-specific differences were detected. Gender-specific differences were relatively small, but girls reached mineralisation stage C earlier than boys, whereas boys showed an accelerated mineralisation between the ages of 15 and 16.

Conclusions

The global equation generated by regression analysis (age = −1.103 + 0.268 × dental maturity score 18 + 28 + 38 + 48) is sufficiently accurate and reliable for clinical use. Age assessment only based on either maxilla or mandible also shows good prognostic reliability.

http://ift.tt/2gb2Amz

Effects of two different removable functional appliances on depth of the posterior airway space

Abstract

Objectives

Aim of the study was the comparison of treatment effects upon pharyngeal depth in patients treated with either (1) S-II-appliance or (2) Activator.

Methods

Pre- and posttreatment lateral cephalograms of 73 patients were analyzed using a customized set of measurements. According to predefined criteria, patients were either treated with S-II-appliance or Activator. Pharyngeal depth was assessed from cranial to caudal at six levels (P1 to P6). Paired t tests were used for intragroup and t tests for independent samples for intergroup comparisons. Results were considered statistically significant at p ≤ 0.05.

Results

37 (22 female, 15 male) patients were treated with the S-II-appliance (mean pretreatment age 11.1 ± 1.07 years), and 36 (20 female, 16 male) patients with an Activator (mean pretreatment age 11.3 ± 1.12 years). Mean treatment time was 14 months for the S-II-appliance and 12 months for the Activator. Most measurements at the different levels showed an average increase ranging from approximately 0.5 mm to almost 2 mm. Changes were more pronounced in S-II patients. In contrast to intergroup comparisons, some intragroup comparisons revealed statistically significant differences at levels P5 (p = 0.0062) and P6 (p = 0.0155) in S-II patients and at P1-level (p = 0.0197) in Activator patients.

Conclusions

Both appliances similarly led to an increase of the pharyngeal depth. The sites of statistically significant changes differed.

http://ift.tt/2fXlRF1

Prevalence of isolated maxillary lateral incisor agenesis in Syrian adolescents

Abstract

Purpose

This research is designed to obtain a better understanding and provide more insight of this phenomenon through evaluating the prevalence of congenital absence of maxillary lateral incisors in a Syrian population.

Methods

The method involved clinical examination of 8000 school children with an equal number of males and females (age range 12–15 years) to identify students only affected by bilateral or unilateral congenital absence of maxillary lateral incisors. Agenesis was determined based on radiological evidence.

Results

The results of this study showed that the prevalence of isolated maxillary lateral incisors agenesis was 1.15%. In the sample studied, 66.3% of the patients were female and 33.7% were male (p < 0.05). Absence was bilateral in 47.8% of patients and unilateral in 52.2%. Of the unilateral cases, 48% occurred on the right side and 52% on the left side, and the contralateral maxillary incisor was found to be microdont in 43.75%, right lateral in 47.6%, and left lateral in 52.4%.

Conclusion

The results of this study allow the conclusion that the prevalence of isolated maxillary lateral incisors agenesis in a Syrian population is within the average range with regard to other populations. A significant familial component to the etiology of maxillary lateral incisors agenesis was found.

http://ift.tt/2gb4Gmi

Effects of enamel sealing on shear bond strength and the adhesive remnant index

Abstract

Objectives

Selected combinations of materials were used to create tooth–adhesive–bracket complexes to evaluate shear bond strength (SBS) and the adhesive remnant index (ARI) with regard to enamel sealing.

Methods

Four adhesive systems also appropriate for use as enamel sealants were combined with four bracket types, resulting in 16 adhesive–bracket combinations, each of which was tested on 15 permanent bovine incisors. Sealant–adhesives included two recently introduced fluoride-releasing systems (Riva bond LC^® and go!^®), one established primer (Opal^® Seal™), and one commonly used adhesive as control (Transbond™ XT). Brackets included two metal (discovery^® by Dentaurum and Sprint^®) and two ceramic (discovery^® pearl and GLAM^®) systems. After embedding the bovine teeth, bonding the brackets to their surface, and storing the resultant samples as per DIN 13990-2 with modifications, an SBS test was performed by applying the shear force directly at the bracket base in an incisocervical direction. Then the ARI scores were determined.

Results

Discovery^® + Transbond™ XT yielded the highest (47.2 MPa) and GLAM^® + go!^® the lowest (17.0 MPa) mean SBS values. Significant differences (p < 0.0001) were found between metal and ceramic brackets of the same manufacturers (Dentaurum and Forestadent). Our ratings of the failure modes upon debonding predominantly yielded ARI 0 or 1. The high SBS values and low ARI scores observed with discovery^® + Transbond XT™ were reflected in a high rate of enamel fracture, which occurred on 11 of the 15 tooth specimens in this group.

Conclusions

All sealant–bracket combinations were found to yield levels of SBS adequate for clinical application. SBS values and ARI scores varied significantly depending on which sealant–brackets were used.

http://ift.tt/2fXffGG

Health Cards by Google: dermatologist review of inclusivity and utility of the medical search application

Abstract

One in twenty Google web searches are related to medical conditions¹ indicating the prominent role of the internet as a resource for medical information. Indeed, 72% of internet users report searching online for medical conditions; 77% began with Google, Bing, or Yahoo.² While 53% additionally sought physician consultation, 46% did not.³ Responding to its place in the medical community, in 2015 Google partnered with academic, government, and business-based ventures to develop "health cards" for searched disorders, and, in summer 2016, debuted a "related conditions" generator, suggesting diagnoses related to input disorders or symptoms.

This article is protected by copyright. All rights reserved.

http://ift.tt/2gOW0n3

An evaluation of high-stage cutaneous squamous cell carcinoma outcomes by gender

Abstract

Data from the World Health Organization indicate that global overall age-adjusted cancer incidence and mortality rates are 1.2- and 1.5-fold higher in men as compared to women, respectively.¹ Non-melanoma skin cancer (NMSC) is the most common cancer among white populations, yet the prognostic significance of gender remains unclear.² A possible relationship may exist given that in melanoma, women have a lower mortality risk as compared to men.^3,4

This article is protected by copyright. All rights reserved.

http://ift.tt/2gCbxna

Not every patient needs triglyceride check, but all can get pancreatitis: A systematic review and clinical characterization of Isotretinoin associated Pancreatitis

Abstract

Isotretinoin is a medication to treat primarily nodulocystic acne vulgaris. A serious complication is pancreatitis, either idiosyncratic, and not preventable or predictable; or due to elevated triglycerides. Triglyceride are elevated in practically all patients on isotretinoin, but may not be abnormal, or too minimally elevated to pose a pancreatitis risk.¹ Elevated triglycerides are not a cause of arteriosclerotic risk. but can be a marker.^2,3 Objective of this review was to clinically characterize patients with isotretinoin induced pancreatitis particularly due to hypertriglyceridemia to evaluate what monitoring is sensible.

This article is protected by copyright. All rights reserved.

http://ift.tt/2gOZh5z

Reply to ‘A phase II randomized controlled trial of nicotinamide for skin cancer chemoprevention in renal transplant recipients’: reply from the authors

Abstract

We thank Yélamos et al. for their interest in our nicotinamide chemoprevention studies.¹ Some of their comments are pertinent, while others are based on a flawed interpretation of our data.

Zhao² previously commented on (nonsignificant) numerical differences in the frequency of adverse-event term groupings (mucocutaneous infections) between the placebo and nicotinamide groups in our ONTRAC chemoprevention study (Oral Nicotinamide To Reduce Actinic Cancer).³ As stated previously, chance remains a highly plausible explanation for the numerically higher mucocutaneous infections in the nicotinamide arm and also, for example, for the numerically lower respiratory infections observed in the nicotinamide arm.⁴

This article is protected by copyright. All rights reserved.

http://ift.tt/2gC6X8i

Short-term efficacy and tolerability of methylphenidate in children with traumatic brain injury and attention problems

Publication date: Available online 28 November 2016
Source:Brain and Development
Author(s): Ozalp Ekinci, Meltem Çobanoğulları Direk, Serkan Gunes, Halenur Teke, Nuran Ekinci, Fatma Yıldırım, Çetin Okuyaz
PurposeThis study aims to investigate the short-term efficacy and tolerability of immediate-release methylphenidate (IR-MPH) in children with a history of traumatic brain injury (TBI).MethodsTwenty children with TBI (mean age: 12.7±3.1years) who had clinically significant attention deficit and/or hyperactivity-impulsivity symptoms and twenty children with primary Attention Deficit Hyperactivity Disorder (ADHD) (mean age: 12.3±3.05years) were included. Study measures, which included the Turgay DSM-IV based ADHD rating Scale (T-DSM-IV-S), Conners' Parent Rating Scale (CPRS), Conners' Teacher Rating Scale (CTRS-R) and Clinical Global Impression-Improvement Scale (CGI-I), were completed at the baseline for both of the groups. For the TBI group, study measures and an adverse effect scale developed by the authors were completed 8weeks after IR-MPH treatment (10mg dose t.i.d).ResultsNo significant difference was found regarding the baseline scale scores between the study groups. Among children with TBI, most of the scores on T-DSM-IV-S, CPRS and CTRS-R were found to improve significantly after MPH treatment, (p<0.05). 70% (N=14) of the sample were much improved at the endpoint. MPH was generally well-tolerated (95% had either no adverse effect or mild adverse effects).ConclusionIn this preliminary open-label study, IR-MPH was found as a safe and effective treatment option for ADHD symptoms after TBI. However, future controlled studies are needed to confirm our findings.



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Therapeutic interventions in severe asthma

The present paper addresses severe asthma which is limited to 5-10% of the overall population of asthmatics. However, it accounts for 50% or more of socials costs of the disease, as it is responsible for hospi...

http://ift.tt/2gOXiyk

Therapeutic interventions in severe asthma

The present paper addresses severe asthma which is limited to 5-10% of the overall population of asthmatics. However, it accounts for 50% or more of socials costs of the disease, as it is responsible for hospi...

http://ift.tt/2gOXiyk

Comprehensive Genetic Characterization of Rosette-Forming Glioneuronal Tumors: Independent Component Analysis by Tissue Microdissection

Abstract

A rosette-forming glioneuronal tumor (RGNT) is a rare, mixed neuronal-glial tumor characterized by biphasic architecture of glial and neurocytic components. The number of reports of genetic analyses of RGNTs is few. Additionally, the genetic background of the unique biphasic pathological characteristics of such mixed neuronal-glial tumors remains unclear. To clarify the genetic background of RGNTs, we performed separate comprehensive genetic analyses of glial and neurocytic components of five RGNTs, by tissue microdissection. Two missense mutations in FGFR1 in both components of two cases, and one mutation in PIK3CA in both components of one case, were detected. In the latter case with PIK3CA mutation, the additional FGFR1 mutation was detected only in the glial component. Moreover, the loss of chromosome 13q in only the neurocytic component was observed in another case. Our results suggested that RGNTs, which are tumors harboring two divergent differentiations that arose from a single clone, have a diverse genetic background. Although previous studies have suggested that RGNTs and pilocytic astrocytomas (PAs) represent the same tumor entity, our results confirm that the genetic background of RGNTs is not identical to that of PA. This article is protected by copyright. All rights reserved.

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Pericardial Effusion due to Primary Malignant Pericardial Mesothelioma: A Common Finding but an Uncommon Cause

This case report describes a 37-year-old female who was admitted to our Emergency Department because of shortness of breath. On physical examination, she had dyspnea and tachycardia and blood pressure was 80/50 mmHg with a pulsus paradoxus of 22 mmHg. Neck veins were distended, heart sounds were distant, and dullness was found on both lung bases. Her chest X-ray revealed bilateral pleural effusion and cardiomegaly. On both computed tomography and echocardiography the heart was of normal size and a large pericardial effusion was noted. The echocardiogram showed signs of impending tamponade, so the patient underwent an emergent pericardiocentesis. No infectious etiology was found and she was assumed to have viral pericarditis and was treated accordingly. However, when the pericardial effusion recurred and empirical therapy for tuberculosis failed, a pericardial window was performed. A typical staining pattern for mesothelioma was found on her pericardial biopsy specimen. Since no other mesodermal tissue was affected, a diagnosis of primary malignant pericardial mesothelioma was made. Chemotherapy was not effective and she passed away a year after the diagnosis was made. This case highlights the difficulties in diagnosing this uncommon disease in patients that present with the common finding of pericardial effusion.

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Reinforcement in removable prosthodontics: a literature review

Abstract

Background

Removable prothodontics are often associated with mechanical troubles in daily use, such as fracture or deformation. These troubles render prostheses unusable and reduce wearers' QOL. Various reinforcements are used to prevent such problems, but consensus on reinforcement has not been reached.

Objective

This review aimed to summarize the effects of reinforcement, and to propose favorable reinforcement based on material, design, and position in the prostheses.

Methods

Initially, 139 articles were selected by electronic and manual searches. After exclusion of 99 articles based on the exclusion criteria, 40 articles were finally included in the review. Electronic searches were performed for articles published from 2005 to 2015 in PubMed, EMBASE, Medline, and Cochrane Library and manual searches were performed in 10 journals relevant to the topic of removable prosthodontics.

Results

For in vitro studies, certain dental alloys and fibers were mainly used. Their forms were different, including complicated forms in dental alloys and various forms in fibers. The materials were examined for mechanical properties like fracture strength, flexural strength, and elastic modulus, and compared with one another or without reinforcement. There were a few clinical studies and one longitudinal study.

Conclusion

Cast metal reinforcement seemed to be most favorable in terms of fracture toughness and stiffness. The most favorable forms differed depending on the prostheses, but placement around thin and deformable areas was effective. However, randomized or longitudinal clinical reports and comparative clinical studies on the use of reinforcement were still lacking and such studies are necessary in the future.

This article is protected by copyright. All rights reserved.

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Effects of low-level laser therapy on burning mouth syndrome

Abstract

Objectives

To investigate low-level laser therapy (LLLT) applied to treat burning mouth syndrome (BMS).

Materials and methods

This prospective. comparative. partially-blinded. single-centre. clinical trial of GaAlAs Laser. with 815 nm wavelength. included 44 BMS patients divided randomly into three groups: Group I (n=16): GaAlAs laser 815 nm wave-length. 1W output power. continuous emissions. 4 seconds .4 Joules and fluence rate is 133.3 joules/cm².

Group II (n=16): GaAlAs infrared laser. 815 nm wavelength. 1W output power. continuous emissions. 6 seconds. 6 Joules and fluence rate 200 joules/cm² Group III (n=12) placebo group. sham laser. All groups received a weekly dose for 4 weeks. Pain intensity was recorded using a 10-cm visual analog scale; patients responded to the oral health impact profile (OHIP-14). xerostomia severity test and the hospital anxiety-depression scale (HAD). These assessments were performed at baseline, 2 weeks and 4 weeks.

Results

LLLT decreased pain intensity and improved OHIP-14 scores significantly from baseline to 2 weeks in Groups I and II compared with the placebo group. No statistically significant differences were found from 2 weeks to 4 weeks. Overall improvements in VAS scores from baseline to the end of treatment were: Group I 15.7%; Group II 15.6%; Group III placebo 7.3%.

Conclusions

LLLT application reduces symptoms slightly in BMS patients.

This article is protected by copyright. All rights reserved.

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Vedolizumab as a successful treatment of CTLA-4–associated autoimmune enterocolitis

Publication date: Available online 28 November 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): Alexander A. Navarini, Petr Hruz, Christoph T. Berger, Tie Zheng Hou, Charlotte Schwab, Annemarie Gabrysch, Rebecca Higgins, Natalie Frede, Barbara-Christina Padberg Sgier, Olle Kämpe, Anne-Valérie Burgener, Florian Marquardsen, Fabian Baldin, Marc Bigler, Anne Kistner, Annaise Jauch, Olivier Bignucolo, Benedikt Meyer, Fabian Meienberg, Matthias Mehling, Lukas T. Jeker, Ingmar Heijnen, Thomas D. Daikeler, Jan-Olaf Gebbers, Bodo Grimbacher, David M. Sansom, Raphael Jeker, Christoph Hess, Mike Recher




http://ift.tt/2gOKg3V

Psychological and Behavioral Issues in the Management of Migraine in Children and Adolescents

Abstract

Purpose of Review

It is sometimes assumed that children and adolescents with migraine have a psychiatric or behavioral comorbidity, a belief that can be stigmatizing. This review will examine the recent literature addressing this area to determine if pediatric and adolescent migraineurs are at increased risk for psychiatric comorbidity and to discuss management strategies.

Recent Findings

A large systematic review of pediatric and adolescent studies concluded anxiety and depression were not associated with onset of recurrent headaches. Children with increasing migraine frequency have reduced school attendance. Pediatric migraineurs have mildly lower quality of life (QOL) scores than healthy peers but not abnormally low. Finally, children with higher migraine frequency as well as migraineurs with aura were more likely to report suicidal ideation.

Summary

Migraine is a primary neurologic disorder. Migraine and psychiatric disorders may be comorbid; however, at this time, it can be difficult to clearly delineate some migraine features from psychiatric diagnoses with the current screening tools available. The majority of pediatric migraineurs do not have behavioral comorbidities; however, when such comorbidities occur, they should be addressed and appropriately managed. We need more accurate ways of delineating psychiatric and behavioral comorbidities from the migraine phenotype.

http://ift.tt/2fWXjMz

Psychological and Behavioral Issues in the Management of Migraine in Children and Adolescents

Abstract

Purpose of Review

It is sometimes assumed that children and adolescents with migraine have a psychiatric or behavioral comorbidity, a belief that can be stigmatizing. This review will examine the recent literature addressing this area to determine if pediatric and adolescent migraineurs are at increased risk for psychiatric comorbidity and to discuss management strategies.

Recent Findings

A large systematic review of pediatric and adolescent studies concluded anxiety and depression were not associated with onset of recurrent headaches. Children with increasing migraine frequency have reduced school attendance. Pediatric migraineurs have mildly lower quality of life (QOL) scores than healthy peers but not abnormally low. Finally, children with higher migraine frequency as well as migraineurs with aura were more likely to report suicidal ideation.

Summary

Migraine is a primary neurologic disorder. Migraine and psychiatric disorders may be comorbid; however, at this time, it can be difficult to clearly delineate some migraine features from psychiatric diagnoses with the current screening tools available. The majority of pediatric migraineurs do not have behavioral comorbidities; however, when such comorbidities occur, they should be addressed and appropriately managed. We need more accurate ways of delineating psychiatric and behavioral comorbidities from the migraine phenotype.

http://ift.tt/2fWXjMz

Bad air gets under your skin

Abstract

Air pollution is increasing beyond previous estimates and is viewed as the world's largest environmental health risk factor. Numerous clinical and epidemiological studies have highlighted the adverse effects of environmental pollutants on health. Although there is comparatively less research investigating the cutaneous effects of ambient pollution, there is growing recognition of the adverse effects on skin. In this article we provide an overview of the nature of environmental pollution and highlight the current evidence detailing the effects on cutaneous health. There is convincing evidence demonstrating that air pollution has a detrimental impact on skin and can exacerbate skin disease. Further epidemiological and experimental studies are required to assess the short and long term deleterious effects of ambient pollutant exposure on skin. The future challenge would be to use this evidence to develop specific strategies to protect against pollution-induced damage and prevent the effects of 'bad air getting under our skin'.

This article is protected by copyright. All rights reserved.

http://ift.tt/2gymWGW

Dihydroavenanthramide D inhibits mast cell degranulation and exhibits anti-inflammatory effects through the activation of neurokinin 1 receptor

Abstract

Chronic pruritus is difficult to treat. Current treatment options are frequently ineffective and new therapeutic approaches are urgently needed. Avenanthramides are active substances in oats that exhibit anti-inflammatory effects. Their potential to interrupt pruritus mechanisms was investigated in this study. It was found that the synthetic analog dihydroavenanthramide D (DHAvD) can interact with the neurokinin-1 receptor (NK1R) and inhibit mast cell degranulation. DHAvD also affects inflammatory processes and reduces secretion of the cytokine interleukin-6. Our findings indicate that DHAvD may act as a NK1R inhibitor and could be a promising candidate for topical treatments of chronic pruritus.

This article is protected by copyright. All rights reserved.

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Polyinosinic-polycytidylic acid (poly(I:C)) attenuates imiquimod-induced skin inflammation in mice by increasing cutaneous PD-L1 expression

Abstract

While the keratinocyte isivation in controlling skin inflammation.

This article is protected by copyright. All rights reserved.

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Low baseline levels of NK cells may predict a positive response to ipilimumab in melanoma therapy

Abstract

The introduction of immune checkpoint blockade (ICB) has been a breakthrough in the therapy of metastatic melanoma. The influence of ICB on T cell populations has been studied extensively but little is known about the effect on NK cells.

In this study, we analysed the relative and absolute amounts of NK cells and of the subpopulations of CD56^dim and CD56^bright NK cells among the peripheral blood mononuclear cells (PBMCs) of 32 patients with metastatic melanoma before and under treatment with ipilimumab or pembrolizumab by flow cytometry.

In 15 (47%) patients an abnormal low amount of NK cells was found at baseline. Analysis of the subpopulations showed also low or normal baseline levels for CD56^dim NK cells, whereas the baseline levels of CD56^bright NK cells were either normal or abnormally high.

The relative and absolute amounts of NK cells and of CD56^dim and CD56^bright NK cell subpopulations in patients with a normal baseline did not change under treatment. However, patients with a low baseline of NK cells and CD56^dim NK cells showed a significant increase in these immune cell subsets, but the amounts remained to be lower than the normal baseline. The amount of CD56^bright NK cells was unaffected by treatment.

The baseline levels of NK cells were correlated to the number of metastatic organs. Their proportion increased whereas the expression of NKG2D decreased significantly when more than one organ was affected my metastases.

Low baseline levels of NK cells and CD56^dim NK cells as well as normal baseline levels of CD56^bright NK cells correlated significantly with a positive response to ipilimumab but not to pembrolizumab.

Survival curves of patients with low amounts of CD56^dim NK cells treated with ipilimumab showed a trend to longer survival. Normal baseline levels of CD56^bright NK cells were significantly correlated with longer survival as compared to patients with high baseline levels.

In conclusion, analysis of the amounts of total NK cells and of CD56^dim and CD56^bright NK cells subpopulations at baseline may help to predict the outcome of treatment with ipilimumab.

This article is protected by copyright. All rights reserved.

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Endothelial cell-derived endothelin-1 is involved in abnormal scar formation by dermal fibroblasts through RhoA/Rho-kinase pathway

Abstract

Hypertrophic scars and keloids are characterized by excessive dermal deposition of extracellular matrix due to fibroblast-to-myofibroblast differentiation. Endothelin-1 (ET-1) is primarily produced by vascular endothelial cells, and plays multiple roles in the wound-healing response and organ fibrogenesis. In this study, we investigated the pathophysiological significance of ET-1 and involvement of RhoA, a member of the Rho GTPases, in hypertrophic scar/keloid formation. We found that ET-1 expression on dermal microvascular endothelial cells (ECs) in hypertrophic scars and keloids was higher than that in normal skin and mature scars. We also confirmed that ET-1 induced myofibroblast differentiation and collagen synthesis in cultured human dermal fibroblasts through the RhoA/Rho-kinase pathway. Finally, since hypertrophic scar/keloid formation was most prominent in areas exposed to mechanical stretch, we examined how mechanical stretch affected ET-1 secretion in human dermal microvascular ECs, and found that mechanical stretch increased ET-1 gene expression and secretion from ECs. Taken together, these results suggest that dermal microvascular ECs release ET-1 in response to mechanical stretch, and thereby contribute to the formation of hypertrophic scars and keloids through the RhoA/Rho-kinase pathway.

This article is protected by copyright. All rights reserved.

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Identification of novel anti-melanogenic hexapeptides via positional scanning of a synthetic peptide combinatorial library

http://ift.tt/2fEFalr

The biomarker landscape in mycosis fungoides and sézary syndrome

Abstract

The practice of preemptive individualized medicine is predicated on the discovery, development, and application of biomarkers in specific clinical settings. Mycosis fungoides and Sézary syndrome are the two most common type of cutaneous T-cell lymphoma, yet diagnosis, prognosis, and disease monitoring remain a challenge. In this review, we discuss the current state of biomarker discovery in mycosis fungoides and Sézary syndrome, highlighting the most promising molecules in different compartments. Further, we emphasize the need for continued multicenter efforts to validate available and new biomarkers and to develop prospective combinatorial panels of already discovered molecules.

This article is protected by copyright. All rights reserved.

http://ift.tt/2gyvHke

EMILIN3, an extracellular matrix molecule with restricted distribution in skin

Abstract

EMILIN3 is an extracellular matrix glycoprotein that displays a dynamic and restricted expression pattern in connective tissues during post-natal life. In this study, we report the characterization of EMILIN3 deposition in the skin. In addition, to unravel the functions of this protein in skin homeostasis, we generated Emilin3 null mice and provide evidence that EMILIN3 is dispensable for hair follicle growth and maintenance throughout adult life.

This article is protected by copyright. All rights reserved.

http://ift.tt/2fEyFiL

Bone marrow-derived mesenchymal stem cells prevent alopecia areata development through the inhibition of NKG2D expression: a pilot study

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Interleukin (IL)-6 modulates transforming growth factor -β receptor I and II (TGF-βRI and II) function in epidermal keratinocytes

Abstract

It been shown that IL-6 modulates TGF-β1 expression in fibroblasts, however; what role IL-6 plays concerning TGF-βR expression and function in skin is unknown. Therefore, the aim of this study was to investigate the mechanism by which IL-6 might modulates TGF-β receptors in skin.

Skin from WT, IL-6 overexpressing mice, and IL-6 treated keratinocyte cultures were analyzed for TGF-βRI and TGF-βRII expression via histology, PCR, and flow cytometry. Receptor function was assessed by cell migration, bromodeoxyuridine (BrdU) proliferation assays, and Smad7 expression and Smad2/3 phosphorylation. Receptor localization within the membrane was determined by co-immunoprecipitation.

IL-6 overexpression and treatment increased TGF-βRII expression in the epidermis. IL-6 treatment of keratinocytes induced TGF-βRI and II expression, and augmented TGF-β1-induced function as demonstrated through increased migration and decreased proliferation. Additionally, IL-6 treatment of keratinocytes altered receptor activity as indicated by altered Smad2/3 phosphorylation and increased Smad7 and membrane localization.

These results suggest that IL-6 regulates keratinocyte function by modulating TGF-βRI and II expression and signal transduction via trafficking of the receptor to lipid raft pools.

This article is protected by copyright. All rights reserved.

http://ift.tt/2gaRvlw

Towards a bacterial treatment for armpit malodour

Abstract

Axillary malodour is a frustrating condition for many people. It can lead to significant discomforts and various psychological effects. The underarm microbiome generally plays a major role in axillary malodour formation. Not only the bacteria on the armpit epidermis, but especially those living in the sweat glands, sweat pores and hair follicles play a pivotal role in malodour development.

In order to treat underarm malodour, this viewpoint paper envisions a bacterial treatment. Replacing the autochthonous malodour causing microbiome with a non-odour causing microbiome, through an armpit bacterial transplantation or direct application of probiotics/non-odour causing bacteria could resolve the condition. Selective steering of the microbiome with prebiotics, biochemicals or plant extracts could likewise greatly help in improving the underarm odour. Elimination/inhibition of the 'bad bugs' and application/stimulation of the 'good bugs' should be part of the future treatment for axillary body odour.

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An Advanced Mouse Model for Human Skin Wound Healing

Abstract

Here we report a model for studying wound repair based on skin regenerated from human tissue culture-expanded cells. The reconstituted skin (hRSK) responds to injury similar to that of intact human skin, and its constituent cells contribute to the healing process. As we have demonstrrated that hRSK composed of GFP-labelled cells also heals "normally", we believe this model will be useful in analyzing the wound repair process using genetically modified human cells.

This article is protected by copyright. All rights reserved.

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SVEP1 plays a crucial role in epidermal differentiation

Abstract

SVEP1 is a recently identified multi-domain cell adhesion protein, homologous to the mouse polydom protein, which has been shown to mediate cell-cell adhesion in an integrin dependent-manner in osteogenic cells. In the present study, we characterized SVEP1 function in the epidermis. SVEP1 was found by qRT-PCR to be ubiquitously expressed in human tissues, including the skin. Confocal microscopy revealed that SVEP1 is normally mostly expressed in the cytoplasm of basal and suprabasal epidermal cells. Down-regulation of SVEP1 expression in primary keratinocytes resulted in decreased expression of major epidermal differentiation markers. Similarly, SVEP1 down-regulation was associated with disturbed differentiation and marked epidermal acanthosis in three-dimensional skin equivalents. In contrast, the dispase assay failed to demonstrate significant differences in adhesion between keratinocytes expressing normal vs. low levels of SVEP1. Homozygous Svep1 knockout mice were embryonic lethal. Thus, to assess the importance of SVEP1 for normal skin homeostasis in vivo, we down regulated SVEP1 in zebra fish embryos with a Svep1-specific splice morpholino. Scanning electron microscopy revealed a rugged epidermis with perturbed microridge formation in the center of the keratinocytes of morphant larvae. Transmission electron microscopy analysis demonstrated abnormal epidermal cell-cell adhesion with disadhesion between cells in Svep1-deficient morphant larvae compared to controls. In summary, our results indicate that SVEP1 plays a critical role during epidermal differentiation.

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Beside to bench: JAK-inhibitor ruxolitinib inhibits the expression of cytokines characteristic of cutaneous lupus erythematosus

Abstract

This study was stimulated by the clinical observation of a rapid response of a chilblain lupus patient to treatment with JAK1/2-kinase inhibitor ruxolitinib. We investigated the in-vivo expression of phospho-JAK2 in CLE skin samples as well as the immunomodulatory in-vitro effect of ruxolitinib in cultured immortalized keratinocytes and in a 3D human epidermis model (epiCS). Our results demonstrate that ruxolitinib significantly decreases the production of CLE-typical cytokines (CXCL10, CXCL9, MxA) and might be a promising drug for future clinical studies in patients with CLE and related autoimmune skin diseases.

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Saliva protein biomarkers to detect oral squamous cell carcinoma (OSCC)

Abstract

In a recent study published in the Proceedings of the National Academy of Sciences of the U.S.A., Jau-Song Yu et al reported of their generated four–protein biomarker panel consisting of MMP1, KNG1, ANXA2, and HSPA5, as based on a risk-score scheme they established (Yu et al, 2016). This panel showed high sensitivity (87.5%) and specificity (80.5%) values in a test set to distinguish OSCC patients' saliva samples from non-OSCC patients' saliva samples. The risk score >0.4 detected 84% of the stage I OSCCs and a significant portion (42%) of the high-risk, visible, oral potentially-malignant disorders (OPMDs). Moreover, among 88 high-risk OPMD patients with available follow-up results, 18 developed OSCC within 5 years; of these nearly 78% had risk scores >0.4. The authors concluded that their four-protein panel may, therefore, offer a clinically effective tool for detecting OSCC and monitoring high-risk OPMDs through a readily available bio-fluid (i.e. saliva).

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Anterior chamber exudation in chronic myeloid leukaemia

Anterior chamber leukaemic hypopyon is a rare occurrence in chronic myeloid leukaemia. We discuss two cases marked by rapid exudation inside the anterior chamber, which were subsequently diagnosed as chronic myeloid leukaemia. The hypopyon in both the cases resolved on induction of chemotherapy.

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Malignant melanoma of cervix

A 68-year-old woman presented with symptoms of bleeding per vaginum. On examination, a growth was seen in the cervix, clinically considered to be squamous cell carcinoma. The growth was confined to the cervix and did not involve the parametria. However, on biopsy it was diagnosed as malignant melanoma. She underwent surgery elsewhere and was advised chemotherapy as these tumours are aggressive; however, she refused chemotherapy. She has been on regular follow-up and has an ongoing survival and disease-free period of more than 5 years. Primary cervical malignant melanomas are very rare as compared with vulval and vaginal counterparts and should be considered in the histological differential diagnosis of poorly differentiated malignant neoplasms involving cervix. Moreover, it is important to rule out metastasis from common primary sites such as skin, oesophagus, uveal tract and anorectal region before considering diagnosis of primary cervical melanoma.

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Why so blue? A case of neonatal cyanosis due to congenital methaemoglobinaemia (HbM Iwate)

Description

A 2.18 kg male baby was born by elective caesarean section at 34+3 weeks to a primiparous mother with autosomal dominant congenital methaemoglobinaemia (HbM Iwate) and gestational diabetes. Having been asymptomatic throughout her life, she developed significant respiratory symptoms in the third trimester, possibly due to a superimposed acquired methaemoglobinaemia, which necessitated hospitalisation, red cell exchange and early delivery of her infant.

At birth, the baby remained cyanosed despite good respiratory effort, and congenital methaemoglobinaemia was presumed. However, he quickly developed moderate respiratory distress (presumably unrelated) and was managed with facial continuous positive airway pressure (CPAP) in the delivery room, demonstrating maximal preductal saturations of 73% in 100% oxygen.

In the neonatal unit, he was started on nasal high-flow therapy. Urgent echocardiography excluded heart disease, and chest X-ray was unremarkable. Saturation monitoring was deemed unreliable; therefore, respiratory support was weaned (and stopped within 48 hours) based on regular normal capillary...

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Unusual cause of pleuritic chest pain in a child

We present the case of a 5-year-old boy with hereditary multiple exostoses who presented with left-sided pleuritic chest pain. A CT scan of the chest revealed an intrathoracic exostosis in close association with the heart.

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VURD syndrome in an infant presenting with potentially fatal staphylococcal urinary tract infection and septicaemia

Description

A newborn (NB) boy was delivered at 39 weeks of gestation with 4160 g weight and an APGAR score of 8/9. The pregnancy was uneventful, with normal first and second trimester ultrasound. The third trimester ultrasound revealed an isolated right kidney hydronephrosis, a normal sized bladder without thickening of wall as well a normal amniotic fluid volume. Kidney and bladder ultrasound (KBU) scan performed 48 hours after birth showed persistence of right kidney hydronephrosis as well dilation of right ureter. The left kidney and ureter were normal and alteration in bladder volume, bladder wall thickness and posterior urethra were observed. Trimethoprim prophylaxis was started, and the NB was discharged home in good condition. At 1 month age he was revaluated and remained asymptomatic, with an appropriate weight gain. The parents reported normal micturition with good urinary stream, without straining or dribbling. No changes were found on physical examination and the bladder...

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Locking plate external fixation and negative pressure wound therapy for treatment of a primary infection in a closed clavicle fracture

Infection in a clavicle fracture is uncommon, but remains a challenging problem. A paucity of soft tissue coverage often combined with significant displacement and interfragmentary movement add complexity to an already difficult situation for effective infection treatment. External fixation in principle offers a means of achieving fracture stability, while the infection is being eradicated. We present the case of a closed clavicle fracture, initially treated conservatively, that presented 5 weeks later with infection. The fracture was definitively treated with external fixation using a locking plate positioned superficially to the skin, plus negative pressure wound therapy and subsequent secondary closure and antibiotic therapy. This case illustrates a novel method of treatment in this unusual presentation that was well tolerated by the patient and resulted in a good clinical outcome.

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Acquired male urethral diverticulum: a rare entity treated in a one-stage procedure

Acquired male urethral diverticulum is a rare entity with most of the literature revolving around case reports or small case series. Up to two-thirds of cases are acquired, mostly as a result of trauma, stricture or infection. Infrequently, some cases develop as a complication of urological procedures, or even penile clamping. We present the case of an adult male with lower urinary tract symptoms, recurrent urinary infections and a history of multiple surgeries to treat a complicated perineal fistulae disease. With the help of imaging techniques, a bulbar urethral diverticulum was discovered. Owing to the symptomatic nature of the diverticulum, an open procedure was performed with excision and primary urethral anastomosis. No urinary symptoms were reported and follow-up imaging and flowmetry demonstrated very good functional outcome.

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Anterior Hypopituitarism and Treatment Response in Hunter Syndrome: A Comparison of Two Patients

Hypopituitarism is a clinically important diagnosis and has not previously been reported in Hunter syndrome. We contrast two cases with anatomic pituitary anomalies: one with anterior panhypopituitarism and the other with intact pituitary function. Patient 1, a 10-year-old boy with Hunter syndrome, was evaluated for poor growth and an ectopic posterior pituitary gland. Endocrine testing revealed growth hormone (GH) deficiency, secondary adrenal insufficiency, and tertiary hypothyroidism. An improvement in growth velocity with hormone replacement (GH, thyroxine, and corticosteroid) was seen; however, final adult height remained compromised. Patient 2, a 13-year-old male with Hunter syndrome, was evaluated for growth failure. He had a large empty sella turcica with posteriorly displaced pituitary. Functional endocrine testing was normal and a trial of GH-treatment yielded no significant effect. Panhypopituitarism associated with pituitary anomalies has not been previously reported in Hunter syndrome and was an incidental finding of significant clinical importance. In the setting of documented anterior hypopituitarism, while hormone replacement improved growth velocity, final height remained impaired. In patient 2 with equivocal GH-testing results, treatment had no effect on linear growth. These cases highlight the importance of careful clinical assessment in Hunter syndrome and that judicious hormone replacement may be indicated in individual cases.

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Pembrolizumab and Lenvatinib in Treating Metastatic or Recurrent Differentiated Thyroid Cancer That Cannot Be Removed by Surgery

Conditions:   Columnar Cell Variant Thyroid Gland Papillary Carcinoma;   Follicular Variant Thyroid Gland Papillary Carcinoma;   Poorly Differentiated Thyroid Gland Carcinoma;   Recurrent Thyroid Gland Carcinoma;   Stage III Differentiated Thyroid Gland Carcinoma;   Stage III Thyroid Gland Follicular Carcinoma;   Stage III Thyroid Gland Papillary Carcinoma;   Stage IV Thyroid Gland Follicular Carcinoma;   Stage IV Thyroid Gland Papillary Carcinoma;   Stage IVA Differentiated Thyroid Gland Carcinoma;   Stage IVA Thyroid Gland Follicular Carcinoma;   Stage IVA Thyroid Gland Papillary Carcinoma;   Stage IVB Differentiated Thyroid Gland Carcinoma;   Stage IVB Thyroid Gland Follicular Carcinoma;   Stage IVB Thyroid Gland Papillary Carcinoma;   Stage IVC Differentiated Thyroid Gland Carcinoma;   Stage IVC Thyroid Gland Follicular Carcinoma;   Stage IVC Thyroid Gland Papillary Carcinoma;   Tall Cell Variant Thyroid Gland Papillary Carcinoma;   Thyroid Gland Oncocytic Follicular Carcinoma
Interventions:   Other: Laboratory Biomarker Analysis;   Drug: Lenvatinib;   Biological: Pembrolizumab
Sponsors:   Academic and Community Cancer Research United;   National Cancer Institute (NCI)
Not yet recruiting - verified November 2016

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Comparison of Concomitant Cisplatin Versus Carboplatin and 5-fluorouracil With Radiotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma

Condition:   Head and Neck Squamous Cell Carcinoma
Interventions:   Drug: cisplatin;   Drug: carboplatin;   Drug: 5-FU
Sponsors:   University Medical Center Groningen;   VU University Medical Center
Recruiting - verified November 2016

http://ift.tt/2gzaKlM

Pembrolizumab and Lenvatinib in Treating Metastatic or Recurrent Differentiated Thyroid Cancer That Cannot Be Removed by Surgery

Conditions:   Columnar Cell Variant Thyroid Gland Papillary Carcinoma;   Follicular Variant Thyroid Gland Papillary Carcinoma;   Poorly Differentiated Thyroid Gland Carcinoma;   Recurrent Thyroid Gland Carcinoma;   Stage III Differentiated Thyroid Gland Carcinoma;   Stage III Thyroid Gland Follicular Carcinoma;   Stage III Thyroid Gland Papillary Carcinoma;   Stage IV Thyroid Gland Follicular Carcinoma;   Stage IV Thyroid Gland Papillary Carcinoma;   Stage IVA Differentiated Thyroid Gland Carcinoma;   Stage IVA Thyroid Gland Follicular Carcinoma;   Stage IVA Thyroid Gland Papillary Carcinoma;   Stage IVB Differentiated Thyroid Gland Carcinoma;   Stage IVB Thyroid Gland Follicular Carcinoma;   Stage IVB Thyroid Gland Papillary Carcinoma;   Stage IVC Differentiated Thyroid Gland Carcinoma;   Stage IVC Thyroid Gland Follicular Carcinoma;   Stage IVC Thyroid Gland Papillary Carcinoma;   Tall Cell Variant Thyroid Gland Papillary Carcinoma;   Thyroid Gland Oncocytic Follicular Carcinoma
Interventions:   Other: Laboratory Biomarker Analysis;   Drug: Lenvatinib;   Biological: Pembrolizumab
Sponsors:   Academic and Community Cancer Research United;   National Cancer Institute (NCI)
Not yet recruiting - verified November 2016

http://ift.tt/2fsuqLP

Comparison of Concomitant Cisplatin Versus Carboplatin and 5-fluorouracil With Radiotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma

Condition:   Head and Neck Squamous Cell Carcinoma
Interventions:   Drug: cisplatin;   Drug: carboplatin;   Drug: 5-FU
Sponsors:   University Medical Center Groningen;   VU University Medical Center
Recruiting - verified November 2016

http://ift.tt/2gzaKlM

Targeting of the WT1 91–138 fragment to human dendritic cells improves leukemia-specific T-cell responses providing an alternative approach to WT1-based vaccination

Abstract

Due to its immunogenicity and overexpression concomitant with leukemia progression, Wilms tumor protein 1 (WT1) is of particular interest for immunotherapy of AML relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). So far, WT1-specific T-cell responses have mainly been induced by vaccination with peptides presented by certain HLA alleles. However, this approach is still not widely applicable in clinical practice due to common limitations of HLA restriction. Dendritic cell (DC) vaccines electroporated with mRNA encoding full-length protein have also been tested for generating WT1-derived peptides for presentation to T-cells. Alternatively, an efficient and broad WT1 peptide presentation could be elicited by triggering receptor-mediated protein endocytosis of DCs. Therefore, we developed antibody fusion proteins consisting of an antibody specific for the DEC205 endocytic receptor on human DCs and various fragments of WT1 as DC-targeting recombinant WT1 vaccines (anti-hDEC205-WT1). Of all anti-hDEC205-WT1 fusion proteins designed for overcoming insufficient expression, anti-hDEC205-WT1_10–35, anti-hDEC205-WT1_91–138, anti-hDEC205-WT1_223–273, and anti-hDEC205-WT1_324–371 were identified in good yields. The anti-hDEC205-WT1_91–138 was capable of directly inducing ex vivo T-cell responses by co-incubation of the fusion protein-loaded monocyte-derived mature DCs and autologous T-cells of either healthy or HSCT individuals. Furthermore, the DC-targeted WT1_91–138-induced specific T-cells showed a strong cytotoxic activity by lysing WT1-overexpressing THP-1 leukemia cells in vitro while sparing WT1-negative hematopoietic cells. In conclusion, our approach identifies four WT1 peptide-antibody fusion proteins with sufficient production and introduces an alternative vaccine that could be easily translated into clinical practice to improve WT1-directed antileukemia immune responses after allo-HSCT.

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