Changes in filaggrin degradation products and corneocyte surface texture by season

Summary

Background

During the winter in northern countries, the risk of dermatitis is increased due to low temperature and humidity. Dermatitis is particularly common on weather-exposed skin such as the cheeks and hands. Recently, increased numbers of unidentified nanosized protrusions on the corneocyte surface were associated with dermatitis and deficiency of natural moisturizing factor (NMF).

Objectives

To investigate the effect of season on NMF levels and corneocyte surface texture in cheek and hand skin of healthy adults.

Methods

Eighty healthy volunteers (40 male and 40 female) were recruited: 40 aged 18–40 years and 40 aged ≥ 70 years. Cheek and dorsal hand skin was tape stripped in the winter and summer. Analysis for NMF and corneocyte surface texture was done (Dermal Texture Index, DTI). Potential confounders were registered and adjusted for.

Results

In cheek skin, NMF levels were reduced and DTI elevated during the winter compared with the summer. Older participants had higher NMF levels than younger participants. In the summer, DTI level was dependent on self-reported ultraviolet exposure. In hand skin, NMF levels were higher during the winter than in the summer, and female participants had higher NMF levels than male participants.

Conclusions

Seasonal effects on NMF and DTI on the cheeks and hands were found, suggesting an influence of climatic factors at the biochemical and ultrastructural levels. Significant variations were also observed regarding age and sex, making it difficult to draw firm conclusions. Our study adds new pieces to the puzzle of seasonal differences in xerosis and dermatitis.

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Bullous pemphigoid with the deposition of IgG2 but not IgG1, IgG3 nor IgG4 autoantibodies at the basement membrane zone

Bullous pemphigoid (BP) is the most common subepidermal autoimmune blistering skin disease, characterized by tense bullae and urticarial erythema with a generalized distribution. BP is induced by autoantibodies to structural proteins of the basement membrane zone (BMZ) such as BP180 and BP230¹. Because the majority of BP skin shows complement deposition², complement activation is considered to be important for blister formation. Among IgG subclasses, IgG1 have a high ability to activate complements, whereas IgG2 and IgG4 have a low and no ability, respectively.

This article is protected by copyright. All rights reserved.

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Mucocutaneous manifestations of cocaine abuse: a review

Abstract

Cocaine is an alkaloid extracted from the leaves of the Erythroxylum coca plant that emerged in the 1970s as a fashionable drug among members of certain social backgrounds. Cocaine abuse is a problem of current interest, which is mostly hidden and under-diagnosed, but dramatically widespread among all socioeconomic strata, and with an incidence which is increasing at an alarming rate. There are 1.5 million cocaine consumers in the USA. In Spain, the prevalence of consumption among the population between 15 and 65 years-old is higher, reaching 3.1%. Because of this, it seems important to understand and recognize all the mucocutaneous manifestations of cocaine abuse which have been reported in the literature in order to clarify and help dermatologists in their daily practice.

In this article, we describe the principal mucocutaneous manifestations of cocaine abuse and we review isolated case reports which have been published in the literature. Because the dermatologist may deal with an unknown problem as well as with an already well-known history of cocaine abuse, it seems logical to separate the mucocutaneous manifestations into those which are frequent and highly suggestive, such as those caused by vascular injury, damage to mucosal membranes, infectious diseases or neutrophilic dermatosis, especially when suffered by young people and in consonance with other systemic manifestations and, those which have been reported in the literature as isolated case reports. We also summarize the main aspects of its pathogeny, principal pharmacodynamic and pharmacokinetic characteristics, and diagnostic tools.

This article is protected by copyright. All rights reserved.

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Lichen planus hypertrophicus-inversus occurring in a patient with Bannayan–Riley–Ruvalcaba syndrome

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Case of pityriasis rubra pilaris with focal acantholytic dyskeratosis

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Angiosarcoma arising in a traumatic scar

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Persistent pruritus in psoriatic patients during administration of biologics

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Tufted angioma of the finger: A case of an uncommon location with unique dermoscopic features

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Color-transition sign: A useful trichoscopic finding for differentiating alopecia areata incognita from telogen effluvium

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Effectiveness of and factors associated with clinical response to methotrexate under daily life conditions in Asian patients with psoriasis: A retrospective cohort study

Abstract

Given the relative scarcity of data concerning the efficacy of methotrexate under daily life conditions in psoriasis, this study aimed to investigate the effectiveness of methotrexate in Asian psoriatic patients and to identify factors associated with clinical response. This observational retrospective cohort study included adult psoriatic patients who had been treated with or were going to start methotrexate. Psoriasis Area and Severity Index (PASI) scores at baseline and at 3, 6 and 12 months were recorded. At 3 months, patients achieving 50% or more reduction from baseline PASI score were defined as responders. One hundred, 74 and 61 patients were followed for 3, 6 and 12 months, respectively. Mean follow-up time was 15.3 ± 10.2 months. A reduction in PASI score of at least 75% was achieved in 26%, 32.5% and 45.2% at 3, 6 and 12 months, respectively. At 12 and 24 months, Kaplan–Meier analysis showed 68.7% and 52.1% probability of drug survival, respectively. Male sex, body mass index (BMI) of less than 25 kg/m² and absence of abdominal obesity were factors associated with response to treatment in univariate analysis. Male sex was the only significant factor in multivariate analysis. The effectiveness of methotrexate in clinical practise seemed to be lower than in clinical trials, but effectiveness increased with longer duration of treatment. Problems associated with methotrexate use in clinical practise may be due to medication adherence rather than lack of medication effectiveness. Female sex, abdominal obesity and BMI of 25 kg/m² or more might decrease response to methotrexate.

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“Dermohscopy” mapping: Correlating dermoscopic findings with histology in Mohs micrographic surgery

Mohs micrographic surgery (MMS) is the treatment of choice for high-risk basal cell carcinoma.^1,2 The technique combines tissue conservation with complete microscopic margin control, leading to superior cure rates while minimizing deformity.³ MMS involves several steps that should be meticulously followed to achieve this high cure rate.⁴

This article is protected by copyright. All rights reserved.

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Psoriasis/Inflammatory Bowel Diseases: A time to solve the liaison

I read with interest a prospective single center study by Kou et al.¹ published recently in the journal of European Academy of Dermatology and Venereology. The authors investigated the prevalence of mucocutaneous manifestations of inflammatory bowel disease (IBDs) in Chinese patients.

This article is protected by copyright. All rights reserved.

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Risk of developing pressure sore in ALS patients: a nationwide cohort study

Abstract

Background

Prior investigations with few cases have disclosed lack of pressure sore (PrS) formation was characteristic in amyotrophic lateral sclerosis (ALS) patients. However, studies with larger samples are lacking to ascertain this concept.

Objective

To investigate whether patients with ALS have higher risk of PrS.

Methods

Utilizing a Taiwan National Insurance claims dataset with 23 million participants, we extracted 514 ALS patients and 2,056 controls from January 1, 2000, to December 31, 2008. Both groups were followed up until PrS occurrence during study period (2000-2011). The PrS risk was calculated with Cox proportional regression model.

Results

The ALS patients had a greater PrS risk (adjusted hazard ratio [aHR] = 8.82, 95% confidence interval [CI] = 4.90–15.9, P < 0.001) than the controls did. PrS risk was much higher in ALS women (aHR = 26.6, 95% CI = 9.05–78.2, P < 0.001) than in ALS men (aHR = 4.38, 95% CI = 1.99–9.68, P < 0.001). Besides, in people aged 20–54, ALS was linked with a much greater PrS risk (aHR = 27.7, 95% CI = 5.79–132, P < 0.001) than in those aged ≥55 (aHR = 6.10, 95% CI = 3.10–12.0, P < 0.001).

Conclusions

ALS is discovered to be correlated with an enhanced PrS risk. For PrS prevention, it is needed to pay more attention to the management of the ALS patients, particularly in women and those with relatively younger age. Further investigations are needed to confirm the findings in this study.

This article is protected by copyright. All rights reserved.

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Isotretinoin treatment and peanut allergy: a new case report and review of the literature

Isotretinoin is a common and effective retinoid drug that remains the gold standard for the treatment of severe acne. The package leaflet clearly mentions its contraindication in patients with peanut and/or soya allergy. As isotretinoin is solubilized in refined soya oil, it is contraindicated in patients with soya IgE mediated allergy. Because of possible cross-reactivity, concerns have been raised about giving the drug to patients presenting with peanut allergy.

This article is protected by copyright. All rights reserved.

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Patient-reported symptoms and signs of moderate-to-severe psoriasis treated with guselkumab or adalimumab: results from the randomized VOYAGE 1 trial

Abstract

Background

How patients experience the symptoms/signs of psoriasis is highly relevant for assessing treatment response.

Objectives

Compare outcomes with guselkumab, placebo, and adalimumab utilizing the novel, validated Psoriasis Symptoms and Signs Diary (PSSD).

Methods

VOYAGE 1 is an on-going, phase III, double-blinded, controlled trial of patients with moderate-to-severe psoriasis. Patients were randomized to guselkumab 100 mg every-8-weeks; placebo-to-guselkumab 100 mg every-8-weeks; or adalimumab 40 mg every-2-weeks. The PSSD was self-administered to assess symptoms (i.e., itch, skin tightness, burning, stinging, pain) and signs (i.e., dryness, cracking, scaling, shedding/flaking, redness, bleeding) of psoriasis (0-10 [absent-to-worst-imaginable]) every 24-hours. Symptom and sign summary scores were derived (0-100) based on average scores of the individual symptoms and signs. Proportions of patients with clinically meaningful improvements and symptom- and sign-free scores of 0 were evaluated across treatment groups at weeks 16, 24, and 48.

Results

At baseline, 652/837 randomized patients had PSSD scores. The proportion of patients achieving clinically meaningful improvements in PSSD summary scores was significantly higher in the guselkumab group compared with the placebo group at week 16 (p<0.001) and compared with the adalimumab group at weeks 24 (p=0.002) and 48 (p<0.001). The proportions of patients achieving PSSD symptom and sign summary scores of 0 (i.e., symptom- and sign-free) were significantly higher for guselkumab vs. placebo at week 16 and vs. adalimumab at weeks 24 and 48 (all p<0.001).

Conclusions

Based on PSSD scores, greater improvements in symptoms and signs of psoriasis were reported by patients treated with guselkumab compared with placebo at week 16 or adalimumab through 48 weeks.

This article is protected by copyright. All rights reserved.

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The Clinical phenotype and a novel COL7A1 mutation in a Chinese family with dystrophic epidermolysis bullosa pruriginosa

Distrophic epidermolysis bullosa pruriginosa(DEB-Pr, OMIM#604129) is a rare subtype of epidermolysis bullosa dystrophica. It is characterized by recurrent vesicles and erosions on the extensor of the limbs at birth or shortly thereafter and pruriginosa papules and nodules accompanied with intense itching and nail dystrophy in adult stage¹. Histology reveals hyperkeratosis, mild acanthosis and a subepidermal blister formation². Electron microscopic studies showed alterations in the number and ultrastructure of anchoring fibrils in lesional, perilesional and non-lesional skin³.Previous studies have revealed that DEB-Pr is due to mutations in the COL7A1 gene located on chromosome 3p21 region, which encodes the collagen VII^2,4.

This article is protected by copyright. All rights reserved.

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Improvement in Itch and Other Psoriasis Symptoms With Brodalumab in Phase 3 Randomized Controlled Trials

Abstract

Background

Patients with psoriasis have lesional symptoms, including itch, which can reduce quality of life. The efficacy and safety of brodalumab, an interleukin-17 receptor A antagonist, in treating moderate-to-severe psoriasis have been reported in 3 randomized, controlled, phase 3 trials (AMAGINE-1/-2/-3).

Objective

The effect of brodalumab on lesional symptoms was assessed using the psoriasis symptom inventory (PSI), a validated patient-reported instrument.

Methods

Patients were randomized to receive brodalumab (140 or 210 mg every 2 weeks [Q2W]), placebo (AMAGINE-1/-2/-3), or ustekinumab (AMAGINE-2/-3) during a 12-week induction phase, followed by a maintenance phase through week 52. Patients electronically rated the severity of PSI items (itch, burning, stinging, pain, redness, scaling, cracking, and flaking) during the previous 24 hours on a scale of 0 (not at all severe) to 4 (very severe). At each visit, the PSI total score responder status was assessed, with responders defined as having an average weekly total inventory score ≤8 with no item score >1 at week 12.

Results

Across AMAGINE-1/-2/-3, brodalumab was associated with improvements in PSI total scores and itch scores vs placebo from week 2 through week 12 (P<0.001 in both domains). In AMAGINE-2/-3, brodalumab 210 mg Q2W demonstrated faster onset of PSI total score and itch responses (week 2, 22.1% and 36.4%, respectively) vs ustekinumab (week 2, 6.9% and 17.1%, respectively), and was associated with improved itch responses vs ustekinumab after 52 weeks of constant treatment.

Conclusion

Brodalumab demonstrated rapid, robust improvements in symptoms assessed by the PSI, including itch, vs placebo and ustekinumab.

This article is protected by copyright. All rights reserved.

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The role of the dermatologist in Raynaud's Phenomenon: a clinical challenge

Abstract

Raynaud's phenomenon (RP) is a functional vascular disorder involving extremities. In his practice, the dermatologist may frequently encounter RP which affects mainly women and is categorized into a primary benign form and a secondary form associated with different diseases (infections, drugs, autoimmune and vascular conditions, hematologic, rheumatologic and endocrinologic disorders). Still today, the differential diagnosis is a clinical challenge. Therefore, a careful history and a physical examination, together with laboratory tests and nailfold capillaroscopy are mandatory. RP is generally benign but a scheduled follow-up for primary RP patients should be established, due to risk of evolution to secondary RP.

A combination of conservative measures and medications can help in the management of RP. The importance of avoiding all potential physical, chemical and emotional triggers, as well as quitting smoking should be strongly suggested to the patient. As first line treatment, dihydropyridine Calcium Channel Blockers should be used. If this approach is not sufficient, prostacyclin derivatives, phosphodiesterases inhibitors and endothelin receptor antagonists can be considered as second line treatment. In cases of acute ischemia nifedipine and intravenous prostanoidsare helpful. In refractory cases, botulinum injections have shown a significant benefit. The approach to the RP patients requires therefore a coordinated care of specialists together with the primary care physician.

This article is protected by copyright. All rights reserved.

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The Author's Reply to Comment on Psoriasis/Inflammatory Bowel Diseases: A time to solve the liaison

I would like to sincerely thank Abdelmaksoud¹ for sharing several valuable suggestions about my study². At the following, the points mentioned by the author will be discussed.

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Utility of whole exome sequencing in detecting novel compound heterozygous mutations in COL7A1 among families with severe recessive Dystrophic Epidermolysis Bullosa in India - implications on diagnosis, prognosis and prenatal testing

Epidermolysis Bullosa (EB) encompasses a number of genetic conditions caused by mutations in genes involved in the formation of basement membrane resulting in blistering of the epidermis on trauma or pressure. At least 18 genes and 30 distinct subtypes of the disease are presently known[1]. Here-in, we report two un-related children with recessive dystrophic EB (RDEB) with novel compound heterozygous variations in collagen VII, one of whom had a fatal outcome and the other with a better sequel.

This article is protected by copyright. All rights reserved.

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Underdiagnosed and undertreated psoriasis: Nuances of treating psoriasis affecting the scalp, face, intertriginous areas, genitals, hands, feet, and nails

Abstract

Psoriasis of the scalp, face, intertriginous areas, genitals, hands, feet, and nails is often underdiagnosed, and disease management can be challenging. Despite the small surface area commonly affected by psoriasis in these locations, patients have disproportionate levels of physical impairment and emotional distress. Limitations in current disease severity indices do not fully capture the impact of disease on a patient's quality of life, and, combined with limitations in current therapies, many patients do not receive proper or adequate care. In this review, we discuss the clinical manifestations of psoriasis in these less commonly diagnosed areas and its impact on patient quality of life. We also examine clinical studies evaluating the effectiveness of therapies on psoriasis in these regions. This article highlights the need to individualize treatment strategies for psoriasis based on the area of the body that is affected and the emerging role of biologic therapy in this regard.

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Glucosylation of T-2 and HT-2 toxins using biotransformation and chemical synthesis: Preparation, stereochemistry, and stability

Abstract

Plant-derived phase II metabolites of T-2 toxin (T2) and HT-2 toxin (HT2) were first described in 2011 and further characterized in the following years. Since then, some efforts have been made to understand their biosynthesis, occurrence, toxicity, toxicokinetics, and finally relevance for consumers. Thus, the probably most important question is whether and how these metabolites contribute to toxicity upon hydrolysis either during food processing or the gastrointestinal passage. To answer this question, firstly, knowledge on the correct stereochemistry of T2 and HT2 glucosides is important as this affects hydrolysis and chemical behavior. So far, contradictory results have been published concerning the number and anomericity of occurring glucosides. For this reason, we set up different strategies for the synthesis of mg-amounts of T2, HT2, and T2 triol glucosides in both α and ß configuration. All synthesized glucosides were fully characterized by NMR spectroscopy as well as mass spectrometry and used as references for the analysis of naturally contaminated food samples to validate or invalidate their natural occurrence. Generally, 3-O-glucosylation was observed with two anomers of HT2 glucoside being present in contaminated oats. In contrast, only one anomer of T2 glucoside was found. The second aspect of this study addresses the stability of the glucosides during thermal food processing. Oat flour was artificially contaminated with T2 and HT2 glucosides individually and extruded at varying initial moisture content and temperature. All four glucosides appear to be more stable during food extrusion than the parent compounds with the glucosidic bond not being hydrolyzed.

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Efficacy and safety of eberconazole 1% otic solution compared to clotrimazole 1% solution in patients with otomycosis

To demonstrate non-inferiority of eberconazole 1% otic solution to clotrimazole 1% solution, and to compare their safety profile in the treatment of otomycosis.

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Contact dermatitis and patch testing for the allergist

Contact dermatitis (CD) is a common disease seen by allergists. Although underutilized, patch testing (PT) remains the gold standard in the diagnosis of allergic CD. It is not difficult to perform, however, the interpretation of the PT, proper classification of the results and determination of their relevance, need an appropriate level of expertise. The objective of this article is to provide a review of CD and its key allergens and provide updates and recommendations for the practicing allergist.

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Abnormal lung function at preschool age – asthma in adolescence?

Asthma often begins early in childhood. However, the risk for persistence is challenging to evaluate.

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Reliability validity of the Japanese version of the Glasgow Edinburgh Throat Scale (GETS-J): Use for a symptom scale of globus sensation

Globus sensation, a feeling of lump or something stuck in the throat, could be caused by structural, functional, and psychogenic diseases. Due to a possible multifactorial nature of the disease, neither diagnosing test battery nor standard treatment for globus sensation has been established. Therefore, a questionnaire to accurately identify globus patients and evaluate the severity of the disease is desired. Glasgow Edinburgh Throat Scale (GETS) is a 10-item questionnaire about the throat symptoms consisting of three subscales relating to dysphagia, globus sensation, and pain/swelling in the throat.

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Longer Omalizumab Use Eases Itch From Chronic Hives

The quality of life of patients with idiopathic urticaria improved when they stayed on the monoclonal antibody for 48 instead of 24 weeks, the XTEND-CIU study shows.
Medscape Medical News

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Claude Migeon, Pediatric Endocrinologist at Johns Hopkins Medicine, Dies at 94

Claude Migeon, M.D., the director of pediatric endocrinology at the Johns Hopkins University School of Medicine from 1961 to 1994 and the scientist whose early focus on steroid metabolism established the norms of adrenal function in infancy and childhood, died on March 4. He was 94.

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Reliability validity of the Japanese version of the Glasgow Edinburgh Throat Scale (GETS-J): Use for a symptom scale of globus sensation

Publication date: Available online 6 March 2018
Source:Auris Nasus Larynx
Author(s): Nao Takahashi, Kaori Mori, Hironori Baba, Takanobu Sasaki, Masaaki Ohno, Fumio Ikarashi, Naotaka Aizawa, Kunihiro Sato, Akio Tsuchiya, Hideyuki Hanazawa, Masahiko Tomita, Yamato Kubota, Yuka Morita, Kuniyuki Takahashi, Arata Horii
ObjectiveGlobus sensation, a feeling of lump or something stuck in the throat, could be caused by structural, functional, and psychogenic diseases. Due to a possible multifactorial nature of the disease, neither diagnosing test battery nor standard treatment for globus sensation has been established. Therefore, a questionnaire to accurately identify globus patients and evaluate the severity of the disease is desired. Glasgow Edinburgh Throat Scale (GETS) is a 10-item questionnaire about the throat symptoms consisting of three subscales relating to dysphagia, globus sensation, and pain/swelling in the throat. It was reported that globus patients marked high scores specifically for the globus scale among three scales, indicating that GETS can be used as a valid symptom scale for globus sensation. Aims of this study were to translate GETS into Japanese and to test its reliability and validity.MethodsFifty-five patients complaining of globus sensation without abnormal endoscopic and CT findings were enrolled into the study. They were asked to answer the questions of GETS translated into Japanese (GETS-J). Reliability (internal consistency) of the questionnaire was tested using Cronbach's coefficient alpha. To test the validity, principal components analysis was used to identify the factorial structure of the questionnaire and GETS-J data were compared with those reported in the original GETS. Contribution of psychiatric comorbidities to globus sensation was also investigated by examining the correlation between Hospital Anxiety and Depression Scale (HADS) and GETS-J.ResultsReliability of the questionnaire examined by the Cronbach's coefficient alpha was satisfactory and all higher than 0.75. Principal components analysis identified following three questions as the globus scale: Q1, Feeling something stuck in the throat; Q5, Throat closing off; Q9, Want to swallow all the time. Somatic distress, i.e., patients' reaction to throat symptoms, was significantly correlated with globus scale (r=0.680). Anxiety component of HADS was significantly correlated with somatic distress but not with globus scale. These results were consistent with those of the original GETS except for the replacement of Q3 (discomfort/irritation in the throat) to Q5 (throat closing off) for globus scale in GETS-J.ConclusionTranslation of GETS into Japanese showed high reliability and validity, suggesting that translation and cross-cultural adaptation were not problematic. High correlation of globus scale of GETS-J with somatic distress indicated that GETS-J could be a useful questionnaire to identify the globus patients and evaluate the severity of the disease. Anxiety may complicate the somatic distress in patients with globus sensation.



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Spongiotic Gingival Hyperplasia Synchronously Involving Multiple Sites: Case Report and Review of the Literature

Abstract

Localized juvenile spongiotic gingival hyperplasia (LJSGH) is a gingival lesion with unique clinicopathologic features that may involve synchronously multiple sites. We present a case with lesions clinically consistent with LJSGH in four jaw quadrants, confirmed by biopsy and review the English literature on multifocal LJSGH cases. A 19 year-old woman presented with circumscribed, erythematous overgrowths on the right and left maxillary and mandibular gingiva. With the provisional diagnosis of multifocal LJSGH, total excision of four maxillary lesions was performed. Clinical, microscopic and immunohistochemical examination with cytokeratin 19 confirmed the diagnosis of LJSGH in multiple sites. The excised lesions showed partial to complete recurrence after 4 months, while spontaneous regression of all but one lesion was observed after 15 months. Twenty cases with synchronous involvement of the gingiva of at least two teeth were previously reported. Their clinical features were comparable to that of solitary LJSGH. Only one case involved all four jaw quadrants. Spontaneous remission has not been documented before. The recognition of multiple lesions with clinicopathologic features diagnostic of LJSGH in the same adult patient argue against the designations "localized" and "juvenile". Recurrences are common, while remission might occur.

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Ubiquitin Immunostaining in Thyroid Neoplasms Marks True Intranuclear Cytoplasmic Pseudoinclusions and May Help Differentiate Papillary Carcinoma from NIFTP

Abstract

Papillary thyroid carcinoma (PTC) is defined by an invasive growth pattern and classic nuclear features: enlarged, grooved, overlapping nuclei with chromatin clearing and intranuclear cytoplasmic pseudoinclusions (INCP). True INCPs are characteristic of PTC, but may infrequently be seen in noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP). Nuclear abnormalities that mimic INCP ("pseudo-pseudoinclusions") are common in a variety of thyroid lesions. H&E and ubiquitin-stained whole tissue sections of classic PTC (n = 25) and NIFTP (n = 35) were evaluated. On H&E, true INCPs were present in all (100%) PTCs and absent in all NIFTPs (0%). Pseudo-pseudoinclusions were present in 13 (37%) NIFTPs. In 24 (96%) PTCs, ubiquitin was strongly expressed within INCPs. In NIFTPs, optically clear nuclei or pseudo-pseudoinclusions did not express ubiquitin (0/35). Occasionally, nuclear vacuoles in NIFTP demonstrated a marginated staining pattern, in which strong ubiquitin expression was seen at the periphery of the nucleus, but the central pale area was negative. In addition, 2 NIFTPs demonstrated intrafollicular psammomatoid calcifications which were strongly ubiquitin-positive. Psammoma bodies in PTC were ubiquitin-negative in the majority of cases. We report a previously undescribed finding: strong ubiquitin expression in true INCPs in PTC, absence of true INCPs in NIFTP, and absence of ubiquitin expression in pseudo-pseudoinclusions in NIFTP. This finding supports the difference between true INCPs (found only in PTC) and pseudo-pseudoinclusions (found in NIFTP). Using strict histologic criteria and ubiquitin immunostaining, the presence of true pseudoinclusions may exclude a diagnosis of NIFTP. Caution should be exercised when interpreting nuclear vacuoles or pseudo-pseudoinclusions.

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Pitch Counts: Why Are They Important for Your Baseball/Softball Player?

Spring training is in full swing right now.  Professional baseball players have migrated south to start honing their skills and getting ready for the long baseball season that lies ahead.  Similarly, youth baseball and softball programs are also starting practice to get ready for the upcoming season.  Softball and baseball have continued to grow in popularity with more than 2.4 million children playing baseball worldwide.  Along with this increase in these athletes, injury rates – particularly in baseball pitchers – have increased.

 

Over the years, USA Baseball and other similar organizations have been developing rules to try and decrease these climbing injury rates.  Before 1996, baseball had inning limits and rest requirements, which have since evolved to more specific rules about number of pitches thrown.  USA baseball has developed a campaign called "PitchSmart." The goal of this campaign is to give guidelines in each age group for pitch counts and rest days along with recommendations on warm ups and types of pitches to try and decrease injury.  Below is a table from MLB.com with the latest pitch counts for youth baseball.

 

A few other guidelines from the American Sports Medicine Institute developed to avoid injury include:

• Don't pitch with fatigue! If an athlete shows signs of fatigue they should be taken out.
• No overhead throwing for 2-3 months per year
• Avoid pitching on multiple teams at a time
• Pitchers should not also play catcher
• Learn good throwing mechanics early

 

Pitch counts are a great thing and can really help decrease injury rates.  BUT—coaches need to follow them!  A survey showed that only 43% of coaches were able to correctly answer questions about pitch counts and 19% allowed players to play with known arm fatigue.  The rules will only work if coaches are knowledgeable and rules are followed.  Talk with your coaches to make sure they are familiar and are adhering to these guidelines.

 

Unfortunately, softball doesn't have specific published guidelines similar to baseball.  STOP sports injuries (a worldwide group aiming to make things safer for kids) has recommended following similar pitch count guidelines as those used in baseball.  This is probably a good guideline for now until more research can be done.

 

Go to http://m.mlb.com/pitchsmart for more information and age related guidelines.

 

The post Pitch Counts: Why Are They Important for Your Baseball/Softball Player? appeared first on ChildrensMD.

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Heritability of trust and distrust remains unknown [Social Sciences]

In "Trust is heritable, whereas distrust is not," Reimann et al. (1) analyze data from monozygotic (MZ) and dizygotic (DZ) twins and conclude that "the disposition to trust is explained to some extent by heritability but not by shared socialization, [whereas] the disposition to distrust is explained by shared socialization...

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Diet-induced mating preference in Drosophila [Biological Sciences]

Diet-induced mating preference was initially observed by Dodd (1). Subsequently, we reported that diet-induced mating preference occurred in Drosophila melanogaster. Treatment of the flies with antibiotics abolished the mating preference, suggesting that fly-associated commensal bacteria were responsible for the phenomenon (2). The hypothesis was confirmed when it was shown that...

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Reply to Rosenberg et al.: Diet, gut bacteria, and assortative mating in Drosophila melanogaster [Biological Sciences]

Rosenberg et al. (1) suggest that the lack of evidence for assortative mating we reported (2) in comparison with a previous study (3) could be due to gut microbiomes in Drosophila melanogaster being affected by differing dietary history before culturing on the CMY (0.65% agar, 7.6% cornmeal, 7.6% molasses, 5%...

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Reply to Goldfarb et al.: On the heritability and socialization of trust and distrust [Social Sciences]

Our article (1) presents evidence for the heritability of trust and the shared socialization of distrust. Goldfarb et al. (2) downloaded our dataset, which we had made publicly available for all researchers. We thank them for their reanalysis, which precisely replicated all point estimates reported in our article (1). Our...

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Origins and genetic legacies of the Caribbean Taino [Anthropology]

The Caribbean was one of the last parts of the Americas to be settled by humans, but how and when the islands were first occupied remains a matter of debate. Ancient DNA can help answering these questions, but the work has been hampered by poor DNA preservation. We report the...

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Revealing nascent proteomics in signaling pathways and cell differentiation [Applied Biological Sciences]

Regulation of gene expression at the level of protein synthesis is a crucial element in driving how the genetic landscape is expressed. However, we are still limited in technologies that can quantitatively capture the immediate proteomic changes that allow cells to respond to specific stimuli. Here, we present a method...

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Correction for Meslin et al., Structural complexity and molecular heterogeneity of a butterfly ejaculate reflect a complex history of selection [Correction]

EVOLUTION Correction for "Structural complexity and molecular heterogeneity of a butterfly ejaculate reflect a complex history of selection," by Camille Meslin, Tamara S. Cherwin, Melissa S. Plakke, Brandon S. Small, Breanna J. Goetz, Nathan I. Morehouse, and Nathan L. Clark, which was first published June 19, 2017; 10.1073/pnas.1707680114 (Proc Natl...

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Correction for Leftwich et al., Gut microbiomes and reproductive isolation in Drosophila [Correction]

EVOLUTION Correction for "Gut microbiomes and reproductive isolation in Drosophila," by Philip T. Leftwich, Naomi V. E. Clarke, Matthew I. Hutchings, and Tracey Chapman, which was first published November 6, 2017; 10.1073/pnas.1708345114 (Proc Natl Acad Sci USA 114:12767–12772). The authors note that on page 12768, left column, first full paragraph,...

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Structure-based discovery of selective positive allosteric modulators of antagonists for the M2 muscarinic acetylcholine receptor [Pharmacology]

Subtype-selective antagonists for muscarinic acetylcholine receptors (mAChRs) have long been elusive, owing to the highly conserved orthosteric binding site. However, allosteric sites of these receptors are less conserved, motivating the search for allosteric ligands that modulate agonists or antagonists to confer subtype selectivity. Accordingly, a 4.6 million-molecule library was docked...

http://ift.tt/2oTV7ew

Epigenetic alterations in longevity regulators, reduced life span, and exacerbated aging-related pathology in old father offspring mice [Medical Sciences]

Advanced age is not only a major risk factor for a range of disorders within an aging individual but may also enhance susceptibility for disease in the next generation. In humans, advanced paternal age has been associated with increased risk for a number of diseases. Experiments in rodent models have...

http://ift.tt/2I9ESTi

Fast flow-based algorithm for creating density-equalizing map projections [Applied Mathematics]

Cartograms are maps that rescale geographic regions (e.g., countries, districts) such that their areas are proportional to quantitative demographic data (e.g., population size, gross domestic product). Unlike conventional bar or pie charts, cartograms can represent correctly which regions share common borders, resulting in insightful visualizations that can be the basis...

http://ift.tt/2I4OEWC

Genetic rescue of lineage-balanced blood cell production reveals a crucial role for STAT3 antiinflammatory activity in hematopoiesis [Immunology and Inflammation]

Blood cell formation must be appropriately maintained throughout life to provide robust immune function, hemostasis, and oxygen delivery to tissues, and to prevent disorders that result from over- or underproduction of critical lineages. Persistent inflammation deregulates hematopoiesis by damaging hematopoietic stem and progenitor cells (HSPCs), leading to elevated myeloid cell...

http://ift.tt/2I4Om1Y

Mitotic waves in the early embryogenesis of Drosophila: Bistability traded for speed [Biophysics and Computational Biology]

Early embryogenesis of most metazoans is characterized by rapid and synchronous cleavage divisions. Chemical waves of Cdk1 activity were previously shown to spread across Drosophila embryos, and the underlying molecular processes were dissected. Here, we present the theory of the physical mechanisms that control Cdk1 waves in Drosophila. The in...

http://ift.tt/2oV4ZEB

Defining the sizes of airborne particles that mediate influenza transmission in ferrets [Microbiology]

Epidemics and pandemics of influenza are characterized by rapid global spread mediated by non-mutually exclusive transmission modes. The relative significance between contact, droplet, and airborne transmission is yet to be defined, a knowledge gap for implementing evidence-based infection control measures. We devised a transmission chamber that separates virus-laden particles by...

http://ift.tt/2Fqg7nt

Prospective forecasts of annual dengue hemorrhagic fever incidence in Thailand, 2010-2014 [Statistics]

Dengue hemorrhagic fever (DHF), a severe manifestation of dengue viral infection that can cause severe bleeding, organ impairment, and even death, affects between 15,000 and 105,000 people each year in Thailand. While all Thai provinces experience at least one DHF case most years, the distribution of cases shifts regionally from...

http://ift.tt/2Ia2E1A

Distinct sets of tethering complexes, SNARE complexes, and Rab GTPases mediate membrane fusion at the vacuole in Arabidopsis [Plant Biology]

Membrane trafficking plays pivotal roles in various cellular activities and higher-order functions of eukaryotes and requires tethering factors to mediate contact between transport intermediates and target membranes. Two evolutionarily conserved tethering complexes, homotypic fusion and protein sorting (HOPS) and class C core vacuole/endosome tethering (CORVET), are known to act in...

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OligoMiner provides a rapid, flexible environment for the design of genome-scale oligonucleotide in situ hybridization probes [Applied Biological Sciences]

Oligonucleotide (oligo)-based FISH has emerged as an important tool for the study of chromosome organization and gene expression and has been empowered by the commercial availability of highly complex pools of oligos. However, a dedicated bioinformatic design utility has yet to be created specifically for the purpose of identifying optimal...

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MHC-mismatched mixed chimerism restores peripheral tolerance of noncross-reactive autoreactive T cells in NOD mice [Immunology and Inflammation]

Autoimmune type 1 diabetes (T1D) and other autoimmune diseases are associated with particular MHC haplotypes and expansion of autoreactive T cells. Induction of MHC-mismatched but not -matched mixed chimerism by hematopoietic cell transplantation effectively reverses autoimmunity in diabetic nonobese diabetic (NOD) mice, even those with established diabetes. As expected, MHC-mismatched...

http://ift.tt/2I4OhLI

Entropy drives selective fluorine recognition in the fluoroacetyl-CoA thioesterase from Streptomyces cattleya [Biochemistry]

Fluorinated small molecules play an important role in the design of bioactive compounds for a broad range of applications. As such, there is strong interest in developing a deeper understanding of how fluorine affects the interaction of these ligands with their targets. Given the small number of fluorinated metabolites identified...

http://ift.tt/2I4OApQ

Rocaglates as dual-targeting agents for experimental cerebral malaria [Microbiology]

Cerebral malaria (CM) is a severe and rapidly progressing complication of infection by Plasmodium parasites that is associated with high rates of mortality and morbidity. Treatment options are currently few, and intervention with artemisinin (Art) has limited efficacy, a problem that is compounded by the emergence of resistance to Art...

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Childhood asthma exacerbations and ADRB2 polymorphism: Caution is needed

Publication date: Available online 6 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Stephen Senn




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Reply

Publication date: Available online 6 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Steve Turner, Ben Francis




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The classroom microbiome and asthma morbidity in children attending three inner-city schools

Publication date: Available online 5 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Peggy S. Lai, Raivo Kolde, Eric A. Franzosa, Jonathan M. Gaffin, Sachin N. Baxi, William J. Sheehan, Diane R. Gold, Dirk Gevers, Ramnik J. Xavier, Wanda Phipatanakul

Teaser

The classroom microbiome is different from the home microbiome. Higher classroom microbial diversity is associated with increased asthma symptoms. In this pilot study, a school-level integrated pest management intervention changed the classroom microbiome.


http://ift.tt/2D56O70

Nasal and Ocular Challenges

Publication date: Available online 6 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Amber N. Pepper, Dennis K. Ledford
Nasal and ocular challenges facilitate the evaluation of subjective and objective responses to defined allergen or irritant exposure. Nasal and ocular allergen challenges (NACs and OACs) are the gold standard to diagnose allergic rhinitis and conjunctivitis, respectively, and aid in the evaluation of novel therapies in clinical trials. Additionally, NACs and OACs may help identify medically relevant allergens in clinical practice. Nonspecific or irritant challenges evaluate mucosal hyperreactivity. Direct mucosal challenges, which can be performed in an office or research setting, expose the participant to higher allergen doses than common in the natural environment. Park studies and environmental chambers, most practical in clinical trials, more closely simulate natural allergen exposure. International consensus guidelines for nasal and ocular challenges do not exist. Therefore, the positivity criteria, methodologies, and extract or allergen preparations utilized in challenges vary in the literature. Regardless of these limitations, nasal and ocular challenges are helpful clinical and research tools for nasal and ocular diseases.



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The Nasal Microbiome in Asthma

Publication date: Available online 5 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Mina Fazlollahi, Tricia D. Lee, Jade Andrade, Kasopefoluwa Oguntuyo, Yoojin Chun, Galina Grishina, Alexander Grishin, Supinda Bunyavanich
BackgroundNasal microbiota may influence asthma pathobiology.ObjectiveWe sought to characterize the nasal microbiome of subjects with exacerbated asthma, non-exacerbated asthma, and healthy controls to identify nasal microbiota associated with asthma activity.Methods16S rRNA sequencing was performed on nasal swabs obtained from 72 primarily adult subjects with exacerbated asthma (n=20), non-exacerbated asthma (n=31), and healthy controls (n=21). Analyses were performed using QIIME, LEfSe, PICRUSt, and STAMP. Species found to be associated with asthma activity were validated using quantitative PCR. Metabolic pathways associated with differentially abundant nasal taxa were also inferred through metagenomic functional prediction.ResultsNasal bacterial composition significantly differed between subjects with exacerbated asthma, non-exacerbated asthma, and healthy controls (PERMANOVA P=2.2x10^-2). Relative to controls, the nasal microbiota of subjects with asthma were enriched with taxa from Bacteroidetes (Wilcoxon-Mann-Whitney r=0.33, P=5.1x10^-3) and Proteobacteria (r=0.29, P=1.4x10^-2). Four species were differentially abundant based on asthma status after correction for multiple comparisons: Prevotella buccalis, Padj=1.0x10^-2; Dialister invisus, Padj=9.1x10^-3; Gardnerella vaginalis, Padj=2.8x10^-3; Alkanindiges hongkongensis, Padj=2.6x10^-3. These phyla and species were also differentially abundant based on asthma activity (exacerbated asthma vs. non-exacerbated asthma vs. controls). qPCR confirmed species overrepresentation in asthma relative to controls for Prevotella buccalis (fold change=130, P=2.1x10^-4) and Gardnerella vaginalis (fold change 160, P=6.8x10^-4). Metagenomic inference revealed differential glycerolipid metabolism (Kruskal-Wallis P=1.9x10^-4) based on asthma activity.ConclusionNasal microbiome composition differs in subjects with exacerbated asthma, non-exacerbated asthma, and healthy controls. The identified nasal taxa could be further investigated for potential mechanistic roles in asthma and as possible biomarkers of asthma activity.

Graphical abstract

Teaser

Upper airway microbiota may play a role in asthma pathobiology. This study characterized the nasal microbiome of subjects with exacerbated asthma, non-exacerbated asthma, and healthy controls, identifying bacterial taxa associated with asthma and asthma activity.


http://ift.tt/2FiiiGd

CD40 ligand deficiency causes functional defects of peripheral neutrophils that are improved by exogenous IFN-γ

Publication date: Available online 5 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Otavio Cabral-Marques, Tabata Takahashi França, Ashraf Al-Sbiei, Lena Friederike Schimke, Taj Ali Khan, Claudia Feriotti, Tania Alves da Costa, Osvaldo Reis Junior, Cristina Worm Weber, Janaíra Fernandes Ferreira, Fabiola Scancetti Tavares, Claudia Valente, Regina Sumiko Watanabe Di Gesu, Asif Iqbal, Gabriela Riemekasten, Gustavo Pessini Amarante-Mendes, José Alexandre Marzagão Barbuto, Beatriz Tavares Costa-Carvalho, Paulo Vitor Soeiro Pereira, Maria J. Fernandez-Cabezudo, Vera Lucia Garcia Calich, Luigi D. Notarangelo, Troy R. Torgerson, Basel K. al-Ramadi, Hans D. Ochs, Antonio Condino-Neto
BackgroundPatients with X-linked Hyper-IgM syndrome (X-HIGM) due to CD40 ligand (CD40L) deficiency often present episodic, cyclic or chronic neutropenia, suggesting abnormal neutrophil development in the absence of CD40L-CD40 interaction. However, even when not neutropenic and despite immunoglobulin (Ig) replacement therapy, CD40L-deficient patients are susceptible to life-threatening infections caused by opportunistic pathogens, suggesting impaired function of phagocytes and the need of novel therapeutic approaches.ObjectivesTo analyze whether peripheral neutrophils from CD40L-deficient patients display functional defects and to explore the in vitro effects of recombinant human interferon (rhIFN)-γ on neutrophil function.MethodsWe investigated the microbicidal activity, respiratory burst and transcriptome profile of neutrophils from CD40L-deficient patients. In addition, we evaluated whether the lack of CD40L in mice also affects neutrophil function.ResultsNeutrophils from CD40L-deficient patients exhibited defective respiratory burst and microbicidal activity which were improved in vitro by rhIFN-γ, but not soluble CD40L (sCD40L). Moreover, neutrophils from patients showed reduced CD16 protein expression and a dysregulated transcriptome suggestive of impaired differentiation. Similar to CD40L-deficient patients, CD40L-knockout mice were found to have impaired neutrophil responses. In parallel, we demonstrated that sCD40L induces the promyelocytic cell line HL-60 to proliferate and mature by regulating the expression of genes of the same gene ontology categories (e.g. cell differentiation) when compared to those dysregulated in peripheral blood neutrophils from CD40L-deficient patients.ConclusionOur data suggest a non-redundant role of CD40L-CD40 interaction in neutrophil development and function that could be improved in vitro by rhIFN-γ, indicating a potential novel therapeutic application for this cytokine.

Teaser

Neutrophils from CD40L-deficient patients exhibit defective development and function that suggest an important role of CD40L-CD40 interaction for neutrophil maturation. These defects improve following in vitro exposure to rhIFN-γ.


http://ift.tt/2FYFVVk

Rational combinations of in vivo cancer antigen priming and adoptive T-cell therapy mobilize immune and clinical responses in terminal cancers

Abstract

Purpose

It is now recognized that solid tumors encroach on the host's immune microenvironment to favor its own proliferation. Strategies to enhance the specificity of the endogenous T-cell population against tumors have been met with limited clinical success. We aimed to devise a two-tier protocol coupling in vivo whole antigen priming with ex vivo cellular expansion to clinically evaluate survival in patients following re-infusion of primed, autologous T cells, thereby determining treatment efficacy.

Experimental design

Treatment commenced with the acquisition of whole tumor antigens from tumor cell lines corresponding with patients' primary malignancy. Lysate mixture was inoculated intradermally, while peripheral blood mononuclear cells (PBMCs) were periodically extracted via phlebotomy and expanded in culture ex vivo for re-infusion. Post-treatment tumor-specific T-cell response and cytotoxicity was confirmed via Elispot and real-time cell analyzing (RTCA) assay. Serum cytokine levels and cytotoxicity scores were evaluated for associations with survival status and duration.

Results

There was a significant increase in cytotoxicity exhibited by T cells measured using both Elispot and RTCA following treatment. Correlation analysis determined significant association between higher post-treatment cytotoxicity scores and survival status (R = 0.52, p = 0.0028) as well as longer survival duration in months (R = 0.59, p = 0.005).

Conclusions

Our treatment protocol successfully demonstrated significant correlation between tumor-associated antigen-specific immune response and objective prolongation of survival. Whole-cell cancer antigen priming and adoptive T-cell therapy is, therefore, a highly feasible clinical model which can be easily replicated to positively influence outcome in end-stage malignancy.

http://ift.tt/2Flq81L

A short-term in vivo model for Merkel Cell Carcinoma

Abstract

In vivo tumour models are essential for studying the biology of cancer, identifying tumour targets and evaluating anti-tumour drugs. Considering the request for the minimization of animal experiments and following the „3R"-rule („replacement", „refinement", „reduction"), it has become crucial to develop alternative experimental models in cancer biology. Several studies have already described the avian chorioallantoic membrane (CAM) model as an alternative to rodents, suitable to investigate growth, progression and metastasis of various types of cancer. In the present work, we grafted three Merkel Cell Carcinoma (MCC) cell lines onto the avian CAM and monitored tumour growth and development of solid tumour nodules. Morphology of xenograft was characterized histologically and immunohistochemically. Our results demonstrate CAM assay as a useful tool to study MCC pathophysiology.

This article is protected by copyright. All rights reserved.

http://ift.tt/2tsJEbp

Myosin 10 is involved in murine pigmentation

Abstract

Myosins are molecular motors that are well known for their role in cell movement and contractile functions. Although extensively studied in muscle physiology, little is known about the function of myosins in mammalian skin. As part of the Sanger Institute Mouse Genetic Project, we have identified a role for Myo10 in pigmentation, with a phenotype unlike those of Myo5a or Myo7a. Adult mice homozygous for a disrupted Myo10 allele on a C57BL/6N background displayed a high degree of penetrance for white patches on their abdomen and dorsal surface. Fore- and hind paw syndactyly was also observed in these mice. Tail epidermal wholemounts showed a complete lack of melanocytes in the hair follicles and interfollicular epidermis. Myo10 previously been implicated in human pigmentation. Our current study reveals involvement of Myo10 in murine pigmentation.

This article is protected by copyright. All rights reserved.

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Capsaicin induces atopic dermatitis-like manifestations through dysregulation of proteolytic system and alteration of filaggrin processing in rats

Abstract

Atopic dermatitis (AD) is a complex disease featuring pruritic skin inflammation. Many animal models have been developed. In a rat model, subcutaneous capsaicin injection within 48 hours after birth induces AD-like skin manifestations of dermatitis and scratching behavior 3 weeks after the injection. When 2-4-week-old rats were injected with capsaicin, the lag period was shortened and the severity of skin manifestations was significantly reduced, suggesting influences of postnatal development. Lgr6 is an epidermal stem cell marker that is normally restricted to the isthmus area of hair follicles at postnatal 2 weeks. Lgr6 persisted in the interfollicular epidermis of capsaicin-injected rats beyond 3 weeks after birth, indicating that capsaicin-induced skin manifestations were influenced by postnatal epidermal development. Capsaicin injection induced alteration of proteolytic processing of filaggrin and corneodesmosin, suggesting epidermal barrier dysfunction. Inappropriate degradation of matriptase was observed. Degrees of proteolysis of these proteins were co-related with the severity of manifestations, suggesting that inappropriate proteolysis might be a possible cause of the skin manifestations. The results strongly suggest that capsaicin may dysregulate the protease system, resulting in alteration of profilaggrin and corneodesmosin proteolysis and skin manifestations. These events may be influenced by postnatal epidermal development.

This article is protected by copyright. All rights reserved.

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Bioglass reconstruction of posterior meatal wall after canal wall down mastoidectomy

Publication date: Available online 6 March 2018
Source:American Journal of Otolaryngology
Author(s): Samir Sorour Sorour, Nasser Nagieb Mohamed, Magdy M. Abdel Fattah, Mohammad El-Sayed Abd Elbary, Mohammad Waheed El-Anwar
BackgroundCanal wall down (CWD) mastoidectomy has many drawbacks including chronic otorrhea, granulations, dizziness on exposure to cold or hot water and tendency of debris accumulation in the mastoid cavity demanding periodic cleaning. Many of these problems can be solved by reconstruction of the posterior meatal wall (PMW).ObjectivesTo assess the results of PMW reconstruction after CWD mastoidectomy for cholesteatoma using bioactive glass (BAG) that is fabricated and built up intraoperatively.Patients and methodsThis study was applied on 20 patients had atticoantral chronic suppurative otitis media. All cases were subjected to CWD mastoid surgery with complete elimination of the disease and reconstruction of the PMW by BAG that was prepared and built up intraoperatively. All patients were exposed to full preoperative evaluation and full postoperative assessment of complications, appearance of the external auditory canal contour, and the hearing gain expressed by the change of the air bone gap postoperatively.ResultsDuring a follow up of 12 to 36 months, postoperative appearance of external auditory canal contour was found smooth without hidden pouches, irregularities nor stenosis in all cases. No registered granulation, foreign body reaction, nor extrusion and/or displacement of the BAG material. No reported facial palsy or recurrent cholesteatoma. Significant hearing improvement was statistically reported (p = 0.0006).ConclusionSurgical reconstruction of the PMW using BAG that operatively fashioned immediately after CWD mastoidectomy appears to be reliable without considerable complications giving smooth appearance of the PMW and improving the hearing.



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Audiological profiling in postmenopausal women with osteoporosis

Publication date: Available online 6 March 2018
Source:American Journal of Otolaryngology
Author(s): K. Kshithi, S. Vijendra Shenoy, M. Panduranga Kamath, Suja Sreedharan, N. Manisha, Meera N. Khadilkar, Vikranth Kamboj, Jayashree S. Bhat
ObjectivesTo compare the audiological profiles in postmenopausal women with and without osteoporosis and to study the pattern of hearing loss in osteoporotic patients.Materials and methods80 postmenopausal women were evaluated at a tertiary referral center and were divided into normal, osteopenic and osteoporotic based on BMD results. The hearing evaluation was done using PTA, Impedance audiometry and DPOAE and the results were compared between the groups and analyzed.ResultsOsteoporotic patients had higher incidence of sensorineural hearing loss than normal and osteopenic patients and the results were statistically significant (P ≤0.001) on PTA and DPOAE testing. The mean pure tone thresholds were significantly higher in osteoporotic patients in comparison with normal and osteopenic patients. The average hearing loss in osteoporotic patients with sensorineural loss was of mild degree.ConclusionThe data reveal that osteoporosis is associated with sensorineural hearing loss in postmenopausal women. The underlying mechanism needs further research but cochlear dysfunction could be an important factor.



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Cortactin expression in nasal polyps of aspirin-exacerbated respiratory disease (aerd) patients

Publication date: Available online 5 March 2018
Source:American Journal of Otolaryngology
Author(s): Giuseppe Brescia, Daniela Parrino, Lorenzo Nicolè, Claudia Zanotti, Cristiano Lanza, Umberto Barion, Filippo Marino, Gino Marioni
PurposeThe term aspirin-exacerbated respiratory disease (AERD) refers to a combination of asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), and acute respiratory tract reactions to nonsteroidal anti-inflammatory drugs. AERD has now been included among the CRSwNP endotypes, and is considered one of the most aggressive in terms of disease recurrence.Cortactin is a multi-domain protein with a part in several cellular mechanisms involving actin assembly and cytoskeleton arrangement. Cortactin seems to have a role in inflammatory responses and to be implicated in human airway secretion and contraction mechanisms.The novel aim of the present study was to examine cortactin expression in nasal polyps of a consecutive cohort of AERD patients.Materials and methodsCortactin expression was assessed immunohistochemically in nasal polyps from 18 consecutive AERD patients who underwent endoscopic sinus surgery.ResultsConcomitant allergy was found in 11 AERD patients, most of them male (8 cases; p = 0.026018). Cortactin expression in nasal polyps was definitely high (+3) in 17 out of 18 cases, in both epithelial cells (cytoplasmic and membranous immunoreactivity) and activated fibroblasts. A higher cortactin expression was seen in female than in male AERD patients (p = 0.05).ConclusionsGiven this preliminary evidence of cortactin upregulation in the polyps of AERD patients, prospective studies could further investigate the role of cortactin in the biology of AERD, and the potential role of cortactin-targeted approaches in integrated AERD treatments.



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Efficacy and safety of eberconazole 1% otic solution compared to clotrimazole 1% solution in patients with otomycosis

Publication date: Available online 6 March 2018
Source:American Journal of Otolaryngology
Author(s): Blanca Regina de la Paz Cota, Pedro Pablo Cepero Vega, Juan José Matus Navarrete, Gerardo Efrain Aguado Mulgado, José Juan Narváez Huerta, Enrique Lamadrid Bautista, Epifanio Fiscal Chauteco
PurposeTo demonstrate non-inferiority of eberconazole 1% otic solution to clotrimazole 1% solution, and to compare their safety profile in the treatment of otomycosis.Materials and methodsMulticenter, randomized, double-blind, active treatment-controlled phase 3 clinical trial. One hundred and ninety patients with diagnosis of otomycosis were randomly assigned to eberconazole 1% otic solution or clotrimazole 1% solution.ResultsBaseline characteristics were comparable between both groups for age, gender, ethnicity, and clinical variables. Both study groups had high complete response rates: 81.8% in the eberconazole group and 83.5% in the clotrimazole group. Although non-inferiority of eberconazole relative to clotrimazole could not be demonstrated, a post-hoc sensitivity analysis demonstrated that eberconazole 1% otic solution was not inferior to clotrimazole 1% solution for the primary efficacy endpoint. Secondary endpoints also demonstrated that eberconazole 1% and clotrimazole 1% solutions were therapeutically similar at the end of the study. The incidence of adverse events was similar in both groups, and none had related AEs and withdrawals due to an AE.ConclusionsEberconazole 1% otic solution is an efficacious and safe option to treat otomycosis-affected patients in the general practice.



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Rapid detection of superficial head and neck squamous cell carcinoma by topically spraying fluorescent probe targeting dipeptidyl peptidase-IV

Abstract

Background

A fluorescent probe glutamylprolyl hydroxymethyl rhodamine green (EP-HMRG), which becomes fluorescent after cleavage by dipeptidyl peptidase-IV (DPP-IV), has been reported to be useful for the detection of esophageal cancer. Thus, we investigated whether head and neck squamous cell carcinoma (HNSCC) can be detected by spraying EP-HMRG.

Methods

Fluorescence imaging of 17 cases of HNSCCs resected using endoscopic or surgical resection was performed ex vivo after spraying EP-HMRG, and then the fluorescence intensity of the tumors and normal mucosa were measured.

Results

Iodine-voiding lesions became fluorescent within a few minutes after the application of EP-HMRG in 12 resected tumors without a history of radiotherapy but this was not observed in the normal mucosa. Fluorescence intensity in tumor lesions was significantly higher than normal lesions. However, 5 other tumors that developed after radiotherapy did not have sufficient contrast against normal mucosa.

Conclusion

Fluorescence imaging with EP-HMRG would be useful for rapid detection of superficial HNSCC without a history of radiotherapy.

http://ift.tt/2FlGffI

Possible association between Helicobacter pylori infection and vocal fold leukoplakia

Abstract

Background

Several studies have indicated the larynx as possible Helicobacter pylori (H. pylori) reservoirs. This study explored the association between H. pylori and vocal fold leukoplakia.

Methods

The case-control study involved 51 patients with vocal fold leukoplakia and 35 control patients with vocal polyps. Helicobacter pylori was detected in tissues by the rapid urease test, nested polymerase chain reaction (PCR), and single-step PCR. The H. pylori-specific immunoglobulin antibodies were detected in plasma by enzyme-linked immunosorbent assay (ELISA).

Results

Helicobacter pylori-positive rate of vocal fold leukoplakia and vocal polyps was 23.5% versus 11.4% (P = .157), 37.2% versus 14.3% (P = .020), 27.5% versus 8.6% (P = .031), and 70.6% versus 68.6% (P = .841) detected by rapid urease test, nested PCR, single-step PCR, and ELISA, respectively. Regression analysis indicated that H. pylori infection (P = .044) was the independent risk factor for vocal fold leukoplakia.

Conclusion

Helicobacter pylori infection exists in the larynx and may be associated with vocal fold leukoplakia.

http://ift.tt/2FYzUIr

Prognostic importance of solid variant papillary thyroid carcinoma: A systematic review and meta-analysis

Abstract

Background

Solid variant papillary thyroid carcinoma (SVPTC) is a rare variant of papillary thyroid cancer (PTC) and its prognostic value is still unclear. The purpose of this systematic clinical review and meta-analysis is to investigate the prognostic value of SVPTC in comparison with classical PTC (cPTC).

Methods

Four electronic databases, including PubMed, Scopus, Web of Science, and Virtual Health Library, were searched in June 2017. Extracted data were pooled into odds ratio (OR) or hazard ratio (HR) and their corresponding 95% confidence interval (CI) using the random-effect model.

Results

From 1439 articles, we finally included 11 studies with 205 SVPTCs for meta-analysis. Overall, SVPTC manifested a significantly higher risk for vascular invasion, tumor recurrence, and cancer mortality as compared to cPTC. The genetic profile of SVPTC was also distinct from that of cPTC.

Conclusion

A case of SVPTC should be regarded as an aggressive variant of PTC because of a higher risk for tumor recurrence and mortality.

http://ift.tt/2FkcV9w

Tax Mistakes Post-Pitt v Holt

Davies, PS; Douglas, S; (2018) Tax Mistakes Post-Pitt v Holt. Trust Law International (In press).

http://ift.tt/2oWFRx8

Identifiability, reducibility, and adaptability in allosteric macromolecules

Bohner, G; Venkataraman, G; (2017) Identifiability, reducibility, and adaptability in allosteric macromolecules. Journal of General Physiology , 149 (5) pp. 547-560. 10.1085/jgp.201611751 . Green open access

http://ift.tt/2I6Onmn

Astronomical tunings of the Oligocene-Miocene transition from Pacific Ocean Site U1334 and implications for the carbon cycle

Beddow, HM; Liebrand, D; Wilson, DS; Hilgen, FJ; Sluijs, A; Wade, BS; Lourens, LJ; (2018) Astronomical tunings of the Oligocene-Miocene transition from Pacific Ocean Site U1334 and implications for the carbon cycle. Climate of the Past , 14 (3) pp. 255-270. 10.5194/cp-14-255-2018 . Green open access

http://ift.tt/2oU9n6M

Explicit and implicit attitudes towards people with intellectual disabilities: The role of contact and participant demographics

Murch, AJ; Choudhury, T; Wilson, M; Collerton, E; Patel, M; Scior, K; (2017) Explicit and implicit attitudes towards people with intellectual disabilities: The role of contact and participant demographics. Journal of Applied Research in Intellectual Disabilities 10.1111/jar.12429 . (In press).

http://ift.tt/2I6I1mF

Molecular dynamics simulations of propane in slit shaped silica nano-pores: direct comparison with quasielastic neutron scattering experiments

Gautam, S; Le, T; Striolo, A; Cole, D; (2017) Molecular dynamics simulations of propane in slit shaped silica nano-pores: direct comparison with quasielastic neutron scattering experiments. Physical Chemistry Chemical Physics , 19 (48) pp. 32320-32332. 10.1039/c7cp05715f .

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CSF Beta-amyloid 1-42 Concentration Predicts Delirium Following Elective Arthroplasty Surgery in an Observational Cohort Study

Cunningham, EL; McGuinness, B; McAuley, DF; Toombs, J; Mawhinney, T; O'Brien, S; Beverland, D; ... Passmore, AP; + view all Cunningham, EL; McGuinness, B; McAuley, DF; Toombs, J; Mawhinney, T; O'Brien, S; Beverland, D; Schott, JM; Lunn, MP; Zetterberg, H; Passmore, AP; - view fewer (2018) CSF Beta-amyloid 1-42 Concentration Predicts Delirium Following Elective Arthroplasty Surgery in an Observational Cohort Study. Annals of Surgery 10.1097/SLA.0000000000002684 . (In press).

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Reverse Myocardial Remodeling Following Valve Replacement in Patients With Aortic Stenosis

Treibel, TA; Kozor, R; Schofield, R; Benedetti, G; Fontana, M; Bhuva, AN; Sheikh, A; ... Moon, JC; + view all Treibel, TA; Kozor, R; Schofield, R; Benedetti, G; Fontana, M; Bhuva, AN; Sheikh, A; López, B; González, A; Manisty, C; Lloyd, G; Kellman, P; Díez, J; Moon, JC; - view fewer (2018) Reverse Myocardial Remodeling Following Valve Replacement in Patients With Aortic Stenosis. Journal of the American College of Cardiology , 71 (8) pp. 860-871. 10.1016/j.jacc.2017.12.035 . Green open access

http://ift.tt/2oS4VW4

Local Voices on Renewable Energy: the performative role of the regulatory process for major offshore infrastructure in England and Wales

Rydin, YJ; Natarajan, L; Lee, M; Lock, S; (2018) Local Voices on Renewable Energy: the performative role of the regulatory process for major offshore infrastructure in England and Wales. Local Environment (In press).

http://ift.tt/2I8S9LE

C9orf72 expansion disrupts ATM-mediated chromosomal break repair

Walker, C; Herranz-Martin, S; Karyka, E; Liao, C; Lewis, K; Elsayed, W; Lukashchuk, V; ... El-Khamisy, SF; + view all Walker, C; Herranz-Martin, S; Karyka, E; Liao, C; Lewis, K; Elsayed, W; Lukashchuk, V; Chiang, S-C; Ray, S; Mulcahy, PJ; Jurga, M; Tsagakis, I; Iannitti, T; Chandran, J; Coldicott, I; De Vos, KJ; Hassan, MK; Higginbottom, A; Shaw, PJ; Hautbergue, GM; Azzouz, M; El-Khamisy, SF; - view fewer (2017) C9orf72 expansion disrupts ATM-mediated chromosomal break repair. Nature Neuroscience , 20 (9) pp. 1225-1235. 10.1038/nn.4604 . Green open access

http://ift.tt/2oS4Gu8

Patient reported outcome and experience measures of oral disease in oral medicine

Ni Riordain, R; Wiriyakijja, P; (2017) Patient reported outcome and experience measures of oral disease in oral medicine. British Dental Journal , 223 (9) pp. 713-718. 10.1038/sj.bdj.2017.889 .

http://ift.tt/2I8iA4c

Black-boxing the evidence: planning regulation and major renewable energy infrastructure projects in England and Wales

Rydin, YJ; Natarajan, L; Lee, M; Lock, S; (2018) Black-boxing the evidence: planning regulation and major renewable energy infrastructure projects in England and Wales. Planning Theory and Practice (In press).

http://ift.tt/2oS4tHm

Investigation on the reactivity of tetranuclear Group 7/8 mixed-metal clusters toward triphenylphosphine

Tocher, DA; Moni, R; Mia, J; Ghosh, S; Mobin, S; Siddiquee, T; Kabir, S; (2018) Investigation on the reactivity of tetranuclear Group 7/8 mixed-metal clusters toward triphenylphosphine. Polyhedron (In press).

http://ift.tt/2I7KIoe

Defined and Scalable Generation of Hepatocyte-like Cells from Human Pluripotent Stem Cells

Wang, Y; Alhaque, S; Cameron, K; Meseguer-Ripolles, J; Lucendo-Villarin, B; Rashidi, H; Hay, DC; (2017) Defined and Scalable Generation of Hepatocyte-like Cells from Human Pluripotent Stem Cells. JOVE-Journal of Visualized Experiments (121) 10.3791/55355 . Green open access

http://ift.tt/2oQf99A

Antisense oligonucleotide therapy for spinocerebellar ataxia type 2

Scoles, DR; Meera, P; Schneider, MD; Paul, S; Dansithong, W; Figueroa, KP; Hung, G; ... Pulst, SM; + view all Scoles, DR; Meera, P; Schneider, MD; Paul, S; Dansithong, W; Figueroa, KP; Hung, G; Rigo, F; Bennett, CF; Otis, TS; Pulst, SM; - view fewer (2017) Antisense oligonucleotide therapy for spinocerebellar ataxia type 2. Nature , 544 (7650) pp. 362-366. 10.1038/nature22044 . Green open access

http://ift.tt/2I5BQj3

Sox7 promotes high-grade glioma by increasing VEGFR2-mediated vascular abnormality

Kim, I-K; Kim, K; Lee, E; Oh, DS; Park, CS; Park, S; Yang, JM; ... Kim, I; + view all Kim, I-K; Kim, K; Lee, E; Oh, DS; Park, CS; Park, S; Yang, JM; Kim, J-H; Kim, H-S; Shima, DT; Kim, JH; Hong, SH; Cho, YH; Kim, YH; Park, JB; Koh, GY; Ju, YS; Lee, HK; Lee, S; Kim, I; - view fewer (2018) Sox7 promotes high-grade glioma by increasing VEGFR2-mediated vascular abnormality. Journal of Experimental Medicine , 215 (3) pp. 963-983. 10.1084/jem.20170123 .

http://ift.tt/2oTB2F6

Decreased surface expression of the 8 subunit of the GABA(A) receptor contributes to reduced tonic inhibition in dentate granule cells in a mouse model of fragile X syndrome

Zhang, N; Peng, Z; Tong, X; Lindemeyer, AK; Cetina, Y; Huang, CS; Olsen, RW; ... Houser, CR; + view all Zhang, N; Peng, Z; Tong, X; Lindemeyer, AK; Cetina, Y; Huang, CS; Olsen, RW; Otis, TS; Houser, CR; - view fewer (2017) Decreased surface expression of the 8 subunit of the GABA(A) receptor contributes to reduced tonic inhibition in dentate granule cells in a mouse model of fragile X syndrome. Experimental Neurology , 297 pp. 168-178. 10.1016/j.expneurol.2017.08.008 .

http://ift.tt/2I3Am8V

Mapping Relapse and Relapse Detection of Wilms Tumour - A Report from The SIOP Renal Tumour Study Group

Brok, J; Lopez, M; Harm, VT; Treger, TD; Furtwaengler, R; Graf, N; Bergeron, C; ... Spreafico, F; + view all Brok, J; Lopez, M; Harm, VT; Treger, TD; Furtwaengler, R; Graf, N; Bergeron, C; van den Heuvel-Eibrink, MM; de Camargo, B; Verschuur, A; Pritchard-Jones, K; Olsen, O; Spreafico, F; - view fewer (2017) Mapping Relapse and Relapse Detection of Wilms Tumour - A Report from The SIOP Renal Tumour Study Group. Presented at: 49th Congress of the International Society of Paediatric Oncology (SIOP), Washington, DC, USA.

http://ift.tt/2oU8JGo

Development of a machine learning potential for graphene

Rowe, P; Csanyi, G; Alfe, D; Michaelides, A; (2018) Development of a machine learning potential for graphene. Physical Review B , 97 (5) , Article 054303. 10.1103/PhysRevB.97.054303 . Green open access

http://ift.tt/2I74vE7

Effect of mass paediatric influenza vaccination on existing influenza vaccination programmes in England and Wales: a modelling and cost-effectiveness analysis

Hodgson, D; Baguelin, M; van Leeuwen, E; Panovska-Griffiths, J; Ramsay, M; Pebody, R; Atkins, KE; (2017) Effect of mass paediatric influenza vaccination on existing influenza vaccination programmes in England and Wales: a modelling and cost-effectiveness analysis. The Lancet Public Health , 2 (2) e74-e81. 10.1016/S2468-2667(16)30044-5 . Green open access

http://ift.tt/2oU6cvZ

Gene co-expression network analysis for identifying modules and functionally enriched pathways in SCA2

Pflieger, LT; Dansithong, W; Paul, S; Scoles, DR; Figueroa, KP; Meera, P; Otis, TS; ... Pulst, SM; + view all Pflieger, LT; Dansithong, W; Paul, S; Scoles, DR; Figueroa, KP; Meera, P; Otis, TS; Facelli, JC; Pulst, SM; - view fewer (2017) Gene co-expression network analysis for identifying modules and functionally enriched pathways in SCA2. Human Molecular Genetics , 26 (16) pp. 3069-3080. 10.1093/hmg/ddx191 .

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Study Advances Research in Pelvic Organ Prolapse Among Women

By measuring the sagging of the vaginal walls in more than a thousand volunteers for up to nine years annually, a team of Baltimore physicians reports the creation of a long-awaited baseline measure of the rate of progression of so-called pelvic organ prolapse. The baseline, they say, should provide a foundation for reliable studies and a more rational search for factors that prevent or ease the condition.

http://ift.tt/2FhylnH

Fibrillin-1 insufficiency alters periodontal wound healing failure in a mouse model of Marfan syndrome

Publication date: Available online 6 March 2018
Source:Archives of Oral Biology
Author(s): Keisuke Handa, Syouta Abe, V. Venkata Suresh, Yoshiyasu Fujieda, Masaki Ishikawa, Ai Orimoto, Yoko Kobayashi, Satoru Yamada, Satoko Yamaba, Shinya Murakami, Masahiro Saito
ObjectiveMarfan syndrome (MFS) is a systemic connective tissue disorder caused by insufficient fibrillin-1 (FBN-1), a major component of microfibrils that controls the elasticity and integrity of connective tissues. FBN-1 insufficiency in MFS leads to structural weakness, which causes various tissue disorders, including cardiovascular and periodontal disease. However, the role of FBN-1 insufficiency in the destruction and regeneration of connective tissue has not yet been clarified. To investigate the role of FBN-1 insufficiency in tissue destruction and regeneration.DesignWe used a ligature-induced (LI) periodontal disease model in fbn-1-deficient mice (fbn-1^c1039G/+ mice) with MFS and investigated the regeneration level of periodontal tissue and as an inflamatic marker, the expression of the matrix metalloproteinase (mmp)-9 and tumor necrosis factor (tnf)-α.ResultsInterestingly, fbn-1^c1039G/+ mice exhibited slowed wound healing compared with wild type mice, but periodontal tissue destruction did not differ between these mice. Moreover, fbn-1^c1039G/+ mice exhibited delayed bone healing in association with continuous mmp-9 and tnf-α expression. Furthermore, inflammatory cells were obvious even after the removal of ligatures.ConclusionThese data suggest that fibrillin-1 insufficiency in fbn-1^c1039G/+ mice interfered with wound healing in connective tissue damaged by inflammatory diseases such as periodontal disease.



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DNA damage response following X-irradiation in oral cancer cell lines HSC3 and HSC4

Publication date: Available online 6 March 2018
Source:Archives of Oral Biology
Author(s): Sirimanas Jiaranuchart, Atsushi Kaida, Yusuke Onozato, Hiroyuki Harada, Masahiko Miura
ObjectiveThe objective of this study was to characterize the DNA damage response in two human oral cancer cell lines following X-irradiation.DesignTo visualize radiation-induced cell cycle alterations, two human oral cancer cell lines, HSC3 and HSC4, expressing fluorescent ubiquitination-based cell cycle indicator (Fucci) were established in this study. G2 arrest kinetics following irradiation were obtained from two-color flow cytometric analysis and pedigrees of Fucci fluorescence. DNA double strand break repair kinetics were obtained from immunofluorescence staining for phosphorylated histone H2AX, p53-binding protein 1, phosphorylated DNA-dependent protein kinase catalytic subunit, and breast cancer susceptibility gene 1.ResultsBoth cell lines showed apparent G2 arrest after 10 Gy of irradiation, but it was more enhanced in the HSC3-Fucci cells. Radiosensitivity was higher in the HSC3-Fucci cells than in HSC4-Fucci cells. Pedigree analysis of Fucci fluorescence revealed that the HSC3-Fucci cells exhibited a significantly longer green phase (normally indicating S/G2/M phases, but here reflective of G2 arrest) when irradiated in the red phase (G1 phase) than HSC4-Fucci cells irradiated in either red or green phases. Non-homologous end joining was marginally suppressed during the G1 phase and markedly more likely to be impaired during the S/G2 phases in HSC3-Fucci cells. When G2 arrest was abrogated by checkpoint kinase 1 or Wee1 inhibitors, only HSC4-Fucci cells exhibited radiosensitization.ConclusionsWe characterized DNA damage response in HSC3-Fucci and HSC4-Fucci cells following irradiation and the former demonstrated inefficient non-homologous end joining, especially during the S/G2 phases, resulting in enhanced G2 arrest. These findings may have clinical implications for oral cancer.



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pH changes of mixed biofilms of Streptococcus mutans and Candida albicans after exposure to sucrose solutions in vitro

Publication date: Available online 6 March 2018
Source:Archives of Oral Biology
Author(s): Thamires Priscila Cavazana, Juliano Pelim Pessan, Thayse Yumi Hosida, Douglas Roberto Monteiro, Alberto Carlos Botazzo Delbem
ObjectiveThis study aimed to standardize an in vitro experimental model able to reproduce the pH changes that occur in dental biofilm under in vivo conditions, using a mixed biofilm of Streptococcus mutans and Candida albicans.DesignBiofilms were developed for 96 hours, and exposed to three different concentrations of sucrose (10, 20 or 30%) during 1, 3 or 5 minutes. The pH was measured before exposure to sucrose, immediately after its removal from the biofilms, and at 1, 3, 5 and 10 minutes after removal.ResultsSucrose solutions at 10 and 20% required 1 minute to significantly reduce the biofilm pH, while for 30% sucrose a significant reduction was already seen immediately after its removal, even for the shortest exposure time. For an exposure of 3 minutes to 20% sucrose, the biofilm pH attained the critical value for hydroxyapatite dissolution when measured 1 minute after sucrose removal, followed by a recovery phase.ConclusionsA mixed biofilm of S. mutans and C. albicans exposed to a 20% sucrose solution for 3 minutes exhibited a pattern of pH change similar to that observed in vivo, despite at a higher speed when compared to in vivo conditions.



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Functional and Molecular Characterization of Transmembrane Intracellular pH Regulators in Human Dental Pulp Stem Cells

Publication date: Available online 6 March 2018
Source:Archives of Oral Biology
Author(s): Gunng-Shinng Chen, Shiao-Pieng Lee, Shu-Fu Huang, Shih-Chi Chao, Chung-Yi Chang, Gwo-Jang Wu, Chung-Hsing Li, Shih-Hurng Loh
ObjectiveHomeostasis of intracellular pH (pHi) plays vital roles in many cell functions, such as proliferation, apoptosis, differentiation and metastasis. Thus far, Na⁺-H⁺ exchanger (NHE), Na⁺-HCO3⁻ co-transporter (NBC), Cl⁻/HCO3⁻ exchanger (AE) and Cl⁻/OH⁻ exchanger (CHE) have been identified to co-regulate pHi homeostasis. However, functional and biological pHi-regulators in human dental pulp stem cells (hDPSCs) have yet to be identified.DesignMicrospectrofluorimetry technique with pH-sensitive fluorescent dye, BCECF, was used to detect pHi changes. NH4Cl and Na⁺-acetate pre-pulse were used to induce intracellular acidosis and alkalosis, respectively. Isoforms of pHi-regulators were detected by Western blot technique.ResultsThe resting pHi was no significant difference between that in HEPES-buffered (nominal HCO3⁻-free) solution or CO2/HCO3-buffered system (7.42 and 7.46, respectively). The pHi recovery following the induced-intracellular acidosis was blocked completely by removing [Na⁺]o, while only slowed (-63%) by adding HOE694 (a NHE1 specific inhibitor) in HEPES-buffered solution. The pHi recovery was inhibited entirely by removing [Na⁺]o, while adding HOE 694 pulse DIDS (an anion-transporter inhibitor) only slowed (-55%) the acid extrusion. Both in HEPES-buffered and CO2/HCO3-buffered system solution, the pHi recovery after induced-intracellular alkalosis was entirely blocked by removing [Cl⁻]o. Western blot analysis showed the isoforms of pHi regulators, including NHE1/2, NBCe1/n1, AE1/2/3/4 and CHE in the hDPSCs.ConclusionsWe demonstrate for the first time that resting pHi is significantly higher than 7.2 and meditates functionally by two Na⁺-dependent acid extruders (NHE and NBC), two Cl⁻-dependent acid loaders (CHE and AE) and one Na⁺-independent acid extruder(s) in hDPSCs. These findings provide novel insight for basic and clinical treatment of dentistry.



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Evaluation of Interleukin-1β Level and Oxidative Status in Gingival Crevicular Fluid during Rapid Maxillary Expansion

Publication date: Available online 6 March 2018
Source:Archives of Oral Biology
Author(s): Nur Ozel, Alev Aksoy, Fatma Yesim Kırzıoglu, Duygu Kumbul Doguc, Tutku Atış Aksoy
ObjectivesThe levels of interleukin-1β (IL-1β), nitric oxide (NO), total antioxidant capacity (TAC), and total oxidant status (TOS) in gingival crevicular fluid (GCF) were determined during rapid maxillary expansion (RME) treatment.Materials and methodsFourteen patients (10–13 years old) were included. A modified hyrax appliance was used for the treatment. After periodontal parameters were recorded, GCF was collected from the first molars at each observation [T1:baseline:14 days after periodontal prophylaxis and instructions; T2:1 day later hyrax inserted, at passive position; T3:1 week later; after the first activation; T4:after 2 × 1/4 activation; T5:after 7 × 1/4 activation; T6:after 14 × 1/4 activation; T7:retention period on the 1 st month; and T8:retention period on the 3rd month].ResultsAlthough the levels of IL1-β, NO, and PD increased significantly from T1 to T2, the GI, BOP%, and PI remained unchanged throughout treatment. GCF volume at buccal and palatal surfaces increased significantly from T1 to T4, T6, T7, and T8. The parameters in GCF and TAC levels were not only higher at palatal side in comparison with buccal, but also TOS levels increased at both buccal and palatal sides.ConclusionsIn this study, the differences of oxidative status and IL-1β levels during RME treatment could be attributable to orthopedic effect of the heavy forces on maxilla and minimal orthodontic forces on teeth applied by the RME apparatus.



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Porcine Isolated Liver Perfusion for the Study of Ischemia Reperfusion Injury: a Systematic Review

AbstractBackgroundUnderstanding ischemia reperfusion injury (IRI) is essential to further improve outcomes after liver transplantation (LT). Porcine isolated liver perfusion (ILP) is increasingly used to reproduce LT-associated IRI in a strictly controlled environment. However, whether ILP is a reliable substitute of LT was never validated.MethodsWe systematically reviewed the current experimental set-ups for ILP and parameters of interest reflecting IRI.ResultsILP was never compared to transplantation in animals. Considerable variability exists between set-ups and comparative data are unavailable. Experience so far suggests that centrifugal pump(s) with continuous flow are preferred to reduce the risk of embolism. Hepatic outflow can be established by cannulation of the inferior vena cava or freely drained in an open bath. Whole blood at ~38°C, hematocrit ≥ 20%, and the presence of leukocytes to trigger inflammation is considered the optimal perfusate. A number of parameters related to the 4 liver compartments (hepatocyte, cholangiocyte, endothelium, immune cells) are available; however, their significance and relation to clinical outcomes is not well described.ConclusionsPorcine ILP provides a reproducible model to study early IRI events. As all models it has its limitations. A standardization of the set-up would allow comparison of data and progress in the field. Background Understanding ischemia reperfusion injury (IRI) is essential to further improve outcomes after liver transplantation (LT). Porcine isolated liver perfusion (ILP) is increasingly used to reproduce LT-associated IRI in a strictly controlled environment. However, whether ILP is a reliable substitute of LT was never validated. Methods We systematically reviewed the current experimental set-ups for ILP and parameters of interest reflecting IRI. Results ILP was never compared to transplantation in animals. Considerable variability exists between set-ups and comparative data are unavailable. Experience so far suggests that centrifugal pump(s) with continuous flow are preferred to reduce the risk of embolism. Hepatic outflow can be established by cannulation of the inferior vena cava or freely drained in an open bath. Whole blood at ~38°C, hematocrit ≥ 20%, and the presence of leukocytes to trigger inflammation is considered the optimal perfusate. A number of parameters related to the 4 liver compartments (hepatocyte, cholangiocyte, endothelium, immune cells) are available; however, their significance and relation to clinical outcomes is not well described. Conclusions Porcine ILP provides a reproducible model to study early IRI events. As all models it has its limitations. A standardization of the set-up would allow comparison of data and progress in the field. These authors contributed equally, Francesca Maione, MD, Nicholas Gilbo. Correspondence: Diethard Monbaliu, MD, PhD, Abdominal Transplant Surgery and Coordination, University Hospitals Leuven, Herestraat 49, B-3000 Leuven (Belgium), E-mail: diethard.monbaliu@uzleuven.be Authorship: FM, NG, IJ and DM designed the study, acquired, analyzed and interpreted the data, wrote the manuscript and take responsibility for the integrity of the data and the accuracy of the data analysis. SL acquired, analyzed and interpreted the data. GC, RR, JP and PF contributed to the interpretation of data, critically revised and approved the manuscript and take responsibility for the integrity of the data and the accuracy of the data analysis. Disclosure: The authors declare no conflicts of interest with regard to the conduction and reporting of the results of the systematic review presented in this manuscript, in line with the editorial policy of Transplantation Funding: JP holds a named chair at the KU Leuven from the Institut Georges Lopez. JP, DM, and IJ hold a named chair at the KU Leuven from the "Centrale Afdeling voor Fractionering". DM is a senior clinical investigator of the research foundation Flanders, Belgium (FWO 18B1916N). No specific funding was sought for the present study. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Specific Immunity to Cytomegalovirus in Pediatric Cardiac Transplantation

ABSTRACTBackgroundCytomegalovirus (CMV) infection is implicated in endothelial dysfunction and graft damage after pediatric heart transplantation. CMV specific immune responses are thought to be necessary for CMV viral control but there is little data in pediatric heart transplantation.MethodsWe studied 28 consecutive pediatric heart transplant recipients for 1-year posttransplant. CMV-specific T cells expressing IFN-γ, TNF-α and IL-2 in response to ex-vivo stimulation with CMV lysates or peptides were measured. Circulating cytokines were measured in plasma. Generalised Additive Models were applied to the data to model changes of cell population dynamics over time.ResultsCMV-specific T cell mediated responses were impaired in the first 8 weeks posttransplant. During this period, 25% of patients had CMV viremia, of which those with viral loads ≥10,000 CMV DNA copies/mL were given ganciclovir. In this group, the frequency of CD4+ and CD8+ T cells producing IFN-γ and the CD8+CD57+GB+ T cell population increased at 12-24 weeks and remained elevated for the duration of the study.ConclusionsWe have shown that CMV viremia is associated with CMV specific immune responses and increased CD8+CD57+GB+ cells at 1-year posttransplant, however early responses were not predictive of impending CMV viremia. It remains to be seen if the early CMV immune response detected is associated with endothelial and allograft damage, in light of previous studies demonstrating increased vasculopathy in pediatric patients with CMV viremia. Background Cytomegalovirus (CMV) infection is implicated in endothelial dysfunction and graft damage after pediatric heart transplantation. CMV specific immune responses are thought to be necessary for CMV viral control but there is little data in pediatric heart transplantation. Methods We studied 28 consecutive pediatric heart transplant recipients for 1-year posttransplant. CMV-specific T cells expressing IFN-γ, TNF-α and IL-2 in response to ex-vivo stimulation with CMV lysates or peptides were measured. Circulating cytokines were measured in plasma. Generalised Additive Models were applied to the data to model changes of cell population dynamics over time. Results CMV-specific T cell mediated responses were impaired in the first 8 weeks posttransplant. During this period, 25% of patients had CMV viremia, of which those with viral loads ≥10,000 CMV DNA copies/mL were given ganciclovir. In this group, the frequency of CD4+ and CD8+ T cells producing IFN-γ and the CD8+CD57+GB+ T cell population increased at 12-24 weeks and remained elevated for the duration of the study. Conclusions We have shown that CMV viremia is associated with CMV specific immune responses and increased CD8+CD57+GB+ cells at 1-year posttransplant, however early responses were not predictive of impending CMV viremia. It remains to be seen if the early CMV immune response detected is associated with endothelial and allograft damage, in light of previous studies demonstrating increased vasculopathy in pediatric patients with CMV viremia. M.C. Jacobsen and M.D.I. Manunta contributed equally to this work Correspondence: E-mail: Marianne.Jacobsen@uregina.ca; Tel: (+1) 306-585-4145; Fax (+1) 306-337-2409; Address: Department of Biology, Laboratory Building, LB244, University of Regina, 3737 Wascana Parkway, Regina, Saskatchewan, S4S 0A2, Canada. Authorship MCJ and MDIM participated in the performance of the research, data analysis, result interpretation, and in the writing of the paper. ESP and MF participated in patient consent and sample acquisition, result interpretation and in writing the paper. GLS participated in data analysis and writing the paper. NJK participated in research design, result interpretation, and writing the paper. MB participated in research design, patient consent and sample collection, result interpretation and writing the paper. DISCLOSURE: The authors have no financial relationships to disclose. Funding: Authors are grateful to the Heart for Kids Charity for funding. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Preemptive Kidney Transplantation: What’s the Hold Up?

No abstract available

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Fulminant Acute Respiratory Distress Syndrome after Calcineurin Inhibitor-belatacept Conversion in a Lung Transplant Recipient

No abstract available

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Treatment of early stage Supraglottic squamous cell carcinoma: meta-analysis comparing primary surgery versus primary radiotherapy

For early stage supraglottic squamous cell carcinoma (SCC), single modality treatment either in the form of primary organ preservation surgery alone or radiation alone is recommended. Thus, a definite treatmen...

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PRO-ACTIVE: Prophylactic Swallow Intervention for Patients Receiving Radiotherapy for Head and Neck Cancer

Condition:   Dysphagia
Interventions:   Behavioral: RE-ACTIVE;   Behavioral: PRO-ACTIVE EAT;   Behavioral: PRO-ACTIVE EAT + EXERCISE
Sponsors:   University Health Network, Toronto;   M.D. Anderson Cancer Center;   Applied Health Research Centre;   Qualitative Health Research Consultants, LLC;   Patient-Centered Outcomes Research Institute
Not yet recruiting

http://ift.tt/2tlNSRN

CPI-006 Alone and in Combination With CPI-444 and With Pembrolizumab for Patients With Advanced Cancers

Conditions:   Non-Small Cell Lung Cancer;   Renal Cell Cancer;   Colorectal Cancer;   Triple Negative Breast Cancer;   Cervical Cancer;   Ovarian Cancer;   Pancreatic Cancer;   Endometrial Cancer;   Sarcoma;   Squamous Cell Carcinoma of the Head and Neck;   Bladder Cancer;   Metastatic Castration Resistant Prostate Cancer
Interventions:   Drug: CPI-006;   Drug: CPI-006 + CPI-444;   Drug: CPI-006 + pembrolizumab
Sponsor:   Corvus Pharmaceuticals, Inc.
Not yet recruiting

http://ift.tt/2oLhrr8

Comparison Between Robotic, Endoscopic and Traditional Open Surgery in Thyroidectomy

Conditions:   Endoscopy;   Robotics;   Thyroidectomy;   Papillary Thyroid Carcinoma
Interventions:   Procedure: conventional open surgery;   Procedure: endoscopic thyroidectomy;   Device: robotic thyroidectomy
Sponsor:   Fujian Medical University
Recruiting

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Evaluation of Central Compartment Dissection Without Thyroidectomy

Conditions:   Thyroidectomy;   Thyroid Cancer;   Central Compartment Neck Dissction
Interventions:   Procedure: Conventional;   Procedure: central neck dissection first
Sponsor:   Fujian Medical University
Recruiting

http://ift.tt/2oMIFhf

Identifying the factors and root causes associated with the unintentional usage of an adrenaline auto-injector in Japanese children and their caregivers

Publication date: Available online 5 March 2018
Source:Allergology International
Author(s): Kemal Sasaki, Tomoko Nakagawa, Shiro Sugiura, Motohiro Ebisawa, Komei Ito
BackgroundThe unintentional usage of adrenaline auto-injectors may cause injury to caregivers or patients. To prevent such incidents, we assessed the causative factors of these incidents.MethodsThe Anaphylaxis Working Group of the Japanese Society of Pediatric Allergy and Clinical Immunology requested that society members register cases in which adrenaline auto-injectors were unintentionally used. One hundred cases were reported from June 2015 to March 2016. We identified the root causes of 70 child and 25 adult cases, separately.ResultsThe incidents occurred with repeated prescriptions as well as the first prescription. Three cases resulted in a failure to administer an adrenaline auto-injector to children with anaphylaxis. Four caregivers used it with improper application (epilepsy or enteritis). Among the child cases, the median age at the time of the incident was 5.5 years (range, 2–14 years). Five children injected the adrenaline auto-injector on their own body trunk. Twenty children were not the allergic patients themselves. Improper management protocol of the device and the child's development were concomitantly involved in most of the cases. A variety of human behaviors were identified as the root causes in the adult cases. At least 34 cases were associated with mix-ups between the actual and training device.ConclusionsHealth workers should provide sufficient education regarding safety use of adrenaline auto-injector for caregivers tailored to their experience levels at both first and repeated prescriptions. Such education must cover anticipatory behavior based on normal child development. Devices should also be further improved to prevent such incidents.



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Anaphylaxis caused by a centipede bite: A “true” type-I allergic reaction

Publication date: Available online 5 March 2018
Source:Allergology International
Author(s): Ken Washio, Taro Masaki, Shotaro Fujii, Mayumi Hatakeyama, Yoshiko Oda, Atsushi Fukunaga, Masaru Natsuaki




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Ethanol-induced urticaria caused by sensitization to acetic acid

Publication date: March 2018
Source:Annals of Allergy, Asthma & Immunology, Volume 120, Issue 3
Author(s): Belén Añíbarro, Francisco J. Seoane




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Table of Contents

Publication date: March 2018
Source:Annals of Allergy, Asthma & Immunology, Volume 120, Issue 3





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Instructions for Authors

Publication date: March 2018
Source:Annals of Allergy, Asthma & Immunology, Volume 120, Issue 3





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