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Τρίτη 26 Φεβρουαρίου 2019

The role of heterogeneous environment and docetaxel gradient in the emergence of polyploid, mesenchymal and resistant prostate cancer cells

Abstract

The ability of a population of PC3 prostate epithelial cancer cells to become resistant to docetaxel therapy and progress to a mesenchymal state remains a fundamental problem. The progression towards resistance is difficult to directly study in heterogeneous ecological environments such as tumors. In this work, we use a micro-fabricated "evolution accelerator" environment to create a complex heterogeneous yet controllable in-vitro environment with a spatially-varying drug concentration. With such a structure we observe the rapid emergence of a surprisingly large number of polyploid giant cancer cells (PGCCs) in regions of very high drug concentration, which does not occur in conventional cell culture of uniform concentration. This emergence of PGCCs in a high drug environment is due to migration of diploid epithelial cells from regions of low drug concentration, where they proliferate, to regions of high drug concentration, where they rapidly convert to PGCCs. Such a mechanism can only occur in spatially-varying rather than homogeneous environments. Further, PGCCs exhibit increased expression of the mesenchymal marker ZEB1 in the same high-drug regions where they are formed, suggesting the possible induction of an epithelial to mesenchymal transition (EMT) in these cells. This is consistent with prior work suggesting the PGCC cells are mediators of resistance in response to chemotherapeutic stress. Taken together, this work shows the key role of spatial heterogeneity and the migration of proliferative diploid cells to form PGCCs as a survival strategy for the cancer population, with implications for new therapies.



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Management of cutaneous T‐cell lymphomas: Established and emergent therapies

Abstract

Cutaneous T‐cell lymphoma is an uncommon group of non‐Hodgkin's lymphoma primarily affecting the skin. It is comprised of a variety of entities with different clinical behaviours and prognosis. Mycosis fungoides is the commonest subtype, and Sézary syndrome is a much rarer form of cutaneous T‐cell lymphoma. At this stage, control rather than cure is the goal of therapy, with particular emphasis placed on preserving quality of life. Our review of the efficacy, safety profile and accessibility of treatment modalities for mycosis fungoides/Sézary syndrome is a tailored guide for the clinician treating these rare conditions.



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Assessment of the efficacy and safety of platelet poor plasma gel as autologous dermal filler for facial rejuvenation

Summary

Background

The popularity of dermal fillers has grown rapidly in the last few years for facial rejuvenation. Plasma gel is an autologous gelatinous material that is prepared from the patient's own platelet poor plasma.

Objective

To evaluate the clinical efficacy and safety of plasma gel injection as a dermal filler for facial rejuvenation.

Patients and Methods

The current study was carried out on 52 females presented with facial aging divided into two groups: Group A included 34 females with facial wrinkles, and Group B included 18 females with tear trough deformity. After taking written informed consent, they received two sessions of plasma gel injections at 2‐week interval and followed up monthly for 3 months. They were assessed clinically before treatment sessions and at the end of follow‐up period.

Results

Both studied groups showed immediate significant clinical improvement after plasma gel injection that maintained till the end of follow‐up period. This finding was confirmed by significant reduction in the mean values of Wrinkle Severity Rating Scale (WSRS) in Group A and Tear Trough Rating Scale (TTRS) in group B, and significant improvement of skin homogeneity and texture in both groups. In general, the reported side effects were minimal and transient.

Conclusion

Autologous platelet poor plasma gel injection seems to be a cost‐effective, safe, well‐tolerated, and minimally invasive technique producing significant aesthetic correction of facial wrinkles and tear trough deformity.



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The impact of fertilizers on the uptake of manganese in Cherry Belle radish plants: implications for human health

Abstract

Miracle-Gro Singles, Miracle-Gro Shake and Feed, and Vigoro fertilizers are associated with net loss/enhancement of Mn, up to an order of magnitude when referenced to controls in soil, radish vegetables, and radish leaves; Mn enhancements are a factor of 4 to 65 below the daily required intake for humans (2–5.5 mg/day). Manganese levels were measured by atomic absorption spectrometry (AAS). Control soil, radish vegetables, and radish leaves contained 65 μg/g to 146 μg/g (median = 108), 65 μg/g to 357 μg/g (median = 281), and 185 μg/g to 401 μg/g (median = 323) of Mn, correspondingly. Manganese uptake was ten times greater in radish leaves compared to radish vegetables and enhanced by a factor of 3 in soils. Edible radish leaves/vegetables contain 65 times less than human Mn daily requirements. This equates eating 140 lb/day of radish vegetables/leaves. The fertilizers have a minor impact on Mn accumulation in radish leaves/vegetables. The USDA Nutrient Database for radish (0.69 μg/g of Mn) contradicts this notion as one would need to consume ~ 7 to 18 lb/day of radish to satisfy their daily intake. This study complements investigations showing that fertilizers induce minimal uptake of heavy metals in food; simultaneously, the net loss of Mn amounts observed in some samples of radish leaves and vegetables is analogous to the dilution effect of minerals/nutrients in edibles. Although a deficiency/excess of Mn in one's diet may lead to adverse health effects, background inhalation exposure in general public, occupational, and emergency response settings has a greater influence on one's propensity toward developing adverse health effects related to Mn inhalation exposure.



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A pigmented and eroded lesion on the buttock



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Global rosacea treatment guidelines and expert consensus points: The differences

Summary

Background

Rosacea is a highly prevalent, chronic inflammatory disease. The treatment of rosacea remains a challenge to dermatologists. Therapies include skin care, medications, lasers, and various combinations of these modalities. The appropriate treatment depends on clinical types and patient's various clinical symptoms.

Purpose

The purpose of this study was to review and compare current therapies for rosacea of all severities from four different guidelines.

Methodology

We searched PubMed using the keywords "rosacea," "treatment" AND ["erythema rosacea" OR "papulopustular rosacea" OR "ocular rosacea" OR "phymatous rosacea"]. We selected randomized controlled trials, observational studies, controlled clinical trials, and clinical trials. We indentified further studies (including the guidelines) by hand‐searching relevant publications and included those that met the inclusion criteria.

Results

The total number of records identified was 421. We limited our search to the specific abovementioned study types. Twenty‐five of these studies met with our inclusion criteria. An additional five manuscripts were selected using the abovementioned method, and four guidelines were included in this review.

Conclusion

Diagnosing and choosing the appropriate treatment options of rosacea according to guidelines is the basis of scientific criteria. More large‐scale randomized controlled clinical trials on new treatment methods, new drugs, or new dosage forms provide a new guideline for future rosacea treatment. Although there are some differences in the treatment of rosacea, it is generally based on anti‐demodex, anti‐inflammatory, and anti‐angiogenesis.



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Predictors of Success of Phase II Pediatric Oncology Clinical Trials

AbstractBackground.There are limited data to predict which novel childhood cancer therapies are likely to be successful. To help rectify this, we sought to identify the factors that impact the success of phase II clinical trials for pediatric malignancies.Materials and Methods.We examined the impact of 24 preclinical and trial design variables for their influence on 132 phase II pediatric oncology clinical trials. Success was determined by an objective assessment of patient response, with data analyzed using Fisher's exact test, Pearson's chi‐square test, and logistic regression models.Results.Trials that evaluated patients with a single histological cancer type were more successful than those that assessed multiple different cancer types (68% vs. 47%, 27%, and 17% for 1, 2–3, 4–7, and 8+; p < .005). Trials on liquid or extracranial solid tumors were more successful than central nervous system or combined trials (70%, 60%, 38%, and 24%; p < .005), and trials of combination therapies were more successful than single agents (71% vs. 28%; p < .005). Trials that added therapies to standard treatment backbones were more successful than trials testing novel therapies alone or those that incorporated novel agents (p < .005), and trials initiated based on the results of adult studies were less likely to succeed (p < .05). For 61% of trials (80/132), we were unable to locate any relevant preclinical findings to support the trial. When preclinical studies were carried out (52/132), there was no evidence that the conduct of any preclinical experiments made the trial more likely to succeed (p < .005).Conclusion.Phase II pediatric oncology clinical trials that examine a single cancer type and use combination therapies have the highest possibility of clinical success. Trials building upon a standard treatment regimen were also more successful. The conduct of preclinical experiments did not improve clinical success, emphasizing the need for a better understanding of the translational relevance of current preclinical testing paradigms.Implications for Practice.To improve the clinical outcomes of phase II childhood cancer trials, this study identified factors impacting clinical success. These results have the potential to impact not only the design of future clinical trials but also the assessment of preclinical studies moving forward. This work found that trials on one histological cancer type and trials testing combination therapies had the highest possibility of success. Incorporation of novel therapies into standard treatment backbones led to higher success rates than testing novel therapies alone. This study found that most trials had no preclinical evidence to support initiation, and even when preclinical studies were available, they did not result in improved success.

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Cost of Disease Progression in Patients with Chronic Lymphocytic Leukemia, Acute Myeloid Leukemia, and Non‐Hodgkin's Lymphoma

AbstractIntroduction.To reduce health care costs and improve care, payers and physician groups are switching to quality‐based and episodic or bundled‐care models. Disease progression and associated costs may affect these models, particularly if such programs do not account for differences in disease severity and progression risk within the cohort. This study estimated the incremental cost of disease progression in patients diagnosed with chronic lymphoid leukemia (CLL), acute myeloid leukemia (AML), and non‐Hodgkin's lymphoma (NHL) and compared costs among patients with and without progression.Methods.This was a retrospective study using U.S. administrative claims data from commercial and Medicare Advantage health care enrollees with evidence of CLL, AML, and NHL and systemic antineoplastic agent use from July 1, 2006 to August 31, 2014. Outcome measures included disease progression, 12‐month health care costs, and 3‐year cumulative predictive health care costs.Results.Of 1,056 patients with CLL, 514 patients with AML, and 7,601 patients with NHL, 31.1% of patients with CLL, 63.8% of those with AML, and 36.9% of those with NHL had evidence of disease progression. Among patients with CLL and NHL, adjusted and unadjusted health care costs were significantly higher among progressors versus nonprogressors. Per‐patient‐per‐month costs, accounting for variable follow‐up time, were almost twice as high among progressors versus nonprogressors in patients with CLL, AML, and NHL. In each of the three cancer types, the longer disease progression was delayed, the lower the health care costs.Conclusion.Progression of CLL, AML, and NHL was associated with higher health care costs over a 12‐month period. Delaying cancer progression resulted in a substantial cost reduction in patients with all three cancer types.Implications for Practice.Data on the rates and incremental health care costs of disease progression in patients with hematologic malignancies are lacking. This study estimated the incremental costs of disease progression in patients diagnosed with chronic lymphocytic leukemia, acute myeloid leukemia, and non‐Hodgkin's lymphoma and compared health care costs in patients with and without evidence of disease progression in a real‐world population. The data obtained in this study will assist future studies in quantifying the cost impact of decreased progression rates and will inform payers and physician groups about setting rates for episode and bundled payment programs.

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Carcinoma Erysipeloides From Metastatic Cutaneous Squamous Cell Carcinoma Initially Mistaken for Intralymphatic Histiocytosis

Abstract: Intralymphatic histiocytosis is a rare dermatologic disorder, commonly associated with inflammatory disorders and rarely malignancy. Carcinoma erysipeloides (CE) is a rare pseudoinflammatory cutaneous eruption that resembles soft -tissue infections as result of intralymphatic metastasis and subsequent lymphatic obstruction. Breast carcinoma represents most of the CE cases, but rarely other malignancies are involved. This report discusses a patient with a history of cutaneous squamous cell carcinoma (SCC) of the temple, who was initially diagnosed with intralymphatic histiocytosis located on his upper extremity, resistant to treatment. Further dermatologic and pathologic review later revealed metastatic SCC restricted to the dermal lymphatics, creating a CE reaction, initially obscured by intralymphatic histiocytes. This case highlights the difficulty in diagnosing metastatic carcinoma when the malignant cells are accompanied by a dense histiocytic infiltrate. The case demonstrates a rare presentation of CE due to metastatic cutaneous SCC and highlights the need for persistent investigation when confronted with nonconforming pathology. Correspondence: Michael S. Heath, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239 (e-mail: heatmi@ohsu.edu). The authors declare no conflicts of interest. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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Polypoid Compound Melanocytic Proliferations: A Clinicopathological Study

Abstract: Nevi can show a polypoid appearance both clinically and histologically. Anecdotally, polypoid compound melanocytic nevus may exhibit a spectrum of junctional architectural and cytologic atypia, at times creating a diagnostic challenge by mimicking the radial growth phase of melanoma. To investigate this issue, we prospectively reviewed 40 polypoid compound melanocytic proliferations without overt malignant features. The lesions frequently occurred in young female patients and were predominantly from the trunk and intertriginous areas. Commonly observed atypical features included asymmetry (30%), shouldering (47.5%), poor circumscription (37.5%), and deep extension of melanocytes along the adnexal structures (67.5%). Severe cytologic junctional atypia (22.5%), dermal mitoses (10%), and pagetoid spread of melanocytes (5%) were less commonly seen. All lesions showed a reassuring dermal component with negligible cytologic atypia and maturation with depth. Overall, 7 lesions could not be readily classified as benign nevus; 5 of these in which a benign diagnosis was strongly favored were classified as atypical polypoid compound melanocytic nevi, whereas 2 lesions with diffuse severe junctional cytologic atypia and dermal mitoses were classified as ambiguous melanocytic proliferations. Atypical/ambiguous lesions were significantly larger and predominantly located in the axilla and groin. On molecular studies, none of the lesions tested showed the molecular profile of melanoma. We confirmed that polypoid compound melanocytic nevus can exhibit a variable degree of junctional atypia, likely related to frequent episodes of trauma and regeneration resulting in melanocytic proliferation. Pathologists should be aware of this phenomenon to avoid overdiagnosis. Correspondence: Nima Mesbah Ardakani, MD, FRCPA, Department of Anatomical Pathology, PathWest Laboratory Medicine, QEII Medical Centre, Perth, Western Australia 6009, Australia (e-mail: Nima.MesbahArdakani@health.wa.gov.au). The authors declare no conflicts of interest. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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Renal Cell Carcinoma Antigen Expression in Primary Cutaneous Endocrine Mucinous Carcinomas: A Case Series of 14 Patients and Review of the Literature

Abstract: Endocrine mucin-producing sweat gland carcinoma (EMPSGC) and primary cutaneous mucinous carcinoma (PCMC) are both uncommon low-grade cutaneous adnexal tumors with predilection for the eyelids of elderly women. Their clinical appearance is nonspecific, typically presenting as a slowly growing poorly circumscribed papule, nodule, plaque, or swelling. Histological features of EMPSGC include a lobulated dermal neoplasm with bland cytology and an invasive mucinous component in up to half of the cases. PCMC exhibits tumor nests suspended in abundant pools of mucin with focal strands or nests of tumor cells infiltrating the dermis. Because of their rarity and banal cytological features, both entities pose a risk for misdiagnosis with other benign/malignant cutaneous adnexal neoplasms. Histomorphological features can suggest a diagnosis of EMPSGC or PCMC, but immunohistochemistry is necessary for confirmation. A review of the literature showed variable results of antigens present in EMPSGC, and many of the positive markers only show sparse or focal immunoreactivity of tumor cells. As a result, diffusely positive markers play a crucial role in identification of these tumors, particularly with initial superficial biopsies. We present 9 cases of EMPSGC and 5 cases of PCMC with strong and diffuse immunoreactivity to renal cell carcinoma antigen. This novel finding can be useful in the diagnosis of EMPSGC and PCMC in combination with other known positive markers to differentiate them from other cutaneous neoplasms. In addition, it provides further evidence that EMPSGC could be a precursor lesion to PCMC with both existing on a spectrum. Correspondence: Carlos A. Cerruto, MD, FCAP, 1923 Lake Markham Preserve Trail, Sanford, FL 32771 (e-mail: cerrutomd@msn.com). Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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Primary Cutaneous Acral CD8+ T-Cell Lymphoma—A Single Center Review of 3 Cases and Recent Literature Review

Abstract: The recently published 2016 revision of the WHO classification of lymphoid neoplasms includes primary cutaneous acral CD8-positive T-cell lymphoma (PCATCL) as a provisional entity. This is a rare indolent lymphoma characterized by papules or nodules on the ear and a dermal infiltrate of CD8-positive T-lymphocytes with cytotoxic marker expression. A retrospective review of a single institutional experience with PCATCL identified 3 patients (mean age 54; range 49–62) with papules or nodules on the ear. Lesional biopsies demonstrated a dense diffuse dermal infiltrate of atypical lymphocytes with a Grenz zone in 2 cases and focal epidermotropism in 1 case. The atypical lymphocytes were predominantly CD3 and CD8 positive with expression of cytotoxic marker TIA1. Staging evaluation failed to reveal systemic disease. Two patients underwent local excision, and the third received local radiation therapy all with complete response and no disease recurrence at last follow-up 3 months (range 2–5 months). Our cases add to the existing limited literature on the clinical and histopathological features of PCATCL. We also performed an updated systematic literature view of the entity. Correspondence: Nneka I. Comfere, MD, 200 First Street SW, Rochester, MN 55905 (e-mail: comfere.nneka@mayo.edu). The authors declare no conflicts of interest. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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Coexistence of a Basal Cell Carcinoma and Leiomyosarcoma: An Unusual Collision Tumor

No abstract available

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Fibrosarcomatous Change in a Dermatofibrosarcoma Protuberans: Significance and Implications in the Differential Diagnosis of the Coexpression of S100 Protein and CD34 in Both Components

No abstract available

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Global PD-L1 Signals and Tumor-Infiltrating Lymphocytes: Markers of Immunogenicity in Different Subsets of Merkel Cell Carcinoma and Potential Therapeutic Implications

Abstract: We previously studied the genetic and immunohistochemical profiles of subsets of Merkel cell carcinoma (MCC) stratified by morphology and Merkel cell polyomavirus (MCPyV) status. Recent advances in the immunotherapy of this disease prompted us to examine markers of immunogenicity [PD-L1 expression and tumor-infiltrating lymphocytes (TILS) in these subsets]. The observed clinical responses to checkpoint inhibition of the PD-1/PD-L1 pathway have not correlated with PD-L1 expression by MCC cells, and recent evidence suggests that functions of this pathway within the immune tumor microenvironment may be relevant. We conducted a semiquantitative (high, moderate, and minimal) immunohistochemical evaluation of the global PD-L1 signal in 52 cases of MCC, segregated in 3 subsets [pure MCPyV-positive (n = 28), pure MCPyV-negative (n = 9), and combined MCPyV-negative (n = 15)]. TILS were categorized as brisk, nonbrisk, or absent. Intersubset comparisons revealed that high global PD-L1 signals were exclusively associated with pure MCPyV-positive MCCs contrasted with virus-negative cases (P = 0.0003). Moderate signals were seen across all 3 groups. Brisk TILS were significantly associated with MCPyV-positive MCCs compared with MCPyV-negative cases (P = 0.029). Neither parameter (PD-L1 or TILS) was significantly different between the MCPyV-negative groups. Of potential clinical relevance, MCPyV seems to convey greater immunogenicity to MCCs than the high mutational burden/greater neoantigen load of MCPyV-negative cases. Interesting too is the fact that subset-related profiles of these markers mirrored those noted at genetic and immunohistochemical levels, separating pure MCPyV-positive MCCs from the virus-negative subsets. Correspondence: Noreen M. Walsh, MD, FRCPC, FRCPath (UK), Division of Anatomical Pathology, Rm 721, Nova Scotia Health Authority (QEII Site), Mackenzie Building, 5788 University Avenue, Halifax, NS B3H 1V8, Canada (e-mail: Noreen.walsh@nshealth.ca). Supported by research grants from the Nova Scotia Health Authority Research Fund and the DPLM Fund for Molecular Pathology housed at the QE II Foundation. The authors declare no conflicts of interest. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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A Rare Soft-Tissue Tumor in a 15-Year-Old Boy With Tuberous Sclerosis Complex: Challenge

No abstract available

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Observational Study Examining the Diagnostic Practice of Ki67 Staining for Melanocytic Lesions

Background: Dermatopathologists routinely use Ki67 immunostaining to assess atypical melanocytic lesions with a dermal component to determine whether an ambiguous tumor is melanoma. However, there is no universal standard of use for Ki67 in melanocytic neoplasms. We sought to observe the real-world use of Ki67 in the diagnosis of melanocytic lesions and establish a best practice recommendation. Methods: We searched dermatopathology reports from 2 academic practices for melanocytic lesions in which Ki67 staining was used for diagnosis. The proliferation rate was compared between cases diagnosed as benign (not requiring re-excision), moderate to severely dysplastic or atypical Spitz nevi (requiring re-excision), and malignant melanoma. The use of other melanocytic markers and consensus review was also recorded and compared between institutions. Results: Pathology reports for 106 cases were reviewed. A high Ki67 proliferation rate (n = 18) favored a diagnosis of melanoma or nevi requiring re-excision (15/18, 83.3%) versus a benign nevus (3/18, 16.67%). A high Ki67 rate was 71.4%–90.9% sensitive and 40%–56% specific for the diagnosis of nevus requiring re-excision or melanoma. Institutional practices differed in regard to reporting of Ki67 staining, the use of multiple markers in the workup of atypical melanocytic lesions (HMB45, Melan-A, Ki67 being most common), and consensus review. Conclusions: A negative or low Ki67 proliferation rate correlates well with rendering of a benign diagnosis. However, a low proliferation rate does not preclude the diagnosis of melanoma. Ki67 staining is most commonly used as an ancillary test to support a diagnosis after other factors have been considered, such as histopathologic morphology and results of additional concurrently used stains. Correspondence: Nikki S. Vyas, MD, Icahn School of Medicine at Mount Sinai, Department of Pathology, 1468 Madison Avenue, Box 1194, New York, NY 10029 (e-mail: nikki.vyas@mountsinai.org). The authors declare no conflicts of interest. Dr Vyas received a 2017 Mentorship Award from the American Society of Dermatopathology (ASDP) for work on this project. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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Cutaneous Crospovidone: A Newly Described Foreign Body Due to Illicit Drug Abuse

Abstract: Crospovidone, a polymer of poly N-vinyl-2-pyrrolidone, is an inert insoluble disintegrant found in pharmaceutical tablets. This material has been encountered in the lungs of intravenous drug users and embolized with other components such as talc and microcrystalline cellulose. More recently, crospovidone has also been described in the gastrointestinal tract. We present 2 cases of cutaneous crospovidone deposition resulting from subcutaneous injection of crushed tablets, commonly known as "skin popping." Clinical presentation includes painful, inflamed papules, nodules, or ulcers with overlying eschar. Crospovidone has a distinct and reproducible histochemical staining profile. Histologic recognition of this material is important because it can guide clinicians in their diagnosis and management decisions. Correspondence: Konstantinos D. Linos, MD, Division of Dermatopathology, Department of Pathology and Laboratory Medicine, One Medical Center Drive, Lebanon, NH 03766 (e-mail: Konstantinos.D.Linos@hitchcock.org). The authors declare no conflicts of interest. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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Extramammary Paget Disease—A Challenging Case

No abstract available

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Vertical variation of bulk and metabolically active prokaryotic community in sediment of a hypereutrophic freshwater lake

Abstract

This study was conducted to acquire novel insight into differences between bulk (16S rDNA) and metabolically active (16S rRNA) prokaryotic communities in the sediment of a hypereutrophic lake (Japan). In the bulk communities, the class Deltaproteobacteria and the order Methanomicrobiales were dominant among bacteria and methanogens. In the metabolically active communities, the class Alphaproteobacteria and the order Methanomicrobiales and the family Methanosaetaceae were frequently found among bacteria and methanogens. Unlike the bulk communities of prokaryotes, the composition of the metabolically active communities varied remarkably vertically, and their diversities greatly decreased in the lower 20 cm of sediment. The metabolically active prokaryotic community in the sediment core was divided into three sections based on their similarity: 0–6 cm (section 1), 9–18 cm (section 2), and 21–42 cm (section 3). This sectional distribution was consistent with the vertical pattern of the sedimentary stable carbon and nitrogen isotope ratios and oxidation–reduction potential in the porewater. These results suggest that vertical disturbance of the sediment may influence the communities and functions of metabolically active prokaryotes in freshwater lake sediments. Overall, our results indicate that rRNA analysis may be more effective than rDNA analysis for evaluation of relationships between actual microbial processes and material cycling in lake sediments.



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Familial oligodontia and regional odontodysplasia associated with a PAX9 initiation codon mutation

Abstract

Objective

Tooth agenesis is one of the most common craniofacial developmental anomalies. In hypodontia, one to five teeth are missing, whereas oligodontia refers to the absence of at least six teeth, excluding the third molars. Mutations in several genes including MSX1, PAX9, AXIN2, and WNT10A have been shown to cause non-syndromic tooth agenesis. Regional odontodysplasia (RO), also known as "ghost teeth," is a rare developmental anomaly of tooth formation affecting both dentitions. Some possible causes of RO have been suggested, yet the etiology remains unknown. Because the phenotypes of both oligodontia and RO co-occur in one Finnish family, the aim here was to investigate the genetic etiology of the two conditions.

Materials and methods

A mutation screening of the genes MSX1, PAX9, AXIN2, and WNT10A was performed for the family members of a RO patient and family history of oligodontia.

Results

An initiation codon mutation of the PAX9 gene was found in the proband and segregating with oligodontia in the family.

Conclusions

The etiology of regional odontodysplasia (RO) may be genetic and the same genes can be involved both in RO and tooth agenesis.

Clinical relevance

Our results give new insights into the etiology of regional odontodysplasia, yet further results are needed.



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Evaluation of underground hydraulic fracturing using transient electromagnetic method

Abstract

The effective area of hydraulic fracturing is the core index to evaluate its effects. Through conducting transient electromagnetic tests, this paper deals with the influential range of the underground hydraulic fracturing as well as water-cut detection and gas extraction in the fracturing area. The resistivity response law of the coal seam in hydraulic fracturing process is explored, and the water-bearing area is determined. The obtained results from the tests show that the water-cut areas of the coal seam, measured by anti-interference transient electromagnetic instrument after fracturing, are commonly placed in the low-resistance area of the transient test. Further, the variations of amplitude of the low-resistance area in various directions of the test line are different. According to the variation law of the apparent resistivity of the coal seam before and after fracturing, the effective influential area of the hydraulic fracturing is defined, and the influence range is evaluated to be 35 m. The water cut and the gas extraction tests of the coal seam before and after fracturing are performed. The results reveal that the growth of water content in the coal seam is inversely proportional to the distance from the hydraulic fracturing borehole. The effective fracturing zone with the increment of the water content reaching 0.2% is the effective fracturing zone, and the effective fracturing zone of #9 and #10 is 38 m. After hydraulic fracturing, the gas extraction concentration would be in the range of 25.4–75.4%, with the average of 70.22%, which is 21.22% higher than that of the original coal body. The net amount of the gas extraction after fracturing is about eight times of that before fracturing. The effective fracturing range, which is determined by transient electromagnetic, is verified successfully. Exploring the effective fracturing regions of the hydraulic fracturing process would be very helpful in improving the evaluation system of the hydraulic fracturing effect.



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Endokrine Funktionsstörungen nach Bestrahlung von Hirntumoren bei Kindern und jungen Erwachsenen



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Immunoregulatory Effects of Neuropeptides on Endothelial Cells: Relevance to Dermatological Disorders

Many skin diseases, including psoriasis and atopic dermatitis, have a neurogenic component. In this regard, bidirectional interactions between components of the nervous system and multiple target cells in the skin and elsewhere have been receiving increasing attention. Neuropeptides released by sensory nerves that innervate the skin can directly modulate functions of keratinocytes, Langerhans cells, dermal dendritic cells, mast cells, dermal microvascular endothelial cells and infiltrating immune cells. As a result, neuropeptides and neuropeptide receptors participate in a complex, interdependent network of mediators that modulate the skin immune system, skin inflammation, and wound healing. In this review, we will focus on recent studies demonstrating the roles of α-melanocyte-stimulating hormone, calcitonin gene-related peptide, substance P, somatostatin, vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide, and nerve growth factor in modulating inflammation and immunity in the skin through their effects on dermal microvascular endothelial cells.
Dermatology

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IMRT Combined With Toripalimab in Unresectable Locally Recurrent Nasopharyngeal Carcinoma.

Conditions:   Nasopharyngeal Carcinoma;   Nasopharyngeal Neoplasms;   Nasopharyngeal Diseases;   Head and Neck Neoplasm
Interventions:   Drug: Tolipalimab;   Radiation: Reirradiation
Sponsor:   Sun Yat-sen University
Not yet recruiting

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Experimental Pain Reporting Accuracy and Clinical Post-operative Pain

Conditions:   Surgical Procedure, Unspecified;   Pain, Postoperative;   ENT Disease
Intervention:   Device: pain reporting accuracy
Sponsors:   Carmel Medical Center;   University of Haifa
Not yet recruiting

https://ift.tt/2UbDmpi

A Dose Escalation Study of PF‑06939999 in Participants With Advanced or Metastatic Solid Tumors.

Conditions:   Advanced Solid Tumors;   Metastatic Solid Tumors
Intervention:   Drug: PF-06939999
Sponsor:   Pfizer
Not yet recruiting

https://ift.tt/2BTUs45

Nivolumab and BMS986205 in Treating Patients With Stage II-IV Squamous Cell Cancer of the Head and Neck

Conditions:   Lip;   Oral Cavity Squamous Cell Carcinoma;   Pharynx;   Larynx;   Squamous Cell Carcinoma
Interventions:   Biological: Nivolumab;   Biological: IDO1 Inhibitor BMS-986205;   Procedure: Therapeutic Conventional Surgery;   Other: Questionnaire Administration
Sponsor:   Thomas Jefferson University
Not yet recruiting

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Serial Epstein-Barr Virus DNA Surveillance in Nasopharyngeal Carcinoma Patients

Condition:   Nasopharyngeal Carcinoma
Intervention:   Diagnostic Test: Plasma EBV DNA
Sponsor:   Sun Yat-sen University
Not yet recruiting

https://ift.tt/2BTUokR

Study of TQB2450 in Patients With Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck(R/M SCCHN)

Condition:   Squamous Cell Carcinoma of the Head and Neck
Interventions:   Drug: TQB2450+cisplatin or carboplatin + 5-Fluorouracil (5-FU);   Drug: placebo+cisplatin or carboplatin + 5-Fluorouracil (5-FU)
Sponsor:   Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Not yet recruiting

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Treatment of intravitreal bevacizumab combined with focal laser photocoagulation in the case of macular telangiectasia type 2 with retinal arterial macroaneurysm

Abstract

Macular telangiectasia type 2 (Mac Tel 2) is a bilateral disease of unknown cause with characteristic changes of the retinal vasculature. To the best of our knowledge, we could not find any reported cases of Mac Tel 2 with retinal arterial macroaneurysm (RAM). Our aim is to report a case of Mac Tel 2 with RAM.



https://ift.tt/2VmWbpH

Comparative study of photodynamic activity of methylene blue in the presence of salicylic acid and curcumin phenolic compounds on human breast cancer

Abstract

Curcumin and salicylic acid are both phenolic compounds and they can both affect cancer treatment efficacy. In this study, the effects of methylene blue-curcumin (CU-MB) and methylene blue-salicylic acid (SA-MB) ion pair complexes on MDA-MB-231 human breast cancer cells are studied. According to the thermodynamic parameters, the stability of curcumin and salicylic acid complexes ion pair complexes was compared. The free energy of ion pair interactions was calculated based on binding constants. A comparison of the free energies of the complexes (CU-MB: ∆G°b1 = − 21.11 kJ/mol and ∆G°b2 = − 8.37 kJ/mol, SA-MB: ∆G°b1 = − 12.92 kJ/mol and ∆G°b2 = − 9.02 kJ/mol) indicates that the interaction of methylene blue in first binding interaction with curcumin is greater than that of methylene blue with salicylic acid. Electrostatic interactions are the main forces in the binding of both compounds to methylene blue. All forces are inter-molecular physical interactions. The results of cellular experiments show that ion pairing has enhanced the reduction of cell viability. By increasing molecular stability and prevention of dimerization of methylene blue, the cell killing potential of methylene blue increases and it subsequently causes enhancement of photodynamic efficacy.



https://ift.tt/2EyejHx

Correction to: Outpatient erbium:YAG (2940 nm) laser treatment for snoring: a prospective study on 40 patients

In the originally published article, the name of the first author was incorrectly labeled. Given name is Isabelle and family name is Fini Storchi.



https://ift.tt/2VfEuIG

Dental acid etchant as a sensitizing agent in photodynamic therapy to reduce S. mutans in dentinal carious lesions

Abstract

The study aims to assess the utility of dental acid etchant containing 37% phosphoric acid and methylene blue dye (DAE) as a sensitizing agent for photodynamic therapy (PDT) to reduce Streptococci mutans in dentinal caries. Forty-five permanent third molars were sectioned and the coronal dentin exposed. A cariogenic challenge was performed using brain-heart infusion (BHI) supplemented with 0.5% yeast extract, 1% glucose, 1% sucrose, and S. mutans ATCC 25175 standardized to 0.5 McFarland turbidity. Specimens were incubated in anaerobic jars at 37 °C for 15 days. During this period, BHI broth was renewed every 24 h. After 15 days, specimens were randomly divided into three groups (n = 15): DAE, application of dental acid etchant containing 37% phosphoric acid and methylene blue dye for 15 s; LLL, application of low-level laser (wavelength 660 nm, energy 4 J/cm2, power 5 W) for 15 s; and PDT, application of DAE for 15 s followed by LLL irradiation (660 nm, 4 J/cm2, 5 W). Carious tissue from each specimen was collected before and after the applications. Five decimal dilutions were performed and the resulting solution was seeded in mitis-salivarius-bacitracin agar. Plates were incubated in anaerobic jars at 37 °C for 48 h. Analysis of variance (ANOVA) with post hoc Tukey's test was used to compare total S. mutans counts. Significant reductions in S. mutans were observed after DAE application (40.70%, p < 0.0001), LLL (12.35%, p = 0.0036), and PDT (55.22%, p < 0.0001). Dental acid etchant containing 37% phosphoric acid and methylene blue dye can be used as a photosensitizing agent for PDT to reduce S. mutans burden in dentinal caries.



https://ift.tt/2EyxqBi

Influence of laser wavelength and beam profile on the coagulation depth in a soft tissue phantom model

Abstract

In laser tissue soldering (LTS), a protein solution is thermally denatured and cross-linked to obtain a strong bond between tissues or tissue and a wound dressing. However, if the extension of the heat-affected zone is too large, wound healing is impaired by thermal tissue injuries. Therefore, heat input and coagulation depth have to be limited. We investigate the influence of wavelength and beam profile on coagulation depth using a soft tissue phantom in case of weakly (980 nm) and strong (1540 nm) absorbed laser radiation. The soft tissue phantom is doped with polystyrene (PS) beads to obtain similar scattering properties as natural tissue. The propagation of the laser radiation in the phantom is simulated by Monte–Carlo method and the optical penetration (OPD) depth calculated from isophotes. The simulation results are compared with the experimental determination of the coagulation volume. The results reveal that scattering effect of tissues on laser radiation increases the losses of a Gaussian beam profile laterally leading to a half-sphere coagulation volume. The depth profile of the coagulation follows approximately the intensity distribution of the laser beams as long as scattering effects are weak. As scattering effects become significant, as for 980-nm radiation, the intensity distribution of the laser beam in the tissue deviates from the original one, leading to different profile of the coagulation depth.



https://ift.tt/2Vmg3t6

Examination of the cellular mechanisms of leukocyte elevation by 10.6 μm and 650 nm laser acupuncture-moxibustion

Abstract

To investigate the cell cycle and cellular mechanisms of leukocyte elevation by laser acupuncture in rats with cyclophosphamide (CTX)-induced leukopenia. Sixty-six rats were randomized into six groups: normal, model control group, sham treatment group, 10.6 μm laser treatment group, 650 nm laser treatment group, and 10.6 μm–650 nm compound laser treatment group. Eleven rats were used in the normal group and 55 were models that were injected with cyclophosphamide to induce leukopenia. For the three laser treatment groups, 10.6-μm and 650-nm lasers, and 10.6-μm–650-nm compound lasers were used to irradiate the DU14 (Dazhui) and bilateral ST36 (Zusanli) for 5 min each. The sham laser group received the same operation as the laser group but without irradiation. The normal group and model group were not treated. Differences in the number of nucleated cells in the femoral bone marrow, and cell cycle and cellular apoptosis of peripheral leukocytes in rats in various groups were compared. Compared with the model group and the sham laser group, the number of nucleated cells in the femoral bone marrow in the 10.6-μm laser, 650-nm laser, and 10.6-μm–650-nm compound laser group was significantly increased after treatment (P = 0.001, 0.002, 0.034, respectively) and did not show any significant difference with the normal group (P = 0.964, P = 0.838, P = 0.287, respectively). The number of cells in G2 phase in the 10.6 μm laser group was similar to that of the normal group (P = 0.973). The number of cells in G2 phase in the model, sham, 650-nm laser group, and 10.6-μm–650-nm compound laser group were significantly lower than in the normal group and 10.6-μm laser group (P = 0.016, P = 0.023, P = 0.044, P = 0.039, respectively). In the model group and the sham treatment group, the apoptosis rates of peripheral leukocytes were increased compared with the normal group (P = 0.001), while the proportion of cells in the G2 phase was significantly lower than in the normal group (P = 0.016), and the proportion of cells in S phase was higher than in the normal group (P = 0.014). The incidence of apoptosis in peripheral blood cells in the three laser treatment groups did not show any statistically significant difference when compared with the normal group (P > 0.05). Treatment with the 10.6-μm, 650-nm, and 10.6-μm–650-nm compound lasers increased the number of nucleated cells in the bone marrow, decreased the unfavorable effects of cyclophosphamide on the cell cycle, induced the cell cycle towards proliferation, decreased apoptosis, improved the intramedullary hematopoietic system, and increased peripheral leukocyte count.



https://ift.tt/2ExyZPX

Environmental etiology of gastric cancer in Iran: a systematic review focusing on drinking water, soil, food, radiation, and geographical conditions

Abstract

The aim of this systematic review study was to investigate the causal relationship between environmental factors and gastric cancer (GC) in Iran. In a narrow definition, the environment includes water, soil, air, and food. This definition was the main criterion for the inclusion of articles in this study. In addition, exposure to radiation and geographical conditions were considered as less investigated environmental factors in the literatures. International (PubMed, Web of Science, ScienceDirect, Scopus, and Cochran) and national (Scientific Information Database) databases were searched for articles on GC and environmental risk factors in Iran. Twenty-six articles were found to meet the inclusion criteria after title, abstract, and full text review. Risk factors identified for GC include consumption of red meat; high fat, fried, and salted meat; smoked, salted, and fried foods; some dairy products; roasted and fried seeds; strong and hot tea; and un-piped and unchlorinated drinking water, as well as exposure to radiation, loess sediment, soft and grassy soil, soil containing low concentration of molybdenum, and proximity to volcanos. Fresh fruits and vegetable, fresh fish, and honey consumption were recognized as protective agents. Given the risk factors identified, strategies to prevent GC would be educating people to choose a healthy diet and to cook and store food properly, providing access to safe drinking water, taking into account topographical and geographical conditions in choosing a right location to build residential areas, and regulating the use of radiation-emitting devices.



https://ift.tt/2SsWpJS

Aluminium foil dampened the adverse effect of 2100 MHz mobile phone–induced radiation on the blood parameters and myocardium in rats

Abstract

Mobile phones emit a radiofrequency radiation (RFR) that might have adverse health effects. We aimed to investigate the possible protective effects of aluminium foil (AF) as a physical shield against the RFR from mobile phones on the blood parameters and the myocardium in rats. The effects of whole body 2100 MHz with 0.84–1.86 W/kg of SAR, 4 h/day for 30 days Global System for Mobile Communications (GSM)-RFR exposure for 4 h/day for 30 days on blood parameters (i.e. haemoglobin, leucocytes, thrombocytes, erythrocyte sedimentation rate, white blood cell differential count, corticosterone, CKMB), and the histology of myocardium were investigated. Three-month-old male rats (n = 32) were studied and randomised equally in the following four groups: K1 (non-AF non-RFR control), K2 (AF non-RFR control), P1 (non-AF RFR-exposed), P2 (AF RFR-exposed). Data were analysed with level of significance of p < 0.05. In P1, lower leucocytes and neutrophils counts with high corticosterone levels were found compared with the control groups, whilst a significantly higher CKMB was observed compared with P2 (p = 0.034). Lower cardiomyocyte counts congruent to the area fraction of the non-fibrotic myocardium were observed in P1 compared with the other groups (p < 0.01). AF might decrease the inflammatory-oxidative stress on rodent's blood cells and myocardium induced by the exposures of radiofrequency radiation of the mobile phones.



https://ift.tt/2XmbfWB

Methylene blue dye removal on silver nanoparticles reduced by Kyllinga brevifolia

Abstract

Silver nanoparticles (AgNPs) were prepared by reacting Kyllinga brevifolia extract (KBE) with AgNO3 aqueous solution at room temperature (22 ± 3 °C). The phytochemical constituents in KBE responsible for the reduction process were identified as carbohydrate, protein, and plant sterols (stigmasterol and campesterol). KBE was also found to function as a capping agent for stabilization of AgNPs. The AgNPs were stable at room temperature and had a quasi-spherical shape with an average particle size 22.3 nm. The use of KBE offers not only eco-friendly and non-pathogenic path for AgNPs formation, it also induced rapid formation of the AgNPs. Methylene blue (MB) removal was then done on the AgNPs in the presence of either KBE or NaBH4. Ninety-three percent removal of MB was achieved with a rate of reaction 0.2663 min−1 in the solution with KBE+AgNPs (pH 2). However, in NaBH4+AgNPs system, 100% MB removal was achieved at pH 8–10. The reaction rate was 2.5715 min−1 indicating a fast removal rate of MB dye. The process of reduction occurs via electron relay effect whereas in KBE+AgNPs system, sedimentation occurred along with the reduction process. Nevertheless, the use of KBE+AgNPs system is preferred as the reducing agent is more benign to the environment.



https://ift.tt/2SqXTEM

Clonal analysis of early-stage bilateral papillary thyroid cancer identifies field cancerization

Abstract

Introduction

Bilaterality is a newly identified indicator for aggressive tumor behavior and poor outcome in papillary thyroid cancer. However, the clonal origin of these bilateral tumors remains unclear.

Methods

Here we analyzed 28 pairs of early-stage papillary thyroid cancers (stage I–II without extra-thyroidal extension, lymph node metastasis or distant metastasis) that underwent surgery at First Affiliated Hospital of Zhejiang University School of Medicine (Hangzhou, China). Genomic DNA was extracted from paraffin-embedded tissues after microdissection and analyzed for BRAF mutation and X-chromosome inactivation.

Results

A total of 16 patients (16/28, 57.1%) harbored different BRAF status in bilateral tumors. Fourteen patients were available for X-chromosome inactivation assay and 10 of them achieved informative results. Bilateral tumors from four cases had distinct patterns of X-chromosome inactivation. Combining the results of X-chromosome inactivation and BRAF analysis, we demonstrated that at least 64.3% (18/28) cases harbored discordant X-chromosome inactivation or BRAF status, indicating their independent clonal origin in bilateral tumors.

Conclusions

The present study confirms "field cancerization" in early-stage bilateral thyroid cancers, suggesting that these subtype papillary thyroid cancers should be treated as independent and localized tumors.



https://ift.tt/2GM6lge

Clonal analysis of early-stage bilateral papillary thyroid cancer identifies field cancerization

Abstract

Introduction

Bilaterality is a newly identified indicator for aggressive tumor behavior and poor outcome in papillary thyroid cancer. However, the clonal origin of these bilateral tumors remains unclear.

Methods

Here we analyzed 28 pairs of early-stage papillary thyroid cancers (stage I–II without extra-thyroidal extension, lymph node metastasis or distant metastasis) that underwent surgery at First Affiliated Hospital of Zhejiang University School of Medicine (Hangzhou, China). Genomic DNA was extracted from paraffin-embedded tissues after microdissection and analyzed for BRAF mutation and X-chromosome inactivation.

Results

A total of 16 patients (16/28, 57.1%) harbored different BRAF status in bilateral tumors. Fourteen patients were available for X-chromosome inactivation assay and 10 of them achieved informative results. Bilateral tumors from four cases had distinct patterns of X-chromosome inactivation. Combining the results of X-chromosome inactivation and BRAF analysis, we demonstrated that at least 64.3% (18/28) cases harbored discordant X-chromosome inactivation or BRAF status, indicating their independent clonal origin in bilateral tumors.

Conclusions

The present study confirms "field cancerization" in early-stage bilateral thyroid cancers, suggesting that these subtype papillary thyroid cancers should be treated as independent and localized tumors.



https://ift.tt/2GM6lge

Photodynamic enhancement of the activity of antibiotics used in urinary tract infections

Abstract

Photodynamic therapy (PDT) has been proven to kill different microbial cells. However, to our knowledge, none of the available reports describes the modulatory effect of this therapy on the antibacterial activity of antibiotics against Escherichia coli rods being the main causative agent of urinary tract infections (UTIs). Therefore, the aim of our study was to verify if the PDT can enhance the antibacterial activity of antibiotics recommended in the treatment of UTIs. An attempt to determine the optimal conditions of PDT to enhance the bactericidal activity of ciprofloxacin, amikacin, and colistin has been made. In order to find the optimal antimicrobial conditions, the efficacy of four protocols associated with the use of different energy doses (70 and 120 J/cm2) and chlorin e6 (Ce6) concentrations (50 and 100 μg/mL) has been verified. The antibacterial effect of combined PDT and antibiotics was assessed by the time-kill assay. The best results were achieved for Ce6 at a concentration of 100 μg/mL and the energy dose 120 J/cm2 for bacterial suspensions treated with ciprofloxacin. Taken together, our results showed that PDT using Ce6 improves the antibacterial activity of antibiotics effectively inhibiting bacterial growth and being promising in the elimination of bacterial UTIs in humans.



https://ift.tt/2ICrtaD

HIV-Related Skin Disease in the Era of Antiretroviral Therapy: Recognition and Management

Abstract

Antiretroviral therapy (ART) has revolutionized the treatment and prognosis of people living with HIV (PLHIV). With increased survival and improved overall health, PLHIV are experiencing dermatologic issues both specific to HIV and common to the general population. In this new era of ART, it is crucial for dermatologists to have a strong understanding of the broad range of cutaneous disease and treatment options in this unique population. In this review, we outline the most common skin diseases in PLHIV, including HIV-associated malignancies, inflammatory conditions, and infections, and focus on the role of ART in altering epidemiology, clinical features, diagnosis, and treatment of cutaneous conditions.



https://ift.tt/2TiZoJs

Analysis of vegetation dynamics, drought in relation with climate over South Asia from 1990 to 2011

Abstract

Drought is the most complex climate-related disaster issue in South Asia, because of the various land-cover changes, vegetation dynamics, and climates. The aims of the current research work were to analyze the performance of AVHRR Normalized Difference Vegetation Index (NDVI) and spatiotemporal differences in vegetation dynamics on a seasonal basis by correlating the results with NASA's MERRA precipitation and air temperature for monitoring vegetation dynamics and drought over South Asia. Our approach is based on the use of AVHRR NDVI data and NASA's MERRA rainfall and air temperature data (1990–2011). Due to the low vegetation and dryness, the NDVI is more helpful in describing the drought condition in South Asia. There were rapid increases in NDVI, VHI, and VCI from April to October. Monthly NDVI, VHI, and VCI stabilize in September and improved once more in October and then show a declining trend in December. The monthly PCI, TCI, VHI, and VCI values showed that the South Asia goes through an extreme drought in 2000, which continues up to 2002, which lead the highest water stress. Spatial correlation maps among NDVI, precipitation, air temperature, VHI, and VCI on a seasonal basis. The correlation between NDVI and precipitation showed a significantly higher correlation value in JJA and SON seasons; the spatial correlation between NDVI and air temperature showed significant high values in DJF, JJA, and SON periods, while the correlation between VHI and TCI showed a significantly higher values in MAM and SON seasons, which indicated a good sign for dryness monitoring, mainly for farming regions during these seasons in South Asia. It was confirmed that these indexes are a comprehensive drought monitoring indicator and a step to monitoring the climate change in South Asia, which will play a relevant role ongoing studies on vegetation types, monitoring climate change, and drought over South Asia.



https://ift.tt/2Exwj4Y

Transcriptome analysis of Oryza sativa in responses to different concentrations of thiocyanate

Abstract

Effective concentrations of potassium thiocyanate (KSCN) to rice seedlings were experimentally determined using relative growth rate as a sensitive endpoint. Agilent 44-K rice microarray was used to profile the molecular responses of rice seedlings exposed to thiocyanate ion (SCN) at three different effective concentrations (EC10, EC20, and EC50). A total of 18,498 known genes were collected from SCN-treated rice microarray analysis. Out of all, 1603, 1882, and 5085 differentially expressed genes (DEGs) were observed at EC10, EC20, and EC50 concentrations, respectively. More upregulated/downregulated DEGs were detected in shoots than in roots after SCN exposure. Gene functions and pathway enrichment analysis of DEGs indicated that different effective concentrations of SCN resulted in multiple enriched GO categories and KEGG pathways and outcomes were quite tissue-specific. Different regulations and adaptations of gene expression in molecular function (MF), biological process (BP), and cellular components (CC) were observed in rice tissues at different effective concentrations of SCN, suggesting their different responsive and adaptive strategies. Information collected here presents a detailed description of SCN-induced alternations of gene expression in rice seedlings and provide valuable information for further searching specific genes participating in transportation, phytotoxic responses, and detoxification of SCN in rice seedlings.



https://ift.tt/2Vj5U09

Effects of individual ozone exposure on lung function in the elderly: a cross-sectional study in China

Abstract

The aim of this study was to assess the acute health effects of individual ozone (O3) exposure on the respiratory system in the elderly. A total of 40 non-smoking elderly volunteers completed personal 24 h of measurement for O3 and fine particulate matter (PM2.5). To assess health effects, we measured the pulmonary function and five inflammatory biomarkers in exhaled breath condensate (EBC), including interleukin-2 (IL-2), interferon-γ (IFN-γ), prostaglandin E2 (PGE2), and tumor necrosis factor α/β (TNFα/β). We used the generalized additive model to analyze the association between O3 and these health effects, after adjusting PM2.5, BMI, and sex as confounders. As a result, we found a negative correlation between O3 and forced vital capacity (FVC) or forced expiratory volume-one second (FEV1). With the increasing of O3 by 10 μg/m3, FVC and FEV1 decreased by 0.13 L (95% CI 0.01, 0.26) and 0.11 L (95% CI 0.02, 0.20), respectively. We found no statistical significance between O3 and biomarkers in EBC. The results suggested that individual 24-h O3 exposure was associated with decreased pulmonary function in the elderly.



https://ift.tt/2ExucOq

Euphorbia leaf extract-assisted sustainable synthesis of Au NPs supported on exfoliated GO for superior activity on water purification: reduction of 4-NP and MB

Abstract

In the present work, the effect of graphene oxide (GO) architecture and synthesis of gold nanoparticles (AuNPs) on the surface of GO by using Euphorbia leaf extract was investigated. The as-synthesized catalyst was utilized for reduction of 4-nitrophenol (4-NP) and methylene-blue (MB). The ethanol/water extract of the leaves of Euphorbia was found as a non-toxic, suitable, eco-friendly natural reducing agent in one-step generation of Au nanoparticles onto the GO. The catalyst was characterized by different analysis such as atomic force microscopy, powder X-ray diffraction, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, SEM-mapping, transmission electron microscopy, and atomic absorption spectrometry. The high catalytic performance of the surfactant exfoliated gold-GO (SE-AuNPs/GO) towards the reduction of 4-NP to 4-aminophenol (4-AP) and reduction of MB to leucomethylene blue (LMB) under mild conditions, in water and at room temperature, was exhibited.

Graphical abstract


https://ift.tt/2Vj5Opj

Traffic noise exposure of high-rise residential buildings in urban area

Abstract

Noise pollution is a major factor of environmental complaints in many cities, which has significant impacts on human health. As a dominating source of environmental noise, the impact of road traffic noise is increasing. Residents living in high-rise buildings along the main road are severely affected by traffic noise. In order to assess the noise level of urban area along the main road in Guangzhou, three buildings were selected to conduct traffic noise measurements, and the questionnaire about traffic noise impact on human being was completed. Through the questionnaire, around 70% of participants consider the traffic noise has negative effect, and about 60% of participants consider the noise has moderate or much higher impact on physical comfort. Around 65% of participants consider the noise had moderately or much higher impact on their psychological comfort. By analyzing the measured data, all of the measured noise levels in three buildings exceed the recommended limit of 55 dB (A) in the daytime and 45 dB (A) in the night for residence, and the exceeded value can be up to 16 dB (A). By comparing the fitting curve of noise level transfer function on each floor relative to the reference floor, the quadratic polynomial was selected to plot the transfer function rather than cubic polynomial.



https://ift.tt/2VoZJb9

Effects of straw returning and feeding on greenhouse gas emissions from integrated rice-crayfish farming in Jianghan Plain, China

Abstract

Great efforts have been devoted to assessing the effects of straw managements on greenhouse gas (GHG) emissions, global warming potential (GWP), and net economic budget in rice monoculture (RM). However, few studies have evaluated the effects of straw managements on GHG emissions and net ecosystem economic budget (NEEB) in integrated rice-crayfish farming (RC). Here, a randomized block field experiment was performed to comprehensively evaluate the effects of aquatic breeding practices (feeding or no feeding of forage) and straw managements (rice straw returning or removal) on soil NH4+–N and NO3–N contents, redox potential (Eh), CH4 and N2O emissions, GWP, and NEEB of fluvo-aquic paddy soil in a rice-crayfish co-culture system in Jianghan Plain of China. We also compared the differences in CH4 and N2O emissions, GWP, and NEEB between RM and RC. Straw returning significantly increased CH4 and N2O emissions by 34.9–46.1% and 6.2–23.1% respectively compared with straw removal. Feeding of forage decreased CH4 emissions by 13.9–18.7% but enhanced N2O emissions by 24.4–33.2% relative to no feeding. Compared with RM treatment, RC treatment decreased CH4 emissions by 18.1–19.6% but increased N2O emissions by 16.8–21.0%. Moreover, RC treatment decreased GWP by 16.8–22.0% while increased NEEB by 26.9–75.6% relative to RM treatment, suggesting that the RC model may be a promising option for mitigating GWP and increasing economic benefits of paddy fields. However, the RC model resulted in a lower grain yield compared with the RM model, indicating that more efforts are needed to simultaneously increase grain yield and NEEB and decrease GWP under RC model.



https://ift.tt/2ExNXW0

SWI processing using a local phase difference modulated venous enhancement filter with noise compensation

Publication date: Available online 26 February 2019

Source: Magnetic Resonance Imaging

Author(s): Sreekanth Madhusoodhanan, Chandrasekharan Kesavadas, Joseph Suresh Paul

Abstract

Susceptibility weighted imaging (SWI) involves post-processing of gradient echo images which are sensitive to the spatial variations in magnetic susceptibility. The aim of this study is to develop an automated filtering scheme to enhance the contrast-to-noise ratio (CNR) and blooming on SWI. Here, the high-pass filtering for SWI processing is designed by applying a weighting function to the neighboring phase differences to enhance the susceptibility-related (SuR) contrast. This is accomplished by summing the neighboring phase differences, weighted with a scaled and shifted error function of the phase difference. Besides using the filter weights of this weighted high-pass (WHP) filter to minimize the filtering artefacts using a filter scale parameter, the CNR is further increased by introduction of the neighborhood-based noise compensation weights into the filtering process. These weights are deduced from the channel phase distribution, conditioned on the channel magnitude and noise variance. Using in vivo SWI data acquired at 1.5 T (16 nos.) and 3.0 T (30 nos.), the magnitude SWI processed using the noise compensated WHP (WHPC) filter is shown to provide an average CNR improvement of 68.40% over that of a homodyne high-pass (HHP) filter. Two tailed t-tests performed separately for different field strengths, show significant differences (p < 0.001) between mean separations of phase masks generated from the WHPC and HHP filtered phase images. In conclusion, the WHPC filter, tuned by the mean separation of the phase mask, enhances the SuR contrast of magnitude SWI for evaluation of mild cognitive impairments, brain tumor and hemorrhagic stroke.



https://ift.tt/2IDaPYy

Comparative evaluation of SPECT/CT and CBCT in patients with mandibular osteomyelitis and osteonecrosis

Abstract

Objectives

Therapy of osteomyelitis and osteonecrosis very often requires surgery. Proper preoperative radiological evaluation of a lesion's localization and extent is a key in planning surgical bone resection. This study aims to assess the differences between single-photon emission computed tomography and cone beam computed tomography when detecting an osteomyelitis/osteonecrosis lesion as well as the lesion's qualitative parameters, extent, and localization.

Material and methods

Identification of candidates was performed retrospectively following a search for patients with histologically or clinically confirmed osteomyelitis or osteonecrosis. They were matched with a list of patients whose disease extent and localization had been evaluated using single-photon emission computed tomography and cone beam computed tomography in the context of clinical investigations. Subsequently, two experienced examiners for each imaging technique separately performed de novo readings. Detection rate, localization, extent, and qualitative parameters of a lesion were then compared.

Results

Twenty-one patients with mandibular osteomyelitis and osteonecrotic lesions were included. Cone beam computed tomography detected more lesions than single-photon emission computed tomography (25 vs. 23; 100% vs. 92%). Cone beam computed tomography showed significantly greater depth, area, and volume, whereas length and width did not differ statistically between the two groups.

Conclusion

Both single-photon emission computed tomography and cone beam computed tomography could sensitively detect osteomyelitis/osteonecrosis lesions. Only single-photon emission computed tomography showed metabolic changes, whereas cone beam computed tomography seemed to display anatomic morphological reactions more accurately. The selection of the most adequate three-dimensional imaging and the correct interpretation of preoperative imaging remains challenging for clinicians.

Clinical relevance

In daily clinical practice, three-dimensional imaging is an important tool for evaluation of osteomyelitis/osteonecrosis lesions. In this context, clinicians should be aware of differences between single-photon emission computed tomography and cone beam computed tomography when detecting and assessing an osteomyelitis/osteonecrosis lesion, especially if a surgical bone resection is planned.



https://ift.tt/2SZw8by

Expression of Toll-like receptors 2 and 4 and its association with matrix metalloproteinases in symptomatic and asymptomatic apical periodontitis

Abstract

To determine Toll-like receptors (TLR)2 and TLR4 expression levels and associate them with matrix metalloproteinases (MMPs) in asymptomatic apical periodontitis (AAP), symptomatic apical periodontitis (SAP), and healthy controls. Apical tissue/lesion samples were obtained from chronic AAP (n = 35) and SAP (n = 29), and healthy periodontal ligament (HPL, n = 10) with indication of tooth extraction, respectively. mRNA expression levels of TLR2, TLR4, MMP-1, MMP-2, MMP-8, and MMP-13 were determined by real-time reverse-transcription polymerase chain reaction. The data were analyzed with Kruskal-Wallis and Dunn's pot hoc test (p < 0.05). The correlation coefficient was obtained using the Spearman correlation (p < 0.05). TLR2, MMP-1, MMP-2, and MMP-13 mRNA levels were the highest in SAP followed by AAP and controls (p < 0.05). TLR4 and MMP-8 were over expressed in AAP and SAP compared to HPL (p < 0.05). TLR2 positively correlated with TLR4, MMP-1, MMP-8, and MMP-13 in SAP (p < 0.05). TLR2 and TLR4 are overexpressed in apical lesions versus healthy periodontal ligament and correlate with collagenolytic MMPs. Particularly, TLR2 is overexpressed in SAP in association with MMP-1, MMP-8, and MMP-13. Our results suggest that the activation of TLR2 along with MMP overexpression might contribute to SAP clinical presentation and progression. TLRs, MMPs, and their interaction can explain the clinical presentations and evolution of apical periodontitis and might represent key targets for new diagnostic and treatment approaches.



https://ift.tt/2BUCYEr

Comparative toxicity of five dispersants to test organisms at different trophic levels: Platymonas helgolandica , Ruditapes philippinarum , and Acinetobacter sp. Tox2

Abstract

Nowadays, although dispersants have been widely applied for emergency response to oil spills, they are potentially hazardous to the marine ecosystem. Therefore, it is necessary to evaluate dispersants' toxicity in a practical and integrated way before their large-scale application. Here, we compared the acute toxicity of five chemical dispersants (concentrate RS-I, conventional RS-I, HLD-501, Fuken-2, and Weipu) to three species (a microalgae Platymonas helgolandica, a mollusk Ruditapes philippinarum, and a luminescent bacterium Acinetobacter sp. Tox2) which represent different trophic levels. Our results showed that (1) conventional RS-I was slightly toxic to all the three test organisms; (2) concentrate RS-I and Weipu were slightly toxic to R. philippinarum, but were not toxic to the other two test species; (3) Fuken-2 and HLD-501 exhibited no acute toxicity to the three test organisms. Our results could provide information on toxicity data derived from multiple test organisms for the use of these five dispersants in the future.



https://ift.tt/2tHXuUd

Localization and age distribution of telangiectases in children and adolescents with hereditary hemorrhagic telangiectasia: A retrospective cohort study

Publication date: Available online 25 February 2019

Source: Journal of the American Academy of Dermatology

Author(s): Cristian D. Gonzalez, Sarah D. Cipriano, Christina A. Topham, David A. Stevenson, Kevin J. Whitehead, Sheryll Vanderhooft, Angela P. Presson, Jamie McDonald

Background

The location of telangiectases in hereditary hemorrhagic telangiectasia (HHT), as set forth in the consensus diagnostic (Curaçao) criteria, is based primarily on adults.

Objective

Document the locations and numbers of telangiectases in a cohort of pediatric patients with HHT.

Methods

A retrospective chart review using a standardized data collection form for site and number of telangiectases was performed for pediatric patients with HHT (age, 0-18 years) from 2005 to 2016.

Results

Of 90 pediatric patients with HHT, 71% had one or more telangiectases. Of all the telangiectases counted (N = 319), cutaneous telangiectases were more common (73%) than oral telangiectases (27%). The hands were the most frequent site, accounting for 33% of all telangiectases. Adolescents were more likely than children to have cutaneous telangiectases (85% vs 50% [Q = 0.005]). The most frequent sites in children younger than 10 years were the hands excluding the fingers (27%), fingers (25%), and face (23%). Only 23% of subjects (21 of 90) presented with multiple (≥3) telangiectases at locations considered characteristic for the current consensus diagnosis guidelines (lips, oral cavity, and fingers).

Limitations

Ascertainment bias based on recruitment.

Conclusions

In this pediatric population, telangiectases at sites not included as "characteristic" by the Curaçao diagnostic criteria were common. The Curaçao criteria in regard to both number and location of telangiectases may be inadequate in the pediatric HHT population.



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Unraveling corticobasal syndrome and alien limb syndrome with structural brain imaging

Publication date: Available online 25 February 2019

Source: Cortex

Author(s): Franziska Albrecht, Karsten Mueller, Tommaso Ballarini, Leonie Lampe, Janine Diehl-Schmid, Klaus Fassbender, Klaus Fliessbach, Holger Jahn, Robert Jech, Jan Kassubek, Johannes Kornhuber, Bernhard Landwehrmeyer, Martin Lauer, Albert C. Ludolph, Epameinondas Lyros, Johannes Prudlo, Anja Schneider, Matthis Synofzik, Jens Wiltfang, Adrian Danek

Abstract

Alien limb phenomenon is a rare syndrome associated with a feeling of non-belonging and disowning toward one's limb. In contrast, anarchic limb phenomenon leads to involuntary but goal-directed movements. Alien/anarchic limb phenomena are frequent in corticobasal syndrome (CBS), an atypical parkinsonian syndrome characterized by rigidity, akinesia, dystonia, cortical sensory deficit, and apraxia.

The structure-function relationship of alien/anarchic limb was investigated in multi-centric structural MRI data. Whole-group and single-subject comparisons were made in 25 CBS and eight CBS-alien/anarchic limb patients vs. controls. Support vector machine was used to see if CBS with and without alien/anarchic limb could be distinguished by structural MRI patterns.

Whole-group comparison of CBS vs. controls revealed asymmetric frontotemporal atrophy. CBS with alien/anarchic limb syndrome vs. controls showed frontoparietal atrophy including the supplementary motor area contralateral to the side of the affected limb. Exploratory analysis identified frontotemporal regions encompassing the pre-/and postcentral gyrus as compromised in CBS with alien limb syndrome. Classification of CBS patients yielded accuracies of 79%. CBS-alien/anarchic limb syndrome was differentiated from CBS patients with an accuracy of 81%. Predictive differences were found in the cingulate gyrus spreading to frontomedian cortex, postcentral gyrus, and temporoparietoocipital regions.

We present the first MRI-based group analysis on CBS-alien/anarchic limb. Results pave the way for individual clinical syndrome prediction and allow understanding the underlying neurocognitive architecture.



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Impaired hypothalamic leptin sensitivity in pseudopregnant rats treated with chronic prolactin to mimic pregnancy

Abstract

Pregnancy in rodents is associated with hyperphagia, increased fat deposition, elevated leptin concentrations and insensitivity to the satiety action of leptin. To investigate the hormonal mechanisms involved in the development of this state of pregnancy‐induced leptin resistance, we have used a pseudopregnancy rat model. We have previously demonstrated that pseudopregnant rats have a normal feeding response to leptin, but if pseudopregnancy is extended using chronic i.c.v. ovine prolactin infusion along with progesterone implants, then leptin no longer suppresses food intake. In this study, we aimed to investigate the effect of chronically high lactogen levels, as seen in mid pregnancy, on leptin‐induced activation of hypothalamic JAK/STAT signal transduction and mRNA expression of leptin (LepR‐B) and prolactin (Prlr‐L) receptors, using pseudopregnant rats chronically infused with ovine prolactin. Groups of virgin (diestrous) and pseudopregnant rats were treated with chronic i.c.v. infusion of either prolactin (2.5 μg/μl/hr for 5 days) or vehicle (aCSF) via a minipump connected to a cannula surgically implanted into the lateral ventricle. Rats were fasted overnight and then received an i.c.v. injection of leptin (400 ng) or vehicle (aCSF), and perfused 30 minutes later. In chronic vehicle‐infused pseudopregnant rats, i.c.v. leptin increased the number of phosphorylated STAT3 positive cells in the arcuate nucleus and ventromedial nucleus (VMH) of the hypothalamus, similar to all acute‐leptin treated virgin groups. This effect of leptin, however, was not observed in the pseudopregnant rats that were chronically infused with prolactin. Quantitative PCR analysis also showed decreased expression of LepR‐B in the arcuate and VMH nuclei, and decreased Prlr‐L in the arcuate nucleus of prolactin‐infused EPSP rats. These data suggest that the attenuation of the leptin‐induced suppression of food intake caused by chronically high lactogen levels in pseudopregnant rats is associated with impaired leptin‐induced activation of the JAK/STAT pathway in specific hypothalamic nuclei.

This article is protected by copyright. All rights reserved.



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Whole body sodium depletion modifies AT1 mRNA expression and serotonin content in the dorsal raphe nucleus

Abstract

Angiotensin II (ANG II) acts on AT1 receptors located in the organum vasculosum and subfornical organ (SFO) of the lamina terminalis as a main facilitatory mechanism of sodium appetite. The brain serotonin (5‐HT) system with soma located in the dorsal raphe nucleus (DRN) provides a main inhibitory mechanism. In the present work, we first investigated the existence of ANG II AT1 receptors in serotonergic DRN neurons. Then, we examined whether whole body sodium depletion affects the gene expression of the AT1a receptor subtype and the presumed functional significance of AT1 receptors. Using confocal microscopy, we found that tryptophan hydroxylase‐2 and serotonin neurons express AT1 receptors in the DRN. Immunofluorescence quantification showed a significant reduction in 5‐HT content, but no change in AT1 receptor expression or AT1/5‐HT colocalisation in the DRN after sodium depletion. Whole body sodium depletion also significantly increased Agtr1a mRNA expression in the SFO and DRN. Oral treatment with the AT1 receptor antagonist losartan reversed the changes in Agtr1a expression in the SFO, but not the DRN. Losartan injection into either the DRN or the mesencephalic aqueduct had no influence on sodium depletion‐induced 0.3 M NaCl intake. The results indicate the expression of Agtr1a mRNA in the DRN and SFO as a marker of sodium depletion. They also suggest that serotonergic DRN neurons are targets for ANG II. However, the function of their AT1 receptors remains elusive.

This article is protected by copyright. All rights reserved.



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A novel moisturizer with high sun protection factor improves cutaneous barrier function and the visible appearance of rosacea‐prone skin

Summary

Background

Consensus guidelines advocate general skincare for rosacea patients.

Objectives

Two independent studies were performed to assess whether a tinted daily SPF‐30 facial moisturizer (DFM30) improves barrier function of dry skin and the efficacy and tolerability of DFM30 on rosacea‐prone skin.

Methods

In study 1, electrical capacitance (EC) and transepidermal water loss (TEWL) were measured at baseline, 2, 4, 8, and 24 hours after a single application of DFM30 and on a control site in 21 healthy females with dry skin. Study 2 evaluated 33 females with mild to moderate rosacea and nontransient erythema. Efficacy and tolerability after once‐daily DFM30 were assessed using a chromameter, image analysis of photographs, and trained rater and patient evaluations up to day 22.

Results

In study 1, EC showed statistically significant increases at 2, 4, and 8 hours, and TEWL showed statistically significant decreases 2, 4, 8, and 24 hours after DFM30 application to healthy females compared to baseline. In study 2, covering skin redness improved significantly after DFM30 application on day 1; 33.3% showed improved covering skin redness compared to baseline. Patients reported significantly less redness on day 8 than day 3. Feelings of dryness and tightness/tension were lower 30 minutes after first application. Feeling of dryness was lower than baseline after 3 days, 1 and 3 weeks. Image analysis suggested redness was significantly lower on day 22 compared to baseline. Chromameter readings showed significantly lower erythema on the cheek compared to baseline. All patients stated that DFM30 relieves and neutralizes visible redness who also indicated that they would purchase DFM30, and the product was well tolerated.

Conclusions

These studies show that DFM30 is suitable as part of the skincare regimens advocated by ROSacea COnsensus (ROSCO) for rosacea patients. DFM30 is an effective moisturizer that improves cutaneous barrier function and the appearance of rosacea‐prone skin.



https://ift.tt/2Ex3DJm

Trotula de Ruggiero: The Magistra mulier sapiens and her medical dermatology treatises

Summary

Trotula de Ruggiero is supposed to be one of the first female physician of the history, or at least the first who practiced, taught, and wrote medical texts inside the illustrious medieval Medical School of Salerno around the XI‐XII centuries. Here we retrace the steps of her fascinating history from historical cues to legendary anecdotes, through the analysis of the medical texts which were ascribed to her in the Middle Ages and that were very popular around Europe for several centuries, prevalently dealing with all the aspects of women's medical problems, with a focus on dermatology, cosmetic science, and obstetrics/gynecology.



https://ift.tt/2VkLm7C

Isotretinoin and Hidradenitis Suppurativa

Abstract

We read with great interest the article by Gallagher et al.1, in which eight patients with severe acne vulgaris, who were treated with Isotretinoin, developed painful nodules in their axillae and groins consistent with Hidradenitis Suppurativa (HS). These observations prompted that systemic Isotretinoin may cause flares of HS, particularly in young, thin males.

This article is protected by copyright. All rights reserved.



https://ift.tt/2GK2ZKH

Hidradenitis Suppurativa and Diabetes: Big Data Bias Masks a True Association

Abstract

Phan et al present an updated meta‐analysis of the association between Hidradenitis Suppurativa (HS) and Type 2 Diabetes Mellitus (DM) which demonstrates a statistically significant elevation in the odds ratio (OR) for DM in HS Patients compared with healthy controls (OR=2.17 95% CI 1.85‐2.55 p<0.001). They astutely highlight that the risk difference of 0.4% between HS patients and controls (16.1% vs 15.7%) implies that this result is clinically non‐significant, quite at odds with clinical experience, data from existing studies and the remainder of the article discussing the importance of DM awareness in HS patients and possible mechanistic links between DM and HS. The reason for this statistical‐common sense disconnect is the lack of acknowledgement of external bias in Phan's analysis. Whilst the methodology is sound, it does not eliminate all bias and residual confounding despite the high reported I2 (which as a point estimate is misleading in the setting of large heterogeneity). Although weighting of studies addresses 'within study variance' and heterogeneity (I2) assesses methodological (internal) heterogeneity, no consideration of external biases (including population bias and outcome bias) is provided by a statistical program, it requires the use of common sense on behalf of the statistician and authors often by plotting and visualising the data. We replicated Phan et al's analysis with the additional step of assessing studies for external bias and threats to generalisability. Visualisation of data in a L'Abbe plot demonstrates lack of clustering on the x axis‐ indicating violation of the assumption of one underlying baseline risk.

This article is protected by copyright. All rights reserved.



https://ift.tt/2Nr4n5F

Epidemiology and Dermatological Comorbidity of Seborrhoeic Dermatitis – Population‐based Study in 161,000 Employees

Summary

Background

Seborrhoeic dermatitis (SD) is a common but epidemiologically poorly researched chronic skin disease.

Objectives

To characterise the prevalence and dermatological comorbidity of SD in Germany.

Methods

In the course of voluntary company skin checks, full body examinations were carried out in more than 500 companies by experienced dermatologists and documented electronically.

Results

161,269 participants were included (55.5% male, mean age 43.2+10.9 years). SD was identified in 3.2% (men: 4.6%, women 1.4%). A significant difference was found between age groups (2.0% in < 35; 3.6% in 35‐64; 4.4% ≥ 65 years). Most frequent concomitant skin conditions were: folliculitis (17.0%, 95% CI 15.9‐18.1), onychomycosis (9.1%, 95% CI 8.3‐10.0), tinea pedis (7.1%, 95% CI 6.3‐7.8), rosacea (4.1%, 95% CI 3.6‐4.7), acne (4.0%, 95% CI 3.4‐4.5) and psoriasis (2.7%, 95% CI 2.3‐3.2).

Regression analysis revealed the following relative dermatological comorbidity when controlling for age and gender: folliculitis (OR 2.1, 95% CI 2.0‐2.3), contact dermatitis (OR 1.8, 95% CI 1.1‐2.8), intertriginous dermatitis (OR 1.8, 95% CI 1.4‐2.2), rosacea (OR 1.6, 95% CI 1.4‐1.8), acne (OR 1.4, 95% CI 1.2‐1.7), pyoderma (OR 1.4, 95% CI 1.1‐1.8), tinea corporis (OR 1.4, 95% CI 1.0‐2.0), pityriasis versicolor (OR 1.3, 95% CI 1.0‐1.7) and psoriasis (OR 1.2, 95% CI 1.0‐1.4).

Conclusions

SD is a common disease which is more prevalent in men and older people and has an increased rate of dermatological comorbidity. However, absolute differences in prevalence of comorbidities are mostly small and negligible. Nevertheless, the findings underline the necessity of integrated, complete dermatological diagnostics and therapy.

This article is protected by copyright. All rights reserved.



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Antipruritic effects of transient heat‐stimulation on histaminergic and non‐histaminergic itch

Abstract

Background

Chronic itch is notoriously difficult to treat. Counter‐stimuli are able to inhibit itch, but this principle is difficult to apply in clinical practice, and the mechanisms behind counter‐stimulation‐induced itch suppression in humans are unclear.

Objectives

1) To analyse the stimulus‐response effects of transient heat stimuli on histaminergic and non‐histaminergic itch; 2) to investigate whether the antipruritic effect depends on homotopic (peripheral mediation) versus heterotopic (central mediation) counter‐stimulation relative to the itch provocation site.

Methods

18 healthy subjects (8 females, 25.7±0.8 y.o.) participated. Itch was evoked on pre‐marked areas of the volar forearms, by either histamine (1% solution), or cowhage (35‐40 spicules). In addition to the itch provocations (Experiment 1), 5‐seconds homotopic heat stimuli of 32, 40, 45 or 50°C were applied. In Experiment 2, heat stimuli were applied either homotopically, intra‐segmentally (next to the provocation site), or extra‐segmentally (dorsal forearm). Itch intensity was evaluated throughout the procedures using a digital Visual Analog Scale.

Results

Homotopic counter‐stimuli inhibited histaminergic itch by 41.27% at 45°C (p<0.01), and by 76.66% at 50°C (p<0.0001). Cowhage‐induced itch was less prone to counter‐stimulation and was only significantly diminished at 50°C by 43.60% (p=0.009). Counter‐stimulations applied heterotopically were not able to significantly inhibit itch.

Conclusions

Itch pathway‐specific effects of counter‐stimuli were observed between homo‐ and heterotopic stimulation. Histaminergic itch was robustly inhibited by short‐term homotopic noxious heat stimuli for up to 10 minutes. Non‐histaminergic itch was only weakly inhibited. The inhibitory effects exerted by the short‐term heat stimuli only occurred following homotopical counter‐stimulation.

This article is protected by copyright. All rights reserved.



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Molecular Imaging, vol. 12

  1. 3D Fusion Framework for Infarction and Angiogenesis Analysis in a Myocardial Infarct Minipig Model

    PhD1PhD, MD2MSc1PhD1PhD1PhD2PhD1
    Molecular Imaging, vol. 16First Published May 11, 2017.
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    Abstract

    The combination of different modality images can provide detailed and comprehensive information for the prognostic assessment and therapeutic strategy of patients with ischemic heart disease. In this study, a 3D fusion framework is designed to integrate coronary computed tomography (CT) angiography (CTA), 2-deoxy-2-[18F]fluoro-D-glucose ([18F]DG) positron emission tomography (PET)/CT, and [68Ga]-1,4,7-triazacyclononane-1,4,7-triacetic acid-(Arg-Gly-Asp)2 ([68Ga]-NOTA-PRGD2) PET/CT images of the myocardial infarction model in minipigs. First, the structural anatomy of the heart in coronary CTA and CT is segmented using a multi-atlas-based method. Then, the hearts are registered using the B-spline-based free form deformation. Finally, the [18F]DG and [68Ga]-NOTA-PRGD2 signals are mapped into the heart in coronary CTA, which produces a single fusion image to delineate both the cardiac structural anatomy and the functional information of myocardial viability and angiogenesis. Heart segmentation demonstrates high accuracy with good agreement between manual delineation and automatic segmentation. The fusion result intuitively reflects the extent of the [18F]DG uptake defect as well as the location where the [68Ga]-NOTA-PRGD2 signal appears. The fusion result verified the occurrence of angiogenesis based on the in vivo noninvasive molecular imaging approach. The presented framework is helpful in facilitating the study of the relationship between infarct territories and blocked coronary arteries as well as angiogenesis.

  2. Open Access

    Whole-Body Distribution of Leukemia and Functional Total Marrow Irradiation Based on FLT-PET and Dual-Energy CT

    Molecular Imaging, vol. 16First Published September 26, 2017.
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    Abstract

    This report describes a multimodal whole-body 3′-deoxy-3′[(18)F]-fluorothymidine positron emission tomography (FLT-PET) and dual-energy computed tomography (DECT) method to identify leukemia distribution within the bone marrow environment (BME) and to develop disease- and/or BME-specific radiation strategies. A control participant and a newly diagnosed patient with acute myeloid leukemia prior to induction chemotherapy were scanned with FLT-PET and DECT. The red marrow (RM) and yellow marrow (YM) of the BME were segmented from DECT using a basis material decomposition method. Functional total marrow irradiation (fTMI) treatment planning simulations were performed combining FLT-PET and DECT imaging to differentially target irradiation to the leukemia niche and the rest of the skeleton. Leukemia colonized both RM and YM regions, adheres to the cortical bone in the spine, and has enhanced activity in the proximal/distal femur, suggesting a potential association of leukemia with the BME. The planning target volume was reduced significantly in fTMI compared with conventional TMI. The dose to active disease (standardized uptake value >4) was increased by 2-fold, while maintaining doses to critical organs similar to those in conventional TMI. In conclusion, a hybrid system of functional–anatomical–physiological imaging can identify the spatial distribution of leukemia and will be useful to both help understand the leukemia niche and develop targeted radiation strategies.

  3. Open Access

    Vulnerable Plaque Detection and Quantification with Gold Particle–Enhanced Computed Tomography in Atherosclerotic Mouse Models

    Molecular Imaging, vol. 14, 6First Published June 1, 2015.
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    Abstract

    Recently, an apolipoprotein E–deficient (ApoE−/−) mouse model with a mutation (C1039G+/−) in the fibrillin-1 (Fbn1) gene (ApoE−/−Fbn1C1039G+/− mouse model) was developed showing vulnerable atherosclerotic plaques, prone to rupture, in contrast to the ApoE−/− mouse model, where mainly stable plaques are present. One indicator of plaque vulnerability is the level of macrophage infiltration. Therefore, this study aimed to measure and quantify in vivo the macrophage infiltration related to plaque development and progression. For this purpose, 5-weekly consecutive gold nanoparticle–enhanced micro–computed tomography (microCT) scans were acquired. Histology confirmed that the presence of contrast agent coincided with the presence of macrophages. Based on the microCT scans, regions of the artery wall with contrast agent present were calculated and visualized in three dimensions. From this information, the contrast-enhanced area and contrast-enhanced centerline length were calculated for the branches of the carotid bifurcation (common, external, and internal carotid arteries). Statistical analysis showed a more rapid development and a larger extent of plaques in the ApoE−/−Fbn1C1039G+/− compared to the ApoE−/−mice. Regional differences between the branches were also observable and quantifiable. We developed and applied a methodology based on gold particle–enhanced microCT to visualize the presence of macrophages in atherosclerotic plaques in vivo.

  4. Open Access

    Complementary Use of Bioluminescence Imaging and Contrast-Enhanced Micro—Computed Tomography in an Orthotopic Brain Tumor Model

    Molecular Imaging, vol. 13, 4First Published January 1, 2015.
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    Abstract

    Small animal models are crucial to link molecular discoveries and implementation of clinically relevant therapeutics in oncology. Using these models requires noninvasive imaging techniques to monitor disease progression and therapy response. Micro–computed tomography (CT) is less studied for the in vivo monitoring of murine intracranial tumors and traditionally suffers from poor soft tissue contrast, whereas bioluminescence imaging (BLI) is known for its sensitivity but is not frequently employed for quantifying tumor volume. A widely used orthotopic glioblastoma multiforme (GBM) tumor model was applied in nude mice, and tumor growth was evaluated by BLI and contrast-enhanced microCT imaging. A strong correlation was observed between CT volume and BLI-integrated intensity (Pearson coefficient (r) = .85, p = .0002). Repeated contouring of contrast-enhanced microCT-delineated tumor volumes achieved an intraobserver average pairwise overlap ratio of 0.84 and an average tumor volume coefficient of variance of 0.11. MicroCT-delineated tumor size was found to correlate with tumor size obtained via histologic analysis (Pearson coefficient (r) = .88, p = .005). We conclude that BLI intensity can be used to derive tumor volume but that the use of both contrast-enhanced microCT and BLI provides complementary tumor growth information, which is particularly useful for modern small animal irradiation devices that make use of microCT and BLI for treatment planning, targeting, and monitoring.

  5. Free Access

    Development and Validation of a Complete GATE Model of the Siemens Inveon Trimodal Imaging Platform

    Molecular Imaging, vol. 12, 7First Published October 1, 2013.
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    Abstract

    This article presents and validates a newly developed GATE model of the Siemens Inveon trimodal imaging platform. Fully incorporating the positron emission tomography (PET), single-photon emission computed tomography (SPECT), and computed tomography (CT) data acquisition subsystems, this model enables feasibility studies of new imaging applications, the development of reconstruction and correction algorithms, and the creation of a baseline against which experimental results for real data can be compared. Model validation was based on comparing simulation results against both empirical and published data. The PET modality was validated using the NEMA NU-4 standard. Validations of SPECT and CT modalities were based on assessment of model accuracy compared to published and empirical data on the platform. Validation results show good agreement between simulation and empirical data of approximately ± 5%.

  6. Free Access

    Use of eXIA 160 XL for Contrast Studies in Micro–Computed Tomography: Experimental Observations

    Molecular Imaging, vol. 12, 6First Published September 1, 2013.
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    Abstract

    The purpose of this study was to evaluate the time course of contrast enhancement of spleen, liver, and blood using eXIA 160 XL in healthy mice. eXIA 160 XL was intravenously injected in C57bl/6 mice (n = 12) at a dose of 0.1 mL/20 g (16 mg iodine [I]/20 g) (n = 6) or 0.2 mL/20 g (32 mg I/20 g) (n = 6). The distribution was analyzed by repeated micro–computed tomographic scans up to 48 hours after contrast administration. Images were analyzed using Amidesoftware. Regions of interest were drawn in the spleen, liver, and left ventricle. Contrast enhancement was measured and expressed as a function of time. Peak contrast enhancement of the spleen was reached at 30 minutes, and peak contrast enhancement of the liver occurred 45 minutes after 16 mg I/20 g. Given that this contrast was found to be rather low in the spleen in comparison with former eXIA 160 products, experiments were done at a higher dose. However, the 32 mg I/20 g dose was lethal for mice. Enhancement inside the heart lasts for 1 hour. Administration of eXIA 160 XL results in long-lasting blood pool contrast with higher contrast enhancement in heart and liver in comparison with eXIA 160; however, the administered dose should be limited to 16 mg I/20 g.

  7. Free Access

    Comparison of Computed Tomography– and Optical Image–Based Assessment of Liposome Distribution

    Molecular Imaging, vol. 12, 3First Published May 1, 2013.
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    Abstract

    The use of multimodal imaging as a tool to assess the in vivo pharmacokinetics and biodistribution of nanocarriers is important in understanding the nature of their in vivo transport. The current study reports the development of a nano-sized liposomal computed tomographic (CT)/optical imaging probe carrying iohexol and Cy5.5 and its use in micro-CT and optical imaging to quantitatively assess the whole-body (macroscopic), intratumoral, and microscopic distribution over a period of 8 days. These multimodal liposomes have a vascular half-life of 30.3 ± 8.9 hours in mice bearing subcutaneous H520 non-small cell lung cancer tumors, with the maximum liposome accumulation in tumor achieved 48 hours postinjection. The in vivo liposome distribution and stability were quantitatively assessed using both micro-CT and fluorescence molecular tomography. The combination of CT and optical imaging enables visualization of the liposomes at the whole-body, tumor, and cellular scales with high sensitivity. Such noninvasive tracking of therapeutic vehicles at the macro- and microscale is important for informed and rational development of novel nanocarrier systems.


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