The prospect of spray pyrolyzed pure, Mn-doped, and Zn-doped nickel oxide thin films as TCO material.

Nickel Oxide films with Manganese (Mn) and Zinc (Zn) doping (NiO, Ni1-xMnxO, and Ni1-xZnxO; where x = 0, 0.02, 0.04, and 0.06) were fabricated using the spray pyrolysis technique on the glass substrates at 400 °C (673K) temperature. The XRD spectra revealed a polycrystalline nature of the films with cubic crystal structure and a favored growth orientation towards the (111) plane. The SEM micrographs revealed a smooth, homogeneous, and uniform surface, while the EDS spectra confirmed the presence of Ni, O, Zn, and Mn elements in the films. Optical analysis using UV-visible absorption spectroscopy demonstrated high transparency of the films in the visible region (400 nm-900 nm), and the transparency increased with higher Zn doping, reaching ∼85 % in Ni0.94Zn0.06O films. Conversely, Ni1-xMnxO films show a slight transmission decline with increasing Mn doping concentrations. The sheet resistance of the films was found to be decreased for low-concentration doping and again began to increase for highly doped Ni0.94Zn0.06O and Ni0.94Mn0.06O films. Among all the films, Ni0.98Zn0.02O exhibited the maximum figure of merit, showing the prospect for optoelectronic applications.

Dermoscopy of glomus tumour: a cross-sectional study of 86 cases.

BACKGROUND: Glomus tumours (GTs) are benign cutaneous neoplasms derived from the neuromyoarterial apparatus with a strong predilection for acral sites, especially the subungual space. Current data regarding dermoscopy of these lesions are very limited. OBJECTIVES: To analyse the dermoscopic structures and patterns seen in a large series of subungual (SUGTs) and extraungual glomus tumours (EUGTs) and to determine their diagnostic significance. METHODS: Clinical and dermoscopic images of 86 histopathologically proven cases of GTs (47 SUGTs and 39 EUGTs) collected from 9 hospitals in Spain, France, Italy, and Brazil were evaluated for the presence of dermoscopic structures and patterns. Similarly, 189 and 185 dermoscopic images of other ungual tumours and other extraungual non-pigmented tumours, respectively, were evaluated for the same structures and patterns. Finally, we evaluate diagnostic testing accuracy calculating sensitivity (S), specificity (Sp), and positive and negative predictive values of the different patterns for the diagnosis of GT. RESULTS: Regarding SUGTs, four patterns were built from the combination of different structures. The pattern composed of a structureless purplish/red subungual spot with or without vessels reached the highest S (S1, 78.8%). The combination of a structureless purplish/red subungual spot and longitudinal erythronychia (LE) (S2) is highly specific (96.3%). Patterns S3 (proximal purplish/red subungual spot, LE, and distal notch) and S4 (bed subungual spot and onycholysis) are the most specific and exclusive of matrix and bed tumours, respectively. The most consistent pattern in EUGTs is composed of a structureless purplish-white to reddish-white homogeneous area and linear unfocused vessels (E) (S: 61.5%, Sp: 95.7%). EUGTs did not show lacunae, unlike other vascular tumours. CONCLUSIONS: Dermoscopy is helpful in improving the diagnostic accuracy of GTs, not only in SUGTs but also when these lesions arise out of the ungual apparatus.

Dermoscopy in Basal Cell Carcinoma: An Updated Review. / Dermatoscopia del carcinoma basocelular: revisión actualizada.

Dermoscopy is a noninvasive technique that has been demonstrated to improve diagnostic accuracy in basal cell carcinoma (BCC). The first dermoscopic model for the diagnosis of BCC, based mainly on the identification of pigmented structures, was described by Menzies et al., and since then dermoscopy has generated an abundance of literature useful to routine clinical practice. From a practical perspective, dermoscopic structures associated with BCC can be classified as pigmented, vascular, or nonpigmented/nonvascular. One of the most recent applications of dermoscopy in BCC is as an aid to predicting histologic subtype and essentially differentiating between superficial and nonsuperficial BCC. It can also, however, help raise suspicion of more aggressive variants with a higher risk of recurrence. A thorough dermoscopic examination during follow-up of patients with actinic damage or a history of multiple BCCs can facilitate the detection of very incipient lesions and significantly impact treatment and prognosis.

Interferometric optical testing to discriminate benign and malignant brain tumors.

When normal cells suffer from the malignant disease, changes occur in cellular size and structure, and their constituents. These changes can affect the biological response of cells and tissues. Conventional hematoxylin and eosin staining, which is the gold standard of tumor diagnosis provide a very detailed view of the tissue by staining cell structures to diagnose a disease based on the deformation of the cells. However, this study shows changes in cells and tissues structure due to malignant diseases can also affect the optical properties. The purpose of this research was to assess and compare these effects to identify benign and malignant brain tissues from each other. Various samples of adult human brain tissues were studied using Mach-Zehnder interferometer as an optical method and using the Fourier transform method as an analytical process. The formed interference patterns of benign and malignant brain tumors were investigated to obtain the phase distribution of tumors. The obtained information demonstrated that the phase distribution of malignant brain tissues was different from benign brain tissues. The phase distribution approximately ranged from 10 to 120 rad for benign samples and from 10 to 160 rad for malignant samples. Moreover, the average of unwrapped phase distribution was 63.79 and 85.69 rad in benign and malignant samples, respectively. This results indicated that the proposed laser-based technique, Mach-Zehnder interferometer method, can be used as an auxiliary procedure along with histological techniques to identify benign and malignant brain tumors from each other. It is suggested that the unwrapped phase distribution of tissues be considered as an optical property for differentiating various brain tumors.

Pharmacological profiling of sigma 1 receptor ligands by novel receptor homomer assays.

The sigma 1 receptor (σ1R) is a structurally unique transmembrane protein that functions as a molecular chaperone in the endoplasmic reticulum (ER), and has been implicated in cancer, neuropathic pain, and psychostimulant abuse. Despite physiological and pharmacological significance, mechanistic underpinnings of structure-function relationships of σ1R are poorly understood, and molecular interactions of selective ligands with σ1R have not been elucidated. The recent crystallographic determination of σ1R as a homo-trimer provides the foundation for mechanistic elucidation at the molecular level. Here we report novel bioluminescence resonance energy transfer (BRET) assays that enable analyses of ligand-induced multimerization of σ1R and its interaction with BiP. Haloperidol, PD144418, and 4-PPBP enhanced σ1R homomer BRET signals in a dose dependent manner, suggesting their significant effects in stabilizing σ1R multimerization, whereas (+)-pentazocine and several other ligands do not. In non-denaturing gels, (+)-pentazocine significantly decreased whereas haloperidol increased the fraction of σ1R multimers, consistent with the results from the homomer BRET assay. Further, BRET assays examining heteromeric σ1R-BiP interaction revealed that (+)-pentazocine and haloperidol induced opposite trends of signals. From molecular modeling and simulations of σ1R in complex with the tested ligands, we identified initial clues that may lead to the differed responses of σ1R upon binding of structurally diverse ligands. By combining multiple in vitro pharmacological and in silico molecular biophysical methods, we propose a novel integrative approach to analyze σ1R-ligand binding and its impact on interaction of σ1R with client proteins.

Altering Metabolic Profiles of Drugs by Precision Deuteration 2: Discovery of a Deuterated Analog of Ivacaftor with Differentiated Pharmacokinetics for Clinical Development.

Ivacaftor is currently used for the treatment of cystic fibrosis as both monotherapy (Kalydeco; Vertex Pharmaceuticals, Boston, MA) and combination therapy with lumacaftor (Orkambi; Vertex Pharmaceuticals). Each therapy targets specific patient populations: Kalydeco treats patients carrying one of nine gating mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein, whereas Orkambi treats patients homozygous for the F508del CFTR mutation. In this study, we explored the pharmacological and metabolic effects of precision deuteration chemistry on ivacaftor by synthesizing two novel deuterated ivacaftor analogs, CTP-656 (d9-ivacaftor) and d18-ivacaftor. Ivacaftor is administered twice daily and is extensively converted in humans to major metabolites M1 and M6; therefore, the corresponding deuterated metabolites were also prepared. Both CTP-656 and d18-ivacaftor showed in vitro pharmacologic potency similar to that in ivacaftor, and the deuterated M1 and M6 metabolites showed pharmacology equivalent to that in the corresponding metabolites of ivacaftor, which is consistent with the findings of previous studies of deuterated compounds. However, CTP-656 exhibited markedly enhanced stability when tested in vitro. The deuterium isotope effects for CTP-656 metabolism (DV = 3.8, DV/K = 2.2) were notably large for a cytochrome P450-mediated oxidation. The pharmacokinetic (PK) profile of CTP-656 and d18-ivacaftor were assessed in six healthy volunteers in a single-dose crossover study, which provided the basis for advancing CTP-656 in development. The overall PK profile, including the 15.9-hour half-life for CTP-656, suggests that CTP-656 may be dosed once daily, thereby enhancing patient adherence. Together, these data continue to validate deuterium substitution as a viable approach for creating novel therapeutic agents with properties potentially differentiated from existing drugs.

In Vivo versus Augmented Reality Exposure in the Treatment of Small Animal Phobia: A Randomized Controlled Trial.

Although in vivo exposure is the treatment of choice for specific phobias, some acceptability problems have been associated with it. Virtual Reality exposure has been shown to be as effective as in vivo exposure, and it is widely accepted for the treatment of specific phobias, but only preliminary data are available in the literature about the efficacy of Augmented Reality. The purpose of the present study was to examine the efficacy and acceptance of two treatment conditions for specific phobias in which the exposure component was applied in different ways: In vivo exposure (N = 31) versus an Augmented Reality system (N = 32) in a randomized controlled trial. "One-session treatment" guidelines were followed. Participants in the Augmented Reality condition significantly improved on all the outcome measures at post-treatment and follow-ups. When the two treatment conditions were compared, some differences were found at post-treatment, favoring the participants who received in vivo exposure. However, these differences disappeared at the 3- and 6-month follow-ups. Regarding participants' expectations and satisfaction with the treatment, very positive ratings were reported in both conditions. In addition, participants from in vivo exposure condition considered the treatment more useful for their problem whereas participants from Augmented Reality exposure considered the treatment less aversive. Results obtained in this study indicate that Augmented Reality exposure is an effective treatment for specific phobias and well accepted by the participants.

Methotrexate in Moderate to Severe Psoriasis: Review of the Literature and Expert Recommendations.

Methotrexate (MTX) is the most frequently used conventional systemic drug in the treatment of psoriasis. Despite over 50years of experience in this setting, certain aspects of the use of this drug in clinical practice are still little standardized and poorly understood. For this reason, a group of 15 experts took part in a consensus development conference to achieve consensus on a series of recommendations on the use of MTX in psoriasis. The guidelines, which were developed on the basis of a systematic review of the literature, were validated by 2 rounds of voting and categorized by level of evidence and grade of recommendation. Before MTX can be used to treat moderate to severe psoriasis, the patient must be evaluated to assess the suitability of the treatment, including consideration of vaccination status and screening for tuberculosis and pregnancy. The recommended starting dose for a patient with no risk factors is 10 to 20mg/wk, the therapeutic dose for most patients is 15mg/wk, and the maximum dose is 20mg/wk. Most patients who respond to treatment will show improvement within 8weeks. Parenteral administration of MTX is desirable when there is a risk of erroroneous dosing, nonadherence, gastrointestinal intolerance, or inadequate response to the therapeutic dose taken orally. Noninvasive methods are preferred for monitoring hepatotoxicity. MTX is a good treatment option for patients with a history of cancer, but is not recommended in patients with chronic hepatitisB infection or individuals who are seropositive for human immunodeficiency virus.

Etanercept combined with systemic drugs or phototherapy for treatment of psoriasis.

Biologic drugs have provided excellent results in the treatment of moderate to severe psoriasis. Nevertheless, in routine clinical practice, combinations of biologic drugs with phototherapy or systemic drugs can increase efficacy, diminish toxicity, and reduce the cost of treatment. Published experience with these combinations is scarce, although the results are often satisfactory. This review examines the most relevant published experience in the combination of the most studied drug in this field-etanercept-with methotrexate, acitretin, ciclosporin, and narrowband UV-B phototherapy. Findings reported in the literature can help when taking major decisions on the management of biologic and systemic drugs in moderate to severe psoriasis.

Antiangiogenic agents and the skin: cutaneous adverse effects of sorafenib, sunitinib, and bevacizumab.

As new antiangiogenic therapies have been introduced and added to the therapeutic arsenal against various types of cancer, previously unknown adverse effects have been detected. These effects negatively impact patients' quality of life and can even make it necessary to suspend treatment. Adverse skin reactions occur in 90% of patients treated with angiogenesis inhibitors. In some cases, a correlation has been observed between the severity of reactions and treatment efficacy and tumor response. It is therefore extremely important that dermatologists be able to recognize and manage these reactions. Moreover, in order to avoid the unjustified withdrawal of potentially life-extending treatments, dermatologists must be able to differentiate between non-life-threatening reactions and life-threatening reactions that necessitate the suspension of treatment. In this review article, we analyze the main cutaneous adverse effects of the most common antiangiogenic agents.

Blood microvessel density, lymphatic microvessel density and lymphatic invasion in predicting melanoma metastases: systematic review and meta-analysis.

In malignant melanoma (MM) there is an urgent need to identify new markers with predictive value superior to the traditional clinical and histological parameters. Angiogenesis and lymphangiogenesis have been recognized as critical processes in tumour growth and metastasis development, and numerous studies have evaluated the significance of these parameters in predicting the prognosis in solid tumours, including MM. We set out to determine whether angiogenesis, lymphangiogenesis and lymphatic invasion (LI) are valuable prognostic markers in MM. We systematically reviewed the available literature and subsequently performed a meta-analysis on the compiled data. To be eligible for the systematic review, a study had to provide the microvessel density (MVD), the lymphatic vessel density (LVD) or information about LI, assessed by immunohistochemistry on the primary site in patients with MM. To be evaluable for the meta-analysis, a study also had to provide information on clinical outcome. We approached selected studies with the Reporting recommendations for tumour marker (REMARK) criteria, verifying whether they had followed the recommendations. In total, nine angiogenesis, seven lymphangiogenesis and 10 LI studies were included in our meta-analysis, representing 419, 474 and 802 patients, respectively. Using meta-analysis, we showed that peritumoral LVD and the presence of LI have prognostic value for patients with MM. In contrast, MVD and intratumoral LVD did not have prognostic value in these patients. LVD and LI seem to have prognostic value for patients with MM.

Seropositivity of Helicobacter Pylori among the fish handlers.

This case control study was done to study the seropositivity of helicobacter pylori among the fish handlers and to find out rapid urease test (RUT) & haematoxillin and eosin staining report correlation of seropositive cases. It was performed among fish handlers in the period of July 2005 to June 2006. Blood samples were collected from fish handlers (Group I) and some non-fish handler control subjects (Group II) to perform Anti-H. Pylori IgG test by ELISA method. Samples were collected from both the sea water area (Paikgacha, Khulna) and fresh water area (Derai, Sunamgonj and Dhaka). Seropositive cases having complaints and treatment history of peptic ulcer diseases were motivated for endoscopic examination to collect biopsy from upper GIT and rapid urease test (RUT) hematoxillin & eosin (H & E) staining were performed. A total of 235 respondents were included in this study, among them 163 were fish handlers (80 sea water and 83 fresh water) and 72 were non fish handler control (25 sea water, 22 fresh water from Sunamgonj, 25 fresh water from Dhaka city). Serum anti- H. pylori test was positive in 126(77.30%) cases in fish handler group (a) and 27(37.5%) cases in the control group (b). Seropositive cases were observed more among the higher age group (>40 years) than in lower age group (<40 years) which was 86% and 67% respectively. Endoscopic examination was done among the seropositive cases having positive PUD features. Total seropositive cases were 153 and among them 81 have positive PUD features, among them 48 cases were selected for endoscopic examination. Among the fish handlers out of 34 cases, 31(91.17%) were RUT positive and out of 14 non-fish handlers 6(42.85%) were RUT positive. Among the fish handlers, 28(82.35%) of the 34-biopsy specimens were H & E positive and among the non-fish handlers, out of 14 samples, 5(35.71%) were H & E positive. Fish handlers have more association of H. Pylori infection than non fish handlers and higher age group persons are more prone to H. Pylori infection. A significant number of seropositive persons have association with positive RUT and H & E staining report.

[Diagnostic agreement between primary care physicians and dermatologists in the health area of a referral hospital]. / Estudio de concordancia diagnóstica en Dermatología entre Atención Primaria y Especializada en el área de salud de un hospital de referencia.

INTRODUCTION: Skin diseases account for a high proportion of presenting complaints in primary health care. In Spain, the growing demand for consultations and the resulting longer waiting lists make it necessary to establish criteria for appropriate referrals to a specialist. This study aimed to investigate the characteristics of referrals from primary care centers to dermatology specialists as well as the correlation between the presenting complaint and the final dermatologic diagnosis. PATIENTS AND METHODS: We collected data from 3164 patients seen for the first time by dermatologists in our specialist service during 1998. Patients were stratified according to the referring primary health care center and the reason for referral. The agreement between the presenting complaint and the final dermatologic diagnosis was studied. For each dermatologic condition, the positive predictive value, diagnostic sensitivity, and k statistic were calculated. RESULTS: The overall diagnostic agreement was 65.52 %. Primary care physicians were found to over diagnose diseases caused by papillomavirus and the diagnostic sensitivity was very low for diseases such as basal cell carcinoma and seborrheic keratosis. CONCLUSIONS: It is necessary to insist on training primary care physicians, ensuring appropriate referral from primary health care clinics, and promoting an effective dialogue with the specialist.

Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sites.

Monocyte recruitment to sites of inflammation is regulated by members of the chemokine family of chemotactic cytokines. However, the mechanisms that govern the migration of monocytes from bone marrow to blood and from blood to inflamed tissues are not well understood. Here we report that CC chemokine receptor 2 (CCR2) is highly expressed on a subpopulation of blood monocytes whose numbers are markedly decreased in CCR2(-/-) mice. In bone marrow, however, CCR2(-/-) mice had an increased number of monocytes, suggesting that CCR2 is critical for monocyte egress. Intravenous infusion of ex vivo-labeled WT or CCR2(-/-) bone marrow into WT recipient mice demonstrated that CCR2 is necessary for efficient monocyte recruitment from the blood to inflamed tissue. Analysis of mice lacking monocyte chemoattractant protein-1 (MCP-1), MCP-3, MCP-5, or MCP-2 plus MCP-5 revealed that MCP-3 and MCP-1 are the CCR2 agonists most critical for the maintenance of normal blood monocyte counts. These findings provide evidence that CCR2 and MCP-3/MCP-1 are critical for monocyte mobilization and suggest new roles for monocyte chemoattractants in leukocyte homeostasis.

Targeted disruption of the scavenger receptor and chemokine CXCL16 accelerates atherosclerosis.

BACKGROUND: The uptake of oxidized low-density lipoprotein (OxLDL) by macrophage scavenger receptors is thought to be a key process in the formation of foam cells, the hallmark of early atherosclerotic lesions. CXCL16/scavenger receptor for phosphatidylserine and OxLDL is a multifunctional chemokine that exhibits scavenger receptor activity toward oxidized lipids in a membrane-bound configuration and may be shed to serve as a chemoattractant for T helper 1-polarized T lymphocytes. These properties, as well as the expression of CXCL16 in human and mouse atheroma, suggest that CXCL16 plays a role in atherosclerosis. METHODS AND RESULTS: To examine the role of CXCL16 in plaque formation, we created CXCL16-deficient mice (CXCL16-/-) and bred them with mice deficient in the LDL receptor (LDLR-/-). In vitro, macrophages from CXCL16-/- mice have a significant reduction in the capacity to bind and internalize OxLDL. We found that CXCL16-/-/LDLR-/- mice have accelerated atherosclerosis, enhanced macrophage recruitment to the aortic arch, and more abundant mRNA for monocyte chemotactic protein-1 and tumor necrosis factor-alpha. CONCLUSIONS: These data suggest that scavenger receptor activity mediated by CXCL16 in vivo is atheroprotective, and they contrast with studies that document protection from atherosclerosis in scavenger receptor class A- and CD36-deficient mice.

Dermoscopic findings of haemosiderotic and aneurysmal dermatofibroma: report of six patients.

BACKGROUND: The clinical diagnosis of dermatofibroma is commonly easy. However, the differentiation of dermatofibroma from other cutaneous tumours is difficult in some instances, primarily in atypical cases and rare variants. Haemosiderotic dermatofibroma is a variant composed of numerous small vessels, extravasated erythrocytes and intra- and extracellular haemosiderin deposits. Aneurysmal dermatofibroma is a variant composed of large, blood-filled spaces without endothelial lining. Some authors consider that haemosiderotic dermatofibroma is an early stage in the development of aneurysmal dermatofibroma. The clinical differential diagnosis of haemosiderotic or aneurysmal dermatofibroma must include melanoma and other melanocytic tumours, vascular neoplasms, adnexal tumours and nonspecific cysts. Dermoscopy improves the diagnostic accuracy in pigmented and nonpigmented skin lesions. OBJECTIVES: To evaluate specific dermoscopic criteria. METHODS: Dermoscopic examination (using the DermLite Foto; 3Gen, LLC, Dana Point, CA, U.S.A.) of six patients with haemosiderotic or aneurysmal dermatofibromas was performed to evaluate specific dermoscopic criteria. RESULTS: A multicomponent pattern with a central bluish or reddish homogeneous area in combination with white structures and a peripheral delicate pigment network along with vascular structures was noted in five of six lesions. CONCLUSIONS: This dermoscopic pattern yielded the diagnosis of haemosiderotic or aneurysmal dermatofibroma in most cases. However, this multicomponent pattern may present in some melanomas and although it is useful in determining a clinical diagnosis of aneurysmal dermatofibroma, it may not be specific to this entity.