Such braces may decrease knee pain, and improve knee function.

Summary

Braces are recommended for treating knee osteoarthritis. The different bracing modalities that are available must be adapted to the symptomatic knee osteoarthritis

compartment. This non pharmacological approach must be added to the other nonpharmacological, and pharmacological modalities to decrease pain and improve function and thereby increase the quality of life of osteoarthritis patients. The structural effect of bracing has not yet been evaluated. High-quality clinical trials of the addition of various treatment modalities for knee osteoarthritis are still necessary.”
“Objective: (1) To determine associations between radiographic features learn more of lumbosacral (LS) spine disc space narrowing (DSN) and osteophytes (OST) and joint metabolism biomarkers (serum cartilage oligomeric matrix protein (COMP), hyaluronic acid (HA), collagen neoepitope (C2C). C-propeptide of type II procollagen (CP-II), urine C-terminal cross-linking telopeptide (CTX-II) and N-terminal telopeptide (NTX-I)). (2) To explore interactions with race, gender and low back symptoms.

Design: Cross-sectional analysis of 547 participants enrolled in the Johnston County (JoCo) Osteoarthritis Project from 2003 to 2004. Mean biomarker levels were estimated with linear regression. Proportional and partial-proportional odds models were used to estimate

associations. CA3 in vitro Interactions were tested with likelihood ratio tests at a P-value < 0.10. Biomarkers

were natural log (In) transformed.

Results: Significant differences in mean biomarker levels were found across severity of SRT1720 nmr DSN for InHA and InC2C and InCTX-II across severity of both DSN and OST. Moderate-to-strong associations were found between biomarkers of type II collagen and DSN, whereas associations with OST were weak. An association between InHA and DSN was seen in women (adjusted odds ratio [aOR] = 1.34 (95% confidence intervals (CI) 1.08, 1.65)) but no association among men (aOR = 0.90 (95% CI 0.63, 1.26)). In Caucasians there was a decreased association with NTX-I and OST (aOR = 0.67 (95% CI 0.49, 0.91)) and no association in African Americans (AAs) (aOR = 1.06 (95% CI 0.76, 1.47)). There was a positive association of InCOMP with DSN among those with low back symptoms (aOR = 1.82 (95% CI 1.02, 3.27)), but no association in those without low back symptoms (aOR = 0.65 (95% CI 0.35, 1.20)).

Conclusion: Joint metabolism biomarkers suggest biological differences in the pathologic process involved in DSN and OST that may be gender (HA) and ethnicity (NTX-I) specific. (C) 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.”
“Purpose of review

The incidence of ankle osteoarthritis has increased in recent years, in part, secondary to vehicular trauma.

PSPH appears to be critical for the proliferation of SCC PD98059 supplier cells; however, this phenomenon may not involve the phosphoserine metabolic pathway.

(C) 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.”
“In higher plants, copper ions, hydrogen peroxide, and cycloheximide have been recognized as very effective inducers of the transcriptional activity of genes encoding the enzymes of the ethylene biosynthesis pathway. In this report, the transcriptional patterns of genes encoding the 1-aminocyclopropane-1-carboxylate synthases (ACSs), 1-aminocyclopropane-1-carboxylate oxidases (ACOs), ETR1, ETR2, and ERS1 ethylene receptors, phospholipase D (PLD)-alpha 1, -alpha 2, -gamma 1, and -delta, and respiratory burst oxidase homologue (Rboh)-NADPH oxidase-D and -F in response to these inducers in Brassica oleracea etiolated seedlings are shown. ACS1, ACO1, ETR2, PLD-gamma 1, and RbohD represent genes whose expression was considerably affected by all of the inducers used. The investigations were performed on the seedlings with (i) ethylene insensitivity and (ii) a reduced level of the PLD-derived phosphatidic acid (PA). The general conclusion is that the expression of ACS1, -3, -4, -5, -7, and -11, ACO1, ETR1, ERS1, and ETR2, PLD-gamma Rabusertib in vitro 1, and RbohD and F genes is undoubtedly under the reciprocal cross-talk of the ethylene and PA(PLD) signalling

routes; both signals affect it in concerted or opposite ways depending on the gene or the type of stimuli. The results of these studies on broccoli seedlings are in agreement with the hypothesis that PA may directly affect the ethylene signal transduction pathway via

an inhibitory effect on CTR1 (constitutive triple response 1) activity.”
“Multilayer Ag/[Ag2Se(t)/FePt(1nm)](10) (thickness t = 0.1-0.4 nm) were alternately deposited on a glass substrate and subsequently annealed by rapid thermal process (RTP) at 800 degrees C for 3 min. After RTP, the interface between FePt and Ag2Se was intermixed to form particulate MS-275 ic50 films. The grains size of the L1(0) FePt decreased from 9.8 to 7.7 nm when the total thickness of Ag2Se intermediate layer increases to 1 nm. The Ag/(Ag2Se/FePt)(10) particulate film showed perpendicular magnetization and a slight increase in out-of-plane coercivity over that of the original thickness of Ag2Se. The Ag2Se atoms were immiscible with FePt phase but the FePt grains were refined and separated well from the Ag2Se phase. Compared with Ag/FePt bilayer, the grains of the FePt were refined and uniformly separated in the Ag/[Ag2Se(t)/FePt](10) multilayer with t = 0.1 nm. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3553943]“
“Background: Human papilloma virus (HPV)-related warts persist, evading host immune surveillance, but sometimes disappear with inflammation.

The prevalence of isolated PFJ damage was greater than isolated TFJ damage using all definitions except the any BML definition. Combretastatin A4 mouse This pattern was similar between genders

and among age and BMI categories. In those with knee pain, isolated PFJ was at least as common as TFJ damage depending on the definition used.

Conclusion: Using MRI to assess knee joint structural damage, isolated PFJ damage was at least as common as, if not more common than, isolated TFJ damage. (C) 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.”
“Rituximab (MabThera (R), Rituxan (R)) is a chimeric mouse anti-human CD20 monoclonal antibody. This article reviews the use of intravenous rituximab in the treatment of chronic lymphocytic leukemia (CLL), low-grade or follicular lymphoma, and diffuse large B-cell lymphoma.

The addition of rituximab to fludarabine plus cyclophosphamide significantly prolonged progression-free survival both in previously untreated patients with CLL and in those with relapsed or refractory CLL, according

to AG-881 molecular weight the results of two randomized, open-label, multicenter trials.

In patients with previously untreated advanced follicular lymphoma, the addition of rituximab to chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP]; cyclophosphamide, vincristine, and prednisone [CVP]; mitoxantrone, chlorambucil, and prednisolone; check details or cyclophosphamide, doxorubicin, etoposide, and prednisolone) was generally associated with better outcomes than chemotherapy alone in randomized, multicenter trials. In a similarly designed trial, progression-free survival was significantly longer

in previously untreated patients with follicular lymphoma, other indolent lymphomas, or mantle-cell lymphoma who received rituximab plus bendamustine than in those receiving rituximab plus CHOP. Monotherapy with rituximab also demonstrated efficacy in patients with relapsed or refractory low-grade or follicular lymphoma, according to the results of noncomparative trials. In terms of maintenance therapy, progression-free survival was significantly prolonged with rituximab maintenance therapy versus observation alone in patients with advanced indolent lymphoma who had not progressed following first-line therapy with CVP and in patients with relapsed or refractory follicular lymphoma who had responded to CHOP (with or without rituximab), according to the results of randomized, open-label, multicenter trials.

In four randomized, open-label, multicenter trials in younger or elderly patients with previously untreated diffuse large B-cell lymphoma, event-free survival, failure-free survival, progression-free survival, and overall survival were generally improved to a significant extent by the addition of rituximab to CHOP or CHOP-like chemotherapy.

Treatments were 1) CON, 2) EOM, 3) EXP, and 4) MON with feeding rates similar to Exp. 1. There were no differences in DMI, OM intake, and apparent total tract DM or OM digestibilities among treatments (P > 0.30). Feed intake patterns were similar among feed additive treatments (P > 0.13). Total VFA (P = 0.10) and acetate (P = 0.06) concentrations tended to be affected by treatment with EOM numerically greater than CON. Average ruminal pH ranged from 5.59 to 5.72 and did not differ among treatments. Addition of a EOM or monensin to a diet containing tylosin

improves G: F, but little difference was observed in metabolism or digestibility.”
“The PLX-4720 aim of the present research was to study the influence of monoglyceride organogel structure on the oxidative stability of cod liver oil. To this MG-132 supplier purpose, organogels were prepared by mixing increasing percentages of saturated monoglycerides with cod liver oil, chosen as a natural source of polyunsaturated fatty acids. The structural characteristics of the systems as well as the kinetics of oxidation product formation were evaluated.

Increasing the monoglyceride concentration, organogels show an increase of the rheological parameters highlighting different macroscopic structures. On the contrary, at nano-level the systems present the same molecular organization consisting in monoglyceride molecules crystallized

in the beta-phase and self-assembled in lamellae with a width of around 46 angstrom.

The selleck chemicals llc presence of the monoglyceride network shows a double effect on the oxidative stability of the oil entrapped in the system. It results to be ineffective in affecting the first steps of oxidation but appears a consisting hurdle against the development of secondary oxidation product formation. These results appear interesting in the light of exploitation of organogels to structure

liquid oil and thus to product novel health value-added foods. (C) 2011 Elsevier Ltd. All rights reserved.”
“The Italian Law 38/2010 assures the citizens’ right to have access to palliative care and to antalgic centres in case of either oncologic or non-oncologic pain. It represents an opportunity for headaches’ managements in Italy, promoting the creation of regional and national networks of headache centres and local diagnostic and therapeutic clinical pathways for patient affected with headache. This law should also support collaborations between both antalgic and headache centres networks in order to promote innovative or experimental procedures for chronic and refractory headaches. Moreover, art. 10 of the Law 38/2010 may facilitate the prescription of many headache prophylactic drugs but it may be a risk for opioids overuse headache. Educational programs and the Continuous Professional Development for physicians and all different healthcare professionals in headache area are warranted.

Segmentation of the maxilla was associated with an increase in tactile thresholds at the palate and gingiva (P < .05), as were self-reported selleck kinase inhibitor complaints involving the palate and gingiva (P < .001), whereas maxillary impaction was related to lower-tooth pulp pain thresholds when compared with maxillary lowering (P < .01). All patients expressed satisfaction with LFO, despite signs of somatosensory disturbances in up to 64% of patients.

Conclusion: Numerous changes in postoperative

somatosensory function are to be expected after LFO. In most patients, these changes are minor, and some are dependent on intraoperative procedures. Nonetheless, all patients reported satisfaction with the Surgical results, and would recommend the procedure to others. (C) 2009 American Association of Oral and Maxillofacial Surgeons”
“The magnetic and structural properties of Co films prepared on various substrates were investigated in situ based on Cytoskeletal Signaling inhibitor the surface-magneto-optical Kerr effect (SMOKE) and using reflection high-energy electron diffraction (RHEED) and scanning tunneling microscopy (STM). The magnetic signals of the Co films were found to change significantly depending on the underlying substrates,

the film thickness, and the temperature. Both STM and RHEED observations revealed that the shape and atomic structure of the Co islands were very different, which explains the observed magnetic anisotropy in SMOKE. We also observed a steep increase in coercivity for Co films thicker than 1.5 bi-layers grown on an Ag(111) film. This increase may be interpreted as a fcc-to-hcp structural transformation. (C) 2011 American Institute SB431542 in vitro of Physics. [doi:10.1063/1.3624662]“
“Mechanical stimulation of trigger hairs on the adaxial surface of the trap of Dionaea muscipula leads to the generation of action potentials and to rapid leaf movement. After rapid closure secures the prey, the struggle against the trigger hairs results in generation of further action potentials which

inhibit photosynthesis. A detailed analysis of chlorophyll a fluorescence kinetics and gas exchange measurements in response to generation of action potentials in irritated D. muscipula traps was used to determine the ‘site effect’ of the electrical signal-induced inhibition of photosynthesis. Irritation of trigger hairs and subsequent generation of action potentials resulted in a decrease in the effective photochemical quantum yield of photosystem II (Phi(PSII)) and the rate of net photosynthesis (A(N)). During the first seconds of irritation, increased excitation pressure in photosystem II (PSII) was the major contributor to the decreased Phi(PSII). Within similar to 1 min, non-photochemical quenching (NPQ) released the excitation pressure at PSII.

One reason for this is that although these organelles are inherent to all cells, drugs are being developed that selectively target the mitochondria LY2109761 inhibitor of malignant cells without adversely affecting those of normal cells. Such anti-cancer drugs destabilize cancer cell mitochondria and these compounds are referred to as mitocans, classified into several groups according to their mode of action and the location or nature of their specific drug targets. Many mitocans selectively interfere with the bioenergetic functions of cancer cell mitochondria, causing major disruptions often associated with ensuing overloads in ROS production

leading to the induction of the intrinsic apoptotic pathway. This in-depth review describes the bases for the bioenergetic differences found between normal and cancer cell mitochondria, focussing on those essential changes occurring during malignancy that clinically may provide the most effective targets for mitocan development. A common theme emerging is that mitochondrially mediated ROS activation as a trigger for apoptosis offers a powerful basis for cancer therapy. Continued research in this area is likely to identify increasing numbers of novel agents that should prove highly effective against a variety of cancers with preferential toxicity

towards malignant tissue, circumventing tumor resistance to the other more established therapeutic anti-cancer approaches. Crown Copyright (C) 2009 Published by Elsevier Ltd. All rights reserved.”
“Silver nanoparticles were coated onto Tozasertib in vitro cotton fabrics with 3-mercaptopropyltrimethoxysilane (3-MPTMS). The coating process was accomplished selleck inhibitor by soaking the cotton fabrics into silver colloid/3-MPTMS solution at 43 degrees C for 90 min. The coated fabrics were characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and thermogravimetric analysis (TGA). SEM images showed a layer of silver nanoparticles and 3-MPTMS on cotton. The XPS data showed that distinguishable binding energy peaks of Ag 3d, Si 2p, Si 2s, S 2p were

368/374, 102, 153, and 162 eV, respectively, which confirms the existence of silver and 3-MPTMS on cotton fabrics. The treated cotton fabrics showed prominent antimicrobial effectiveness against Staphylococcus aureus (ATCC 6538) and Klebsiella pneumonia (ATCC 4352). Furthermore, the laundry test showed that 66% of silver nanoparticles were retained after five washing cycles. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 119:2261-2267, 2011″
“Based on semiempirical generalized embedded atom method (GEAM), we carried out molecular dynamics and Monte Carlo simulations to study the structural properties of FeCo and FeNi nanoparticles. It is found that these two kinds of nanoparticles possess a new stable quasicore-shell structure, no matter whether they are in molten or condensed state and whether they are prepared by annealing or quenching.

7%, P=0.002). The incontinence rate at 12 months was significantly higher for the first 100 cases compared with that for the next 100 cases

(9.0% vs 1.0%, P=0.009). For the surgeon to optimize total operative time, PSM rate, complication rate, and incontinence rate, slope learning curves of 25, 50, 50, and 100 cases were needed. Conclusions: The functional and pathologic results of this minimally invasive procedure seemed to be promising. Distinct learning curves were observed with respect to operative time, PSM, complication rate, and incontinence rate. Exposure to 100 surgeries would be necessary for a surgeon to adequately master the required skills.”
“Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder of childhood, and congenital heart disease (CHD) is the most common form of birth defect. Children with Epigenetics inhibitor CHD are at increased risk for neurodevelopmental disorders such as ADHD. Stimulant medications, specifically methylphenidates and amphetamines, are frequently prescribed and effective in reducing the symptoms

PS-341 concentration of ADHD. Despite their efficacy and long history of use, the safety of these medications has recently come into question due to isolated reports describing sudden unexplained death of children undergoing treatment. This review summarizes the current literature on the cardiovascular risks associated with the use of pharmacologic therapy for ADHD, with an emphasis on patients who had CHD.”
“Case description: An 11-year-old Arabian mare was presented for investigation of a visible, pale-colored intraocular mass in the right eye.

Clinical findings: An intraocular mass was detected clinically and ultrasonographically as originating from the superior temporal quadrant of the ciliary body and iris and causing

secondary glaucoma. The echodense mass was occupying p38 MAPK phosphorylation the majority of the vitreous chamber and extended into the anterior chamber. The left eye appeared normal.

Treatment and Outcome: Enucleation was recommended for therapeutic and diagnostic purposes. No adjuvant treatment was given. Histopathological examination demonstrated a benign intraocular teratoid medulloepithelioma located at the ciliary body. Immunohistochemical studies showed that neoplastic cells were positive for vimentin, S-100 protein, neuron-specific enolase (NSE), and nestin and negative for glial fibrillary acidic protein (GFAP). Electron microscopy revealed abundant cellular matrix and blood vessels surrounding tumor cells, which had indented, round to oval nuclei. There were also apoptotic bodies and cells containing melanosomes of variable shape and size. Eight years later, the horse has had no recurrence and maintains normal vision in the left eye.

Non-pharmacologic therapies selleck chemical were those considered in the 2008 OARSI OA guidelines. Identified articles were reviewed for quality; those of highest quality and deemed to have greatest potential impact on the management of OA were summarized.

Results: The search identified 117 unique articles. Of these, four studies were chosen to highlight. A nested two-stage trial found that traditional Chinese acupuncture (TCA) was not superior to sham acupuncture, but that the providers’ style affected both pain reduction and satisfaction with treatment, suggesting that the analgesic benefits of acupuncture may be partially mediated

by the acupuncturists’ behavior. A systematic review found little evidence of a significant effect for electrostimulation vs sham or no intervention on pain in knee OA. A single-blinded trial of Tai Chi vs attention controls found that 12 weeks of Tai Chi was associated with improvements

in symptoms and disability in patients with knee OA. A randomized trial of early ACL reconstructive surgery and rehabilitation vs structured rehabilitation alone in subjects with acute anterior cruciate ligament tears find more found that, at 24 months following randomization, all study participants had improved, suggesting that a strategy of structured rehabilitation followed acute ACL injury may preclude the need for surgical reconstruction.

Conclusions: High quality studies of the safety and efficacy of non-pharmacologic agents in the management of OA remain challenging due to difficulties with adequate blinding and appropriate selection of attention controls. High quality studies suggest modest, if any, benefit of many non-pharmacologic therapies over attention control or placebo,

but a significant impact of both over no intervention at all. (C) 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.”
“Mesenteric traction PLX-4720 mouse syndrome (MTS) is caused by PGI(2) release during abdominal procedures and is often observed during abdominal surgery. We have demonstrated that MTS occurs more frequently in cases using remifentanil than in those that are not. The aim of this study was to assess the prophylactic benefit of flurbiprofen axetil on MTS in patients undergoing abdominal surgery using remifentanil.

Thirty ASA physical status I and II patients were enrolled. They were scheduled to undergo abdominal surgery under general anesthesia with remifentanil and were randomly assigned to receive flurbiprofen axetil (group F) or saline (group C) preoperatively (n = 15 each). MTS was defined according to our simplified diagnostic criteria.

All patients were placed on a patient-controlled i.v. analgesia regimen with morphine after surgery. Time to the first morphine request and amount of morphine SNS-032 consumption within 24h after surgery were compared in patients with and without TAP block. Plasma concentrations of local anesthetics were determined at 15, 30 and 60min after TAP block.

Results: Forty and 54 patients were allocated to the control and TAP group, respectively. The median time to the first morphine request was longer (555 vs 215min), and the median cumulative

morphine consumption within 24h was lower (5.3 vs 7.7mg) in the TAP group than in the control group. The maximum median concentrations of ropivacaine and bupivacaine after TAP block were 784 and 553ng/mL, respectively.

Conclusion: TAP block had additional analgesic effects to epidural morphine alone.”
“Ultraviolet B (UVB) radiation provokes the generation of reactive oxygen species (ROS) in the cells and skin, which induce oxidative stress in

the exposed cells, leading to photoaging and cancer. Using the human keratinocytes HaCaT cell line, we investigated the photoprotective effects of aucubin isolated from Eucommia ulmoides. Pretreatment with aucubin markedly suppressed UVB-induced oxidative stress, which manifests as a decrease in intracellular lipid peroxidation, elevation of AR-13324 order catalase activity, and reduced glutathione content. In addition, aucubin significantly reduced expression of matrix metalloproteinase-1 (MMP-1) protein (54%) and mRNA. Taken together, these results suggest that aucubin may offer protection against UVB-induced oxidative stress and may be used as a potential agent in prevention of UVB-induced photoaging.”
“Purpose of review

Osteoarthritis is strongly linked to aging but the mechanisms for this link are incompletely understood. The recent literature was reviewed to find studies providing new insights into the connection between aging and osteoarthritis.

Recent findings

Basic aging studies in nonarticular cells suggest that a cell stress or cell damage response contributes to chronic inflammation that promotes

age-related diseases. This cellular response results in the senescence-associated secretory phenotype which has many of the characteristics of S3I-201 JAK/STAT inhibitor an osteoarthritic chondrocyte in terms of the cytokines, chemokines, and proteases produced. Oxidative stress can promote cell senescence and studies have shown a role for oxidative stress in altering cell signaling pathways in chondrocytes that can disrupt the response to growth factors. Mitochondria are an important source of reactive oxygen species and studies continue to support a role for the mitochondria in osteoarthritis, including work suggesting changes in energy production. Cell death occurs in osteoarthritic cartilage and recent studies suggest autophagy may play a role in determining if a cell lives or dies when stressed.

“
“SETTING: A DOTS clinic in an academic tertiary referral hospital in South India.

OBJECTIVE: To evaluate the performance

of two rapid enzyme-linked immunoassays (EIAs) for the detection of human immunodeficiency virus (HIV) infection in sputum samples of patients with tuberculosis (TB).

DESIGN: We prospectively recruited 522 consecutive outpatients presenting to the DOTS clinic with confirmed TB of any type to undergo HIV testing using reference serum EIA and index-blinded parallel sputum HIV testing ABT-263 in vivo with two rapid EIAs designed for oral mucosal transudate.

RESULTS: HIV positivity was 14.9% (95%CI 12.1-18.4). Compared to reference serum EIA, the Oraquick (TM) assay was 93.1% sensitive (95%CI 83.8-97.4) and 95.3% specific (95%CI 92.7-96.9), while the Aware

(TM) assay was 92.3% sensitive (95%CI 83.4-96.8) and 96.6% specific (95%CI 94.4-98.0). The positive predictive values were respectively 77.0% and 82.7%. After freezing of sputum, the sensitivity of both assays declined, but the specificity significantly increased. Higher sputum volume reduced the odds of obtaining a true result with both assays.

CONCLUSION: HIV testing of fresh sputum is not sufficiently accurate for Temsirolimus purchase anonymous HIV surveillance among TB patients in a setting of low (<10%) HIV prevalence. Freezing sputum samples and limiting sputum volume for HIV testing may improve assay specificity.”
“Proliferative (cellular) nodules (PN) which mimic malignant melanoma clinically and histologically are described in congenital melanocytic nevi (CMN) and may pose significant diagnostic challenges. We report the case of a 10-day-old male with a giant congenital nevus involving the neck, upper chest, back, and left shoulder containing several nodular lesions, some crusted. Biopsy of a nodule revealed densely packed nevus cells with hyperchromatic round to oval and occasionally irregularly shaped

nuclei. There was no necrosis or pushing border, and the nodule blended with the adjacent nevus; however, the lesion demonstrated a significant number of mitoses (27 per mm(2)) and a 60% labeling index with Ki-67. Further analysis by fluorescence in situ hybridization (FISH) with a 4-color probe set targeting 6p25, 6q23, 11q13, and centromere 6 revealed increased chromosomal copy numbers of all 4 probes, which was interpreted as evidence buy Ilomastat of polyploidy. In addition, analysis of DNA copy number changes using a single nucleotide polymorphism microarray (Affymetrix, Santa Clara, CA) showed no chromosomal aberrations. The diagnosis of PN in a giant congenital nevus was eventually rendered. At 13-month follow-up, the nodules showed no evidence of growth. Our case illustrates that PNs in the neonatal period might demonstrate extreme mitotic activity. This feature is worrisome when encountered in melanocytic lesions; however, it should not trigger by itself a diagnosis of melanoma in the absence of other histologic criteria of malignancy.