Differential Effects of Platelet Factor 4 (CXCL4) and Its Non-Allelic Variant (CXCL4L1) on Cultured Human Vascular Smooth Muscle Cells.

Platelet factor 4 (CXCL4) is a chemokine abundantly stored in platelets. Upon injury and during atherosclerosis, CXCL4 is transported through the vessel wall where it modulates the function of vascular smooth muscle cells (VSMCs) by affecting proliferation, migration, gene expression and cytokine release. Variant CXCL4L1 is distinct from CXCL4 in function and expression pattern, despite a minor three-amino acid difference. Here, the effects of CXCL4 and CXCL4L1 on the phenotype and function of human VSMCs were compared in vitro. VSMCs were found to constitutively express CXCL4L1 and only exogenously added CXCL4 was internalized by VSMCs. Pre-treatment with heparin completely blocked CXCL4 uptake. A role of the putative CXCL4 receptors CXCR3 and DARC in endocytosis was excluded, but LDL receptor family members appeared to be involved in the uptake of CXCL4. Incubation of VSMCs with both CXCL4 and CXCL4L1 resulted in decreased expression of contractile marker genes and increased mRNA levels of KLF4 and NLRP3 transcription factors, yet only CXCL4 stimulated proliferation and calcification of VSMCs. In conclusion, CXCL4 and CXCL4L1 both modulate gene expression, yet only CXCL4 increases the division rate and formation of calcium-phosphate crystals in VSMCs. CXCL4 and CXCL4L1 may play distinct roles during vascular remodeling in which CXCL4 induces proliferation and calcification while endogenously expressed CXCL4L1 governs cellular homeostasis. The latter notion remains a subject for future investigation.

Improved Neutron Lifetime Measurement with UCNτ.

We report an improved measurement of the free neutron lifetime τ_{n} using the UCNτ apparatus at the Los Alamos Neutron Science Center. We count a total of approximately 38×10^{6} surviving ultracold neutrons (UCNs) after storing in UCNτ's magnetogravitational trap over two data acquisition campaigns in 2017 and 2018. We extract τ_{n} from three blinded, independent analyses by both pairing long and short storage time runs to find a set of replicate τ_{n} measurements and by performing a global likelihood fit to all data while self-consistently incorporating the ß-decay lifetime. Both techniques achieve consistent results and find a value τ_{n}=877.75±0.28_{stat}+0.22/-0.16_{syst} s. With this sensitivity, neutron lifetime experiments now directly address the impact of recent refinements in our understanding of the standard model for neutron decay.

Rapid Internalization and Nuclear Translocation of CCL5 and CXCL4 in Endothelial Cells.

The chemokines CCL5 and CXCL4 are deposited by platelets onto endothelial cells, inducing monocyte arrest. Here, the fate of CCL5 and CXCL4 after endothelial deposition was investigated. Human umbilical vein endothelial cells (HUVECs) and EA.hy926 cells were incubated with CCL5 or CXCL4 for up to 120 min, and chemokine uptake was analyzed by microscopy and by ELISA. Intracellular calcium signaling was visualized upon chemokine treatment, and monocyte arrest was evaluated under laminar flow. Whereas CXCL4 remained partly on the cell surface, all of the CCL5 was internalized into endothelial cells. Endocytosis of CCL5 and CXCL4 was shown as a rapid and active process that primarily depended on dynamin, clathrin, and G protein-coupled receptors (GPCRs), but not on surface proteoglycans. Intracellular calcium signals were increased after chemokine treatment. Confocal microscopy and ELISA measurements in cell organelle fractions indicated that both chemokines accumulated in the nucleus. Internalization did not affect leukocyte arrest, as pretreatment of chemokines and subsequent washing did not alter monocyte adhesion to endothelial cells. Endothelial cells rapidly and actively internalize CCL5 and CXCL4 by clathrin and dynamin-dependent endocytosis, where the chemokines appear to be directed to the nucleus. These findings expand our knowledge of how chemokines attract leukocytes to sites of inflammation.

Evaluating the Credibility and Reliability of Online Information on Cannabidiol (CBD) for Epilepsy Treatment in Poland.

The interest in the potential therapeutic use of cannabis, especially cannabidiol (CBD), has increased significantly in recent years. On the Internet, users can find lots of articles devoted to its medical features such as reducing seizure activity in epilepsy. The aim of our work was to evaluate the information contained on the websites, including social media, in terms of the credibility and the reliability of current knowledge about the usage of products containing cannabidiol in epilepsy treatment. We used online available links found using the Newspointtool. The initial database included 38,367 texts, but after applying the inclusion and exclusion criteria, 314 texts were taken into consideration. Analysis was performed using the DISCERN scale and the set of questions created by the authors. In the final assessment, we observed that most of the texts (58.9%) were characterized by a very poor level of reliability and the average DISCERN score was 26.97 points. Additionally, considering the form of the text, the highest average score (35.73) came from entries on blog portals, whereas the lowest average score (18.33) came from comments and online discussion forums. Moreover, most of the texts do not contain key information regarding the indications, safety, desired effects, and side effects of CBD therapy. The study highlights the need for healthcare professionals to guide patients towards reliable sources of information and cautions against the use of unverified online materials, especially as the only FDA-approved CBD medication, Epidiolex, differs significantly from over-the-counter CBD products.

[First manifestation of a leucocytoclastic vasculitis in the colon: case report and differential diagnostic aspects]. / Erstmanifestation einer leukozytoklastischen Vaskulitis im Dickdarm: Fallbericht und differenzialdiagnostische Überlegungen.

This report presents a female patient suffering from chronic diarrhea, who developed palpable purpura on the lower extremities 8 weeks after onset of the gastrointestinal symptoms. Biopsies obtained from the colon and skin showed leukocytoclastic vasculitis. Possible triggers or underlying diseases could not be found, and the patient recovered without specific treatment for vasculitis. Possible differential diagnoses and the difficulties in classifying vasculitides are discussed in the present report.

Social Media as a Source of Knowledge about Gene Therapy for Spinal Muscular Atrophy.

Social media is one of the most common sources of medical information. We aimed to evaluate the information contained on websites, including social media and descriptions of fundraisers, in terms of the reliability of knowledge about SMA and gene therapy with onasemnogen abeparvovec. We used a set of available online links found using the Newspointtool. Initially, 1525 texts were included in the study, and after applying the inclusion and exclusion criteria, 112 texts were qualified for analysis using the DISCERN scale and the set of questions prepared by the authors. We observed that most of the texts had poor (48.65%) and medium (27.03%) reliability in the final reliability assessment. All the texts selected for the study were related to gene therapy, although few contained key information about it. In addition, the authors of the entries used various words and phrases that influenced the readers' perceptions of the text. Of the analyzed sources, 68.8% had an emotional component. Social media is a poor source of information about gene therapy for SMA in Poland. The analyzed texts do not provide a full and complete description of the SMA problem. However, it is important to remember that the Internet is a changing source of information and will hopefully contain more relevant entries in the future.

New insights into cell apoptosis and proliferation: the potential role of vaspin.

Vaspin, also known as visceral adipose tissue-derived serine protease inhibitor; expression of this adipokine has been confirmed in many parts of the body like the hypothalamus, pancreas, thyroid gland, ovaries, placenta, and testes, where it may play a crucial role in osteogenesis, steroidogenesis, the formation of blood vessels, and food intake. In addition, there are many studies supporting an interaction between vaspin and cell proliferation and apoptosis, which are crucial processes for maintaining homeostasis of the body. Vaspin has an anti-apoptotic effect in ovarian cells, osteoblasts, macrophages, aortic endothelial cells, hepatocellular carcinoma cells, and cardiomyocytes. On the other hand, vaspin has no effect on apoptosis in aortic smooth muscle cells and cardiomyocytes. Interestingly, vaspin also promotes proliferation in normal and cancerous ovarian cells, pre-adipocytes, hepatocellular carcinoma cells, and bone mesenchymal stem cells, although other studies showed that this adipokine reduces the proliferation of aortic, and vascular smooth muscle cells. Furthermore, vaspin has no effect on the proliferation of chondrocytes, osteoblasts, macrophages, pre-adipocytes, umbilical vein endothelial cells, and coronary artery smooth muscle cells. Dysfunction and dysregulation in the apoptosis/proliferation ratio may lead to cancer development and progression as well as pathogenesis of many diseases. The molecular mechanism of vaspin action on cell apoptosis and proliferation is reviewed in this paper.

Social class-specific secular trends in height among 19-year old Polish men: 6th national surveys from 1965 till 2010.

The results presented in this study concern the assessment of the secular trend of body height in 10 % a random national sample (N = 134,224) representing all regions of Poland in 8 homogeneous social groups over 45 years in Poland (1965-2010). Very significant political, social and economic changes in Poland occurred in the period studied. The political revolution that began in Poland at the turn of the 1980s and 1990s dramatically changed the picture of social inequalities in the country. It rapidly transformed (in different directions and to a different degree) the economic situation, working conditions, lifestyles and the prestige of particular social classes and professional groups. A positive secular trend was observed in 19-year-old participants in the period analysed in all homogeneous socio-professional groups, however, with different intensity in each group. The highest body height increases in 1965-2010 were observed in the sons of farmers with post-primary father's education (7.77 cm). The lowest were observed among the sons of professionals, only 5.45 cm. Although social distances between extreme socio-economic groups significantly decreased (from 4.89 cm in 1965 to 2.76 cm in 2010), social gradients of body height, despite the improvement in the standards of living of the entire society remained exceptionally stable and unchanged for nearly half a century.

T helper 2 biased de novo immune response to Keyhole Limpet Hemocyanin in humans.

BACKGROUND: Allergen-specific T helper 2 (Th2) cells play an important role in the pathogenesis of atopic disorders. To date, no model system exists in humans that would allow the monitoring of a developing de novo Th2 immune response in vivo. OBJECTIVE: The aim of the experiment was to establish an immunization protocol inducing a de novo Th2 response in humans using Keyhole Limpet Hemocyanin (KLH) as neo-antigen. METHODS: The double-blind placebo-controlled, parallel-group study was conducted in two groups of subjects (16 healthy volunteers and 16 patients with allergic rhinitis). Subjects received three i.m. injections of 100 microg KLH adsorbed to aluminium hydroxide or matching placebo (alum alone) in intervals of 2 weeks. On day 43, KLH alone (10 microg) was given intra-dermally (i.d.) to all subjects to assess immediate and late-phase skin responses. RESULTS: The immunization protocol was well tolerated, highly specific and efficient. Antigen-specific production of Th2-cytokines (mainly IL-5 and IL-13) by PBMCs suggested a Th2 pattern, as did the presence of KLH-specific IgG4 in sera. Intra-dermal KLH challenge induced an immediate-type of response predominantly in atopic subjects followed by a late-phase skin reaction. The latter was accompanied by the presence of IgE(+) cells, eosinophils and a strong up-regulation of IL-4 and IL-13 along with the absence of Th1 transcripts in biopsies taken from the site of antigen challenge. IL-17 and IL-22 transcripts were detected only in healthy subjects skin following KLH challenge, while IL-1beta and IL-33 expression did not differ between the healthy and the atopics. CONCLUSIONS: The immunization protocol resulted in the elicitation of a local and peripheral Th2 immune response in both healthy and atopic individuals. This may permit the investigation and monitoring of novel immunomodulatory strategies aiming to interfere with Th2 responses in man. The relevance of lack of Th17 cells in atopic skin in this model remains to be determined.

Apelin decreased placental hormone secretion by human trophoblast BeWo cells via apelin receptor, protein kinase A and extracellular signal-regulated kinases 1/2 activation.

Apelin was thought to be an adipocyte-specific hormone, but recent studies have indicated a link between apelin and placenta function e.g. cell proliferation. The aim of the study was investigating dose- and time-dependent effect of apelin on hormone secretion including steroids: progesterone (P4) and estradiol (E2) and proteins: chorionic gonadotropin (hCG), human placental lactogen (hPL), placental growth factor (PLGF), as well as protein expression of steroid enzymes (3ßHSD, CYP19) and protein hormones (hCG, hPL and PLGF) in placental cells. Syncytiotrophoblast BeWo cells, as human trophoblast models, were treated for 24, 48, and 72 hours with the human recombinant apelin at doses 0.02, 0.2, 2.0, 20 and 200 ng/ml followed by culture medium. Concentrations of the above hormones were studied by ELISA kits. Furthermore, protein expression of steroid enzymes and protein hormones were measured using Western blot. Our results showed that apelin significantly decreased both steroid and protein hormones by inhibiting steroid enzymes or protein hormone expression. Moreover, we demonstrated that apelin at dose 2.0 ng/ml increased phosphorylation of protein kinase A (PKA) from 1 to 60 min of BeWo cell incubation. Inhibitory effect of apelin on P4, E2 and PLGF secretion were abolished when BeWo cells were cultured in the presence of ML221, an apelin receptor antagonist, PD98059, an extracellular signal-regulated kinases (ERK1/2) antagonist and KT5720, a PKA antagonist. In turn, secretion of hCG and hPL occurs only in the presence of ML221 and PD98059. In conclusion, our results indicate that apelin can be considered as a gestational hormone implied in the endocrine function of the human placenta, with an important role in controlling the production of steroid and protein hormones in placental BeWo cells.

Breakdown of the strong multiplet description of the Sm2+ ion in the topological Kondo insulator SmB6: specific heat studies.

We have theoretically confirmed the existence of in-gap real quantum-mechanical states in SmB6, which have been suggested by experiments. These in-gap states, below the hybridization gap of 20 meV, are related to the Sm2+ ion states and can be revealed by calculations within the spin-orbital |LSLzSz〉 space, with L = 3 and S = 3. Our approach overcomes difficulties related to the singlet J = 0 multiplet ground state. The in-gap states originate from the 49-fold degenerated term 7F (4f 6), which is split by cubic crystal-field (CEF) and spin-orbit (s - o) interactions. There is competition between these interactions: the six-order CEF interactions produce a 7-fold degenerated ground state, whereas the s - o interactions, even the weakest one, produce a singlet (J = 0) ground state. We have found preliminary CEF and s - o parameters that produce the lowest states at 0 K (singlet) and 91 K (triplet) and the next triplet at 221 K, i.e., within the hybridization gap. The derived states well explain the large extra specific heat of SmB6, confirming the consistency and adequateness of our theoretical approach with the breakdown of the strong multiplet description of the Sm2+ ion in SmB6.

Initiation and Propagation of Vascular Calcification Is Regulated by a Concert of Platelet- and Smooth Muscle Cell-Derived Extracellular Vesicles.

The ageing population continues to suffer from its primary killer, cardiovascular disease (CVD). Despite recent advances in interventional medicinal and surgical therapies towards the end of the 20th century, the epidemic of cardiovascular disease has not been halted. Yet, rather than receding globally, the burden of CVD has risen to become a top cause of morbidity and mortality worldwide. Most CVD arises from thrombotic rupture of an atherosclerotic plaque, the pathologic thickening of coronary and carotid artery segments and subsequent distal ischemia in heart or brain. In fact, one-fifth of deaths are directly attributable to thrombotic rupture of a vulnerable plaque. Atherosclerotic lesion formation is caused by a concert of interactions between circulating leukocytes and platelets, interacting with the endothelial barrier, signalling into the arterial wall by the release of cytokines and extracellular vesicles (EVs). Both platelet- and cell-derived EVs represent a novel mechanism of cellular communication, particularly by the transport and transfer of cargo and by reprogramming of the recipient cell. These interactions result in phenotypic switching of vascular smooth muscle cells (VSMCs) causing migration and proliferation, and subsequent secretion of EVs. Loss of VSMCs attracts perivascular Mesenchymal Stem Cells (MSCs) from the adventitia, which are a source of VSMCs and contribute to repair after vascular injury. However, continuous stress stimuli eventually switch phenotype of cells into osteochondrogenic VSMCs facilitating vascular calcification. Although Virchow's triad is over 100 years old, it is a reality that is accurate today. It can be briefly summarised as changes in the composition of blood (platelet EVs), alterations in the vessel wall (VSMC phenotypic switching, MSC infiltration and EV release) and disruption of blood flow (atherothrombosis). In this paper, we review the latest relevant advances in the identification of extracellular vesicle pathways as well as VSMCs and pericyte/MSC phenotypic switching, underlying vascular calcification.

Performance of different Sporomusa species for the microbial electrosynthesis of acetate from carbon dioxide.

Sporomusa ovata DSM-2662 produces high rate of acetate during microbial electrosynthesis (MES) by reducing CO2 with electrons coming from a cathode. Here, we investigated other Sporomusa for MES with cathode potential set at -690mVvsSHE to establish if this capacity is conserved among this genus and to identify more performant strains. S. ovata DSM-2663 produced acetate 1.8-fold faster than S. ovata DSM-2662. On the contrary, S. ovata DSM-3300 was 2.7-fold slower whereas Sporomusa aerivorans had no MES activity. These results indicate that MES performance varies among Sporomusa. During MES, electron transfer from cathode to microbes often occurs via H2. To establish if efficient coupling between H2 oxidation and CO2 reduction may explain why specific acetogens are more productive MES catalysts, the metabolisms of the investigated Sporomusa were characterized under H2:CO2. Results suggest that other phenotypic traits besides the capacity to oxidize H2 efficiently are involved.

Effect of tungstate on acetate and ethanol production by the electrosynthetic bacterium Sporomusa ovata.

BACKGROUND: Microbial electrosynthesis (MES) and gas fermentation are bioenergy technologies in which a microbial catalyst reduces CO2 into organic carbon molecules with electrons from the cathode of a bioelectrochemical system or from gases such as H2. The acetogen Sporomusa ovata has the capacity of reducing CO2 into commodity chemicals by both gas fermentation and MES. Acetate is often the only product generated by S. ovata during autotrophic growth. RESULTS: In this study, trace elements in S. ovata growth medium were optimized to improve MES and gas fermentation productivity. Augmenting tungstate concentration resulted in a 2.9-fold increase in ethanol production by S. ovata during H2:CO2-dependent growth. It also promoted electrosynthesis of ethanol in a S. ovata-driven MES reactor and increased acetate production 4.4-fold compared to unmodified medium. Furthermore, fatty acids propionate and butyrate were successfully converted to their corresponding alcohols 1-propanol and 1-butanol by S. ovata during gas fermentation. Increasing tungstate concentration enhanced conversion efficiency for both propionate and butyrate. Gene expression analysis suggested that tungsten-containing aldehyde ferredoxin oxidoreductases (AORs) and a tungsten-containing formate dehydrogenase (FDH) were involved in the improved biosynthesis of acetate, ethanol, 1-propanol, and 1-butanol. AORs and FDH contribute to the fatty acids re-assimilation pathway and the Wood-Ljungdahl pathway, respectively. CONCLUSIONS: This study presented here shows that optimization of microbial catalyst growth medium can improve productivity and lead to the biosynthesis of different products by gas fermentation and MES. It also provides insights on the metabolism of biofuels production in acetogens and demonstrates that S. ovata has an important untapped metabolic potential for the production of other chemicals than acetate via CO2-converting bioprocesses including MES.

The first 2,2-dialkoxythiirane.

[reaction: see text] Thermolysis of 1 at 110 degrees C in benzene containing adamantanethione leads to thiirane 2 in 92% yield, as an isolable, stable solid. Compound 2 is the first example of the hitherto unknown 2,2-dialkoxythiiranes. It shows some reactions characteristic of thiiranes.

Frequency and characteristics of enlarging common melanocytic nevi.

OBJECTIVE: To analyze the frequency and characteristics of enlarging common melanocytic nevi. DESIGN: Cohort study using digital epiluminescence microscopy (ELM) for documentation and follow-up, with a median follow-up interval of 11.4 months. SETTING: A dermatology department at a university hospital in Vienna, Austria. PATIENTS: One thousand six hundred twelve melanocytic nevi appearing clinically as common nevi, obtained from 385 patients (mean [+/-SD] age, 34.2 +/- 14.8 y; 55.6% female). INTERVENTIONS: Follow-up examination and documentation by digital ELM. MAIN OUTCOME MEASURES: Frequency of enlarging nevi according to age and comparison of ELM features observed in enlarging and nonenlarging nevi. RESULTS: Enlargement was found in 5.3% (n = 86) of nevi. The frequency of enlarging nevi was inversely related to age (P<.001), in that enlarging nevi were common in patients younger than 20 years and relatively rare in older age groups. Epiluminescence microscopy revealed a peripheral rim of brown globules in 48.8% (n = 42) of enlarging nevi. In contrast, a peripheral rim of brown globules was found in only 0.7% (n = 11) of nevi without enlargement (P<.001). Enlarging nevi that were excised in children and adolescents showed no histological signs of atypia. In older age groups, 48.1% of excised enlarging nevi that were clinically diagnosed as common nevi showed some histological signs of atypia. None of the excised enlarging lesions was histologically diagnosed as melanoma. CONCLUSIONS: The frequency of enlarging common nevi is inversely related to age. In the absence of clinical signs of atypia, enlargement alone does not indicate malignancy. A peripheral rim of brown globules is a characteristic ELM feature of symmetrically enlarging melanocytic nevi.

Changes in the dermoscopic appearance of melanocytic naevi after photochemotherapy or narrow-band ultraviolet B phototherapy.

BACKGROUND: Although phototherapeutic modalities are commonly used for the treatment of skin diseases, the effects of therapeutic ultraviolet (UV) irradiation on the dermoscopic appearance of melanocytic naevi are unknown. OBJECTIVES: We aimed to analyse the effects of photochemotherapy (psoralen plus ultraviolet A, PUVA) and narrow-band ultraviolet B phototherapy (NB-UVB) on the dermoscopic appearance of naevi. PATIENTS AND METHODS: We monitored 187 melanocytic naevi of 38 patients receiving NB-UVB or PUVA treatment for miscellaneous skin diseases. Dermoscopic images of naevi were taken before, shortly after, and after a median of 31 weeks after the UV therapy. A random selection of naevi was covered during UV treatment, the others remained uncovered. Baseline and follow-up images of naevi were viewed side by side on a computer screen to compare size, pigmentation, and dermoscopic structure of naevi. RESULTS: Twenty-one patients received NB-UVB treatment, and 17 patients received PUVA treatment. Of 187 naevi, 70 (37%) were covered and 117 (63%) were uncovered during UV treatment. When NB-UVB- and PUVA-treated patients were analysed together, an increase in size of uncovered lesions was seen in both treatment groups. Pigmentation appeared darker at the end of UV treatment in 67.5% (n=79) of uncovered naevi compared with 41.4% (n=29) of covered naevi (P<0.001). In patients receiving NB-UVB therapy, a significant increase in the number of dots or globules in 20.3% (n=14) of uncovered naevi compared with only 5.0% (n=2) of covered naevi (P=0.03) was found. This effect was not observed after PUVA therapy. With the exception of four naevi with continuous enlargement and seven naevi with a persisting increase in dots and globules, the observed changes were reversible. All naevi with persistent changes belonged to the NB-UVB group. CONCLUSION: In general, PUVA and NB-UVB therapy cause reversible dermoscopic changes in melanocytic naevi. Increase in dots and globules is more frequent with NB-UVB.

Reevaluation of the ABCD rule for epiluminescence microscopy.

BACKGROUND: Epiluminescence microscopy (ELM) provides for increased accuracy in the clinical diagnosis of pigmented skin lesions (PSL). It is based on pattern analysis of ELM criteria, which requires experience. The recently introduced application of the ABCD score to ELM facilitates this by permitting lesion evaluation on the basis of predefined clinical criteria. OBJECTIVE: The present study was performed to evaluate the diagnostic performance of the ABCD rule for ELM in pigmented skin lesions testing dermatologists with varying skills from novice to expert. METHODS: Two hundred fifty electronic images of randomly selected, histologically proven PSL including 41 early melanomas (16.4%) were presented to the raters, and each image was scored according to the rules of the ABCD score and rated without the guidance of a scoring system on a scale from 1 = definitely benign to 5 = definitely melanoma. RESULTS: Our data show that the application of the ABCD rule significantly enhances diagnostic ability in less experienced dermatologists compared with rating without the guidance of a scoring system. In contrast, the diagnostic accuracy of dermatologists who are moderately to greatly experienced is not improved by use of the ABCD rule. CONCLUSION: Our experiments indicate that the application of the ABCD rule to ELM introduced by Stolz et al represents a useful enhancement for diagnosis of pigmented skin lesions in less experienced users. However, the method does fail to detect melanomas with 100% accuracy. Therefore further effort has to be made to make the diagnosis of melanoma easier and more accurate.

Morphologic changes of pigmented skin lesions: a useful extension of the ABCD rule for dermatoscopy.

BACKGROUND: Epiluminescence microscopy (ELM) significantly increases the early diagnosis of pigmented skin lesions (PSL) using established criteria and pattern analysis. The ABCD rule for dermatoscopy (ie, ELM) provides a simplified approach to the interpretation of ELM images on the basis of asymmetry (A), border (B), color (C), and dermatoscopic structure (D). OBJECTIVE: We set out to determine whether the diagnostic accuracy of the ABCD scoring algorithm can be significantly improved by incorporating information about morphologic changes of the lesion observed and provided by the patient. METHODS: We prospectively collected 356 small pigmented skin lesions (< 1 cm) including 73 (20.5%) melanomas. Before excision all patients were asked whether the lesion had changed in size, color, or shape within the last year or whether they experienced any sign of ulceration or spontaneous bleeding. ELM images of the lesions were evaluated according to the ABCD rule for dermatoscopy to yield a semiquantitative score. Accuracy of diagnosis was evaluated in terms of sensitivity, specificity, and area under receiver operating characteristic curves (AUC). RESULTS: The frequency of reported changes was significantly higher for melanomas than benign PSL (65.8% vs 29.7%, P < .001). In a multivariate model morphologic change was a significant independent predictor of malignancy (odds ratio = 3.17, 95% confidence interval [CI]: 1.96 to 5.14, P < .001). The mean final score achieved when using the enhanced ABCD-E criteria including morphologic change (E) was significantly higher for melanomas (5.7, 95% CI: 5.3 to 6.0) than benign PSL (2.9, 95% CI: 2.8 to 3.1, P < .001). Diagnostic accuracy was significantly higher when the lesions were evaluated by the enhanced ABCD-E criteria as compared with the standard ABCD score (AUC(ABCD) = 0.87 vs AUC(ABCD-E) = 0.90; P = .006). CONCLUSION: Information about morphologic changes of PSL as reported by the patient is a useful extension of the ABCD rule for dermatoscopy.