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Introduction The Verbal Fluency Test (VF) is commonly used in neuropsychology. Some studies have demonstrated a marked impairment of semantic VF compared to phonemic VF in Alzheimer's disease (AD). Since amnestic Mild Cognitive Impairment (aMCI) is associated with increased risk of conversion to incident AD, it is relevant to examine whether a similar impairment is observed in this population. The objective of the present empirical study is to compare VF performance of aMCI patients to those of AD and elderly controls matched one-to-one for age and education. Method Ninety-six participants divided into three equal groups (N = 32: AD, aMCI and Controls) were included in this study. Participants in each group were, on average, 76 years of age and had 13 years of education. A repeated measures ANOVA with the Group (AD, aMCI, NC) as between-subject factor and the Fluency condition ("P" and "animals") as within-subject factor was performed. T -tests and simple ANOVAs were also conducted to examine the interaction. Results There was a significant interaction between the groups and the verbal fluency condition. In AD, significantly fewer words were produced in both conditions. In contrast, participants with aMCI demonstrated a pattern similar to controls in the phonemic condition, but generated significantly fewer words in the semantic condition. Conclusion These results indicate a semantic memory impairment in aMCI revealed by a simple, commonly-used neuropsychological test. Future studies are needed to investigate if semantic fluency deficits can help predict future conversion to AD. [ABSTRACT FROM AUTHOR]

We present the first results that focus on the influence of lateral Earth structure on Greenland glacial isostatic adjustment (GIA) using a model that can explicitly incorporate 3-D Earth structure. In total, eight realizations of lateral viscosity structure were developed using four global seismic velocity models and two global lithosphere (elastic) thickness models. Our results show that lateral viscosity structure has a significant influence on model output of both deglacial relative sea level (RSL) changes and present-day rates of vertical land motion. For example, lateral structure changes the RSL predictions in the Holocene by several tens of metres in many locations relative to the 1-D case. Modelled rates of vertical land motion are also significantly affected, with differences from the 1-D case commonly at the mm yr−1 level and exceeding 2 mm yr−1 in some locations. The addition of lateral structure considered here is unable to account for previously identified data model RSL misfits in northern and southern Greenland, suggesting limitations in the adopted ice model and/or the existence of processes not included in our model. Our results show large data model discrepancies in uplift rates when applying a 1-D viscosity model tuned to fit the RSL data; these discrepancies cannot be reconciled by adding the realizations of lateral structure considered here. In many locations, the spread in model output for the eight different 3-D earth models is of similar amplitude or larger than the influence of lateral structure (as defined by the average of all eight model runs). This reflects the differences between the four seismic and two lithosphere models used and implies a large uncertainty in defining the GIA signal given that other aspects that contribute to this uncertainty (e.g. scaling from seismic velocity to viscosity) were not considered in this study. In order to reduce this large model uncertainty, an important next step is to develop more accurate constraints on Earth structure beneath Greenland based on regional geophysical data sets. [ABSTRACT FROM AUTHOR]

Background Intolerably high doses of systemic corticosteroids and additional immunosuppressants may be required to control disease activity in autoimmune bullous skin diseases. New therapeutic options are needed for such patients. Objectives To determine the efficacy and adverse effects of adjuvant rituximab. Methods Seven patients with refractory autoimmune blistering diseases (pemphigus vulgaris, PV, n = 4; bullous pemphigoid, BP, n = 2; mucous membrane pemphigoid, MMP, n = 1) were treated four times with rituximab at an individual dose of 375 mg m−2 at weekly intervals. Results All lesions cleared in three patients (two PV, one BP), while they were reduced by more than 50% in three others (two PV, one BP). The concomitant immunosuppressive medication was reduced in five patients (four PV, one BP). The patient with MMP developed bilateral blindness while nasopharyngeal lesions resolved. Three patients (two BP, one PV) experienced severe adverse events including fatal pneumonia. Conclusions Adjuvant B-cell depletion by rituximab is effective in otherwise therapy-resistant bullous autoimmune disorders but may be associated with substantial adverse effects including fatal outcomes. [ABSTRACT FROM AUTHOR]

Background The expression of calcium-binding S100 molecules organized within the epidermal differentiation complex on chromosome 1q21 is disturbed in hyperproliferative skin diseases such as psoriasis. Objectives We studied whether serum levels of S100 proteins A8 (S100A8) and A9 (S100A9) are elevated in psoriasis, correlated their amounts with disease activity and identified potential cellular sources. Methods Serum obtained from psoriasis patients or from healthy individuals was studied for S100A8 and S100A9 levels by enzyme-linked immunosorbent assay. Data were correlated to disease activity as reflected by the Psoriasis Area and Severity Index (PASI). Cellular sources of S100A8 and S100A9 were identified by in situ hybridization and immunohistochemistry of lesional psoriatic and nonlesional, nonpsoriatic skin. Results A significant increase of S100A8/S100A9 serum levels was found in patients with psoriasis compared with healthy controls. Grading the patients into two groups of severity, individuals with a PASI of <15 showed serum levels of 705 ± 120 ng mL−1 (mean ± SEM, n = 18), those with a PASI of ≥15 showed levels of 1315 ± 150 ng mL−1 ( n = 32) while controls presented with 365 ± 50 ng mL−1. Performing in situ hybridization of lesional psoriatic skin we detected a dramatic induction of both S100A8 and S100A9 mRNA and protein primarily in the suprabasal layers of the epidermis while expression was negligible in nonlesional, nonpsoriatic interfollicular epidermis. Conclusions Our data demonstrate that hyperproliferation and abnormal differentiation of psoriatic skin is associated with a massive upregulation and secretion of S100A8 and S100A9, suggesting not only a prominent role of these molecules during intracellular calcium-dependent signalling but also implying distinct extracellular functions. [ABSTRACT FROM AUTHOR]

Tumour necrosis factor (TNF)-α is thought to play a major role in the pathophysiology of psoriasis. Good clinical responses of psoriasis to anti-TNF-α-based therapies have recently been demonstrated. We studied the effect of infliximab, a monoclonal antibody against TNF-α, on chemokine expression in pustular psoriasis. A 61-year-old man with a 2-year history of severe pustular psoriasis of von Zumbusch type who did not respond to conventional therapies responded rapidly to treatment with infliximab. The clinical response was reflected by an immediate and effective reduction of the neutrophil-attractant chemokines interleukin (IL)-8 and growth-related oncogene (Gro)-α as well as of monocyte chemoattractant protein (MCP)-1, as determined by mRNA in situ hybridization of lesional skin. No expression before or after treatment was seen for monokine induced by interferon (IFN)-γ (MIG) and IFN-inducible protein (IP)-10. Thus, in pustular psoriasis the chemokine expression pattern is dominated by neutrophil-attractant chemokines and MCP-1 while, in contrast to plaque psoriasis, IFN-γ-inducible lymphocyte-attractant chemokines such as IP-10 and MIG are not abundant. We conclude that anti-TNF-α treatment with infliximab is an effective therapy in severe pustular psoriasis which is reflected by downregulation of disease-promoting chemokines such as IL-8, Gro-α and MCP-1. [ABSTRACT FROM AUTHOR]

A letter to the editor concerning a study on the well-circumscribed erythematous lesion located on the thenar region of the right palm of a 73-year-old man is presented.

The article focuses on the impact of usage of pembrolizumab for anti-programmed death-1 (PD-1) for treating metastatic melanoma or nonsmall cell lung cancer. It discusses the reporting of bullous pemphigoid (BP), oral mucous membrane pemphigoid (MMP), immunofluorescence of perilesional skin and autoimmune blistering disease (AIBDs).

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Summary: Bullous pemphigoid (BP) is a rare, chronic skin disease that causes blistering and severe itching, mainly in elderly patients. It is an autoimmune skin disease, in which the body's own immune system is directed against structures of the skin. Specific proteins, named autoantibodies, are produced and lead to inflammation. It affects about 259 per million people in Germany. In a recent published clinical trial, two different therapies for BP were compared in 253 BP patients in the U.K. and Germany. This additional study, again from Germany and the U.K., aimed to find out if there are any markers in the blood of these patients that tell us about the course of the disease. Therefore the authors investigated the blood of 143 patients taking part in a trial called the BLISTER trial. Several tests were performed to check for the amount of autoantibodies in the blood of these patients. Afterwards the results were linked with basic parameters including age, general condition, number of blisters, side effects, and mortality. The study revealed that patients with a poor general condition had higher levels of both specific autoantibodies which cause the disease. Patients who died within one year of inclusion to the study had higher amounts of one of the specific autoantibodies. The presence of the other specific autoantibody was more frequent in older patients. In conclusion, analyzing the autoantibody profile not only helps in diagnosis, but may also be helpful in predicting the course of the disease. Linked Article: Holtsche et al. Br J Dermatol 2018; 179:918–924 [ABSTRACT FROM AUTHOR]