A brief synopsis on scalp melanoma

Melanoma constitutes one of the most sinister and troublesome malignancies encountered by humanity. Generally, the diagnosis of advanced melanoma connotes a grave prognosis, prompting a sense of looming threat of death, however, the early‐stage detected disease responds well to robust treatment resulting in reasonable survivorship. Scalp melanomas are even more troublesome, because they typically exhibit more aggressive biologic behavior and are often diagnosed at a late stage. This review tries to comprehensively highlight the various diagnostic, therapeutic, and outcome aspects of scalp melanomas. The literature research includes peer‐reviewed articles (clinical trials or scientific reviews). Studies were identified by searching electronic databases (MEDLINE and PubMed) till May 2020 and reference lists of respective articles. Only articles published in English language were included.     

5‐Alpha reductase inhibitors in androgenetic alopecia: Shifting paradigms,current concepts,comparative efficacy,and safety

Androgenetic alopecia (AGA) is a multifactorial disease that carries a significant psychological burden with it. Dihydrotestosterone, the main pathogenic androgen in AGA, is produced by conversion of testosterone, which is catalyzed by the 5‐alpha reductase (5‐AR) isoenzyme family. Finasteride and dutasteride are inhibitors of these enzymes. Finasteride, which is a single receptor 5‐alpha reductase inhibitor (5‐ARI), acts by blocking dihydrotestosterone (DHT). Dutasteride, a dual receptor DHT blocker, has a higher potency than its predecessor, finasteride. This review corroborates the evidence of superiority of dutasteride over finasteride, and its comparable safety profile concerning fertility, teratogenicity, neurotoxicity, and hepatotoxicity.     

SUDEP („sudden unexpected death in epilepsy“) bei Kindern und Jugendlichen – Zahlen,Daten, Fakten

Clinical Epileptology - Das Thema SUDEP („sudden unexpected death in epilepsy“) ist in den letzten Jahren auch in Bezug auf Kinder und Jugendliche mit Epilepsie zunehmend in den Fokus...     

EEG bei Autoimmunenzephalitiden

Clinical Epileptology - Das Elektroenzephalogramm (EEG) ist eine wichtige paraklinische, nichtinvasive, reproduzierbare Untersuchungsmethode bei der diagnostischen Abklärung einer autoimmunen...     

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Psychotherapie Forum -     

From clock to functional pacemaker

In mammals, the central pacemaker that coordinates 24‐hr rhythms is located in the suprachiasmatic nucleus (SCN). Individual neurons of the SCN have a molecular basis for rhythm generation and hence, they function as cell autonomous oscillators. Communication and synchronization among these neurons are crucial for obtaining a coherent rhythm at the population level, that can serve as a pace making signal for brain and body. Hence, the ability of single SCN neurons to produce circadian rhythms is equally important as the ability of these neurons to synchronize one another, to obtain a bona fide pacemaker at the SCN tissue level. In this chapter we will discuss the mechanisms underlying synchronization, and plasticity herein, which allows adaptation to changes in day length. Furthermore, we will discuss deterioration in synchronization among SCN neurons in aging, and gain in synchronization by voluntary physical activity or exercise.     

Pathological responses to single‐pulse electrical stimuli in epilepsy: The role of feedforward inhibition

Delineation of epileptogenic cortex in focal epilepsy patients may profit from single‐pulse electrical stimulation during intracranial EEG recordings. Single‐pulse electrical stimulation evokes early and delayed responses. Early responses represent connectivity. Delayed responses are a biomarker for epileptogenic cortex, but up till now, the precise mechanism generating delayed responses remains elusive. We used a data‐driven modelling approach to study early and delayed responses. We hypothesized that delayed responses represent indirect responses triggered by early response activity and investigated this for 11 patients. Using two coupled neural masses, we modelled early and delayed responses by combining simulations and bifurcation analysis. An important feature of the model is the inclusion of feedforward inhibitory connections. The waveform of early responses can be explained by feedforward inhibition. Delayed responses can be viewed as second‐order responses in the early response network which appear when input to a neural mass falls below a threshold forcing it temporarily to a spiking state. The combination of the threshold with noisy background input explains the typical stochastic appearance of delayed responses. The intrinsic excitability of a neural mass and the strength of its input influence the probability at which delayed responses to occur. Our work gives a theoretical basis for the use of delayed responses as a biomarker for the epileptogenic zone, confirming earlier clinical observations. The combination of early responses revealing effective connectivity, and delayed responses showing intrinsic excitability, makes single‐pulse electrical stimulation an interesting tool to obtain data for computational models of epilepsy surgery.     

Negative prognostic effect of low nuclear GLI1 expression in glioblastomas

This is preliminary study assessing the efficacy and safety of concurrent use of radiation therapy (RT) and T-DM1 for the treatment of brain metastases (BM) in patients with HER2-positive metastatic breast cancer (BC). We retrospectively studied 12 patients treated for BM at the Institut Curie in 2014–2015 with T-DM1 and concurrent (4) or sequential (8) radiosurgery with or without whole brain irradiation. The following variables were studied: local control, clinical and radiological response as well as early and late side effects. The mean age of the population was 38 years at the time of diagnosis of BC and 46 years at of BM. All patients were with good PS. The response rate of the concurrent treatment group was 75?% with 1 complete response, 1 partial response, one stable disease and 1 progression. Comparatively, the response rate in the sequential group was as follows: two complete responses, two partial responses, six cases of stable disease and two cases of local progression. No patient experienced interruption of irradiation because of side effects. About 50?% of patients were asymptomatic after treatment. Radiation necrosis was observed in 50?% of patients in the concurrent group and 28.6?% of patients in the sequential group with a similar rate of oedema in the two groups. We found that the combination of T-DM1 and radiosurgery was feasible but can increase the incidence of radiation necrosis. Larger prospective studies with longer follow-up are needed to more clearly evaluate this association.     

Dendritic cell based vaccination strategy: an evolving paradigm

The basement membrane collagen IV-degrading matrix metalloproteinases -2 and -9 (MMPs) are most often linked to the malignant phenotype of tumor cells by playing a critical role in invasion, metastasis, angiogenesis, and vasculogenesis. We verified the activity of these two MMPs in the sera of patients affected by brain tumors (20 gliomas, 28 meningiomas and 20 metastasis) by zymography. The sera of 25 healthy volunteers with no concomitant illnesses were used for controls. Zymography showed four dominant gelatinolytic bands of 240, 130, 92 (MMP-9) and 72 (MMP-2) kDa. No statistically significant variations of MMP-2 proteolytic activity between patients and healthy individuals were observed. On the contrary, MMP-9 (both monomeric and multimeric forms) lytic activities were significantly higher in tumors specimens compared to healthy controls (p?<?0.001). Moreover, MMP-9 immunohistochemistry revealed: (1) a strong reactivity in neoplastic vessels of high-grade gliomas showing an inverse correlation with serum multimeric gelatinolytic activity; (2) a cytoplasmatic reactivity in meningiomas with a significantly increase in atypical meningioma compared with low-grade ones (p?=?0.036); (3) a positive correlation between MMP-9 and Ki-67 (Sperman Rho coefficient r?=?0.418 and p?=?0.034). Our results suggest that serum and tissue MMP-9 might provide clinicians additional objective information in intracranial neoplasms. Finally, it should be possible to use MMP-9 as a target for new forms of therapy. Nevertheless, due to the small number of patients included in the study, the conclusion may not be transferable to the general population and therefore further evaluations are needed.