[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

Objective
To present the International Parkinson and Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Parkinson9s disease.
Background
Although several diagnostic criteria for Parkinson9s disease have been proposed, none have been officially adopted by an official Parkinson society. Moreover, the commonest-used criteria, the UK brain bank, were created more than 25 years ago. In recognition of the lack of standard criteria, the MDS initiated a task force to design new diagnostic criteria for clinical Parkinson9s disease.
Methods/Results
The MDS-PD Criteria are intended for use in clinical research, but may also be used to guide clinical diagnosis. The benchmark is expert clinical diagnosis; the criteria aim to systematize the diagnostic process, to make it reproducible across centers and applicable by clinicians with less expertise. Although motor abnormalities remain central, there is increasing recognition of non-motor manifestations; these are incorporated into both the current criteria and particularly into separate criteria for prodromal PD. Similar to previous criteria, the MDS-PD Criteria retain motor parkinsonism as the core disease feature, defined as bradykinesia plus rest tremor and/or rigidity. Explicit instructions for defining these cardinal features are included. After documentation of parkinsonism, determination of PD as the cause of parkinsonism relies upon three categories of diagnostic features; absolute exclusion criteria (which rule out PD), red flags (which must be counterbalanced by additional supportive criteria to allow diagnosis of PD), and supportive criteria (positive features that increase confidence of PD diagnosis). Two levels of certainty are delineated: Clinically-established PD (maximizing specificity at the expense of reduced sensitivity), and Probable PD (which balances sensitivity and specificity).
Conclusion
The MDS criteria retain elements proven valuable in previous criteria and omit aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of PD expands, criteria will need continuous revision to accommodate these advances. Disclosure: Dr. Postuma has received personal compensation for activities with Roche Diagnostics Corporation and Biotie Therapies. Dr. Berg has received research support from Michael J. Fox Foundation, the Bundesministerium fur Bildung und Forschung (BMBF), the German Parkinson Association and Novartis GmbH.

MDS Clinical Diagnostic Criteria for Parkinson's Disease (S19.001)

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Design Of Analog Cmos Integrated Circuits

IEEE transactions on computer-aided design of integrated circuits and systems : a publication of the IEEE Circuits and Systems Society

The regulatory mechanisms by which hydrogen peroxide (H2O2) modulates the activity of transcription factors in bacteria (OxyR and PerR), lower eukaryotes (Yap1, Maf1, Hsf1 and Msn2/4) and mammalian cells (AP-1, NRF2, CREB, HSF1, HIF-1, TP53, NF-κB, NOTCH, SP1 and SCREB-1) are reviewed The complexity of regulatory networks increases throughout the phylogenetic tree, reaching a high level of complexity in mammalians Multiple H2O2 sensors and pathways are triggered converging in the regulation of transcription factors at several levels: (1) synthesis of the transcription factor by upregulating transcription or increasing both mRNA stability and translation; (ii) stability of the transcription factor by decreasing its association with the ubiquitin E3 ligase complex or by inhibiting this complex; (iii) cytoplasm–nuclear traffic by exposing/masking nuclear localization signals, or by releasing the transcription factor from partners or from membrane anchors; and (iv) DNA binding and nuclear transactivation by modulating transcription factor affinity towards DNA, co-activators or repressors, and by targeting specific regions of chromatin to activate individual genes We also discuss how H2O2 biological specificity results from diverse thiol protein sensors, with different reactivity of their sulfhydryl groups towards H2O2, being activated by different concentrations and times of exposure to H2O2 The specific regulation of local H2O2 concentrations is also crucial and results from H2O2 localized production and removal controlled by signals Finally, we formulate equations to extract from typical experiments quantitative data concerning H2O2 reactivity with sensor molecules Rate constants of 140 M−1 s−1 and ≥13 × 103 M−1 s−1 were estimated, respectively, for the reaction of H2O2 with KEAP1 and with an unknown target that mediates NRF2 protein synthesis In conclusion, the multitude of H2O2 targets and mechanisms provides an opportunity for highly specific effects on gene regulation that depend on the cell type and on signals received from the cellular microenvironment

https://repositorio.ipl.pt/bitstream/10400.21/3303/1/Hydrogen%20peroxide%20sensing,%20signaling%20and%20regulation%20of%20transcription%20factors.pdf

Hydrogen peroxide sensing, signaling and regulation of transcription factors

wir berichten über eine 54-jährige Patientin, die sich 2012 erstmalig in unserer onkologischen Hochschulambulanz vorstellte. Bei der Patientin seien initial eine Ptosis des rechten Auges und starke, rechtsbetonte thorakale Schmerzen aufgetreten. Obwohl zusätzliche typische Symptome wie Miosis, Enophthalmus und Anhidrose fehlten, wurde der Verdacht auf ein Horner-Syndrom gestellt. Zur weiteren Diagnostik wurde ein Thorax-MRT veranlasst, wobei sich ein Tumor in der Spitze des rechten Lungenoberlappens (Pancoast-Tumor) sowie vergrößerte Lymphknoten hilär rechts und mediastinal darstellten (Abbildung 1). In der Ausbreitungsdiagnostik mittels PET-CT und cMRT fand sich kein Hinweis auf eine Metastasierung. Zur Bestimmung der Entität des Tumors erfolgte eine Biopsie. In der Histologie wurde eine Metastase Clinical Letter

Neoadjuvante Therapie mit Vemurafenib bei Horner-Syndrom als sehr seltene Erstdiagnose eines CUP-Syndroms bei malignem Melanom.

cilia on the anterior surface of the eyelids have been reported in the literature. Ectopic cilia are divided into two categories according to the origination region of cilia; in the anterior type, cilia stem from anterior of the tarsal plate and protrude through the eyelid skin. In the posterior type, cilia originates from the posterior of the tarsal plate and protrude either from the eyelid margin or through the palpebral conjunctiva. Ectopic cilia are mostly localized on upper lateral quadrant of the anterior surface of the upper eyelid. They may show a variable degree of vertical separation from the lid margin. Ectopic cilia may consist of one or more lash follicles. The present case is an anterior type of ectopic cilia which is localized on the lateral upper eyelid, at 3 mm distance from eyelid margin and it contained approximately 20 hairs. The cause of ectopic cilia is still unknown. While anterior ectopic cilia are congenital, posterior ectopic cilia may be acquired due to the chronic inflammation. There are several hypotheses to explain the development of congenital ectopic cilia. Firstly, it was suggested that cilia replaced and substituted meibomian glands. However, a new hypothesis suggesting that, this anomaly is likely due to inappropriate differentiation during embryogenesis, has becoming to be more accepted. Ectopic cilia are isolated congenital anomaly but it can be associated with congenital distichiasis, a complex choristoma, cutaneous features of atopic eczema in the periorbital region, pre-septal cellulitis and hypocromic naevus. The present case did not have another pathology. Surgical excision suggested for cosmetical reason in asymptomatic anterior ectopic cilia cases but recurrences may be seen particularly after incomplete excision. The present case has been reported because ectopic cilia are a very rarely seen entity in dermatological practice.

Subcutaneous non-absorbable polypropylene (SNAP) sutures in serial excision of congenital naevi: A new time-saving technique reducing dehiscence with optimized aesthetic results

Immuncheckpoint‐Inhibitor getriggerter Parkinsonismus bei einem Patienten mit metastasiertem Melanom.

BACKGROUND In melanoma, preclinical data suggest a possible role of polyunsaturated fatty acids inhibiting cell growth. A new target molecule for free fatty acids, the G protein-coupled receptor GPR40, was identified in melanoma cells. OBJECTIVES The aim of this study was to investigate GPR40 expression in human melanocytic tissues and to evaluate its potential as a prognostic marker. METHODS AND RESULTS A total of 114 tissue sections of naevi, primary melanoma and melanoma metastasis were immunohistochemically stained with anti-GPR40. The staining was evaluated, using the immunoreactivity scoring system. Compared to naevi, primary melanoma and melanoma metastasis showed significantly higher levels of GPR40 (P < 0.05). In primary melanoma, GPR40 expression positively correlated with tumour thickness (P = 0.044) and AJCC level (P = 0.017) and in melanoma metastasis with AJCC level (P = 0.035). Primary melanoma patients with high levels of GPR40 had a significantly poorer overall survival (P = 0.004) and shorter disease-free survival (0.040). CONCLUSION The present study identified GPR40 as a novel target molecule in melanoma. First evidence for a potential role of the receptor in tumour progression and metastases was found, and it could be demonstrated that GPR40 expression is negatively correlated with patient's survival.

https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdv.15924

G protein-coupled receptor 40 expression in human melanoma - correlation with tumour thickness, AJCC stage and survival.

Die Elektrochemotherapie (ECT) ist ein Verfahren, bei dem mittels kurzer elektrischer Pulse lokal eine Erhohung der Zellmembranpermeabilitat erzielt wird. Gleichzeitig applizierte Chemotherapeutika konnen so in Tumorzellen gelangen und dort ihre Wirkung entfalten. Die Methode ist einfach anzuwenden und Nebenwirkungen sind gering. Sie eignet sich zur Therapie kutaner und subkutaner Tumoren, die durch chirurgische oder andere Verfahren nicht oder nur schwer zu behandeln sind. Bei fortgeschrittenen Tumorerkrankungen kann so eine gute lokale Tumorkontrolle erreicht und die Lebensqualitat der Betroffenen, die haufig unter Blutungen und Geruchsentwicklung der Metastasen leiden, verbessert werden. Bei alten und/oder multimorbiden Patienten ist die Therapie einfach durchzufuhren und weitgehend schonend. Neuere Erkenntnisse uber immunologische Effekte bei der Kombination aus ECT und Immuntherapien eroffnen moglicherweise neue Therapieoptionen fur Patienten mit metastasiertem Melanom.

https://www.thieme-connect.com/products/ejournals/pdf/10.1055/s-0042-120582.pdf

Markus Meissner

Papers

Neoadjuvante Therapie mit Vemurafenib bei Horner-Syndrom als sehr seltene Erstdiagnose eines CUP-Syndroms bei malignem Melanom.

Subcutaneous non-absorbable polypropylene (SNAP) sutures in serial excision of congenital naevi: A new time-saving technique reducing dehiscence with optimized aesthetic results

Immuncheckpoint‐Inhibitor getriggerter Parkinsonismus bei einem Patienten mit metastasiertem Melanom.

G protein-coupled receptor 40 expression in human melanoma - correlation with tumour thickness, AJCC stage and survival.

Elektrochemotherapie – Möglichkeiten lokaler Tumorkontrolle