Clinical, histological, and immunohistochemical analysis in search for the cause of epidermal thickening in prurigo nodularis

Dept. of Medicine/석사Prurigo nodularis (PN) is a chronic pruritic skin disorder characterized by multiple hyperkeratotic nodules. Although several hypotheses have been suggested, the exact mechanisms of the pathogenesis have not been elucidated. Also, PN is known to be associated with atopic dermatitis (AD), yet their associations remain largely unknown. In this study, patients of PN and PN with AD (PN-AD) were compared with normal subjects clinically, histologically and through immunohistochemical studies. The results showed that PN-AD patients had significantly higher total IgE levels and eosinophil counts than that of PN group. Histologic assessment revealed increased epidermal thicknesses and dermal inflammatory cell counts of PN and PN-AD groups when compared to normal subjects. Immunohistochemical analyses showed that uptake of SDF 1- α, TSLP, IFN- γ, IL-4, IL-13, IL-18, IL-31, and IL-33 were increased in the tissues of PN and PN-AD groups, in which the staining intensities of SDF 1- α, TSLP, IL-4, and IL-13 of PN-AD group were higher than that of PN group. In the contrary, the staining intensities of IL-18, IFN- γ, and IL-33 were statistically higher in the PN-AD group than PN group. Through the findings of this study, the pathogenesis of PN without AD may be different from that of PN with AD, in which IL-18, IFN- γ, and IL-33 may be associated, suggesting that epidermal injury may be the initial cause that induces IL-18 and IL-33, which then enhances IFN- γ, resulting in the inflammatory process of PN. 결절성 소양진은 만성적인 가려움증을 동반하는 피부 질환으로 다수의 과각화된 결절을 특징으로 한다. 여러 가설들이 제시되어 왔으나 아직 발병기전에 대해서는 명확히 밝혀져 있지는 않다. 또한 아토피피부염이 연관이 되어 있는 것으로 알려져 있으나 아직 이와 연관성은 잘 알려져 있지 않다. 이 연구에서는 결절성 소양진 환자 (PN), 아토피피부염이 동반된 결절성 소양진 환자 (PN-AD), 그리고 정상 대조군과 임상적, 조직학적, 그리고 면역화학적으로 비교를 하였다. PN과 PN-AD 환자들을 비교한 결과, PN-AD군에서 혈청 전체 IgE 수치와 eosinophil count가 통계적으로 유의미하게 높았다. 조직학적으로 분석을 하였을 때, PN과 PN-AD 군에서 표피의 두께 및 진피에 침윤된 염증 세포의 수가 정상 대조군에 비해서 유의미하게 증가하였다. 면역화학적 분석에서는 SDF 1- α, TSLP, IFN- γ, IL-4, IL-13, IL-18, IL-31 및 IL-33에 대한 염색이 PN과 PN-AD군에서 증가되었다. 염색된 강도를 분석하였을 때 PN-AD군에서 SDF 1- α, TSLP, IL-4 및 IL-13의 염색 강도가 PN군에 비해서 더 높게 나타났다. 반면에 PN군에서는 IL-18, IFN- γ 그리고 IL-33의 염색 강도가 PN-AD군에 비해서 유의미하게 강하게 나타났다. 이러한 결과들을 통해서 아토피피부염이 동반되지 않은 결절성 소양진의 발병 기전은 아토피피부염이 동반된 경우와 다를 것으로 생각되며, IL-18, IFN- γ 그리고 IL-33이 연관이 있을 것으로 사료된다. 따라서 아토피피부염이 동반되지 않은 결절성 소양진의 경우 긁음 등 경미한 기계적 자극에 의해 손상된 표피에서 증가된 IL-18과 IL-33이 초기 염증 작용을 하여 궁극적으로 표피의 만성화에 관여하는 IFN- γ을 유도함으로써 결절성 소양진의 표피의 증가, 즉 극세포증을 일으키고 침윤된 염증 세포가 이 과정에 관여하리라 생각된다.ope

Comparative Effectiveness Research, COURAGE, and Technological Abandonment

When a major study finds that a widely used medical treatment is no better than a less expensive alternative, do physicians stop using it? Policymakers hope that comparative effectiveness research will identify less expensive substitutes for widely-used treatments, but physicians may be reluctant to abandon profitable therapies. We examine the impact of the COURAGE trial, which found that medical therapy is as effective as percutaneous coronary intervention (PCI) for patients with stable angina, on practice patterns. Using hospital discharge data from US community, Veterans Administration, and English hospitals, we detect a moderate decline in PCI volume post-COURAGE. However, many patients with stable angina continue to receive PCI. We do not find differences in PCI volume trends by reimbursement scheme or hospitals’ teaching status, ownership, or degree of vertical integration.

Comparison of Test Your Memory and Montreal Cognitive Assessment Measures in Parkinson’s Disease

Background. MoCA is widely used in Parkinson’s disease (PD) to assess cognition. The Test Your Memory (TYM) test is a cognitive screening tool that is self-administered. Objectives. We sought to determine (a) the optimal value of TYM to discriminate between PD patients with and without cognitive deficits on MoCA testing, (b) equivalent MoCA and TYM scores, and (c) interrater reliability in TYM testing. Methods. We assessed the discriminant ability of TYM and the equivalence between TYM and MoCA scores and measured the interrater reliability between three raters. Results. Of the 135 subjects that completed both tests, 55% had cognitive impairment according to MoCA. A MoCA score of 25 was equivalent to a TYM score of 43-44. The area under the receiver operator characteristic (ROC) curve for TYM to differentiate between PD-normal and PD-cognitive impairment was 0.82 (95% CI 0.75 to 0.89). The optimal cutoff to distinguish PD-cognitive impairment from PD-normal was ≤45 (sensitivity 90.5%, specificity 59%) thereby correctly classifying 76.3% of patients with PD-cognitive impairment. Interrater agreement was high (0.97) and TYM was completed in under 7 minutes (interquartile range 5.33 to 8.52 minutes). Conclusions. The TYM test is a useful and less resource intensive screening test for cognitive deficits in PD

Asymmetric transfer hydrogenation of unsaturated ketones ; factors influencing 1,4- vs 1,2- regio- and enantioselectivity, and alkene vs alkyne directing effects

A detailed study has been completed on the asymmetric transfer hydrogenation (ATH) of a series of enones using Ru(II) catalysts. Electron-rich rings adjacent to the C=O group reduce the level of C=O reduction compared to C=C. The ATH reaction can readily discriminate between double and triple bonds adjacent to ketones, reducing the double bond but leaving a triple bond intact in the major product

Antihypertensive Agents and Incident Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Observational Studies

Background Hypertension is a recognized risk factor for dementia. However, evidence for using antihypertensive agents to reduce the risk of Alzheimer’s disease in people with hypertension is inconclusive. Objective To examine the association between antihypertensive agents and the incidence of Alzheimer’s disease in adults with hypertension and normal cognition. Design We conducted a systemic review and performed meta-analyses using Ovid MEDLINE, Ovid Embase, Ovid PsycINFO, Web of science and Scopus, from inception to 18th February 2022. Setting Cohort and case-control studies. Participants Adults ≥ 40 years with hypertension and normal cognition. Intervention Antihypertensive agents. Measurements We performed two separate meta-analyses, pooling the adjusted relative risk (RR) of non-antihypertensive comparator and antihypertensive comparator study design. Results We included nine studies, totalling 1,527,410 individuals. Meta-analysis of non-antihypertensive user comparator studies found that the use of antihypertensive agents is associated with a reduced risk of incident Alzheimer’s disease (RR= 0.94, 95% CI 0.90–0.99; p=0.01). Meta-analysis of antihypertensive comparator studies found evidence that angiotensin II receptor blocker users are associated with a reduction in the risk of Alzheimer’s disease compared to other antihypertensive agents (RR= 0.78, 95% CI 0.68–0.88; p< 0.001). Conclusion Our review provides evidence that the use of antihypertensive agents is associated with a lower incidence of Alzheimer’s disease. The use of angiotensin II receptor blockers may provide the most benefit among antihypertensive agents. Lowering raised blood pressure may not be the only mechanism for cognitive protection and further investigation of the effects of angiotensin II on cognition is indicated

pp-wave limits and orientifolds

We study the pp-wave limits of various elliptic models with orientifold planes and D7-branes, as well as the pp-wave limit of an orientifold of adS_5 x T^{11}. Many of the limits contain both open and closed strings. We also present pp-wave limits of theories which give rise to a compact null direction and contain open strings. Maps between the string theory states and gauge theory operators are proposed.Comment: 33 pages, no figures, LaTeX. v2: reference fixe

Model for an Intelligent Operating System for Executing Tasks on a Reconfigurable Parallel Architecture

Parallel processing is one approach to achieve the large computational processing capabilities required by many real-time computing tasks. One of the problems that must be addressed in the use of reconfigurable multiprocessor systems is matching the architecture configuration to the algorithms to be executed. This paper presents a conceptual model that explores the potential of artificial intelligence tools, specifically expert systems, to design an Intelligent Operating System for multiprocessor systems. The target task is the implementation of image understanding systems on multiprocessor architectures. PASM is used as an example multiprocessor. The Intelligent Operating System concepts developed here could also be used to address other problems requiring real-time processing. An example image understanding task is presented to illustrate the concept of intelligent scheduling by the Intelligent Operating System. Also considered is the use of the conceptual model when developing an image understanding system in order to test different strategies for choosing algorithms, imposing execution order constraints, and integrating results from various algorithms