The exposome in atopic dermatitis

Atopic dermatitis (AD) is a complex inflammatory disorder with multiple interactions between genetic, immune and external factors. The sum of external factors that an individual is exposed to throughout their lifetime is termed the exposome. The exposome spans multiple domains from population to molecular levels and, in combination with genetic factors, holds the key to understanding the phenotypic diversity seen in AD patients. Exposomal domains are categorized into nonspecific (human and natural factors affecting populations), specific (eg humidity, ultraviolet radiation, diet, pollution, allergens, water hardness) and internal (cutaneous and gut microbiota and host cell interaction) exposures. The skin, as the organ that most directly interacts with and adapts to the external environment, is a prime target for exploration of exposomal influences on disease. Given the well-recognized physical environmental influences on AD, this condition could be much better understood through insightful exposomal research. In this narrative review, we examine each domain in turn, highlighting current understanding of the mechanisms by which exposomal influences modulate AD pathogenesis at distinct points in time. We highlight current approaches to exposome modification in AD and other allergic disease and propose future directions for exposome characterization and modification using novel research techniques.     

Restitution of reaching and grasping promoted by functional electrical therapy

Functional electrical therapy (FET) is a new term describing a combination of functional electrical stimulation that generates life-like movement and intensive exercise in humans with central nervous system lesions. We hypothesized that FET can promote a significant recovery of functioning if applied in subacute stroke subjects. The study included 16 stroke subjects divided into a low functioning group (LFG) and a high functioning group (HFG) based on their ability to control wrist and fingers and randomly associated into FET and controls. The FET consisted of 30 min daily sessions during 3 weeks. The exercise comprised functional use of daily necessary activities (e.g., writing, using a telephone receiver, and drinking from a can). The outcome presented in this article is the upper-extremity function test performed before and after the therapy. The change in performance of the HFG group was significant. The number of successful repetitive movements in 2 min was doubled and 1.6 times increased for controls, and the time to perform the movement was decreased by 71% percent and by 36% in controls. In the LFG FET group, the difference in performance was the following. First, the number of tasks was increased from 0 to 6 (total of 11 tasks). Second, the averaged number of successful repetitive movements was increased from 0 to 3. The functional improvement in the FET LFG is probably not sufficient to make the more affected arm/hand effective for daily necessities; thus, the FET effects could deteriorate over a longer time. The subjects from the control LFG made only a marginal improvement. The follow-up for each subject will continue for 12 months after the beginning of the treatment.     

Overlap Technique Improves Results of Primary Surgery after Obstetric Anal Sphincter Tear

Purpose This study was designed to evaluate prospectively the results of the overlap technique in primary sphincter reconstruction after obstetric tear. Methods Obstetric tears in 44 women were operated on with primary overlap reconstruction. These women were investigated six to nine months after the operation. Results were compared with those of a historical control group of 52 women whose obstetric sphincter rupture had been treated with the end-to-end technique. Results The overlap group had significantly more incontinence symptoms after delivery and repair of the sphincter tear than before delivery (P < 0.0001); however, their incontinence symptoms were significantly fewer than those of the end-to-end group (P = 0.004). The prevalence of persistent rupture of the external anal sphincter was significantly lower in the overlap group (6/44, 13.6 percent) than in the end-to-end group (39/52, 75 percent; P < 0.0001). Internal anal sphincter rupture occurred in 5 patients (11.4 percent) in the overlap group and in 40 patients (76.9 percent) in the end-to-end group (P < 0.0001). Conclusions The overlap technique should be adopted as the method of choice for primary sphincter repair after obstetric tear.     

Severe cerebral aspergillosis after liver transplant

V. Leung, A. Stefanovic, D. Sheppard. Severe cerebral aspergillosis after liver transplant.
Transpl Infect Dis 2010: 12: 51–53. All rights reserved
Abstract: Cerebral aspergillosis is a rare complication of liver transplantation. We present the case of a 34-year-old woman with multiple brain lesions discovered 8 days after orthotopic liver transplant for autoimmune hepatitis. The epidemiology, differential diagnosis, diagnostic strategies, and management of cerebral aspergillosis are discussed.     

Central nervous system manifestations of marginal zone B-cell lymphoma

Primary or secondary central nervous system (CNS) involvement by marginal zone B-cell lymphoma (MZBCL) is rare. A retrospective analysis of patients was done with MZBCL involving the CNS, diagnosed and treated at our institution between 2004 and 2010. We identified 10 MZBCL patients with primary (six) or secondary (four) CNS involvement. Five patients presented with primary dural lymphoma and were treated with surgical resection, whole-brain radiation, or systemic chemotherapy. Only one patient had CNS relapse 5 years later. A single patient with primary intraocular lymphoma achieved clinical remission with ocular radiotherapy and systemic chemotherapy. Four patients had ocular MZBCL within 5 years of the initial diagnosis of primary ocular adnexal MZBCL and primary splenic MZBCL. There was no evidence of local recurrence in all but one who developed systemic relapse after 3 years of follow-up. Primary or secondary CNS involvement by MZBCL display indolent clinical behavior and have a generally favorable prognosis, underlining the importance of their differentiation from aggressive lymphomas that more commonly involve the CNS.     

Gene expression profile of quiescent and activated rat hepatic stellate cells implicates Wnt signaling pathway in activation

BACKGROUND/AIMS: Liver fibrosis is characterized by accumulation of extracellular matrix proteins synthesized by activated hepatic stellate cells (HSCs). To understand molecular mechanisms of HSCs activation a comprehensive comparison of gene expression between quiescent and activated HSCs is needed. METHODS: Using DNA microarrays we compared expression of 31,100 genes between quiescent rat HSCs and culture activated rat HSCs. Expression of the components of Wnt signaling was analyzed in HSCs and fibrotic livers by RT-PCR. Activation of beta-catenin was analyzed by Western blot. RESULTS: Nine hundred genes were upregulated more than 4.6-fold and 500 genes were downregulated more than 5.7-fold in activated HSCs. The upregulated genes included Wnt receptor frizzled 2, ligands Wnt4 and Wnt5, which was confirmed in fibrotic livers. Expression of the target genes of Wnt signaling was increased from 5- to 70-fold. Phosphorylation and nuclear translocation of beta-catenin were unchanged, indicating activation of the noncanonical Wnt pathway. CONCLUSIONS: Highly upregulated expression of Wnt5a and its receptor frizzled 2 implicates this pathway in differentiation of quiescent HSCs into myofibroblasts. Activation of Wnt signaling pathway in HSCs and in animal models of liver fibrosis has not been described previously, suggesting an important role of Wnt signaling in development of liver fibrosis.     

Vaginal leukocyte characteristics in urogenital trichomoniasis.

Morphological and functional characteristics of vaginal exudate leukocytes were examined in 47 patients with urogenital trichomoniasis. Electron microscopic morphology, viability, phagocytosis of Candida albicans blastospores and ability to undergo respiratory burst in the iodonitrotetrazolium reductase test were evaluated in these cells. Vaginal inflammatory leukocytes were almost exclusively polymorphonuclear neutrophils, and their concentration was positively correlated (r = 0.58; p less than 0.001) with the number of trichomonads in the exudate. Median leukocyte viability reached 39% and both phagocytic and tetrazolium reductase activities of these cells were significantly reduced in comparison with those of circulating polymorphonuclear leukocytes. Patients with a clinical picture of severe mucosal inflammation had significantly higher vaginal exudate leukocyte concentrations and viability than those without inflammatory signs. The possible role of vaginal leukocytes in the pathogenesis of urogenital trichomoniasis is discussed.