Home-based therapy programmes for upper limb functional recovery following stroke

Background: With an increased focus on home-based stroke services and the undertaking of programmes, targeted at upper limb recovery within clinical practice, a systematic review of home-based therapy programmes for individuals with upper limb impairment following stroke was required. Objectives: To determine the effects of home-based therapy programmes for upper limb recovery in patients with upper limb impairment following stroke. Search methods: We searched the Cochrane Stroke Group's Specialised Trials Register (May 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), MEDLINE (1950 to May 2011), EMBASE (1980 to May 2011), AMED (1985 to May 2011) and six additional databases. We also searched reference lists and trials registers. Selection criteria: Randomised controlled trials (RCTs) in adults after stroke, where the intervention was a home-based therapy programme targeted at the upper limb, compared with placebo, or no intervention or usual care. Primary outcomes were performance in activities of daily living (ADL) and functional movement of the upper limb. Secondary outcomes were performance in extended ADL and motor impairment of the arm. Data collection and analysis: Two review authors independently screened abstracts, extracted data and appraised trials. We undertook assessment of risk of bias in terms of method of randomisation and allocation concealment (selection bias), blinding of outcome assessment (detection bias), whether all the randomised patients were accounted for in the analysis (attrition bias) and the presence of selective outcome reporting. Main results: We included four studies with 166 participants. No studies compared the effects of home-based upper limb therapy programmes with placebo or no intervention. Three studies compared the effects of home-based upper limb therapy programmes with usual care. Primary outcomes: we found no statistically significant result for performance of ADL (mean difference (MD) 2.85; 95% confidence interval (CI) -1.43 to 7.14) or functional movement of the upper limb (MD 2.25; 95% CI -0.24 to 4.73)). Secondary outcomes: no statistically significant results for extended ADL (MD 0.83; 95% CI -0.51 to 2.17)) or upper limb motor impairment (MD 1.46; 95% CI -0.58 to 3.51). One study compared the effects of a home-based upper limb programme with the same upper limb programme based in hospital, measuring upper limb motor impairment only; we found no statistically significant difference between groups (MD 0.60; 95% CI -8.94 to 10.14). Authors' conclusions: There is insufficient good quality evidence to make recommendations about the relative effect of home-based therapy programmes compared with placebo, no intervention or usual care

The Role of AldoKeto Reductase 1C3 in Human Epidermis, Atopic Dermatitis and Cutaneous Squamous Cell Carcinoma

Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Pharmacology and Physiology, 2011.Aldoketo reductase 1C3 (AKR1C3) has been shown to mediate the metabolism of sex hormones and prostaglandins (PGs), both of which play a role in epidermal function and pathology. AKR1C3 expression has been initially characterized in normal human epidermis by immunofluorescence, revealing a strong expression in the differentiated epidermal layers compared with the proliferative compartment. In addition, AKR1C3 expression was up regulated during calciuminduced differentiation of primary human keratinocytes (PHKs). This suggested a possible function of AKR1C3 in keratinocyte differentiation, a tightly choreographed process that is crucial for proper function of the epidermis. The current work demonstrated that impairment of AKR1C3 during PHK differentiation altered the expression of the differentiation markers keratin 10 and loricrin, suggesting a role in keratinocyte differentiation. Prostaglandin D2 (PGD2), a preferred substrate of AKR1C3, is a lipid mediator that has been shown to be upregulated and promote inflammation in atopic dermatitis (AD). The current data showed that AKR1C3 expression is markedly upregulated by PHKs in response to PGD2, as well as in lesions of AD but of psoriasis, another inflammatory skin condition. These findings suggest a novel role for epidermal keratinocytes in regulating PGD2mediated inflammatory actions in AD. Data described in the current thesis show that AKR1C3 was overexpressed in squamous cell carcinoma (SCC), but its expression was completely undetectable in the tumor mass of basal cell carcinoma. Following this observation, several SCC cell lines have been derived from surgically excised human cutaneous SCC tumors. These cells demonstrated a defective terminal differentiation capacity compared with PHK and were able to generate SCClike tumors in immunocompromised mice, in vivo. In order to investigate the role of AKR1C3 overexpression in SCC growth and survival, one SCC cell line has been genetically manipulated to overexpress AKR1C3 and the proliferation of these cells has been assessed under various conditions. Taken together, this work characterizes the expression of AKR1C3 in normal epidermis, demonstrates a function for this enzyme in differentiation associated gene regulation, and suggests a role in supporting inflammation in AD. In addition, this work characterizes the expression patterns of AKR1C3 in SCC and suggests at least one possible role for this enzyme in SCC proliferation. Finally, human cutaneous SCC cell lines derived from tumors from sunexposed areas are currently unavailable; therefore, the establishment of these cell lines adds a significant contribution to this field of research

Aldo-Keto Reductase 1C3 Is Expressed in Differentiated Human Epidermis, Affects Keratinocyte Differentiation, and Is Upregulated in Atopic Dermatitis

Aldo-keto reductase 1C3 (AKR1C3) has been shown to mediate the metabolism of sex hormones and prostaglandin D2 (PGD2), a lipid mediator that promotes skin inflammation in atopic dermatitis (AD). As both have a role in skin function and pathology, we first sought to investigate the expression pattern of AKR1C3 in normal human epidermis. Immunofluorescence revealed a strong expression of AKR1C3 in the differentiated suprabasal layers compared with the basal layer. Western blot analysis and quantitative PCR confirmed that AKR1C3 expression was also upregulated in differentiation-induced primary human keratinocytes (PHKs). To investigate the functional role of AKR1C3 during PHK differentiation, its expression and activity (measured as PGD2 reduction to 9α,11β-PGF2 by ELISA) were impaired by small interfering RNA or 2′-hydroxyflavanone, respectively. Cytokeratin 10 (K10) and loricrin expression were then examined by western blot analysis, thus revealing altered expression of these differentiation markers. Finally, following an observation that the AD-associated mediator, PGD2, upregulated AKR1C3 expression in PHKs, we used immunofluorescence to examine AKR1C3 expression in AD and psoriasis lesions. AKR1C3 was found to be upregulated in AD but not in psoriasis lesions compared with non-lesional skin. Our work demonstrates a function for AKR1C3 in differentiation-associated gene regulation and also suggests a role in supporting inflammation in AD