A novel autosomal dominant GDAP1 mutation in an Italian CMT2 family

We report the clinical, electrophysiological, and skin biopsy findings of an Italian Charcot-Marie-Tooth disease type 2 (CMT2) family with a novel heterozygous GDAP1 mutation. We observed a marked intra-familial phenotypic variability, in age at onset and disease severity which ranged from a typical CMT phenotype to an asymptomatic status. Electrophysiological study, consistent with an axonal sensory-motor neuropathy, confirmed a different degree of severity and disclosed minimal electrophysiological abnormalities also in the asymptomatic subjects. Skin biopsy findings showed a variable loss of large and small somatic nerve fibers. Molecular analysis identified a novel heterozygous missense mutation (Arg120Gly) in the GDAP1 gene which co-segregated with the disease within the pedigree. In conclusion, our findings confirm that the GDAP1 autosomal dominant mutations underlie a pronounced phenotypic variability, mimicking the effects of reduced penetrance. Notably, electrophysiological study in this family allowed to reveal hidden positive family history and assess a dominant inheritance pattern, revealing subclinical neuropathy in asymptomatic mutation carriers.     

Eye movements modulate the spatiotemporal dynamics of word processing

Active reading requires coordination between frequent eye movements (saccades) and short fixations in text. Yet, the impact of saccades on word processing remains unknown, as neuroimaging studies typically employ constant eye fixation. Here we investigate eye-movement effects on word recognition processes in healthy human subjects using anatomically constrained magnetoencephalography, psychophysical measurements, and saccade detection in real time. Word recognition was slower and brain responses were reduced to words presented early versus late after saccades, suggesting an overall transient impairment of word processing after eye movements. Response reductions occurred early in visual cortices and later in language regions, where they colocalized with repetition priming effects. Qualitatively similar effects occurred when words appeared early versus late after background movement that mimicked saccades, suggesting that retinal motion contributes to postsaccadic inhibition. Further, differences in postsaccadic and background-movement effects suggest that central mechanisms also contribute to postsaccadic modulation. Together, these results suggest a complex interplay between visual and central saccadic mechanisms during reading.     

The effectiveness of the Liverpool care pathway in improving end of life care for dying cancer patients in hospital. A cluster randomised trial

Background  

Most cancer patients still die in hospital, mainly in medical wards. Many studies in different countries have shown the poor quality of end-of-life care delivery in hospitals. The Program "Liverpool Care Pathway for the dying patient" (LCP), developed in the UK to transfer the hospice model of care into hospitals and other care settings, is a complex intervention to improve the quality of end-of-life care. The results from qualitative and quantitative studies suggest that the LCP Program can improve significantly the quality of end-of-life care delivery in hospitals, but no randomised trial has been conducted till now.     

Does laparoscopic management of deep infiltrating endometriosis improve quality of life? A prospective study

Background

Deep infiltrating endometriosis (DIE) can affect importantly patients' quality of life (QOL). The aim of this study is to evaluate the impact of the laparoscopic management of DIE on QOL after six months from treatment.

Methods

It is a prospective cohort study. In a tertiary care university hospital, between April 2008 and December 2009, 100 patients underwent laparoscopic management of DIE and completed preoperatively and 6-months postoperatively a QOL questionnaire, the short form 36 (SF-36).Quality of life was measured through the SF-36 scores. Intra-operative details of disease site, number of lesions, type of intervention, period of hospital stay and peri-operative complications were noted.

Results

Six months postoperatively all the women had a significant improvement in every scale of the SF-36 (p < 0,0005). Among patients with intestinal DIE, significant differences in postoperative scores of SF-36 were not detected between patients submitted to nodule shaving and segmental resection (p > 0.05). There was no significant difference in the SF-36 scores at 6 months from surgery between patients who received postoperative medical treatment and patients who did not (p > 0.05).

Conclusions

Laparoscopic excision of DIE lesions significantly improves general health and psycho-emotional status at six months from surgery without differences between patients submitted to intestinal segmental resection or intestinal nodule shaving.

     

Photoprotective effects of two natural products on ultraviolet B-induced oxidative stress and apoptosis in SKH-1 mouse skin

Solar ultraviolet radiation (UV) is the major cause of nonmelanoma skin cancer in humans. Photochemoprevention with natural products represents a simple but very effective strategy for the management of cutaneous neoplasia. We studied the photoprotective activity of Calluna vulgaris and red grape seed (Vitis vinifera L, Burgund Mare variety [BM]) extracts in vivo in an SKH-1 hairless mice skin model. Fifty 8-week-old female SKH-1 hairless mice were randomly divided into 5 groups (n?=?10 each): controls, UVB-irradiated, C. vulgaris plus UVB-irradiated, BM plus UVB-irradiated, and epigallocatechin gallate (EGCG) plus UVB-irradiated. A dose of 4 mg/mouse per cm2 of skin area for both extracts was topically applied to the mice 30 minutes before a single-dose (240 mJ/cm2) UVB exposure. EGCG dissolved in phosphate-buffered saline (pH 6.6; 0.067 M) was administered at 2 mg/mouse per cm2. Glutathione peroxidase and catalase activities, reduced glutathione (GSH), malondialdehyde, nitric oxide, and caspase 3 activity were determined in skin homogenates 24 hours after irradiation. A single dose of UVB increased GSH levels and glutathione peroxidase activity in the exposed skin. C. vulgaris and BM pretreatment significantly decreased GSH formation and glutathione peroxidase activity (P?相似文献