Changes of cancer diagnosis disclosure to children in Japan in the last 20 years

International Journal of Clinical Oncology - The practice of cancer diagnosis disclosure to children has been changed with the times. The regulations of clinical trials in the 2000s might change...     

Efficacy of istradefylline for gait disorders with freezing of gait in Parkinson’s disease: A single-arm,open-label,prospective, multicenter study

Background: Gait disorders are common in Parkinson’s disease patients who respond poorly to dopaminergic treatment. Blockade of adenosine A_2A receptors is expected to improve gait disorders. Istradefylline is a first-in-class selective adenosine A_2A receptor antagonist with benefits for motor complications associated with Parkinson’s disease.

Research design and methods: This multicenter, open-label, single-group, prospective interventional study evaluated changes in total gait-related scores of the Part II/III Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and Freezing of Gait Questionnaire (FOG-Q) in 31 Parkinson’s disease patients treated with istradefylline. Gait analysis by portable gait rhythmogram was performed.

Results: MDS-UPDRS Part III gait-related total scores significantly decreased at Weeks 4–12 from baseline with significant improvements in gait, freezing of gait, and postural stability. Significant decreases in MDS-UPDRS Part II total scores and individual item scores at Week 12 indicated improved daily living activities. At Week 12, there were significant improvements in FOG-Q, new FOG-Q, and overall movement per 48 h measured by portable gait rhythmogram. Adverse events occurred in 7/31 patients.

Conclusions: Istradefylline improved gait disorders in Parkinson’s disease patients complicated with freezing of gait, improving their quality of life. No unexpected adverse drug reactions were identified.

Trial registration: UMIN-CTR (UMIN000020288).     

Outcomes After Aortic Valve Replacement for Asymptomatic Severe Aortic Regurgitation and Normal Ejection Fraction

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1‐(2‐Hydroxyethyl)‐2‐imidazolidinone,a heparanase and matrix metalloproteinase inhibitor,improves epidermal basement membrane structure and epidermal barrier function

Daily exposure to sunlight is known to affect the structure and function of the epidermal basement membrane (BM), as well as epidermal differentiation and epidermal barrier function. The aim of this study is to clarify whether the inhibition of BM‐degrading enzymes such as heparanase and matrix metalloproteinase 9 (MMP‐9) can improve the epidermal barrier function of facial skin, which is exposed to the sun on a daily basis. 1‐(2‐hydroxyethyl)‐2‐imidazolidinone (HEI) was synthesized as an inhibitor of both heparanase and MMP‐9. HEI inhibited not only the BM damage at the DEJ but also epidermal proliferation, differentiation, water contents and transepidermal water loss abnormalities resulting from ultraviolet B (UVB). This was determined in this study by the use of UVB‐induced human cultured skins as compared with the control without HEI. Moreover, topical application of HEI improved epidermal barrier function by increasing water content and decreasing transepidermal water loss in daily sun‐exposed facial skin as compared with non‐treated skins. These results suggest that the inhibition of both heparanase and MMP‐9 is an effective way to care for regularly sun‐exposed facial skin by protecting the BM from damage.     

Therapeutic potential of AMPA receptor antagonist perampanel against cerebral ischemia: beyond epileptic disorder

<正>Stroke is a leading cause of mortality and severe neurological disability worldwide; however, curative therapeutic options are limited. Although recanalization therapy using endovascular thrombectomy has demonstrated great benefits in the functional outcome of patients with acute ischemic stroke, the rate of excellent clinical outcomes remains limited. Therefore, the current recanalization     

Parenchymal calcification is associated with the neurological prognosis in patients with congenital rubella syndrome

Congenital rubella syndrome (CRS) results from maternal rubella virus infection in early pregnancy. Abnormal neuroimaging findings have been analyzed in a small number of CRS patients in the past; however, their clinical significance has been poorly addressed. Therefore, we have investigated the neuroimaging findings of 31 patients with CRS from previous studies. The most common finding was parenchymal calcification, which was observed in 18 of 31 patients (58.1%). A multivariable logistic regression model showed that it was associated with psychomotor or mental retardation (p = 0.018), suggesting that parenchymal calcification in CRS could be a prognostic factor.     

Hair shaft miRNA‐221 levels as a new tumor marker of malignant melanoma

miRNA‐221 (miR‐221) is known to be abnormally expressed in many human cancers. The serum levels of miR‐221 have been reported as a tumor marker for malignant melanoma (MM). We hypothesized that the hair shaft miR‐221 levels may be increased in patients with MM. We therefore assessed the possibility that hair shaft miR‐221 levels could be a marker for MM. The hair shaft miR‐221 levels were significantly higher in patients with MM than controls. The rates of increased hair shaft miR‐221 levels above the cut‐off value were comparable to those of serum 5‐S‐CD, which is a tumor marker commonly used for MM. Measurements of the hair shaft miR‐221 levels could have potential clinical value in the detection of MM. This is the first report investigating the hair shaft levels of an miRNA in patients with MM. Our investigations offer new insight into the relationship between miR‐221 and MM, and may provide a new, non‐invasive way to screen for melanoma.     

Spontaneous recovery of fear differs among early – late adolescent and adult male mice

Adolescence is a vulnerable period for developing anxiety-related mental disorders such as post-traumatic stress disorder (PTSD), which requires a long-term course of therapy when a traumatic event has been experienced during childhood. However, the biological mechanism underlying these age-dependent characteristics remains unclear. In the present study, we used early adolescent, late adolescent and adult (4-, 8-, and 15-week old) male mice to examine age differences in fear memory, fear extinction, and spontaneous recovery of fear. We also measured the activation of extracellular signal-regulated kinase (ERK) 2 in the dorsal hippocampus (dHip) and the basolateral amygdala (BLA) following a spontaneous recovery test. Our major findings were as follows: (1) early adolescent and adult mice did not recover the fear response; only late adolescent mice recovered the fear response. (2) The ERK2 in the dHip was more activated after the spontaneous recovery test in late adolescent mice than in adult mice, and the ERK2 in the BLA was more activated after the spontaneous recovery test in adult mice than in late adolescent mice. These results suggest that there exists a unique period in which spontaneous recovery occurs and that these late adolescent behavioral signatures may be related to alteration in the ERK2 phosphorylation in the dHip and BLA.