Environmental Impact on Direct Neuronal Reprogramming In Vivo in the Adult Brain

Direct reprogramming of non-neuronal cells to generate new neurons is a promising approach to repair damaged brains. Impact of the in vivo environment on neuronal reprogramming, however, is poorly understood. Here we show that regional differences and injury conditions have significant influence on the efficacy of reprogramming and subsequent survival of newly generated neurons in the adult rodent brain. A combination of local exposure to growth factors and retrovirus-mediated overexpression of the neurogenic transcription factor Neurogenin2 (Neurog2) can induce new neurons from non-neuronal cells in the adult neocortex and striatum where neuronal turnover is otherwise very limited. These two regions respond to growth factors and Neurog2 differently and instruct new neurons to exhibit distinct molecular phenotypes. Moreover, ischemic insult differentially affects differentiation of new neurons in these regions. These results demonstrate strong environmental impact on direct neuronal reprogramming in vivo

Prognostic significance of cribriform adenocarcinoma of the lung: validation analysis of 1,057 Japanese patients with resected lung adenocarcinoma and a review of the literature

Background: Cribriform-predominant adenocarcinoma of the lung (Cribri-ADC) is a recently described tumor growth pattern. However, its prognostic impact has not been clearly determined. We analyzed the data of a series of 1, 057 Japanese patients with resected lung adenocarcinoma to identify the clinical significance of Cribri-ADC. Methods: Cribriform pattern (Cribri-p) is defined as invasive back-to-back fused tumor glands with poorly formed glandular spaces or invasive tumor nests comprising tumors cells that produced glandular lumina. We investigated the correlations of Cribri-p and Cribri-ADC with clinicopathological factors as well as disease-free survival (DFS) and overall survival (OS). Results: Cribri-p was present in 217 patients (20.5%) and Cribri-ADC was determined in 25 patients (2.4%). Cribri-p was associated with larger tumor size, pleural invasion, vascular invasion, lymphatic invasion, and spreading through air spaces (STAS) (all, P<0.0001). Cribri-ADC was associated with younger age (P=0.019), vascular invasion (P=0.0025), STAS (P<0.0001), and ALK rearrangement (P=0.012). The DFS curve of patients with Cribri-ADC was identical to that of patients with solid adenocarcinoma; however, the OS curve was located between that of patients with papillary and acinar adenocarcinoma. Of the 10 patients who had tumor recurrences, eight had EGFR mutations or ALK rearrangement, six of whom achieved relatively long survival (median, 64.6, range, 37.4–113 months) following treatment with tyrosine kinase inhibitors (TKIs). In multivariate analysis, Cribri-ADC was not an independent prognostic factor of either recurrence or death. Conclusions: Cribri-ADC is associated with a higher risk of recurrence; however, most patients can be successfully treated with TKIs

Theanine, the Main Amino Acid in Tea, Prevents Stress-Induced Brain Atrophy by Modifying Early Stress Responses.

Chronic stress can impair the health of human brains. An important strategy that may prevent the accumulation of stress may be the consumption of functional foods. When senescence-accelerated mice prone 10 (SAMP10), a stress-sensitive strain, were loaded with stress using imposed male mouse territoriality, brain volume decreased. However, in mice that ingested theanine (6 mg/kg), the main amino acid in tea leaves, brain atrophy was suppressed, even under stress. On the other hand, brain atrophy was not clearly observed in a mouse strain that aged normally (Slc:ddY). The expression level of the transcription factor (neuronal PAS domain protein 4), which regulates the formation and maintenance of inhibitory synapses in response to excitatory synaptic activity, decreased in the hippocampus and prefrontal cortex of stressed SAMP10 mice, but increased in mice that ingested theanine. Lipocalin 2 (, the expression of which increased in response to stress, was significantly high in the hippocampus and prefrontal cortex of stressed SAMP10 mice, but not in mice that ingested theanine. These data suggest that and are involved in the brain atrophy and stress vulnerability of SAMP10 mice, which are prevented by the consumption of theanine, causing changes in the expression of these genes

Theanine, the Main Amino Acid in Tea, Prevents Stress-Induced Brain Atrophy by Modifying Early Stress Responses

Chronic stress can impair the health of human brains. An important strategy that may prevent the accumulation of stress may be the consumption of functional foods. When senescence-accelerated mice prone 10 (SAMP10), a stress-sensitive strain, were loaded with stress using imposed male mouse territoriality, brain volume decreased. However, in mice that ingested theanine (6 mg/kg), the main amino acid in tea leaves, brain atrophy was suppressed, even under stress. On the other hand, brain atrophy was not clearly observed in a mouse strain that aged normally (Slc:ddY). The expression level of the transcription factor Npas4 (neuronal PAS domain protein 4), which regulates the formation and maintenance of inhibitory synapses in response to excitatory synaptic activity, decreased in the hippocampus and prefrontal cortex of stressed SAMP10 mice, but increased in mice that ingested theanine. Lipocalin 2 (Lcn2), the expression of which increased in response to stress, was significantly high in the hippocampus and prefrontal cortex of stressed SAMP10 mice, but not in mice that ingested theanine. These data suggest that Npas4 and Lcn2 are involved in the brain atrophy and stress vulnerability of SAMP10 mice, which are prevented by the consumption of theanine, causing changes in the expression of these genes

Variations in cephalic vein venography for device implantation–Relationship to success rate of lead implantation

Introduction: Lead implantation using the cephalic vein (CV) cutdown technique has been well established, but is not always expected to achieve high success rates. We studied the relationship between preoperative CV venography and the success rate of lead implantation. Methods: Two hundred and twenty one CV venographies were performed in 205 patients (mean age 75 years, 113 males). Leads were inserted via the CV cutdown technique with a guidewire and sheath. Variations in CV venography included usage of the right and left CVs. The success rate of lead implantation was studied. Results: No major kink was observed in 71% of the right CV cases and 43% of the left CV cases. Leads were successfully implanted in over 90% of these patients. A major kink in the CV was found in 15% of the right CV cases and 34% of the left CV cases and successful lead implantation was around 80% in this population. The overall success rate tended to be higher for the right side (83%) than for the left side (71%). Conclusion: Severe kinks or variations in the CV that hinder lead manipulation were less frequent in the right CV. Therefore, a higher success rate of lead implantation by the cutdown technique is expected for the right CV