Jeong‐Ho Lee

Abstract Variants of UNC13A , a critical gene for synapse function, increase the risk of amyotrophic lateral sclerosis and frontotemporal dementia 1–3 , two related neurodegenerative diseases defined by mislocalization of the RNA-binding protein TDP-43 4,5 . Here we show that TDP-43 depletion induces robust inclusion of a cryptic exon in UNC13A , resulting in nonsense-mediated decay and loss of UNC13A protein. Two common intronic UNC13A polymorphisms strongly associated with amyotrophic lateral sclerosis and frontotemporal dementia risk overlap with TDP-43 binding sites. These polymorphisms potentiate cryptic exon inclusion, both in cultured cells and in brains and spinal cords from patients with these conditions. Our findings, which demonstrate a genetic link between loss of nuclear TDP-43 function and disease, reveal the mechanism by which UNC13A variants exacerbate the effects of decreased TDP-43 function. They further provide a promising therapeutic target for TDP-43 proteinopathies.

A self-powered deep brain stimulation has been demonstrated by a flexible piezoelectric PIMNT energy harvester to induce behavioural changes in a mouse.

In this review, we describe the application of thermosensitive hydrogels composed of poloxamer in medicine, especially for oral cavities. Thermosensitive hydrogels remain fluid at room temperature; at body temperature, they become more viscous gels. In this manner, the gelling system can remain localized for considerable durations and control and prolong drug release. The chemical structure of the poloxamer triblock copolymer leads to an amphiphilic aqueous solution and an active surface. Moreover, the poloxamer can gel by forming micelles in an aqueous solution, depending on its critical micelle concentration and critical micelle temperature. Owing to its controlled-release effect, a thermosensitive gel based on poloxamer 407 (P407) is used to deliver drugs with different characteristics. As demonstrated in studies on poloxamer formulations, an increase in gelling viscosity decreases the drug release rate and gel dissolution time to the extent that it prolongs the drug's duration of action in disease treatment. This property is used for drug delivery and different therapeutic applications. Its unique route of administration, for many oral diseases, is advantageous over traditional routes of administration, such as direct application and systemic treatment. In conclusion, thermosensitive gels based on poloxamers are suitable and have great potential for oral disease treatment.

BACKGROUND: An aplastic or twiglike middle cerebral artery (Ap/T-MCA) is an extremely rare congenital anomaly related to interference in the normal embryonic development of the MCA. OBJECTIVE: To evaluate the clinical and radiological features of patients with an Ap/T-MCA. METHODS: A total of 1749 conventional cerebral angiography procedures were performed in 1282 patients from January 2005 to July 2011 at Daegu Fatima Hospital. The images were evaluated for cerebral arterial anomalies. The radiological features of an Ap/T-MCA, coexisting anomalies, and clinical manifestations were recorded. These prospectively maintained databases were analyzed retrospectively. RESULTS: Ap/T-MCAs were found in 15 patients (1.17% angiographic incidence). The anomalies were confined to unilateral M1 segment, and no stenoses were seen in the adjacent major arteries. Of 15 patients, 6 (40%) had hemorrhagic strokes, 5 (33.3%) had ischemic strokes, and 4 (26.7%) had no symptoms. Aneurysms were found in 5 patients (33.3%). Coexisting cerebral arterial anomalies were seen in 12 patients (80%). Ten patients underwent conservative treatments, and the remaining 5 underwent surgical treatments, such as hematoma aspiration, indirect revascularization, and clipping or coiling of aneurysms. CONCLUSION: An Ap/T-MCA is a rare anomaly and should be differentiated from moyamoya conditions and degenerative steno-occlusive diseases of the middle cerebral artery. Coexisting anomalies of the anterior or middle cerebral arteries are frequent. This anomaly is vulnerable to both hemorrhagic and ischemic strokes.

The number of diabetic patients worldwide is increasing, and complications such as stroke and cardiovascular disease are becoming a serious cause of death. Diabetes mellitus is classified into two types according to the etiopathogenic mechanism and insulin dependence. Type 1 diabetes (T1D), an insulin-dependent diabetes mellitus, is caused by damage and destruction of pancreatic β cells that produce insulin. It is a disease that is characterized by hyperglycemia and hypoinsulinemia. Aronia berry has been used as a medicinal food in Europe. Aronia contains a variety of ingredients such as polyphenols, anthocyanins, flavonoids, and tannins. Especially, anthocyanin content in aronia berry is known to be much higher than in other plants and berries. It is known for exerting antioxidant, anti-inflammation, and anti-aging effects. Therefore, this study was conducted to investigate the effects of aronia berry extract intake in multiple low-dose streptozotocin (STZ)-induced T1D and to confirm the functional properties of aronia berry. ICR mice (6-week male) were divided into four groups: control (normal control group), STZ (100 mg/kg of STZ-induced T1D group), AR 10 (STZ with oral administration of aronia 10 mg/kg), and AR 100 (STZ with oral administration of aronia 100 mg/kg). Afterward, STZ was injected in a single dose to induce T1D, and the extract was orally administered daily. Dietary intake and body weight were measured twice a week. We confirmed that aronia berry has the effect of decreasing the increase of blood glucose level and also has the protection effect of pancreas β cell (RINm5F cell). This study confirms the anti-diabetic activity of aronia berry, and it can be expected to increase the utilization according to the results.