Nonmotor Symptoms in Patients with PARK2 Mutations

Decreased 123I-meta-iodobenzylguanidine (MIBG) uptake in MIBG myocardial scintigraphy, olfactory dysfunction, and rapid eye movement (REM) sleep behavior disorder (RBD) are considered useful early indicators of Parkinson disease. We investigated whether patients with PARK2 mutations exhibited myocardial sympathetic abnormalities using MIBG scintigraphy, olfactory dysfunction using the Sniffin' Sticks olfactory test, and RBD using polysomnography. None of the examined patients had RBD, and all except 1 patient exhibited an increase in the olfactory threshold. Moreover, one of the oldest patients exhibited impairment in identification and discrimination. Of 12 patients with PARK2 mutations, 4 patients, who were older than patients without abnormal uptake, exhibited decreased MIBG uptake. The results obtained in this study suggest that some patients with PARK2 mutations have increased thresholds of olfactory function and myocardial sympathetic dysfunction as nonmotor symptoms

Fungal pyrrolidine-containing metabolites inhibit alkaline phosphatase activity in bone morphogenetic protein-stimulated myoblastoma cells

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant congenital disorder characterized by progressive heterotopic ossification in muscle tissues. A constitutively activated mutation of a bone morphogenetic protein (BMP) receptor, ALK2, has been identified in patients with FOP. We report here that four structurally related compounds, lucilactaene, hydroxylucilactaene, NG-391 and NG-393, produced by fungal strain Fusarium sp. B88, inhibit BMP signaling in vitro. Alkaline phosphatase activity, a marker enzyme of osteoblastic differentiation, was decreased in C2C12 myoblasts stably expressing mutant ALK2 by treatment with those compounds with IC50 values of 5.7, 6.8, 6.9 and 6.1 μM, respectively. Furthermore, NG-391 and NG-393 inhibited BMP-specific luciferase reporter activity, which is directly regulated by transcription factor Smads, with IC50 values of 1.4 and 2.1 μM, respectively. These findings suggest that these fungal metabolites may provide a new direction in the development of FOP therapeutics

Feasibility of management of hemodynamically stable patients with acute myocardial infarction following primary percutaneous coronary intervention in the general ward settings.

BackgroundAlthough current guidelines recommend admission to the intensive/coronary care unit (ICU/CCU) for patients with ST-segment elevation myocardial infarction (MI), routine use of the CCU in uncomplicated patients with acute MI remains controversial. We aimed to evaluate the safety of management in the general ward (GW) of hemodynamically stable patients with acute MI after primary percutaneous coronary intervention (PCI).MethodsUsing a large nationwide administrative database, a cohort of 19426 patients diagnosed with acute MI in 52 hospitals where a CCU was available were retrospectively analyzed. Patients with mechanical cardiac support and Killip classification 4, and those without primary PCI on admission were excluded. A total of 5736 patients were included and divided into the CCU (n = 3488) and GW (n = 2248) groups according to the type of hospitalization room after primary PCI. Propensity score matching was performed, and 1644 pairs were matched. The primary endpoint was in-hospital mortality at 30 days.ResultsThe CCU group had a higher rate of Killip classification 3 and ambulance use than the GW group. There was no significant difference in the incidence of in-hospital mortality within 30 days among the matched subjects. Multivariable Cox proportional hazard model analysis among unmatched patients supported the findings (hazard ratio 1.12, 95% confidence interval 0.66-1.91, p = 0.67).ConclusionsThe use of the GW was not associated with higher in-hospital mortality in hemodynamically stable patients with acute MI after primary PCI. It may be feasible for the selected patients to be directly admitted to the GW after primary PCI