Two-minute standing endurance test for axial postural abnormalities in patients with Parkinson's disease.

BACKGROUND: Photo-based measurement methods are used to assess axial postural abnormalities (PA) in Parkinson's disease (PD). However, they capture only moments in time. We developed the 2-minute standing endurance test (2 M-SET), which specifically captures temporal changes in posture, as a novel dynamic method for measuring axial PA in patients with PD. RESEARCH QUESTION: This study aimed to verify the effectiveness and validity of the 2 M-SET for capturing temporal changes in axial PA in patients with PD. METHODS: Twenty-eight patients with PD participated. The participants attempted to maintain an upright posture for 2 minutes during three tasks: standing, stepping in place, and walking. The rate of change in postural angle was recorded at 10-second intervals. Based on the results, the 2 M-SET was developed. Therapists evaluated the 2 M-SET using the NeuroPostureApp© to measure anterior trunk flexion (ATF) angles and lateral trunk flexion (LTF) angles at 0, 10, 30, 60, and 120 seconds. To assess reliability, the congruence between the measurements obtained by the therapists and those obtained using a three-dimensional motion-analysis system was examined. For validity, we assessed whether the ATF and LTF angles measured by the therapists could accurately capture postural changes at regular intervals over time. RESULTS: The average postural changes over 2 minutes for the standing, stepping in place, and gait tasks were 59.2±83.5%, 37.6±30.7%, and 45.4±50.6%, respectively. The intraclass correlation coefficients showed high reliability, with values of 0.985 and 0.970 for the ATF and LTF angles, respectively. SIGNIFICANCE: The results of our proposed 2 M-SET method, which uses temporal photo-based measurements to assess the patient's ability to maintain an upright standing position for 2 minutes, demonstrate the potential to capture temporal changes in axial PA. DATA AVAILABILITY STATEMENT: The data supporting the findings of this study are available upon reasonable request and approval from the local ethics committee.

Exacerbation of Epilepsy by Astrocyte Alkalization and Gap Junction Uncoupling.

Seizures invite seizures. At the initial stage of epilepsy, seizures intensify with each episode; however, the mechanisms underlying this exacerbation remain to be solved. Astrocytes have a strong control over neuronal excitability and the mode of information processing. This control is accomplished by adjusting the levels of various ions in the extracellular space. The network of astrocytes connected via gap junctions allows a wider or more confined distribution of these ions depending on the open probability of the gap junctions. K+ clearance relies on the K+ uptake by astrocytes and the subsequent diffusion of K+ through the astrocyte network. When astrocytes become uncoupled, K+ clearance becomes hindered. Accumulation of extracellular K+ leads to hyperexcitability of neurons. Here, using acute hippocampal slices from mice, we uncovered that brief periods of epileptiform activity result in gap junction uncoupling. In slices that experienced short-term epileptiform activity, extracellular K+ transients in response to glutamate became prolonged. Na+ imaging with a fluorescent indicator indicated that intercellular diffusion of small cations in the astrocytic syncytium via gap junctions became rapidly restricted after epileptiform activity. Using a transgenic mouse with astrocyte-specific expression of a pH sensor (Lck-E2GFP), we confirmed that astrocytes react to epileptiform activity with intracellular alkalization. Application of Na+/HCO3- cotransporter blocker led to the suppression of intracellular alkalization of astrocytes and to the prevention of astrocyte uncoupling and hyperactivity intensification both in vitro and in vivo Therefore, the inhibition of astrocyte alkalization could become a promising therapeutic strategy for countering epilepsy development.SIGNIFICANCE STATEMENT We aimed to understand the mechanisms underlying the plastic change of forebrain circuits associated with the intensification of epilepsy. Here, we demonstrate that first-time exposure to only brief periods of epileptiform activity results in acute disturbance of the intercellular astrocyte network formed by gap junctions in hippocampal tissue slices from mice. Moreover, rapid clearance of K+ from the extracellular space was impaired. Epileptiform activity activated inward Na+/HCO3- cotransport in astrocytes by cell depolarization, resulting in their alkalization. Our data suggest that alkaline pH shifts in astrocytes lead to gap junction uncoupling, hampering K+ clearance, and thereby to exacerbation of epilepsy. Pharmacological intervention could become a promising new strategy to dampen neuronal hyperexcitability and epileptogenesis.

Phylogeny of epilachna, henosepilachna, and some minor genera of phytophagous ladybird beetles (coleoptera: coccinellidae: coccinellinae: epilachnini), with an analysis of ancestral biogeography and host-plant utilization.

Ladybird beetles in the tribe Epilachnini include notorious crop pests and model species studied intensively in various fields of evolutionary biology. From a combined dataset of mitochondrial (ND2) and nuclear (28S) DNA sequences, we reconstructed the phylogeny of 46 species of Epilachnini from Asia, Africa, America, and the Australian region: 16 species in Epilachna, 24 species in Henosepilachna, and one species each in Adira, Afidenta, Afidentula, Afissula, Chnootriba, and Epiverta. In our phylogenetic trees, both Epilachna and Henosepilachna were reciprocally polyphyletic. Asian Epilachna species were monophyletic, except for the inclusion of Afissula sp. Asian and Australian Henosepilachna species likewise formed a monophyletic group, excluding H. boisduvali. African Epilachna and Henosepilachna species did not group with their respective Asian and American congeners, but were paraphyletic to other clades (Epilachna species) or formed a separate monophyletic group (Henosepilachna species) together with Chnootriba similis. The American Epilachna species were monophyletic and formed a clade with American Adira clarkii and Asian Afidentula manderstjernae bielawskii; this clade was the sister group to Asian and Australian Henosepilachna, but was distant from Asian Epilachna. Chnootriba was embedded in the African Henosepilachna clade, and Afissula in the Asian Epilachna clade. Epiverta, which is morphologically unique, was the sister group to Asian Epilachna, although with weak support. From reconstructions of biogeographical distribution and host-plant utilization at ancestral nodes, we inferred an African origin for the common ancestor of the species studied, and found the frequency of host shifts to differ greatly between the two major lineages of Epilachnini examined.