In Vivo Assessment of Astrocyte Reactivity in Patients with Progressive Supranuclear Palsy.

OBJECTIVE: Although astrocytic pathology is a pathological hallmark of progressive supranuclear palsy (PSP), its pathophysiological role remains unclear. This study aimed to assess astrocyte reactivity in vivo in patients with PSP. Furthermore, we investigated alterations in brain lactate levels and their relationship with astrocyte reactivity. METHODS: We included 30 patients with PSP-Richardson syndrome and 30 healthy controls; in patients, tau deposition was confirmed through 18F-florzolotau positron emission tomography. Myo-inositol, an astroglial marker, and lactate were quantified in the anterior cingulate cortex through magnetic resonance spectroscopy. We measured plasma biomarkers, including glial fibrillary acidic protein as another astrocytic marker. The anterior cingulate cortex was histologically assessed in postmortem samples of another 3 patients with PSP with comparable disease durations. RESULTS: The levels of myo-inositol and plasma glial fibrillary acidic protein were significantly higher in patients than those in healthy controls (p < 0.05); these increases were significantly associated with PSP rating scale and cognitive function scores (p < 0.05). The lactate level was high in patients, and correlated significantly with high myo-inositol levels. Histological analysis of the anterior cingulate cortex in patients revealed reactive astrocytes, despite mild tau deposition, and no marked synaptic loss. INTERPRETATION: We discovered high levels of astrocyte biomarkers in patients with PSP, suggesting astrocyte reactivity. The association between myo-inositol and lactate levels suggests a link between reactive astrocytes and brain energy metabolism changes. Our results indicate that astrocyte reactivity in the anterior cingulate cortex precedes pronounced tau pathology and neurodegenerative processes in that region, and affects brain function in PSP. ANN NEUROL 2024.

Assessment of Protein Content and Phosphorylation Level in Synechocystis sp. PCC 6803 under Various Growth Conditions Using Quantitative Phosphoproteomic Analysis.

The photosynthetic apparatus and metabolic enzymes of cyanobacteria are subject to various controls, such as transcriptional regulation and post-translational modifications, to ensure that the entire cellular system functions optimally. In particular, phosphorylation plays key roles in many cellular controls such as enzyme activity, signal transduction, and photosynthetic apparatus restructuring. Therefore, elucidating the governing functions of phosphorylation is crucial to understanding the regulatory mechanisms underlying metabolism and photosynthesis. In this study, we determined protein content and phosphorylation levels to reveal the regulation of intracellular metabolism and photosynthesis in Synechocystis sp. PCC 6803; for this, we obtained quantitative data of proteins and their phosphorylated forms involved in photosynthesis and metabolism under various growth conditions (photoautotrophic, mixotrophic, heterotrophic, dark, and nitrogen-deprived conditions) using targeted proteomic and phosphoproteomic analyses with nano-liquid chromatography-triple quadrupole mass spectrometry. The results indicated that in addition to the regulation of protein expression, the regulation of phosphorylation levels of cyanobacterial photosynthetic apparatus and metabolic enzymes was pivotal for adapting to changing environmental conditions. Furthermore, reduced protein levels of CpcC and altered phosphorylation levels of CpcB, ApcA, OCP, and PsbV contributed to the cellular response of the photosynthesis apparatus to nitrogen deficiency.

[Ranking assessment of the General Health Questionnaire using Latent Rank Theory].

The latent rank structure of the General Health Questionnaire (GHQ) was examined and a methodology for "ranking assessment" for use in clinical screening was suggested. Clinical screening is conducted by using dichotomous methods, which is problematic. Recent research has introduced the concept of ranking assessment, which is conducted by dividing clients into ordinal groups according to the Latent Rank Theory (LRT). Participants (N = 949, including 80 neurotic patients) completed the GHQ. They were then divided into four ordinal groups according to LRT. The usual cut-off point of the GHQ (16/17 points) distinguished the third and fourth rank group as the clinical group and the first-rank group as the healthy group. However, the second rank group was classified as neither a healthy or clinical group. These results indicate that the LRT has the potential to facilitate practical and flexible clinical screening.

The medial hypothalamus is required for the feeding response to glucoprivation but not to food deprivation.

While the hypothalamus has been implicated in the regulation of energy balance, the central mechanisms and neural circuit that coordinate the feeding response to energy deficit have not been fully clarified. To better understand the role of the hypothalamus in mediating hyperphagic responses to food deprivation or glucoprivation, we examined the feeding responses in rats in which the medial hypothalamus (MH) was isolated from the rest of the brain. The isolation of the MH was performed with a Halasz's knife cut, and experiments were performed 7 days after the operation. Food consumption between 9:00 a.m. and 11:00 a.m. in rats which had been fasted overnight was significantly increased compared to that in rats which had access to food ad libitum before the measurement in both the sham and MH-isolated groups, and the absolute values of food consumption in fasted rats were not significantly different between the groups. On the other hand, while an injection of 2-deoxy-d-glucose, which blocks glucose utilization, significantly increased food consumption for 2h after injection compared to a saline injection in the sham group, it did not increase food intake compared to saline injection in the MH-isolated groups. Thus, it is demonstrated that glucoprivation is not an effective stimulus to induce feeding in MH-isolated rats.

What factors are affecting physician payment by acute care hospitals in rural Japan?

The regional discrepancies of physician supply have been a growing concern in Japan. To find out how hospitals are responding in terms of physician payment (by monthly salaries and additional benefits), we conducted a survey of acute care hospitals in Yamagata, Japan. We asked about the salary and additional benefits of full-time physicians and the structural and functional characteristics of health care service provision. From these data we set out to assemble a model that can explain effectively the variability of physician payment in acute care hospitals within the prefecture. We found that physician payment was associated with variables such as type of management, staff employed per bed, full time doctors employed per bed and average length of stay. Hospital location was found to have a significant effect on payment. Variables expressing workload, like number of in-patients per doctor and number of surgical operations per doctor were inversely related. Our results suggest that hospitals may have adapted to physician preferences of workplace in terms of physician payment. To further address the problems of unbalanced geographic distribution of physicians in rural areas, work-sharing and educational and technical support schemes may also help.

Staging and assessment of lymph node involvement by 18F-fluorodeoxyglucose-positron emission tomography in invasive extramammary Paget's disease.

BACKGROUND: 18F-Fluorodeoxyglucose (FDG)-positron emission tomography (PET) is a functional and metabolic imaging modality that is efficacious in nodal staging and detection of extranodal involvement for malignant tumors. OBJECTIVE: We describe the novel use of PET for staging patients with invasive extramammary Paget's disease (EMPD) and discuss the potential advantages of this technology relative to other diagnostic modalities. METHODS: We evaluated three patients with invasive EMPD whose staging was made by PET at Hokkaido University Hospital. RESULTS: All lymph nodes detected by PET were over 10 mm. Distant internal metastases were not seen in all cases. PET failed to detect 10 and 5 to 7 mm nodal involvement but succeeded in detecting nodes over 10 mm. CONCLUSIONS: These data suggest that PET may be useful in determining disease activity at the time of initial diagnosis but is less useful and proves difficult to detect a small or subclinical involvement. This is the first report of PET being used for invasive EMPD.

Probability of failure of highly filled indirect resin-veneered implant-supported restorations: an in vitro study.

PURPOSE: The study compared the probability of failure of three highly filled resin-veneered restorations to that of conventional metal-ceramic restorations when used as implant-supported prostheses. The effect of the location of load application on the fracture resistance of the restorations was also studied. MATERIALS AND METHODS: Twenty samples each of the three resins, Artglass, Targis, and Estenia, were applied on type IV gold frameworks. Twenty metal-ceramic restorations of equal dimensions (VMK 95 and Degudent Universal) were used as controls. Compressive load was applied vertically at 1 mm (n = 10) and 2 mm (n = 10) from the periphery of the occlusal table until the restorations failed. Weibull analysis was applied to the data. RESULTS: There was no significant difference in the probability of failure among the metal-ceramic restorations and three resin-veneered restoration systems. Loading the resin-veneered restorations at the 1-mm location significantly increased their probability of failure when compared to the 2-mm loading location. The loading location did not significantly change the probability of failure of the metal-ceramic restorations. CONCLUSION: The probability of failure of resin-veneered restorations tested was not significantly different from that of the metal-ceramic restoration under two compressive loading conditions. Eccentric loading of resin-veneered restorations should be minimized in light of the higher probability of failure associated with such a loading condition.