Gender-Dependent Characteristics of Serum 1,25-Dihydroxyvitamin D/25-Hydroxyvitamin D Ratio for the Assessment of Bone Metabolism

Y Objectives Vitamin D deficiency, which is common worldwide, increases the risks of falls and fractures and can lead to increased morbidity and mortality. However, the clinical utility and relevance of vitamin D activation remain unknown. The aim of the present study was to clarify the clinical usefulness of serum 1,25-dihydroxyvitamin D (1,25D)/25-hydroxyvitamin D (25D) ratio for assessment of the extent of bone metabolism. Methods We retrospectively screened data for 87 patients whose serum 1,25D and 25D levels were measured. Eight patients who were taking vitamin D preparations were excluded, and data for 79 patients (33 males and 46 females) were analyzed. Since menopausal status can be associated with serum vitamin D level, we divided the patients by gender and divided the female patients into two groups at the age of 50 years. Results The median serum 1,25D/25D ratio was significantly lower in males than in females, with the most considerable difference in all males [4.1 (interquartile range: 2.3-5.8) x 10(-3)] versus elderly females (aged >= 50 years) [7.9 (3.3-10.1) x 10(-3)). Main disorders were endocrine (30.6%), inflammatory (18.5%), and bone related (16.7%) disorders. The ratios of serum 1,25D/25D had significant negative correlations with femoral dual-energy X-ray absorptiometry % young adult mean (DEXA %YAM) (R=-0.35) and lumbar DEXA %YAM (R=-0.32). Significant correlations were found between the 1,25D/25D ratio and serum levels of inorganic phosphate (iP), parathyroid hormone, and alkaline phosphatase (ALP). The 1,25D/25D ratio had gender specific characteristics: the ratio was significantly correlated with age in males (R=-0.49), while it was significantly correlated with BMI in females (R=0.34). Conclusions The results of this study suggested that vitamin D activity is negatively correlated with bone mineral density, being reduced in aged males but enhanced in obese females

Characteristics of Persistent Symptoms Manifested after SARS-CoV-2 Vaccination: An Observational Retrospective Study in a Specialized Clinic for Vaccination-Related Adverse Events

Background: Although many adverse reactions after SARS-CoV-2 vaccination have been reported, there have been few comprehensive studies on persistent symptoms after SARS-CoV-2 vaccination. The aim of this study was to determine the clinical characteristics of patients with various persistent symptoms after SARS-CoV-2 vaccination. Methods: A retrospective descriptive study was performed for patients who visited a specialized clinic established at Okayama University Hospital to evaluate adverse events after SARS-CoV-2 vaccination during the period from April 2021 to March 2023. Results: Descriptive analysis was performed for 121 of 127 patients who visited the clinic during the study period, and separate analysis was performed for the other 6 patients who had serious complications, who required treatment with prednisolone, and who had persistent symptoms. The median [interquartile range] age of the patients was 48 years [31-64 years], and the patients included 44 males (36.4%) and 77 females (63.6%). The most frequent symptoms were sensory impairment (34 patients, 28.1%), general fatigue (30 patients, 24.8%), fever/low-grade fever (21 patients, 17.4%), and headache (21 patients, 17.4%). Serious complications included myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), sarcoidosis, aseptic meningitis, neuromyelitis optica spectrum disorders (NMOSDs), tendon adhesions, and idiopathic thrombocytopenia. Conclusions: Although causal relationships were not determined, 15 persistent symptoms after SARS-CoV-2 vaccination were characterized. All of the symptoms had onset from 12 hours to one week after vaccination, with 10 symptoms persisting for 6 months or longer. The most frequent symptom was sensory impairment

Prestate of Stress and Fault Behavior During the 2016 Kumamoto Earthquake (M7.3)

Fault behavior during an earthquake is controlled by the state of stress on the fault. Complex coseismic fault slip on large earthquake faults has recently been observed by dense seismic networks, which complicates strong motion evaluations for potential faults. Here we show the three‐dimensional prestress field related to the 2016 Kumamoto earthquake. The estimated stress field reveals a spatially variable state of stress that forced the fault to slip in a direction predicted by the “Wallace and Bott Hypothesis.” The stress field also exposes the pre‐condition of pore fluid pressure on the fault. Large coseismic slip occurred in the low‐pressure part of the fault. However, areas with highly pressured fluid also showed large displacement, indicating that the seismic moment of the earthquake was magnified by fluid pressure. These prerupture data could contribute to improved seismic hazard evaluations

Safety of venipuncture sites at the cubital fossa as informed by ultrasonography

金沢大学医薬保健研究域保健学系Objective The aim of the present observational study was to identify safe and suitable venipuncture sites for nursing in the clinical setting using ultrasonography to measure the depth and cross-sectional area of each superficial vein before and after tourniquet application as well as the distance between each superficial vein and the median nerve or brachial artery.\nMethods and Results Twenty healthy volunteers (21.8 [0.6] y) were recruited. The visible rate of each superficial vein before and after tourniquet application was 65% for the basilic vein, 90% to 95% for the median cubital vein, and 65% to 80% for the cephalic vein. The cross-sectional area of the median cubital vein after tourniquet application was significantly larger than that of the basilic vein and cephalic vein. The distance between the basilic vein or median cubital vein and median nerve was significantly smaller than that between the cephalic vein and median nerve. The distance between the basilic vein or median cubital vein and brachial artery was significantly smaller than that between the cephalic vein and brachial artery.\nConclusions These results demonstrated that the cephalic vein at the cubital fossa is a relatively safe venipuncture site because of its distance from the median nerve and brachial artery. When puncturing the cephalic vein is difficult because it is not visible, the median cubital vein at the cubital fossa may be selected for venipuncture due to its cross-sectional area and visibility; however, care is needed to avoid penetrating the vein because the median nerve and brachial artery are located underneath

Seismicity controlled by resistivity structure : the 2016 Kumamoto earthquakes, Kyushu Island, Japan

The M JMA 7.3 Kumamoto earthquake that occurred at 1:25 JST on April 16, 2016, not only triggered aftershocks in the vicinity of the epicenter, but also triggered earthquakes that were 50–100 km away from the epicenter of the main shock. The active seismicity can be divided into three regions: (1) the vicinity of the main faults, (2) the northern region of Aso volcano (50 km northeast of the mainshock epicenter), and (3) the regions around three volcanoes, Yufu, Tsurumi, and Garan (100 km northeast of the mainshock epicenter). Notably, the zones between these regions are distinctively seismically inactive. The electric resistivity structure estimated from one-dimensional analysis of the 247 broadband (0.005–3000 s) magnetotelluric and telluric observation sites clearly shows that the earthquakes occurred in resistive regions adjacent to conductive zones or resistive-conductive transition zones. In contrast, seismicity is quite low in electrically conductive zones, which are interpreted as regions of connected fluids. We suggest that the series of the earthquakes was induced by a local accumulated stress and/or fluid supply from conductive zones. Because the relationship between the earthquakes and the resistivity structure is consistent with previous studies, seismic hazard assessment generally can be improved by taking into account the resistivity structure. Following on from the 2016 Kumamoto earthquake series, we suggest that there are two zones that have a relatively high potential of earthquake generation along the western extension of the MTL

FXYD3 functionally demarcates an ancestral breast cancer stem cell subpopulation with features of drug-tolerant persisters

乳がんの再発を起こす原因細胞を解明. 京都大学プレスリリース. 2023-11-16.The heterogeneity of cancer stem cells (CSCs) within tumors presents a challenge in therapeutic targeting. To decipher the cellular plasticity that fuels phenotypic heterogeneity, we undertook single-cell transcriptomics analysis in triple-negative breast cancer (TNBC) to identify subpopulations in CSCs. We found a subpopulation of CSCs with ancestral features that is marked by FXYD domain–containing ion transport regulator 3 (FXYD3), a component of the Na⁺/K⁺ pump. Accordingly, FXYD3⁺ CSCs evolve and proliferate, while displaying traits of alveolar progenitors that are normally induced during pregnancy. Clinically, FXYD3⁺ CSCs were persistent during neoadjuvant chemotherapy, hence linking them to drug-tolerant persisters (DTPs) and identifying them as crucial therapeutic targets. Importantly, FXYD3⁺ CSCs were sensitive to senolytic Na⁺/K⁺ pump inhibitors, such as cardiac glycosides. Together, our data indicate that FXYD3⁺ CSCs with ancestral features are drivers of plasticity and chemoresistance in TNBC. Targeting the Na⁺/K⁺ pump could be an effective strategy to eliminate CSCs with ancestral and DTP features that could improve TNBC prognosis

Prestate of Stress and Fault Behavior During the 2016 Kumamoto Earthquake (M7.3)

Fault behavior during an earthquake is controlled by the state of stress on the fault. Complex coseismic fault slip on large earthquake faults has recently been observed by dense seismic networks, which complicates strong motion evaluations for potential faults. Here we show the three‐dimensional prestress field related to the 2016 Kumamoto earthquake. The estimated stress field reveals a spatially variable state of stress that forced the fault to slip in a direction predicted by the “Wallace and Bott Hypothesis.” The stress field also exposes the pre‐condition of pore fluid pressure on the fault. Large coseismic slip occurred in the low‐pressure part of the fault. However, areas with highly pressured fluid also showed large displacement, indicating that the seismic moment of the earthquake was magnified by fluid pressure. These prerupture data could contribute to improved seismic hazard evaluations

Enhancement of Both Long-Term Depression Induction and Optokinetic Response Adaptation in Mice Lacking Delphilin

In the cerebellum, Delphilin is expressed selectively in Purkinje cells (PCs) and is localized exclusively at parallel fiber (PF) synapses, where it interacts with glutamate receptor (GluR) δ2 that is essential for long-term depression (LTD), motor learning and cerebellar wiring. Delphilin ablation exerted little effect on the synaptic localization of GluRδ2. There were no detectable abnormalities in cerebellar histology, PC cytology and PC synapse formation in contrast to GluRδ2 mutant mice. However, LTD induction was facilitated at PF-PC synapses in Delphilin mutant mice. Intracellular Ca2+ required for the induction of LTD appeared to be reduced in the mutant mice, while Ca2+ influx through voltage-gated Ca2+ channels and metabotropic GluR1-mediated slow synaptic response were similar between wild-type and mutant mice. We further showed that the gain-increase adaptation of the optokinetic response (OKR) was enhanced in the mutant mice. These findings are compatible with the idea that LTD induction at PF-PC synapses is a crucial rate-limiting step in OKR gain-increase adaptation, a simple form of motor learning. As exemplified in this study, enhancing synaptic plasticity at a specific synaptic site of a neural network is a useful approach to understanding the roles of multiple plasticity mechanisms at various cerebellar synapses in motor control and learning

Contribution of postsynaptic GluD2 to presynaptic R-type Ca(2+) channel function, glutamate release and long-term potentiation at parallel fiber to Purkinje cell synapses.

Glutamate-receptor-like molecule delta2 (GluD2) is selectively expressed on the postsynaptic membranes at parallel fiber to Purkinje cell (PF-PC) synapses in the cerebellum. GluD2 plays critical roles not only in postsynaptic long-term depression but also in the induction of presynaptic differentiation through trans-synaptic interaction with neurexin. However, how GluD2 influences the presynaptic function remains unknown. Here, effects of the deletion of postsynaptic GluD2 on the presynaptic properties were studied focusing on the paired pulse ratio (PPR) of two consecutive EPSC amplitudes, which was larger in GluD2 knockout mice. The PPR difference remained even if saturation of glutamate binding to postsynaptic receptors was suppressed, confirming the presynaptic difference between the genotypes. We then explored the possibility that presynaptic voltage-gated Ca(2+) channels (VGCCs) are affected in GluD2 knockout mice. Application of selective blockers for specific VGCCs indicated that R-type but not P/Q- or N-type VGCC, was affected in the mutant mice. Furthermore, presynaptic long-term potentiation (LTP) at PF-PC synapses, which requires R-type VGCC, was impaired in GluD2 knockout mice. These results suggest that GluD2 deletion impairs presynaptic R-type VGCC, resulting in decreased release of synaptic vesicles, and also in the impairment of presynaptic LTP at PF-PC synapses