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Ren Kawamura, Yukinori Harada, Masashi Yokose, Shogo Hanai, Yudai Suzuki, Taro Shimizu Department of Diagnostic and Generalist Medicine, Dokkyo Medical University Hospital, Mibu, Tochigi, JapanCorrespondence: Taro Shimizu, Department of Diagnostic and Generalist Medicine, Dokkyo Medical University Hospital, 880 Kitakobayashi, Shimotsuga, Mibu, Tochigi, 321-0293, Japan, Tel +8128286-1111, Email shimizutaro7@gmail.comPurpose: The general internal medicine (GIM) department can be an effective diagnostic coordinator for undiagnosed outpatients. We investigated the contribution of GIM consultations to the diagnosis of patients admitted to specialty departments in hospitals in Japan that have not yet adopted a hospitalist system.Patients and Methods: This single-center, retrospective observational study was conducted at a university hospital in Japan. GIM consultations from other departments on inpatients aged ≥ 20 years, from April 2016 to March 2021, were included. Data were extracted from electronic medical records, and consultation purposes were categorized into diagnosis, treatment, and diagnosis and treatment. The primary outcome was new diagnosis during hospitalization for patients with consultation purpose of diagnosis or diagnosis and treatment. The secondary outcomes were the purposes of consultation with the Diagnostic and Generalist Medicine department.Results: In total, 342 patients were included in the analysis. The purpose of the consultations was diagnosis for 253 patients (74%), treatment for 60 (17.5%), and diagnosis and treatment for 29 patients (8.5%). In 282 consultations for diagnosis and diagnosis and treatment, 179 new diagnoses were established for 162 patients (57.5%, 95% confidence interval [CI], 51.5– 63.3).Conclusion: The GIM department can function as a diagnostic consultant for inpatients with diagnostic problems admitted to other specialty departments in hospitals where hospitalist or other similar systems are not adopted.Keywords: diagnosis, diagnostic excellence, consultation, consultative medicine, hospital admission

Ryosuke Kawamura1,2, Hidenao Ideta1, Hideyuki Hori1, Kenya Yuki2, Tsuyoshi Uno1, Tatsurou Tanabe1, Kazuo Tsubota2, Tsutomu Kawasaki11Ideta Eye Hospital, Kumamoto, Japan; 2Keio University, School of Medicine, Department of Ophthalmology, Tokyo, JapanBackground: Central serous chorioretinopathy (CSC) has been traditionally treated with laser photocoagulation. We thought that transpupillary thermotherapy (TTT) utilizing a lower temperature than that of conventional laser photocoagulation might minimize permanent retinal and choroidal damage. Studies suggest that undesirable effects on vision due to TTT are minimal even if it is applied to foveal and/or parafoveal lesions when TTT requires a larger irradiation spot. The aim of this study was to evaluate the efficacy of TTT in the management of atypical CSC.Methods: We defined atypical CSC as bullous retinal detachment with diffuse or several leakages, severe leakage with fibrin formation under serous retinal detachment, or leakage within a pigment epithelium detachment. Eight consecutive patients with atypical CSC underwent visual acuity testing, ophthalmic examination, color photography, fluorescein angiography, and optical coherence tomography to evaluate the results of transpupillary thermotherapy. Retreatment of atypical CSC was based on ophthalmic examination, optical coherence tomography, and fluorescein angiography. TTT was performed on the leaking spots shown in fluorescein angiography, with a power of 50–250 mW, spot size of 500–1200 µm, and exposure time of 13–60 seconds to minimize retinal damage.Results: In five of eight affected eyes, serous detachments completely resolved within 1 month after the initial TTT. One eye had persistent subretinal fluid and required a second TTT treatment. Two eyes showed no resolution of CSC and were treated by conventional photocoagulation. Initial best-corrected visual acuity (BCVA) ranged from 20/600 to 20/20 (mean, 20/40; median, 20/30). Final BCVA ranged from 20/200 to 20/20 (mean, 20/25; median, 20/20). BCVA improved in all cases. Only two eyes with persistent subretinal fibrin and existing retinal pigment epithelial alternations in macular area showed limited improvement of BCVA despite the absence of subretinal exudation. The presence of retinal attachment was confirmed by optical coherence tomography in six eyes (75%).Conclusions: TTT seems to be effective for the treatment of atypical CSC in the short term. Additional studies are necessary to evaluate the long-term effectiveness and safety.Keywords: transpupillary thermotherapy, central serous chorioretinopathy, optical coherence tomography, fluorescein angiography, serous detachment

In most terrestrial environments, our knowledge of the elemental composition and stoichiometry of microorganisms stems from indirect whole community analyses. In contrast, we have little direct knowledge of the elemental composition of specific microorganisms and the variation between and within Fungi and Bacteria. To address this issue, we isolated and identified the elemental content of 87 strains of Fungi and Bacteria isolated from grassland leaf litter. The isolated strains were affiliated with a broad range of diversity including Ascomycota and Basidiomycota for Fungi, and Proteobacteria, Bacteroidetes, and Actinobacteria for Bacteria. The C:P and C:N but not N:P ratios were significantly higher in Fungi than in Bacteria. Extensive strain variation in elemental composition was partly linked to phylogeny and growth rate. Across all strains, the geometric mean C:N:P was 88:15:1. This overall ratio was significantly higher than reported for other leaf litter and terrestrial whole communities but closer to the canonical Redfield ratio characterizing marine microorganisms. This result warrants further investigation into the discrepancy between whole community and isolated strain elemental ratios. © 2014 Elsevier Ltd.

Background: The field of structural dynamics of cytoskeletons in living cells is gathering wide interest, since better understanding of cytoskeleton intracellular organization will provide us with not only insights into basic cell biology but may also enable development of new strategies in regenerative medicine and cancer therapy, fields in which cytoskeleton-dependent dynamics play a pivotal role. The nanoneedle technology is a powerful tool allowing for intracellular investigations, as it can be directly inserted into live cells by penetrating through the plasma membrane causing minimal damage to cells, under the precise manipulation using atomic force microscope. Modifications of the nanoneedles using antibodies have allowed for accurate mechanical detection of various cytoskeletal components, including actin, microtubules and intermediate filaments. However, successful penetration of the nanoneedle through the plasma membrane has been shown to vary greatly between different cell types and conditions. In an effort to overcome this problem and improve the success rate of nanoneedle insertion into the live cells, we have focused here on the fluidity of the membrane lipid bilayer, which may hinder nanoneedle penetration into the cytosolic environment. Results: We aimed to reduce apparent fluidity of the membrane by either increasing the approach velocity or reducing experimental temperatures. Although changes in approach velocity did not have much effect, lowering the temperature was found to greatly improve the detection of unbinding forces, suggesting that alteration in the plasma membrane fluidity led to increase in nanoneedle penetration. Conclusions: Operation at a lower temperature of 4 °C greatly improved the success rate of nanoneedle insertion to live cells at an optimized approach velocity, while it did not affect the binding of antibodies immobilized on the nanoneedle to vimentins for mechanical detection. As these experimental parameters can be applied to various cell types, these results may improve the versatility of the nanoneedle technology to other cell lines and platforms. [ABSTRACT FROM AUTHOR]

Introduction: The release of trophic factors from mesenchymal stem cells (MSCs) is critical for tissue regeneration. A systematic investigation of the regenerative potential of trophic factors from different MSCs, however, has not been performed. Thus, in the present study, the regenerative potential of conditioned medium (CM) from dental pulp, bone marrow, and adipose tissue-derived CD31- side population (SP) cells from an individual source was compared in an ectopic tooth transplantation model. Methods: The tooth root transplantation in an ectopic site model was used for investigation of the regenerative potential and trophic effects in vivo. Either pulp CD31- SP cell populations (1×106 cells) at the third to fourth passage or 5 µg/ml of CM from dental pulp, bone marrow, and adipose stem cells from four different individuals were injected into the root with collagen TE. Each root was transplanted subcutaneously in 5-week-old severe combined immunodeficiency mice. Each root with surrounding tissue was harvested for histology on days 7, 21, and 28 and for Western blot analysis and real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis on day 28. Furthermore, the trophic factors responsible for the regenerative potential were identified as the upregulated genes present in pulp CD31- SP cells when compared with the genes in both bone marrow and adipose CD31- SP cells by using microarray analysis, real-time RT-PCR, and Western blot analysis. Results: Transplantation of pulp CM yielded increased volume of pulp regeneration, more bromodeoxyuridine (BrdU)-positive migrated cells, and fewer caspase 3-positive cells in the regenerated pulp compared with the others. Pulp CM also demonstrated significantly increased cell migration, anti-apoptosis, and angiogenesis in C2C12 cells. Higher expression of CXCL14 and MCP1 in pulp SP cells suggested candidate trophic factors. The stimulatory effects on both migration and angiogenesis of CXCL14 and MCP1 were demonstrated in vitro. In the regenerated tissue, BrdU-positive migrated cells expressed CXCR4 and CCR2, receptors for CXCL14 and MCP1, respectively. Conclusions: The higher regenerative potential of pulp SP cells may be due to potent trophic factors, including CXCL14 and MCP1, which promote migration and angiogenesis. [ABSTRACT FROM AUTHOR]

Histone deacetylase (HDAC) inhibitors modify transcription of selected genes and eventually induce apoptosis. However, molecular mechanisms for their proapoptotic activity remain unclear. We here demonstrate that HDAC inhibitors FK228 and CBHA preferentially upregulated the BH3-only protein Bmf in a broad range of cancer cells. In contrast, HDAC1 overexpression distinctly reduced Bmf expression. FK228 induced histones H3 and H4 acetylation at Bmf promoter region, but not at its 3′ region, suggesting that histone hyperacetylation causes Bmf transcriptional activation. Knockdown of Bmf transcripts rescued cells from FK228 or CBHA-induced cell death, disruption of mitochondrial membrane potential (ΔΨm) and DNA fragmentation. Taken together, FK228 and CBHA activate Bmf transcription by histone hyperacetylation at its promoter region, and inhibition of this action decreased their proapoptotic activity, thereby highlighting a central role of Bmf in HDAC inhibitor-mediated apoptosis.Cell Death and Differentiation (2006) 13, 129–140. doi:10.1038/sj.cdd.4401686; published online 10 June 2005 [ABSTRACT FROM AUTHOR]

The aim of the present study was to assess the effects of the face-down position on ventilatory function after macular hole surgery. The transcutaneous carbon dioxide tensions (tcPCO2) were measured in five patients who had undergone intraocular tamponade and in 17 normal subjects. The tcPCO2 measurements were done in patients following vitrectomy in the sitting position and in the prone position with their faces down over the semi-closed spaces of the conventional mats. In normal subjects, minute ventilatory volumes (V.E) were measured simultaneously with tcPCO2 in the sitting position and prone position. The newly introduced face-down mats (new mats) for the prone position were also tested in the normal subjects. In normal subjects, VE in the prone position with the conventional mats was significantly lower than that found in the sitting position (5.06 +/- 1.55 vs 6.06 +/- 1.64 L/min; P < 0.002). The tcPCO2 in the prone position was significantly higher than that in the sitting position (41.7 +/- 2.1 vs 38.0 +/- 1.9 mmHg; P < 0.0001). In post-vitrectomy patients, tcPCO2 in the prone position with the conventional mats was significantly higher than that in the sitting position (41.4 +/- 1.7 vs 38.6 +/- 2.2 mmHg; P < 0.02). The tcPCO2 in the prone position in normal subjects was significantly lower using new mats than that when using conventional mats. The use of conventional mats during a prone position, increased the tcPCO2 values when compared to the tcPCO2 values obtained during the sitting position in patients following vitrectomy. This could be due to either a decrease of the VE caused by limited thoracic movement or rebreathing of the exhaled gas over the semi-closed space, or both. The new mats might be useful in alleviating the increase of tcPCO2 by eliminating the rebreathing of the exhaled gas. [ABSTRACT FROM AUTHOR]

Objectives: Vocal cord abductor paralysis (VCAP) is a life threatening complication which may cause nocturnal sudden death in patients with multiple system atrophy. However, the early diagnosis of VCAP is often difficult to make on routine laryngoscopy performed during wakefulness, as stridor, which is the sole symptom of VCAP in the early stage, develops only during sleep. The aim was to investigate laryngeal dysfunction in patients with multiple system atrophy while awake and asleep.Methods: Seven patients with multiple system atrophy with nocturnal stridor and five control patients were studied. Vocal cord movement was analysed by laryngoscopy while the patients were awake and also during sleep induced by intravenous diazepam.Results: When awake, for the seven patients with multiple system atrophy normal movement of the vocal cords occurred in three, mild abduction restriction in three, and paradoxical movement in one. When asleep, however, all showed obvious paradoxical movement with high pitched inspiratory stridor. In controls, there were no differences in the vocal cord movement between wakefulness and sleep. From these findings, VCAP could be divided into four stages: stage 0 (normal) with normal vocal cord movement during both wakefulness and sleep, stage 1 (mild VCAP) with normal movement during wakefulness and paradoxical movement during sleep, stage 2 (moderately severe VCAP) with abduction restriction during wakefulness and paradoxical movement during sleep, and stage 3 (severe VCAP) with an almost midline position for the vocal cords during both wakefulness and sleep.Conclusions: Laryngoscopy during sleep can disclose subclinical VCAP, making an early diagnosis of VCAP in patients with multiple system atrophy. Stage 2 of VCAP seems to be a suitable stage for tracheostomy in patients with multiple system atrophy. [ABSTRACT FROM AUTHOR]

Abstract Background Resistin, secreted from adipocytes, causes insulin resistance in mice. The relationship between resistin and coronary artery disease is highly controversial, and the information regarding resistin and ischemic stroke is limited. In the present study, the association between serum resistin concentration and cardiovascular disease (CVD) was investigated in a general Japanese population. Methods A total of 3,201 community-dwelling individuals aged 40 years or older (1,382 men and 1,819 women) were divided into quintiles of serum resistin, and the association between resistin and CVD was examined cross-sectionally. The combined effect of either diabetes or hypertension and high serum resistin was also assessed. Serum resistin was measured using ELISA. Results Compared to those without CVD, age- and sex-adjusted mean serum resistin concentrations were greater in subjects with CVD (p = 0.002) or ischemic stroke (p < 0.001), especially in those with lacunar and atherothrombotic infarction, but not elevated in subjects with hemorrhagic stroke or coronary heart disease. When analyzed by quintile of serum resistin concentration, the age- and sex-adjusted odds ratio (OR) for having CVD and ischemic stroke increased with quintile of serum resistin (p for trends, 0.02 for CVD, < 0.001 for ischemic stroke), while such associations were not observed for hemorrhagic stroke or coronary heart disease. Compared to the first quintile, the age- and sex-adjusted OR of ischemic stroke was greater in the third (OR = 3.54; 95% confidence interval [CI], 1.17-10.67; p = 0.02), fourth (OR = 4.48; 95% CI, 1.53-13.09; p = 0.006), and fifth quintiles (OR = 4.70; 95% CI, 1.62-13.61; p = 0.004). These associations remained substantially unchanged even after adjustment for other confounding factors including high-sensitivity C-reactive protein. In the stratified analysis, the combination of high serum resistin and either diabetes or hypertension markedly increased the risk of ischemic stroke. Conclusion Elevated serum resistin concentration appears to be an independent risk factor for ischemic stroke, especially lacunar and atherothrombotic infarction in the general Japanese population. The combination of high resistin and the presence of either diabetes or hypertension increased the risk of ischemic stroke.

Aims/hypothesis: Resistin, inducing insulin resistance, is elevated in the sera of individuals with the G-A haplotype at c.-420 C>G (rs1862513) and c.-358 G>A (rs3219175). This haplotype is associated with visceral obesity and low grip strength. To elucidate the hidden relationship between the G-A haplotype and insulin resistance, integration of specific phenotypes defined by body composition and 75 g OGTT would be a promising strategy., Methods: The 803 Japanese participants (average age: 62 years), attending annual medical checkups, were evaluated every 5 years. Participants were categorised by skeletal muscle mass, visceral fat score and OGTT results. Hierarchical clustering was performed using body composition and glucose metabolism parameters. Whole blood cells from participants homozygous for the G-A or C-G haplotype (n=25 and 33, respectively), matched for age, sex and BMI, using propensity score matching, were used for RNA-seq, pathway analysis and RT-PCR., Results: Multivariate analysis showed that individuals with the G-A haplotype, when accompanied by latent skeletal muscle loss and visceral obesity (latent sarcopenic obesity), presented a pronounced deterioration in insulin resistance over a 5 year period. Cluster 2, identified using hierarchical clustering, was characterised by low skeletal muscle mass, visceral obesity and insulin resistance. This cluster, with the G-A haplotype, demonstrated deterioration in insulin resistance. RNA-seq and RT-PCR revealed altered expression of mitophagy-related genes in whole blood cells of the G-A homozygotes., Conclusions/interpretation: The G-A haplotype, accompanied by latent low skeletal muscle mass and visceral obesity, led to the deterioration of insulin resistance over a 5 year period in this cohort, possibly through the altered expression of mitophagy-related genes., Competing Interests: Acknowledgements: The authors wish to thank all of the members of the Department of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, for their critical discussions. We are also grateful to staff of the Toon Genome Study, especially A Otaki, R Kagawa and M Sano, for supporting the medical checkups, and for technical assistance in this study. Data availability: Raw data were generated at Ehime University. Derived data supporting the findings of this study may be available from the corresponding author on reasonable request. Funding: This work was supported by grants from Ehime University, Takeshi Ikeda, JSPS KAKENHI (23K14738), the Japan Association for Diabetes Education and Care (Z22-100105) and the Clinical Research Promotion Foundation 2023 (Z23-100084). Authors’ relationships and activities: The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: All authors confirm that they meet the uniform requirements of the International Committee of Medical Journal Editors for authorship. YI, RK, YTak and HO designed the experiments. YI, RK, YTab, KM, MT, TH, YTak and IS collected data. YI, RK, DS, JO and YO analysed the data. YI, RK and HO wrote the first draft of the manuscript. All authors edited, reviewed and approved the final version of the manuscript. All of the authors are responsible for the integrity of the work as a whole. YI, RK and HO accept full responsibility for the work and/or the conduct of the study, had access to the data and controlled the decision to publish., (© 2024. The Author(s).)

We developed an advanced optical microscope for the simultaneous visualization of membrane fluidity and morphology to define cell adhesion signatures. This microscope combines ratiometric spectral imaging of membrane fluidity and interferometric imaging of membrane morphology. As a preliminary demonstration, we simultaneously visualized the interface between a giant unilamellar vesicle (GUV) and a glass substrate at different temperatures. We identified more fluid regions of the membrane and membrane adhesion sites (conversely, low-fluidic, ordered membrane domains correlate with nonadhered regions). This microscopic system was applied to human breast cancer cell lines with different malignancies; then, we identified adhesion signature of cancer cells: 1) low-fluidic, ordered membrane domains at the cell periphery and 2) large fluidic deviation at the nonadhered region. Inhibition of the cholesterol synthesis pathway suppresses the ordered membrane domains at the cancer cell periphery; thus, high level of cholesterol supports the appearance. Furthermore, an inhibitor of the unsaturated lipid synthesis pathway suppressed the large fluidic deviation at the nonadhered region; variation of unsaturated lipids contributes to heterogeneity of the cancer membrane. Therefore, our advanced optical microscopy enables us to couple membrane physical properties with cell adhesion, leading to definition of adhesion signatures of broad cell types, not just for cancer cells, that regulate life phenomena., Competing Interests: Competing interests statement:The authors declare no competing interest.

Spindles are essential for accurate chromosome segregation in all eukaryotic cells. This study presents a novel approach for isolating fresh mammalian spindles from mouse oocytes, establishing it as a valuable in vitro model system for a wide range of possible studies. Our method enables the investigation of the physical properties and migration force of meiotic spindles in oocytes. We found that the spindle length decreases upon isolation from the oocyte. Combining this observation with direct measurements of spindle mechanics, we examined the forces governing spindle migration during oocyte asymmetric division. Our findings suggest that the spindle migration is regulated by a pulling force and a net tensile force of approximately 680 pN is applied to the spindle in vivo during the migration process. This method, unveiling insights into spindle dynamics, holds promise as a robust model for future investigations into spindle formation and chromosome separation. We also found that the same approach could not isolate spindles from somatic cells, indicative of mammalian oocytes having a unique spindle organization amenable to isolation., Competing Interests: Disclosures: The authors declare no competing interests exist.

Competing Interests: The authors declare that they have no conflict of interest.