Communication between physicians, patients, their companions and other healthcare professionals in home medical care in Japan.

OBJECTIVE: To examine communication in home medical care. METHODS: Conversations that happened during home medical care involving physicians at nine clinics were recorded and analyzed using the Roter Interaction Analysis System (RIAS). Additional categories were developed to code aspects of home medical care. RESULTS: Overall, 55 conversations were analyzed. The mean age of the patients was 82.9 ± 10.1 years old. The most common triad was physician, patient, and patient's companion. Information about home medical care professionals who were not present during the conversation was provided by the physician in 21 cases (38.2%), the patient in nine cases (16.4%), and companions in 21 (39.6%) cases. CONCLUSION: In home medical care, the participants mentioned home medical care professions who were not present at the time, suggesting that these conversations may have facilitated interprofessional collaboration. PRACTICE IMPLICATIONS: Physicians should be aware that during home medical care, the presence of multiple attendants and other medical professionals contributing to communicate with the patient.

Key determinants for signaling in the sensory rhodopsin II/transducer complex are different between Halobacterium salinarum and Natronomonas pharaonis.

The cell membrane of Halobacterium salinarum contains a retinal-binding photoreceptor, sensory rhodopsin II (HsSRII), coupled with its cognate transducer (HsHtrII), allowing repellent phototaxis behavior for shorter wavelength light. Previous studies on SRII from Natronomonas pharaonis (NpSRII) pointed out the importance of the hydrogen bonding interaction between Thr204NpSRII and Tyr174NpSRII in signal transfer from SRII to HtrII. Here, we investigated the effect on phototactic function by replacing residues in HsSRII corresponding to Thr204NpSRII and Tyr174NpSRII . Whereas replacement of either residue altered the photocycle kinetics, introduction of any mutations at Ser201HsSRII and Tyr171HsSRII did not eliminate negative phototaxis function. These observations imply the possibility of the presence of an unidentified molecular mechanism for photophobic signal transduction differing from NpSRII-NpHtrII.

Prediction of hub genes and key pathways associated with the radiation response of human hematopoietic stem/progenitor cells using integrated bioinformatics methods.

Hematopoietic stem cells (HSCs) are indispensable for the maintenance of the entire blood program through cytokine response. However, HSCs have high radiosensitivity, which is often a problem during radiation therapy and nuclear accidents. Although our previous study has reported that the combination cytokine treatment (interleukin-3, stem cell factor, and thrombopoietin) improves the survival of human hematopoietic stem/progenitor cells (HSPCs) after radiation, the mechanism by which cytokines contribute to the survival of HSPCs is largely unclear. To address this issue, the present study characterized the effect of cytokines on the radiation-induced gene expression profile of human CD34+ HSPCs and explored the hub genes that play key pathways associated with the radiation response using a cDNA microarray, a protein-protein interaction-MCODE module analysis and Cytohubba plugin tool in Cytoscape. This study identified 2,733 differentially expressed genes (DEGs) and five hub genes (TOP2A, EZH2, HSPA8, GART, HDAC1) in response to radiation in only the presence of cytokines. Furthermore, functional enrichment analysis found that hub genes and top DEGs based on fold change were enriched in the chromosome organization and organelle organization. The present findings may help predict the radiation response and improve our understanding of this response of human HSPCs.

Chemotherapy-induced leukopenic septic shock treated with veno-arterial extracorporeal membrane oxygenation: A case report.

We present a case of chemotherapy-induced leukopenic septic shock treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Although the indication for VA-ECMO for septic shock in immunosuppressed states remains controversial, her relatively young age and a slightly increasing leukocyte count led to VA-ECMO induction and resulted in recovery.

Validation of the patient State Index for monitoring sedation state in critically ill patients: a prospective observational study.

PURPOSE: The Patient State Index (PSI) is a newly introduced electroencephalogram-based tool for objective and continuous monitoring of sedation levels of patients under general anesthesia. This study investigated the potential correlation between the PSI and the Richmond Agitation‒Sedation Scale (RASS) score in intensive care unit (ICU) patients and established the utility of the PSI in assessing sedation levels. METHODS: In this prospective observational study, PSI values were continuously monitored via SedLine® (Masimo, Irvine, CA, USA); the RASS score was recorded every 2 h for patients on mechanical ventilation. Physicians and nurses were blinded to the PSI values. Overall, 382 PSI and RASS score sets were recorded for 50 patients. RESULTS: The PSI score correlated positively with RASS scores, and Spearman's rank correlation coefficient between the PSI and RASS was 0.79 (95% confidence interval [CI]: 0.75‒0.83). The PSI showed statistically significant difference among the RASS scores (Kruskal‒Wallis chi-square test: 242, df = 6, P < 2.2-e16). The PSI threshold for distinguishing light (RASS score ≥ - 2) sedation from deep sedation (RASS score ≤ - 3) was 54 (95% CI: 50-65; area under the curve, 0.92 [95% CI: 0.89‒0.95]; sensitivity, 0.91 [95% CI: 0.86‒0.95]; specificity, 0.81 [95% CI: 0.77-0.86]). CONCLUSIONS: The PSI correlated positively with RASS scores, which represented a widely used tool for assessing sedation levels, and the values were significantly different among RASS scores. Additionally, the PSI had a high sensitivity and specificity for distinguishing light from deep sedation. The PSI could be useful for assessing sedation levels in ICU patients. University Hospital Medical Information Network (UMIN000035199, December 10, 2018).

[Exploration of Indole Compounds as Candidate for Radiation Mitigators].

PURPOSE: In this study, to develop radiomitigators capable of the emergency medical care of patients involved in radiation accidents, we investigated the radiomitigative effects and their underlying mechanisms of indole compounds such as DIM, GRM, and INM. METHODS: The human normal fibroblast cell line, MRC-5 cells were administered 0.1% DMSO or each indole compound at 10 µM within 50-60 minutes after X-irradiated with 0-4 Gy. Next, we evaluated the alteration in the number of alive cells, clonogenic potential, DNA double-strand breaks, DNA damage repair activities, and protein expression related to regulate the oxidative stress response. RESULTS: Our results showed that DIM treatment suppressed radiation-induced decrease in the number of alive cells and clonogenic potential. Then, DIM treatment significantly decreased DNA double-strand breaks and highly increased Nrf2 via increased phospho-GSK-3ß (Ser9) expression. These findings suggest that, in part, increased expression of p-GSK-3ß (Ser9) by DIM treatment reduced DNA double-strand breaks via activation of Nrf2, resulting mitigated radiation-induced a decrease in the number of alive cells and clonogenic potential. CONCLUSION: Therefore, DIM, not GRM and INM, is a potential candidate for radiomitigators that can be applied to the radiation emergency medicine.

An Automated Algorithm for Determining Sleep Using Single-Channel Electroencephalography to Detect Delirium: A Prospective Observational Study in Intensive Care Units.

The relationship between polysomnography-based objective sleep and delirium in the intensive care unit (ICU) is inconsistent across studies, suggesting limitations in manually determining the sleep stage of critically ill patients. We objectively measured 24-h sleep using a single-channel electroencephalogram (SleepScope [SS]) and an under-mattress sleep monitor (Nemuri SCAN [NSCAN]), both of which have independent algorithms that automatically determine sleep and wakefulness. Eighteen patients (median age, 68 years) admitted to the ICU after valvular surgery or coronary artery bypass grafting were included, and their sleep time was measured one day after extubation. The median total sleep times (TSTs) measured by SS (TST-SS) and NSCAN were 548 (48−1050) and 1024 (462−1257) min, respectively. Two patients with delirium during the 24-h sleep measurement had very short TST-SS of 48 and 125 min, and the percentage of daytime sleep accounted for >80% in both SS and NSCAN. This preliminary case series showed marked sleep deprivation and increased rates of daytime sleeping in ICU patients with delirium. Although data accuracy from under-mattress sleep monitors is contentious, automated algorithmic sleep/wakefulness determination using a single-channel electroencephalogram may be useful in detecting delirium in ICU patients and could even be superior to polysomnography.

Catheter-related thrombosis after cardiac surgery in patients with both central venous and pulmonary artery catheters inserted into the right internal jugular vein: a single-center, prospective, observational study.

Central venous catheters (CVCs) and pulmonary artery catheters (PACs) are widely used in intensive care and perioperative management. The detection and prevention of catheter-related thrombosis (CRT) are important because CRT is a complication of catheter use and can cause pulmonary embolism and bloodstream infection. Currently, there is no evidence for CRT in patients using both CVC and PAC. We conducted a single-center, prospective, observational study to identify the incidence, timing, and risk factors for CRT in patients undergoing cardiovascular surgery and using a combination of CVC and PAC through the right internal jugular vein (RIJV). Out of 50 patients, CRT was observed using ultrasonography in 39 patients (78%), and the median time of CRT formation was 1 day (interquartile range: 1-1.5) after catheter insertion. The mean duration of PAC placement was 3 days (interquartile range: 2-5), and the maximum diameter of CRT was 12 mm (interquartile range: 10-15). In short-axis images, CRT occupied more than half of the cross-sectional area of the RIJV in five patients (10%), and CRT completely occluded the RIJV in one patient (2%). Platelet count, duration of PAC placement, and intraoperative bleeding amount were found to be high-risk indicators of CRT. In conclusion, patients who underwent cardiovascular surgery and using both CVC and PAC had a high incidence of CRT. Avoiding unnecessary PAC placement and early removal of catheters in patients at high risk of developing CRT may prevent the development of CRT.

Life-Threatening Complications Related to Delayed Diagnosis of Euglycemic Diabetic Ketoacidosis Associated with Sodium-Glucose Cotransporter-2 Inhibitors: A Report of 2 Cases.

BACKGROUND Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are widely used owing to their effective glycemic control and protective effects against heart and kidney failure. Euglycemic diabetic ketoacidosis (eu-DKA) is a complication of treatment with SGLT2is. Eu-DKA often leads to delayed diagnosis and results in life-threatening complications. We report 2 critical cases of SGLT2i-associated eu-DKA. CASE REPORT Case 1 was 52-year-old woman with unstable angina scheduled for elective coronary artery bypass grafting surgery. Preoperatively, she underwent tooth extraction which led to poor food intake because of pain. Three days before surgery, the patient had SGLT2i-associated eu-DKA and myocardial infraction, requiring percutaneous coronary intervention and peripheral venoarterial extracorporeal membrane oxygenation. The patient had taken SGLT2i until the morning of admission to the intensive care unit. Case 2 was a 76-year-old woman experiencing SGLT2i-associated eu-DKA and sinus arrest, necessitating a temporary pacemaker, followed by elective gastrojejunal bypass surgery. The SGLT2i was discontinued the day before surgery. On day 3 following surgery, the patient's metabolic acidosis improved, and sinus arrest resolved. CONCLUSIONS Precipitating factors of eu-DKA (caloric restriction and surgical stress) and delay in diagnosis because of a lack of evidence of hyperglycemia could contribute to the development and worsening of life-threatening complications. This reiterates the importance of reviewing ongoing medications of patients with diabetes and considering eu-DKA as a differential diagnosis for patients with high anion gap metabolic acidosis to ensure early intervention. SGLT2i-associated DKA likely develops perioperatively; therefore, clinicians should pay attention to the discontinuation period of SGLT2i before any surgical intervention.

Transient systolic anterior motion with junctional rhythm after mitral valve repair in the intensive care unit.

Systolic anterior motion (SAM) after mitral valve repair (MVR) can adversely affect hemodynamics due to exacerbation of left ventricular outflow tract obstruction and mitral regurgitation. Intraoperative transient SAM after MVR can usually be managed with hemodynamic maneuvers under continuous monitoring by transesophageal echocardiography (TEE). However, during postoperative intensive care management, transient SAM is seldom diagnosed and the start of treatment may be delayed. We present a case of transient SAM after MVR with abrupt deterioration due to junctional rhythm in the intensive care unit (ICU). TEE revealed that conversion from normal sinus rhythm into junctional rhythm induced the exacerbation of SAM. TEE was useful for identifying the etiology of unstable hemodynamics after cardiac surgery in the ICU, similar to its use in the operating room.

Contribution of 2-Propenesulfenic Acid to the Antioxidant Activity of Allicin.

We re-examined the antioxidative mechanism of allicin as a radical scavenger on the basis of the reactivity toward 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and peroxyl radicals. Initially, it was found that allicin decomposed more rapidly in n-hexane and chlorobenzene than in acetonitrile, ethanol, and ethanol/water solutions and decomposed into ajoene and vinyldithiins in these solvents. Furthermore, the decomposition of allicin and the following formations of ajoene and vinyldithiins from allicin were accelerated by the reaction of allicin with DPPH and peroxyl radicals. These results show that 2-propenesulfenic acid, which arises by Cope elimination from allicin, is proposed to contribute to scavenge these radicals because ajoene and vinyldithiins were produced from allicin through the use of 2-propenesulfenic acid. Next, allicin was more effective at inhibiting the linoleic acid oxidation at 50 °C than at 30 °C and in cyclohexane than in acetonitrile. These results indicate that allicin decomposed rapidly at high temperatures in a hydrogen-bond-acceptor solution to 2-propenesulfenic acid. In addition, 2-propene-1-sulfinothionic acid S-methyl ester, which does not produce sulfenic acid through Cope elimination, has no activity against the radicals. On the other hand, methanesulfinothionic acid S-2-propenyl ester, which produces methanesulfenic acid through Cope elimination, has the same or increased activity as its allicin against the radicals. Based on these results, the Cope elimination product, sulfenic acid, from thiosulfinates with an α-sulfenyl proton was found to make a larger contribution to the radical scavenger than that of allicin itself. PRACTICAL APPLICATION: We examined the antioxidant activity of allicin on the oxidation of cumene and linoleic acid in homogeneous solutions. It is obvious from these results that 2-propenesulfenic acid was found to make a larger contribution to the radical scavenger than that of allicin itself.

Effects of ionizing radiation on differentiation of murine bone marrow cells into mast cells.

Mast cells, immune effector cells produced from bone marrow cells, play a major role in immunoglobulin E-mediated allergic responses. Ionizing radiation affects the functions of mast cells, which are involved in radiation-induced tissue damage. However, whether ionizing radiation affects the differential induction of mast cells is unknown. Here we investigated whether bone marrow cells of X-irradiated mice differentiated into mast cells. To induce mast cells, bone marrow cells from X-irradiated and unirradiated mice were cultured in the presence of cytokines required for mast cell induction. Although irradiation at 0.5 Gy and 2 Gy decreased the number of bone marrow cells 1 day post-irradiation, the cultured bone marrow cells of X-irradiated and unirradiated mice both expressed mast cell-related cell-surface antigens. However, the percentage of mast cells in the irradiated group was lower than in the unirradiated group. Similar decreases in the percentage of mast cells induced in the presence of X-irradiation were observed 10 days post irradiation, although the number of bone marrow cells in irradiated mice had recovered by this time. Analysis of mast cell function showed that degranulation of mast cells after immunoglobulin E-mediated allergen recognition was significantly higher in the X-irradiated group compared with in the unirradiated group. In conclusion, bone marrow cells of X-irradiated mice differentiated into mast cells, but ionizing radiation affected the differentiation efficiency and function of mast cells.

Mitigative Effects of a Combination of Multiple Pharmaceutical Drugs on the Survival of Mice Exposed to Lethal Ionizing Radiation.

It is important to establish an easy-to-use therapeutic protocol for the emergency medical care of patients involved in radiation accidents to reduce the radiation-related casualties. The present study aimed to establish an optimum therapeutic protocol using currently approved pharmaceutical drugs to increase the survival of victims exposed to lethal radiation. Different combinations of four drugs-recombinant human erythropoietin (EPO), granulocyte-colony stimulating factor (G-CSF), c-mpl receptor agonist romiplostim (RP) and nandrolone decanoate (ND)-were administered to mice within 2 h after exposure to a lethal 7 Gy dose of γ-irradiation. On day 30 after irradiation, the condition of the mice was analyzed using various hematological parameters, such as the number of peripheral blood cells, bone marrow cells, hematopoietic progenitor cells and the expression of cell surface antigens. Approximately 10% of the untreated irradiated control mice survived for 21 days, but all of the control mice died by day 30. The combined administration of G-CSF, EPO and RP for five days immediately after irradiation led to a complete survival of the irradiated mice until day 30. However, the treatment with G-CSF, EPO and RP with ND led to only 75% survival at day 30. The hematological analyses showed that the numbers of almost all of hematopoietic cells in the surviving mice treated with effective medications recovered to the levels of non-irradiated mice. The present findings show that the combination of G-CSF, EPO and RP may be a useful countermeasure for victims exposed to accidental lethal irradiation.

Characteristics of human CD34+ cells exposed to ionizing radiation under cytokine-free conditions.

To clarify the mechanisms underlying radiation-induced hematopoietic stem cell death, we investigated the effects of excessive ionizing radiation on the clonogenic potential of CD34(+) cells obtained from human umbilical cord blood under cytokine-free conditions. The CD34(+) cells were X-ray-irradiated (up to 2 Gy) and were cultured for 0-48 h under cytokine-free conditions. At various time-points, the CD34(+) cells were investigated for survival, clonogenic potential and the generation of mitochondrial superoxide. At 12 h after X-ray irradiation, the number of viable cells had decreased to ∼70-80% compared with the 0-h non-irradiated control, whereas the clonogenic potential in the X-ray-irradiated cells had decreased to ∼50%-60% compared with the 0-h non-irradiated control. Furthermore, significant generation of mitochondrial superoxide was observed at 6 h, and reached a maximum value between 12 and 24 h after X-ray irradiation. However, no significant differences were observed between non-irradiated and X-ray-irradiated cells in terms of the generation of reactive oxygen species or in the intracellular mitochondrial contents. In addition, a cDNA microarray analysis showed that the majority of the altered genes in the CD34(+) cells at 6 h after X-ray irradiation were apoptosis-related genes. These results suggest the possibility that the elimination of the clonogenic potentials of CD34(+) cells involves the generation of mitochondrial superoxide induced by ionizing radiation.

Synthesis and anticancer properties of phenyl benzoate derivatives possessing a terminal hydroxyl group.

To assess the cytotoxic effects on A549 human lung cancer cells, we investigated a liquid-crystalline compound possessing a terminal hydroxyl group at concentrations of 0.1-20 µM. The compound, 4-butylphenyl 4-(6-hydroxyhexyloxy)benzoate (2), showed marked cell-growth inhibition at concentrations higher than 5 µM. Cell accumulation in the Sub-G1 phase indicating apoptosis was observed only at the highest concentration. Dynamic light scattering measurements show that the molecules form a spherical nanoparticle with a diameter of 130-170 nm at concentrations of 5-20 µM. We prepared the corresponding dimeric compounds and investigated their anticancer activity. The 1,2-benzene derivative, 1,2-bis[4-(6-hydroxyhexyloxy)benzoyloxy]benzene (4), exhibited cell-growth inhibition without affecting the cell cycle. However, the 1,3-benzene derivative, 1,3-bis[4-(6-hydroxyhexyloxy)benzoyloxy]benzene (5), was found to induce marked cell accumulation in the Sub-G1 phase. Furthermore, we assessed the cytotoxic effects of compounds 2, 4 and 5 on SW480 colon cancer cells and THP1 leukemic cells, as well as on WI-38 normal fibroblast cells. Both compounds 2 and 5 suppressed the growth of the solid cancer cells (A549 and SW480) more strongly compared with that of the hematological cancer cells (THP1). Unexpectedly, they also exhibited a strong cytotoxicity against the normal cells. We discuss the structure-property relationship in the anticancer activity of the mesogenic compounds.

RNA tectonics (tectoRNA) for RNA nanostructure design and its application in synthetic biology.

RNA molecules are versatile biomaterials that act not only as DNA-like genetic materials but also have diverse functions in regulation of cellular biosystems. RNA is capable of regulating gene expression by sequence-specific hybridization. This feature allows the design of RNA-based artificial gene regulators (riboregulators). RNA can also build complex two-dimensional (2D) and 3D nanostructures, which afford protein-like functions and make RNA an attractive material for nanobiotechnology. RNA tectonics is a methodology in RNA nanobiotechnology for the design and construction of RNA nanostructures/nanoobjects through controlled self-assembly of modular RNA units (tectoRNAs). RNA nanostructures designed according to the concept of RNA tectonics are also attractive as tools in synthetic biology, but in vivo RNA tectonics is still in the early stages. This review presents a summary of the achievements of RNA tectonics and its related researches in vitro, and also introduces recent developments that facilitated the use of RNA nanostructures in bacterial cells.

An in vitro-selected RNA receptor for the GAAC loop: modular receptor for non-GNRA-type tetraloop.

Although artificial RNA motifs that can functionally replace the GNRA/receptor interaction, a class of RNA-RNA interacting motifs, were isolated from RNA libraries and used to generate designer RNA structures, receptors for non-GNRA tetraloops have not been found in nature or selected from RNA libraries. In this study, we report successful isolation of a receptor motif interacting with GAAC, a non-GNRA tetraloop, from randomized sequences embedded in a catalytic RNA. Biochemical characterization of the GAAC/receptor interacting motif within three structural contexts showed its binding affinity, selectivity and structural autonomy. The motif has binding affinity comparable with that of a GNRA/receptor, selectivity orthogonal to GNRA/receptors and structural autonomy even in a large RNA context. These features would be advantageous for usage of the motif as a building block for designer RNAs. The isolated motif can also be used as a query sequence to search for unidentified naturally occurring GANC receptor motifs.

Evaluating the fundamental critical care support course in critical care education in Japan: a survey of Japanese fundamental critical care support course experience.

BACKGROUND: The Fundamental Critical Care Support (FCCS) course has been introduced after minimal adaptation according to Japanese clinical settings. The original course in the USA is often used to prepare residents for rotations in the intensive care unit (ICU). Therefore, the FCCS program can be appropriate for the basic training of critical care in Japan to standardize critical care management. The purpose of this study is to evaluate whether Japanese FCCS course is useful and has a possibility to deserve a basis of critical care management in Japan. METHODS: The course program was provided with the form of lecture and skills stations. Pre- and post-training knowledge was assessed. After completion of the 2-day course, a questionnaire survey was administered to all course participants. Participants were asked to fill out the questions regarding socio-demographic characteristics. Participants were also asked to identify which lectures or skill stations they thought to be useful for clinical practice. Then, they were asked to rate their performance of each field: 'Assessment,' 'Diagnosis,' 'Recognition,' 'Response,' and 'Transfer'. RESULTS: The number of participants increased year after year and reached 1,804 during the past 4 years. Nearly 70% of the participants were physicians. Most of the others were nurses. In the established year, the percentage of physicians who had clinical experience more than 5 years exceeded 50%, however, this percentage gradually decreased. On the contrary, the percentages of residents and nurses increased. Regarding useful sessions, nearly half of the participants thought that mechanical ventilation was the most useful. With regard to the results of pre- and post-tests, the participants had already shown a high average mark (78.8 ± 14.1) at the pre-test. Furthermore, the score at the post-test was significantly improved (82.0 ± 6.6, p < 0.01). The participants' confidence in any field regarding critical care management was almost 4 points (5-point scale). CONCLUSIONS: It is considered that Japanese FCCS course is useful and has a promising basis of critical care management in Japan. Therefore, it is reasonable to think that Japanese FCCS mission has been successfully achieved.