Alteration of Sweet and Bitter Taste Sensitivity with Development of Glucose Intolerance in Non-insulin-Dependent Diabetes Mellitus Model OLETF Rats.

Patients with diabetes exhibit altered taste sensitivity, but its details have not been clarified yet. Here, we examined alteration of sweet taste sensitivity with development of glucose intolerance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats as a model of non-insulin-dependent diabetes mellitus. Compared to the cases of Long Evans Tokushima Otsuka (LETO) rats as a control, glucose tolerance of OLETF rats decreased with aging, resulting in development of diabetes at 36-weeks-old. In brief-access tests with a mixture of sucrose and quinine hydrochloride, OLETF rats at 25 or more-weeks-old seemed to exhibit lower sweet taste sensitivity than age-matched LETO ones, but the lick ratios of LETO, but not OLETF, rats for the mixture and quinine hydrochloride solutions decreased and increased, respectively, aging-dependently. Expression of sweet taste receptors, T1R2 and T1R3, in circumvallate papillae (CP) was almost the same in LETO and OLETF rats at 10- and 40-weeks-old, while expression levels of a bitter taste receptor, T2R16, were greater in 40-weeks-old rats than in 10-weeks-old ones in both strains. There was no apparent morphological alteration in taste buds in CP between 10- and 40-weeks-old LETO and OLETF rats. Metagenomic analysis of gut microbiota revealed strain- and aging-dependent alteration of mucus layer-regulatory microbiota. Collectively, we concluded that the apparent higher sweet taste sensitivity in 25 or more-weeks-old OLETF rats than in age-matched LETO rats was due to the aging-dependent increase of bitter taste sensitivity in LETO rats with alteration of the gut microbiota.

Sub-chronic and mild social defeat stress exposure to C57BL/6J mice increases visceral fat mass and causes accumulation of cholesterol and bile acids in the liver.

Major depressive disorder is accompanied by a high metabolic illness comorbidity and patients with atypical depression are a subgroup with particularly high risk of obesity, dyslipidemia, and metabolic syndrome; however, the underlying mechanisms have not been fully elucidated. In this study, we examined visceral fat deposition, lipid profiles in the liver, and gut microbiota in sub-chronic and mild social defeat stress (sCSDS)-exposed C57BL/6J mice, which exhibit atypical depression-like phenotypes, i.e., increased body weight and food and water intake. We found that visceral fat mass and levels of hepatic cholesterol and bile acids in sCSDS-exposed mice were significantly increased compared to those in controls. The expression of hepatic small heterodimer partner, a negative regulator of cholesterol metabolism, was significantly elevated in sCSDS-exposed mice. We also found that gut microbial diversity and composition including lower relative abundance of Bacteroides spp. and Bifidobacterium spp. in sCSDS-exposed mice were different from those in controls. In addition, relative abundance of Bacteroides spp. and Bifidobacterium spp. was significantly and negatively correlated with body weight, visceral fat mass, and hepatic cholesterol and bile acids levels. These results indicate that sCSDS-exposure induces dysbiosis, and thereby contributes to metabolic disorder development.

Prophylactic Administration of Magnesium Oxide Prevents Dextran Sulfate Sodium-Induced Colonic Injury in Mice.

We previously demonstrated that per os administration and ad libitum ingestion of a magnesium chloride (MgCl2) solution had a prophylactic effect on dextran sulfate sodium (DSS)-induced colitis in mice, magnesium being considered to play a role in this preferable action. Magnesium oxide (MgO) is a commercially available magnesium formulation, but whether or not it prevents development of colitis is unknown. In this study, we investigated the effect of MgO administration on development of colitis in DSS-treated male C57BL/6J mice. Experimental colitis was induced by ad libitum ingestion of 1% (w/v) DSS, and the colitis severity was evaluated by disease activity index (DAI) scores, histological assessment and colonic expression of inflammatory cytokines. A 1 mg/mL MgO solution was administered to mice through ad libitum ingestion from a day before DSS treatment to the end of the experimental period of 12 d. In addition, the effects of DSS, MgO and their combination on the gut microbiota were investigated by 16S ribosomal RNA metagenome analysis. DSS-induced elevation of DAI scores was partially but significantly decreased by MgO administration, while MgO administration had no apparent effect on the shortened colonic length, elevated mRNA expression of colonic interleukin-1ß and tumor necrosis factor-α, increased accumulation of colonic mast cells, or altered features of the gut microbiota in DSS-treated mice. Overall, we demonstrated that MgO had a prophylactic effect on the development of colitis in DSS-treated mice by preventing histological colonic damage, but not colonic inflammation or alteration of the gut microbiota.

Current status of delirium assessment tools in the intensive care unit: a prospective multicenter observational survey.

Delirium is a critical challenge in the intensive care unit (ICU) or high care unit (HCU) setting and is associated with poor outcomes. There is not much literature on how many patients in this setting are assessed for delirium and what tools are used. This study investigated the status of delirium assessment tools of patients in the ICU/HCU. We conducted a multicenter prospective observational study among 20 institutions. Data for patients who were admitted to and discharged from the ICU/HCU during a 1-month study period were collected from each institution using a survey sheet. The primary outcome was the usage rate of delirium assessment tools on an institution- and patient-basis. Secondary outcomes were the delirium prevalence assessed by each institution's assessment tool, comparison of delirium prevalence between delirium assessment tools, delirium prevalence at the end of ICH/HCU stay, and the relationship between potential factors related to delirium and the development of delirium. Result showed that 95% of institutions used the Intensive Care Delirium Screening Checklist (ICDSC) or the Confusion Assessment Method for the ICU (CAM-ICU) to assess delirium in their ICU/HCU, and the remaining one used another assessment scale. The usage rate (at least once during the ICU/HCU stay) of the ICDSC and the CAM-ICU among individual patients were 64.5% and 25.1%, and only 8.2% of enrolled patients were not assessed by any delirium assessment tool. The prevalence of delirium during ICU/HCU stay was 17.9%, and the prevalence of delirium at the end of the ICU/HCU stay was 5.9%. In conclusion, all institutions used delirium assessment tools in the ICU/HCU, and most patients received delirium assessment. The prevalence of delirium was 17.9%, and two-thirds of patients had recovered at discharge from ICU/HCU.Trial registration number: UMIN000037834.

Dextran sulfate sodium-induced colitis in C57BL/6J mice increases their susceptibility to chronic unpredictable mild stress that induces depressive-like behavior.

AIMS: In patients with colitis, the high comorbidity of depressive disorders is well-known, but the detailed mechanisms remain unresolved. In this study, we examined whether colitis induced by dextran sulfate sodium (DSS) increased the susceptibility to chronic unpredictable mild stress (CUMS) in C57BL/6J mice with resilience to CUMS. MAIN METHODS: To induce experimental colitis and depressive-like behaviors, male 7-weeks old C57BL/6J mice were administered ad libitum 1% DSS solution for 11 days, and subjected to various mild stressors in a chronic, inevitable and unpredictable way according to a random schedule for 21 days, respectively. KEY FINDINGS: In naïve mice exposed to CUMS, their immobility times in a forced swim (FS) test were almost equal to those in control mice. The DSS administration to naïve mice induced colitis without depressive-like behavior, and at 18 days after termination of the DSS administration, the colitis had recovered to control levels, while altered diversity and composition of bacterial genera such as Bacteroides spp., Alistipes spp., etc., were found in the gut microbiota. Exposure of mice with DSS-induced colitis to CUMS (DSS + CUMS) significantly increased the immobility times in the FS test. In the gut microbiota of DSS + CUMS mice, the alteration profile of the relative abundance of bacterial genera differed from in the DSS ones. SIGNIFICANCE: These findings indicate that mice with colitis exhibit increased susceptibility to psychological stress, resulting in induction of depressive-like behavior, and this might be due, at least in part, to altered characteristics of the gut microbiota.

Reproducible induction of depressive-like behavior in C57BL/6J mice exposed to chronic social defeat stress with a modified sensory contact protocol.

AIMS: C57BL/6J mice are well-known to exhibit resilience to chronic social defeat stress (CSDS) for induction of depressive-like behavior. Establishment of protocols for reproducible induction of depressive-like behavior in C57BL/6J mice would be useful to elucidate the underlying molecular mechanisms using target gene-knock-in and -out mice whose background is generally C57BL/6J. Here, we developed a modified CSDS protocol for reproducible induction of depressive-like behavior in C57BL/6J mice, and compared the profile of their gut microbiota with that with the standard CSDS protocol. MAIN METHODS: To prevent acclimation of defeated C57BL/6J mice to aggressive ICR mice, the sensory contact following a daily 10 min-defeat episode was performed by housing an individual defeated mouse in a cage set next to a cage for the aggressor one. KEY FINDINGS: The number of attacks by ICR mice on C57BL/6J ones was significantly increased with the modified CSDS protocol, and the susceptible mice exhibited greater hippocampal inflammation and an increased immobility time in the forced swim test, compared in the case of the standard CSDS protocol, and the reproducibility was confirmed in another set of experiments. Both the standard and modified CSDS protocols changed the diversity and relative composition of gut microbiota in the susceptible mice, but there was no apparent difference in them between the standard and modified CSDS-susceptible mice. SIGNIFICANCE: We established a CSDS protocol for reproducible induction of depressive-like behavior in C57BL/6J mice, and the features of the gut microbiota were similar in the susceptible mice with and without the depressive-like behavior.

Current Ventilator and Oxygen Management during General Anesthesia: A Multicenter, Cross-sectional Observational Study.

BACKGROUND: Intraoperative oxygen management is poorly understood. It was hypothesized that potentially preventable hyperoxemia and substantial oxygen exposure would be common during general anesthesia. METHODS: A multicenter, cross-sectional study was conducted to describe current ventilator management, particularly oxygen management, during general anesthesia in Japan. All adult patients (16 yr old or older) who received general anesthesia over 5 consecutive days in 2015 at 43 participating hospitals were identified. Ventilator settings and vital signs were collected 1 h after the induction of general anesthesia. We determined the prevalence of potentially preventable hyperoxemia (oxygen saturation measured by pulse oximetry of more than 98%, despite fractional inspired oxygen tension of more than 0.21) and the risk factors for potentially substantial oxygen exposure (fractional inspired oxygen tension of more than 0.5, despite oxygen saturation measured by pulse oximetry of more than 92%). RESULTS: A total of 1,786 patients were found eligible, and 1,498 completed the study. Fractional inspired oxygen tension was between 0.31 and 0.6 in 1,385 patients (92%), whereas it was less than or equal to 0.3 in very few patients (1%). Most patients (83%) were exposed to potentially preventable hyperoxemia, and 32% had potentially substantial oxygen exposure. In multivariable analysis, old age, emergency surgery, and one-lung ventilation were independently associated with increased potentially substantial oxygen exposure, whereas use of volume control ventilation and high positive end-expiratory pressure levels were associated with decreased potentially substantial oxygen exposure. One-lung ventilation was particularly a strong risk factor for potentially substantial oxygen exposure (adjusted odds ratio, 13.35; 95% CI, 7.24 to 24.60). CONCLUSIONS: Potentially preventable hyperoxemia and substantial oxygen exposure are common during general anesthesia, especially during one-lung ventilation. Future research should explore the safety and feasibility of a more conservative approach for intraoperative oxygen therapy.

Do radial arterial pressure curves have diagnostic validity for identify severe aortic stenosis?

PURPOSE: A pulsus parvus et tardus of the carotid artery, i.e., a small weak pulse with a delayed systolic peak, is a well-recognized clinical finding of aortic stenosis (AS). However, the diagnostic value of radial arterial pressure curves has not been specifically investigated. In this study, we investigated whether the radial arterial curves of patients with AS had distinguishable characteristics. METHODS: We studied 17 AS patients (valve area less than 0.8 cm2) and 17 control patients. The durations for the following intervals were measured, from the ECG-R to the beginning of the arterial pressure wave upstroke (PTT(Up)), from the ECG-R to the peak of the arterial pressure (PTT(peak)), and the difference between PTT(peak) and PTT(Up) (T(Upstroke)). RESULTS: The radial arterial pulse pressures did not differ significantly, indicating absence of a pulsus paruvus in the radial pressure of the AS patients. The PTT(Up) and PTT(peak) in the AS patients were 134 +/- 18 and 337 +/- 44 ms, respectively, while these values in the control patients were 143 +/- 21 and 286 +/- 64 ms. As a result of the differences in PTT(Up) and PTT(peak), the T(Upstroke) in the AS patients was greater than that in the control patients. The T(Upstroke) cutoff point that gave the maximal sensitivity (0.93) and specificity (0.65) was 156 ms. CONCLUSION: Our study using the radial arterial curve validated a pulsus tardus as a diagnostic sign for severe AS, while the validity of a pulsus parvus as a diagnostic sign was not confirmed.

Deep-sea water improves cardiovascular hemodynamics in Kurosawa and Kusanagi-Hypercholesterolemic (KHC) rabbits.

Deep-sea water is rich in minerals, e.g., Mg, Ca, and K which have been considered to be associated with prevention of cardiovascular disease. We investigated the effect of deep-sea water on cardiovascular hemodynamics in Kurosawa and Kusanagi-Hypercholesterolemic (KHC) rabbits. Deep-sea water was pumped in the offing of Cape Muroto in Japan and the mineral constituents were refined to a degree of hardness of 1,000. Twenty four 4-month-old KHC rabbits were given refined deep-sea water (n=12) and tap water (n=12) for 6 months. Pressure and flow waves at the ascending aorta were recorded under pentobarbital anesthesia. Systolic, diastolic, pulse and mean arterial pressures and total peripheral resistance were significantly lower in the deep-sea water group than in the control group. There were no significant differences in changes in serum lipid levels, plasma renin and angiotensin converting enzyme activities and electrolyte levels except for Mg(2+) after the feeding of the water between the two groups. A slight increase in serum Mg(2+) level in the deep-sea water group may not account for the inhibition of mild hypertension. From our results, we conclude that deep-sea water could improve cardiovascular hemodynamics, even though the factors which affect the blood pressure are still unknown.

Central venous pulse pressure analysis using an R-synchronized pressure measurement system.

OBJECTIVE: The information derived from central venous catheters is underused. We developed an EKG-R synchronization and averaging system to obtained distinct CVP waveforms and analyzed components of these. METHODS: Twenty-five paralyzed surgical patients undergoing CVP monitoring under mechanical ventilation were studied. CVP and EKG signals were analyzed employing our system, the mean CVP and CVP at end-diastole during expiration were compared, and CVP waveform components were measured using this system. RESULTS: CVP waveforms were clearly visualized in all patients. They showed the a peak to be 1.8+/- 0.7 mmHg, which was the highest of three peaks, and the x trough to be lower than the y trough (-1.6+/- 0.7 mmHg and -0.9+/- 0.5 mmHg, respectively), with a mean pulse pressure of 3.4 mmHg. The difference between the mean CVP and CVP at end-diastole during expiration was 0.58+/- 0.81 mmHg. CONCLUSIONS: The mean CVP can be used as an index of right ventricular preload in patients under mechanical ventilation with regular sinus rhythm. Our newly developed system is useful for clinical monitoring and for education in circulatory physiology.

Cloning and characterization of a 4-nitrophenol hydroxylase gene cluster from Rhodococcus sp. PN1.

A 4-nitrophenol (4-NP)-degrading bacterium was isolated from activated sludge and identified as a Rhodococcus sp. This bacterium, designated as strain PN1, could utilize 4-NP as a sole carbon, nitrogen and energy source. Degradation tests of 4-NP using cell suspensions of strain PN1 revealed that the degradation was induced by 4-NP and that 4-nitrocatechol (4-NC) was one of the metabolites. A gene library was constructed from the total DNA of strain PN1 and introduced into Rhodococcus rhodochrous ATCC 12674. Two recombinant strains showed 4-NP hydroxylase activity, and a 9.1-kb DNA fragment encoding the activity was isolated from one of the strains. In addition, a 2.4-kb smaller fragment expressing the activity was subcloned from the 9.1-kb fragment and sequenced. The sequence analysis showed that the fragment encodes a two-component 4-NP hydroxylase, the predicted amino acid sequence of which exhibits significant similarity to those of phenol hydroxylases and 4-hydroxyphenylacetate 3-hydroxylases belonging to the two-component flavin diffusible monooxygenase (TC-FDM) family proposed by Galán et al. (J. Bacteriol., 182, 627-636, 2000).