Ag-Catalyzed Cyanomethylation of Amines Using Nitromethane as a C1 Source.

A new methodology to afford α-amino nitriles through oxidative cyanomethylation of amines using nitromethane as the methylene source in the presence of Me3SiCN without the addition of an external oxidant was developed. A catalytic amount of AgCN and a stoichiometric amount of LiBF4 cooperatively promoted the transformation. A wide variety of the amines, including both aromatic compounds and aliphatic ones, which are labile under oxidative conditions, were applicable to the reaction.

The effect of high-flow nasal cannula on diaphragm dysfunction including paradoxical diaphragmatic contraction in the intensive care unit.

Background : Diaphragm dysfunction is a serious problem. However, a few management techniques exist for diaphragm dysfunction. Methods : Adult patients treated with high-flow nasal cannula (HFNC) in the intensive care unit were included in this study. The diaphragm function was evaluated using ultrasound measurement of thickening fraction before and after HFNC liberation. Normal diaphragm contraction was defined as thickening fraction ≥ 15% without HFNC, whereas decreased or paradoxical diaphragm contractions were 0%-15% or < 0%, respectively. Results : Forty patients were enrolled, and 16 (40%) had normal diaphragm contraction, whereas 19 (48%) or 5 (13%) had decreased or paradoxical diaphragm contractions, respectively. Thickening fraction increased after HFNC liberation (27.0% ±â€…25.7% vs. 38.8% ±â€…34.5%, p = 0.03 in HFNC vs. no HFNC) in patients without diaphragm dysfunction. In patients with decreased diaphragm contraction, thickening fraction did not change with or without HFNC (8.9% ±â€…11.7% vs. 6.7% ±â€…5.2%, p = 0.35), whereas paradoxical contraction decreased with HFNC (1.0% ±â€…10.2% vs. -10.3% ±â€…2.7%, p = 0.04) in patients with paradoxical diaphragm contraction. Conclusions : The work of breathing decreased with HFNC in patients without diaphragm dysfunction, but did not decrease in patients with decreased diaphragm contraction. Paradoxical diaphragm contraction decreased with HFNC. J. Med. Invest. 68 : 159-164, February, 2021.

Effect of controlled ventilation during assist-control ventilation on diaphragm thickness†:†a post hoc analysis of an observational study.

Background : Since diaphragm passivity induces oxidative stress that leads to rapid atrophy of diaphragm, we investigated the effect of controlled ventilation on diaphragm thickness during assist-control ventilation (ACV). Methods : Previously, we measured end-expiratory diaphragm thickness (Tdiee) of patients mechanically ventilated for more than 48 hours on days 1, 3, 5 and 7 after the start of ventilation. We retrospectively investigated the proportion of controlled ventilation during the initial 48-hour ACV (CV48%). Patients were classified according to CV48% : Low group, less than 25% ; High group, higher than 25%. Results : Of 56 patients under pressure-control ACV, Tdiee increased more than 10% in 6 patients (11%), unchanged in 8 patients (14%) and decreased more than 10% in 42 patients (75%). During the first week of ventilation, Tdiee decreased in both groups : Low (difference, -7.4% ; 95% confidence interval [CI], -10.1% to -4.6% ; p < 0.001) and High group (difference, -5.2% ; 95% CI, -8.5% to -2.0% ; p = 0.049). Maximum Tdiee variation from baseline did not differ between Low (-15.8% ; interquartile range [IQR], -22.3 to -1.5) and High group (-16.7% ; IQR, -22.6 to -11.1, p = 0.676). Conclusions : During ACV, maximum variation in Tdiee was not associated with proportion of controlled ventilation higher than 25%. J. Med. Invest. 67 : 332-337, August, 2020.

Urinary Titin Is a Novel Biomarker for Muscle Atrophy in Nonsurgical Critically Ill Patients: A Two-Center, Prospective Observational Study.

OBJECTIVES: Although skeletal muscle atrophy is common in critically ill patients, biomarkers associated with muscle atrophy have not been identified reliably. Titin is a spring-like protein found in muscles and has become a measurable biomarker for muscle breakdown. We hypothesized that urinary titin is useful for monitoring muscle atrophy in critically ill patients. Therefore, we investigated urinary titin level and its association with muscle atrophy in critically ill patients. DESIGN: Two-center, prospective observational study. SETTING: Mixed medical/surgical ICU in Japan. PATIENTS: Nonsurgical adult patients who were expected to remain in ICU for greater than 5 days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Urine samples were collected on days 1, 2, 3, 5, and 7 of ICU admission. To assess muscle atrophy, rectus femoris cross-sectional area and diaphragm thickness were measured with ultrasound on days 1, 3, 5, and 7. Secondary outcomes included its relationship with ICU-acquired weakness, ICU Mobility Scale, and ICU mortality. Fifty-six patients and 232 urinary titin measurements were included. Urinary titin (normal range: 1-3 pmol/mg creatinine) was 27.9 (16.8-59.6), 47.6 (23.5-82.4), 46.6 (24.4-97.6), 38.4 (23.6-83.0), and 49.3 (27.4-92.6) pmol/mg creatinine on days 1, 2, 3, 5, and 7, respectively. Cumulative urinary titin level was significantly associated with rectus femoris muscle atrophy on days 3-7 (p ≤ 0.03), although urinary titin level was not associated with change in diaphragm thickness (p = 0.31-0.45). Furthermore, cumulative urinary titin level was associated with occurrence of ICU-acquired weakness (p = 0.01) and ICU mortality (p = 0.02) but not with ICU Mobility Scale (p = 0.18). CONCLUSIONS: In nonsurgical critically ill patients, urinary titin level increased 10-30 times compared with the normal level. The increased urinary titin level was associated with lower limb muscle atrophy, occurrence of ICU-acquired weakness, and ICU mortality.

Muscle atrophy in critically ill patients†:†a review of its cause, evaluation, and prevention.

Critically ill patients exhibit prominent muscle atrophy, which occurs rapidly after ICU admission and leads to poor clinical outcomes. The extent of atrophy differs among muscles as follows: upper limb: 0.7%-2.4% per day, lower limb: 1.2%-3.0% per day, and diaphragm 1.1%-10.9% per day. This atrophy is caused by numerous risk factors such as inflammation, immobilization, nutrition, hyperglycemia, medication, and mechanical ventilation. Muscle atrophy should be monitored noninvasively by ultrasound at the bedside. Ultrasound can assess muscle mass in most patients, although physical assessment is limited to almost half of all critically ill patients due to impaired consciousness. Important strategies to prevent muscle atrophy are physical therapy and electrical muscular stimulation. Electrical muscular stimulation is especially effective for patients with limited physical therapy. Regarding diaphragm atrophy, mechanical ventilation should be adjusted to maintain spontaneous breathing and titrate inspiratory pressure. However, the sufficient timing and amount of nutritional intervention remain unclear. Further investigation is necessary to prevent muscle atrophy and improve long-term outcomes. J. Med. Invest. 67 : 1-10, February, 2020.

Monitoring of muscle mass in critically ill patients: comparison of ultrasound and two bioelectrical impedance analysis devices.

BACKGROUND: Skeletal muscle atrophy commonly occurs in critically ill patients, and decreased muscle mass is associated with worse clinical outcomes. Muscle mass can be assessed using various tools, including ultrasound and bioelectrical impedance analysis (BIA). However, the effectiveness of muscle mass monitoring is unclear in critically ill patients. This study was conducted to compare ultrasound and BIA for the monitoring of muscle mass in critically ill patients. METHODS: We recruited adult patients who were expected to undergo mechanical ventilation for > 48 h and to remain in the intensive care unit (ICU) for > 5 days. On days 1, 3, 5, 7, and 10, muscle mass was evaluated using an ultrasound and two BIA devices (Bioscan: Malton International, England; Physion: Nippon Shooter, Japan). The influence of fluid balance was also evaluated between each measurement day. RESULTS: We analyzed 93 images in 21 patients. The age of the patients was 69 (interquartile range, IQR, 59-74) years, with 16 men and 5 women. The length of ICU stay was 11 days (IQR, 9-25 days). The muscle mass, monitored by ultrasound, decreased progressively by 9.2% (95% confidence interval (CI), 5.9-12.5%), 12.7% (95% CI, 9.3-16.1%), 18.2% (95% CI, 14.7-21.6%), and 21.8% (95% CI, 17.9-25.7%) on days 3, 5, 7, and 10 (p <  0.01), respectively, with no influence of fluid balance (r = 0.04, p = 0.74). The muscle mass did not decrease significantly in both the BIA devices (Bioscan, p = 0.14; Physion, p = 0.60), and an influence of fluid balance was observed (Bioscan, r = 0.37, p <  0.01; Physion, r = 0.51, p <  0.01). The muscle mass assessment at one point between ultrasound and BIA was moderately correlated (Bioscan, r = 0.51, p <  0.01; Physion, r = 0.37, p <  0.01), but the change of muscle mass in the same patient did not correlate between these two devices (Bioscan, r = - 0.05, p = 0.69; Physion, r = 0.23, p = 0.07). CONCLUSIONS: Ultrasound is suitable for sequential monitoring of muscle atrophy in critically ill patients. Monitoring by BIA should be carefully interpreted owing to the influence of fluid change. TRIAL REGISTRATION: UMIN000031316. Retrospectively registered on 15 February 2018.

Action spectrum for the suppression of arylalkylamine N-acetyltransferase activity in the two-spotted spider mite Tetranychus urticae.

An action spectrum was obtained for the suppression of arylalkylamine N-acetyltransferase (NAT) activity in the two-spotted spider mite Tetranychus urticae by irradiating the mite with monochromatic lights of various wavelengths using the Okazaki Large Spectrograph at the National Institute for Basic Biology, Okazaki, Japan. Fluence-response curves were obtained for wavelengths between 300 and 650 nm by irradiating the mite for 4 h day(-1). The samples were frozen after the third exposure. A negative correlation between the logarithmic fluence rate and NAT activity was detected in the range of 0.01-1 micromol m(-2) s(-1) for wavelengths between 300 and 500 nm and in the range of 0.1-10 micromol m(-2) s(-1) for wavelengths between 550 and 650 nm. The constructed action spectrum indicated that the photoreceptors mediating the circadian and/or photoperiodic systems might be UV-A- and blue-type photoreceptors with absorption peaks at 350 and 450 nm.

UV radiation elevates arylalkylamine N-acetyltransferase activity and melatonin content in the two-spotted spider mite, Tetranychus urticae.

Ultraviolet (UV) radiation produces reactive oxygen species (ROS) in mammals, where melatonin plays the role of a ROS scavenger. The melatonin synthetic enzyme arylalkylamine N-acetyltransferase (NAT) is a significant element in a possible ROS removal system. Changes in NAT activity and melatonin content were determined in the two-spotted spider mite Tetranychus urticae by irradiating it with monochromatic light using the Okazaki Large Spectrograph at the National Institute for Basic Biology, Okazaki, Japan. The NAT activity and melatonin content were suppressed by blue light (450nm). No effects of red light (650nm) on the NAT activity and melatonin content were observed. UV radiation had intensity-dependent dual effects on the NAT activity and melatonin content. In the UV-B (300nm) treatment, the NAT activity and melatonin content were suppressed at the intensity below 1micromolm(-2)s(-1) but elevated when the intensity was as high as 10micromolm(-2)s(-1). In the UV-A (350nm) treatment, the melatonin content was elevated when the intensity was as high as 10micromolm(-2)s(-1), though the NAT activity and melatonin content were suppressed at the intensity below 10 and 1micromolm(-2)s(-1), respectively. Elevation of the NAT activity and melatonin content by high intensity UV irradiation may indicate that the UV signals initiate melatonin synthesis for ROS removal in mites.