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2.2. Structure elucidation of compounds 1–8 from Alchornea rugosa 25 Compound 1 was isolated as an amorphous powder with [α] D = + 54.9 (c 0.20, MeOH). The molecular formula, C 32 H 41 N 3 O 10, was deduced from its HRESIMS ion peak at m / z 628.2859 [M + H] + (calcd for C 32 H 42 N 3 O 10, 628.2865). The IR spectrum of 1 showed absorption bands characterized by hydroxyl or amine (3704 cm 1), C–H in heteroaromatic rings (2967 cm 1), C––NH or aromatic C (1682 cm 1), benzofuran (1203 cm 1), and C–O (1032 cm 1). The 1 H NMR spectrum of 1 showed two N–H protons (δ H 11.93, 11.65 ppm, Fig. S14), four aromatic signals (δ H 6.76, 6.73, 6.66, and 6.10), one olefinic proton at δ H 5.26 (t, J = 6.9 Hz), an anomeric signal (δ H 4.35 ppm), one N -methylene group at δ H 3.81 (d, J = 6.9 Hz), six protons on oxygenated carbons (δ H 3.33–4.71 ppm), one methylene group (δ H 2.86/2.75 ppm), one methine group (δ H 2.78 ppm), and five methyl groups (δ H 1.73, 1.69, 1.25, 1.13, and 1.11 ppm). The 13 C NMR spectrum of 1 showed 32 carbon signals, including a guanidine carbon (δ C 147.6), fourteen aromatic signals (δ C 95.9–158.8), two olefinic carbons (δ C 120.1/138.5), one anomeric carbon at δ C 102.0 ppm, six oxygenated carbons (δ C 70.3–81.2), an N - methylene group (δ C 41.9), a methylene group (δ C 27.3), one methine group (δ C 26.2), and five methyl group signals (δ C 17.9–25.7). The HMBC correlations from H-2 (δ H 4.71) to C-1’ (δ C 131.6), C-3 (δ C 75.4), C-4 (δ C 27.3), and C-9 (δ C 155.5); from H-6 (δ H 6.10) to C-5 (δ C 158.8), C-7 (δ C 157.3), C-10 (δ C 100.8), and C-8 (δ C 95.9); and from H 2 -4 (δ H 2.86/ 2.75) to C-5, C-9, and C-10 suggested the presence of a C 6 –C 3 –C 6 unit. A hexose sugar moiety was revealed by the mass loss of 146 Da in HRMS/ MS data as well as signals of an anomeric signal (δ H 4.35/ δ C 102.0), four oxygenated methine groups (δ H 3.33–3.65; δ C 70.3–73.9), and a doublet methyl group (δ H 1.25 (d, J = 6.3 Hz)/ δ C 17.9). This rhamnose unit was proven by the 1 H– 1 H COSY spin system (Fig. 2). The HMBC cross peak from H-1’’’’ (δ H 4.35) to C-3 indicated that the rhamnose was linked to the catechin moiety of 1 at C-3. The small coupling constant of H-1’’’’ (d, J = 1.5 Hz), as well as the large 1 J C-H (169.6 Hz), indicated that the relative configuration of the sugar moiety was α -oriented. In addition, the NMR data of 1 exhibited a guanidine unit characterized by the carbon signal at δ C 147.6 with two N–H signals at δ H 11.93 and 11.65 that shared similarities to those of guanidine derivatives reported in the Alchornea genus (Barrosa et al., 2014; Tapondjou et al., 2016). An isoprenyl unit in 1 elongated from the guanidine group was indicated by the presence of the N -methylene group (δ H 3.81/ δ C 41.9), a double bond (δ H 5.26/ δ C 120.1, 138.5), and two methyl groups (δ H 1.69/ δ C 18.0; δ H 1.73/ δ C 25.7), and the HMBC cross-peaks from H 2 -1 ′′′ to guanidine carbon (δ C 147.6). Moreover, the HMBC correlations from two doublet methyls (Me-4 ′′, δ H 1.11, and Me-5 ′′, δ H 1.13) to methine C-3’’ (δ C 26.2) and the other olefinic carbon (δ C 131.3, C-2 ′′), as well as from 1 ′′ -NH (δ H 11.93) and C––NH (δ H 11.65) to the double bond C-1’’/C-2 ′′, suggested that the other five-carbon chain was linked to the guanidine moiety (Fig. 2). As suggested by HRESIMS, the molecular formula of 1 was C 32 H 41 N 3 O 10, which consisted of 14 double bond equivalents (DBE); however, only 13 out of 14 DBEs had been assigned. Therefore, an additional ring of 1 through C-8/C-1 ′′ and C-1’’/7-OH was suggested because of the consistency with the conjugation reported in alchornealaxine (Tapondjou et al., 2016). The relative orientations of the rhamnose moiety were determined by the coupling constants; in particular, 2 J H-H of H-1’’’’ and H-2’’’’ indicated the equatorial orientation of H-2’’’’ while the large coupling constants of H-3’’’’, H-4’’’’, and H-5’’’’ suggested axial orientations of those protons in the sugar unit. Moreover, the NOESY correlations between H-1’’’’/H-2’’’’, H-3’’’’/H-5’’’’, and H-4’’’’/Me-6’’’’ demonstrated the relative configuration of rhamnose sugar in 1 (Fig. 3). The absolute configuration of rhamnose was established by acid hydrolysis, followed by conversion to the corresponding thiocarbamoyl-thiazolidine carboxylate derivative with L- cysteine methyl ester and o -tolyl isothiocyanate (Tanaka et al., 2007). According to the consistent retention times on HPLC chromatography between derivatives of sugar in 1 and the authentic L- rhamnose, the sugar was identified as α -L- rhamnose. The stereocenters at C-2 and C-3 of 1 were determined to be 2 R, 3 S based on their large coupling constants of H-2 (d, J = 7.3 Hz)/H-3 (q, J = 7.3 Hz), which suggested a 2,3- trans flavan-3-ol, and its CD data with negative CEs of approximately 290 and 240 nm (Fig. S73A) (Slade et al., 2005). Thus, the structure of 1 was identified as (2 R,3 S)-rugonine A. Compound 2 was isolated as an amorphous powder with [α] 25 = D 78.0 (c 0.10, MeOH). The molecular formula, C 32 H 41 N 3 O 10, was deduced from its HRESIMS ion peak at m / z 628.2870 [M + H] + (calcd for C 32 H 42 N 3 O 10, 628.2865). The IR spectrum of 2 exhibited the absorption bands of hydroxyl or amine (3252 cm 1), C–H in heteroaromatic rings (2976 cm 1), C––NH or aromatic C (1668 cm 1), benzofuran (1200 cm 1), and C–O (1072 cm 1). The 1 H and 13 C NMR spectra of 2 shared similarities to those of 1, suggesting a similar planar structure. The configuration of the sugar moiety in 2 was also determined by analyzing its NMR coupling constants and NOESY correlations and by comparing the HPLC retention time with the derivative of authentic L- rhamnose, suggesting the presence of an α -L- rhamnose. Moreover, the 2,3- trans flavan-3-ol, which was identified in 1, was also seen in 2 based on its NMR data for the same positions (δ H 4.67, d, J = 7.3 Hz/ δ C 81.1 for C-2 and δ H 3.93, d, 7.3 Hz/ δ C 75.2 for C-3). The different features in 1 and 2 were observed in their optical rotations (+ 55 and 78, respectively) and the opposite CE at 290 nm in the CD spectra. The CD data of 2 showed a positive CE at 290 nm and a negative CE at 240 nm (Fig. S78B), indicating that the absolute configuration of 2 was 2 S, 3 R (Slade et al., 2005). Therefore, the structure of compound 2 was identified as (2 S,3 R)-rugonine B. Compound 3 was acquired as an amorphous powder with [α] D 25 = + 199.6 (c 0.10, MeOH). The molecular formula, C 32 H 43 N 3 O 10, was deduced from its HRESIMS ion peak at m / z 646.2974 [M + H] + (calcd for C 32 H 44 N 3 O 11, 646.2976). The IR spectrum of 3 displayed the absorption bands of hydroxyl or amine (3704 cm 1), C–H in heteroaromatic rings (2922 cm 1), C––NH or aromatic C (1682 cm 1), benzofuran (1195 cm 1), and C–O (1057 cm 1) functional groups. The NMR data of 3, which were similar to those of 1 and 2 (Table 1), indicated that 3 shared a similarity in the planar structure to 1 and 2 excluding the absence of an olefinic bond at δ H 5.26/ δ C 120.1 and 138.5, an additional methylene group (δ H 1.75/ δ C 42.4), and an oxygenated quaternary carbon signal (δ C 70.9 ppm) in 3. The COSY correlation between H 2 -1 ′′′ (δ H 3.34) and H 2 -2 ′′′ (δ H 1.75), as well as HMBC cross-peaks from H 2 -2 ′′′ to C-3 ′′′ (δ C 70.9), C-4 ′′′, and C-5 ′′′ (δ C 29.5) revealed the presence of a 4-hydroxyl-4-methyl pentyl moiety in 3 instead of the isoprenyl moiety in 1. The rhamnose moiety in 3 was also determined by the same method as in 1 and 2 by analyzing NMR coupling constants, NOESY correlations, and comparing the retention times to the derivative of authentic L- rhamnose suggesting that the sugar moiety of 3 was α - L-rhamnose. The absolute configuration at C-2 and C-3 was identified based on the large coupling constants of H-2 (δ H 4.70, J = 7.3 Hz)/H-3 (δ H 3.96, J = 7.7, 5.4 Hz), indicating a 2,3- trans flavan-3-ol, and the CD data showed negative CEs at approximately 290 and 240 nm similar to those of 1 (Fig. S78A). Therefore, the structure of compound 3 was identified as (2 R,3 S)-rugonine C. Compound 4 was isolated as an amorphous powder with [α] D 25 = + 27.5 (c 0.20, MeOH). The chemical formula, C 21 H 23 N 3 O 6, was deduced from its HRESIMS ion peak at m / z 414.1649 [M + H] + (calcd for C 21 H 24 N 3 O 6, 414.1665). The 1 H and 13 C NMR spectra of 4 showed a similar pattern to the core guanidine-fused catechin skeleton of 1 without sugar and isopentenyl moieties. The relative configurations at C-2 and C-3 of 4 were assigned based on the large J coupling constants of H-2 (δ H 4.54, J = 6.9 Hz), H-3 (δ H 3.83, J = 12.6, 6.9 Hz) that indicated a 2,3- trans flavan-3-ol as those of 1–3. The absolute configuration of 4 was determined to be 2 R, 3 S by experimental CD data that showed negative CEs at approximately 290 nm and 240 nm (Fig. S78A), which is typical for (+)-catechin (Slade et al., 2005). Thus, the structure of 4 was determined to be (2 R,3 S)- rugonine D. 25 Compound 5 was isolated as an amorphous powder with [α] D = 16.4 (c 0.20, MeOH). The molecular formula of 5 was the same as that of 4, C 21 H 23 N 3 O 6, which was deduced from its HRESIMS ion peak at m/z 414.1675 [M + H] + (calcd for C 21 H 24 N 3 O 6, 414.1665). The 1 H and 13 C NMR spectra of 5 shared similarity to those of 4, excluding signals at δ H 4.79 (s) (H-2) and 4.02 (s) (H-3). These features and the opposite optical rotation between 4 and 5 suggested that they might have different orientations at C-2 and C-3. In particular, based on the small coupling constants at C-2 and C-3 of 5, the relative configurations were identified as 2,3- cis flavan-3-ol (Slade et al., 2005). Moreover, the negative CEs at 290 and 240 nm in the CD spectrum of 5 (Fig. S78C) suggested that the absolute configurations of 5 were 2 S, 3 S (Slade et al., 2005). Hence, compound 5 was identified as (2 S,3 S)- rugonine E. Compound 6 was acquired as an amorphous powder with [α] D 25 = + 34.1 (c 0.20, MeOH). The molecular formula, C 26 H 31 N 3 O 6, was deduced from its HRESIMS ion peak at m / z 482.2316 [M + H] + (calcd for C 26 H 32 N 3 O 6, 482.2291). The 1 H and 13 C NMR spectra of 6 shared a pattern similar to those of 1 except for the absence of sugar moiety. This led to the conclusion that 6 is another derivative of guanidine-catechin with an isoprenyl substituent that included two methyl groups at C-4 ′′′ (δ H 1.64, δ C 25.3) and C-5 ′′′ (δ H 1.68, δ C 17.8), an olefinic bond at C-3 ′′′ (δ C 135.0), C-2 ′′′ (δ H 5.22, δ C 120.2), and methylene at C-1 ′′′ (δ H 3.75, δ C 44.1). The connection between the isopentyl group and guanidine moiety was confirmed via the HMBC correlation from H-1 ′′′ (δ H 3.75 ppm) to δ C 146.8 ppm. Similar to 1, the absolute configuration of 6 was elucidated as 2 R, 3 S by the large coupling constants of H-2 (J = 5.8 Hz), H-3 (J = 6.2 Hz) indicating a 2,3- trans flavan-3-ol, and negative CEs at approximately 280–290 nm and 240 nm in CD spectra (Fig. S78A). Therefore, compound 6 was determined to be (2 R,3 S)-rugonine F. Compound 7 was isolated as an amorphous powder with [α] D 25 = + 47.5 (c 0.20, MeOH). The molecular formula, C 27 H 33 N 3 O 10, was deduced from its HRESIMS ion peak at m / z 560.2272 [M + H] + (calcd for C 27 H 34 N 3 O 10, 560.2244). The 1 H and 13 C NMR data of compound 7 shared similarity with compound 1, excluding the absence of the isoprenyl substituent. The sugar moiety was determined by an anomeric signal (δ H 4.30, δ C 99.9 ppm), four oxygenated carbons (δ H 3.15–3.47 ppm, and δ C 69.0–72.0 ppm), and an additional methyl at δ H 1.14, δ C 17.9 ppm, which indicated the presence of a rhamnose unit in 7. Based on the HMBC correlations from anomeric proton H-1’’’’ (δ H 4.30) to C-3 (δ C 72.04 ppm), the sugar moiety of 7 was identified as 3-O-rhamnoside. The relative configuration of the sugar unit was determined by analyzing J coupling constants and NOESY correlations. The small coupling constant of H-1’’’’ (δ H 4.30, s) and large 1 J C-H (170.0 Hz) suggested an α orientation of C-1’’’’, and the observed large coupling constants 3 J H-H of H-4’’’’ (9.1 Hz) and H-5’’’’ (12.4, 6.1 Hz) indicated that H-3’’’’/H-4’’’’/H-5’’’’ were in axial orientation. Furthermore, the relative configuration of the sugar, which was established by its J values, was supported by the NOESY correlations of 7 (Fig. 3). The absolute configuration of rhamnose moiety was also determined to be α -L-rhamnose by Tanaka’ s method as the same as in 1–3 (Tanaka et al., 2007). The stereocenters at C-2 and C-3 of 7 were determined to be 2 R, 3 S based on their large J values at H-2 (J = 6.7 Hz) and H-3 (J = 12.7, 6.5 Hz), which indicated a 2,3- trans flavan-3-ol, and negative CEs at approximately 290 nm and 240 nm in experimental CD data (Fig. S78A). Finally, the structure of 7 was identified as (2 R,3 S)- rugonine G. 25 Compound 8 was obtained as an amorphous powder with [α] D = + 20.3 (c 0.20, MeOH). The molecular formula, C 21 H 23 N 3 O 5, was deduced from its HRESIMS ion peak at m / z 396.1581 [M H] (calcd. for C 21 H 22 N 3 O 5, 396.1565). The 1 H NMR and 13 C NMR data of 8 showed similarities to those of 4 and 5, and the mass was different by 16 Da, suggesting that the structure of 8 differed from those of 4 and 5 by less than one hydroxy group. The differences were also indicated by the presence of methylene at δ C 28.6/ δ H 2.00, 1.82 instead of an oxygenated group as in 4 and 5 and the greater upfield shift of C-4 (δ C 18.8) in 8 compared to the other compounds. Correlations from H-2 (δ H 4.80) to C-3 (δ C 28.6) and C-4 on the HMBC spectrum and the 1 H– 1 H COSY spin system of H-2/H 2 -3/H 2 -4 suggested that 8 contained a C 6 –C 3 –C 6 ring similar to that of luteoliflavan (Roemmelt et al., 2003). Hence, the planar structure of 8 was identified as shown in Fig. 2. The configuration of C-2 was determined by comparing its ECD and NMR data with references. To date, only a few flavans have been reported to occur naturally and all of them have the 2 R absolute configuration that would be expected from the flavanone origin (Slade et al., 2005). Flavans showed a low specific rotation, making firm conclusions difficult, and their configuration could be determined only by studying their CD data (Slade et al., 2005). Experimentally, the CD spectrum of 8 showed a negative cotton effect (CE) at a 1 L b of 285 nm (Fig. S78A), which indicated the 2 R absolute configuration (Slade et al., 2005). Moreover, the NMR data of 8 shared similarity with those of luteoliflavan 5-glucoside (Roemmelt et al., 2003), suggesting a 2 R configuration. Therefore, compound 8 was identified as (2 R)-rugonine H. Table 1 1 H and 13 C NMR data for compounds 1–3 in methanol- d 4. a 1 H and 13 C NMR spectra were acquired at 500 and 125 MHz, respectively. b 1 H and 13 C NMR spectra were acquired at 600 and 150 MHz, respectively. c 1 H and 13 C NMR spectra were acquired at 800 and 200 MHz, respectively. d Data recorded in DMSO‑ d (Fig. S14). 6 2.3. Biological activities of compounds 1–9 in autophagy modulation To screen the autophagy regulatory activities of compounds 1–9, HEK293 cells stably expressing GFP-LC3 were administered. In HEK293 cells, the formation of puncta could be observed by using chloroquine (CQ) and rapamycin (RAPA), which are known to inhibit and induce autophagy, respectively. In the confocal microscopic image, the tested CQ and RAPA showed the formation of puncta, and a GFP signal was detected in the cell cytosol. The results indicated that the formation of puncta in the HEK293 cells stably expressing GFP-LC revealed autophagy regulation of the compounds. Nine isolated compounds from A. rugosa (1–9) were treated at a concentration of 20 μM for 24 h, and the cytosol were checked under a confocal microscope. Compared with the control groups, a significant increase in LC3 puncta in HEK293-GFP-LC3 cells was observed in the cells treated with c, Published as part of Doan, Thi-Phuong, Park, Eun-Jin, Ryu, Byeol, Cho, Hyo-Moon, Yoon, Sang-Jun, Jung, Gwan-Young, Thuong, Phuong-Thien & Oh, Won-Keun, 2023, Unique guanidine-conjugated catechins from the leaves of Alchornea rugosa and their autophagy modulating activity, pp. 113521 in Phytochemistry (113521) (113521) 206 on pages 2-8, DOI: 10.1016/j.phytochem.2022.113521, http://zenodo.org/record/8160626, {"references":["Barrosa, K., Pinto, E., Tempone, A., Martins, E., Lago, J., 2014. Alchornedine, a new antitrypanosomal guanidine alkaloid from Alchornea glandulosa. Planta Med. 80, 1310 - 1314. https: // doi. org / 10.1055 / s- 0034 - 1382994.","Tapondjou, L. A., Kristina, J., Siems, K., 2016. 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Additional file 1: Supplementary Table 1. Subgroup analysis of the case-crossover design by CCI (0–1, 2–4, 5 or more). Supplementary Table 2. Sensitivity analysis of the case-crossover design with an additional washout period (control periods: 120–180 and 240–300 days prior to the index date).

The neurodegenerative synucleinopathies, including Parkinson’s disease and dementia with Lewy bodies, are characterized by a typically lengthy prodromal period of progressive subclinical motor and non-motor manifestations. Among these, idiopathic REM sleep behaviour disorder is a powerful early predictor of eventual phenoconversion, and therefore represents a critical opportunity to intervene with neuroprotective therapy. To inform the design of randomized trials, it is essential to study the natural progression of clinical markers during the prodromal stages of disease in order to establish optimal clinical end points. In this study, we combined prospective follow-up data from 28 centres of the International REM Sleep Behavior Disorder Study Group representing 12 countries. Polysomnogram-confirmed REM sleep behaviour disorder subjects were assessed for prodromal Parkinson’s disease using the Movement Disorder Society criteria and underwent periodic structured sleep, motor, cognitive, autonomic and olfactory testing. We used linear mixed-effect modelling to estimate annual rates of clinical marker progression stratified by disease subtype, including prodromal Parkinson’s disease and prodromal dementia with Lewy bodies. In addition, we calculated sample size requirements to demonstrate slowing of progression under different anticipated treatment effects. Overall, 1160 subjects were followed over an average of 3.3 ± 2.2 years. Among clinical variables assessed continuously, motor variables tended to progress faster and required the lowest sample sizes, ranging from 151 to 560 per group (at 50% drug efficacy and 2-year follow-up). By contrast, cognitive, olfactory and autonomic variables showed modest progression with higher variability, resulting in high sample sizes. The most efficient design was a time-to-event analysis using combined milestones of motor and cognitive decline, estimating 117 per group at 50% drug efficacy and 2-year trial duration. Finally, while phenoconverters showed overall greater progression than non-converters in motor, olfactory, cognitive and certain autonomic markers, the only robust difference in progression between Parkinson’s disease and dementia with Lewy bodies phenoconverters was in cognitive testing. This large multicentre study demonstrates the evolution of motor and non-motor manifestations in prodromal synucleinopathy. These findings provide optimized clinical end points and sample size estimates to inform future neuroprotective trials.

Objective To develop and evaluate the Korean version of a hospital-based transitional rehabilitation program (TRP), using daily living home for spinal cord injury (SCI) patients.Methods In this study, we developed the Korean version of a hospital-based TRP through domestic and overseas surveys and focus group meetings. By applying this to chronic SCI patients, we observed the functional and quality of life (QOL) changes and evaluated the degree of achievement of the core goals set for each patient during hospital-based TRP.Results Hospital-based TRP, for 21.8±3.9 days on average, was applied to four chronic SCI patients (two patients with long-term hospital stays and two homebound disabled individuals) with an average injury period of 736.8±185.4 days. The Korean version of the Spinal Cord Independence Measure (49.3±6.9 vs. 62.5±6.0; p

Snow is an important driver of ecosystem processes in cold biomes. Snow accumulation determines ground temperature, light conditions, and moisture availability during winter. It also affects the growing season’s start and end, and plant access to moisture and nutrients. Here, we review the current knowledge of the snow cover’s role for vegetation, plant-animal interactions, permafrost conditions, microbial processes, and biogeochemical cycling. We also compare studies of natural snow gradients with snow experimental manipulation studies to assess time scale difference of these approaches. The number of tundra snow studies has increased considerably in recent years, yet we still lack a comprehensive overview of how altered snow conditions will affect these ecosystems. Specifically, we found a mismatch in the timing of snowmelt when comparing studies of natural snow gradients with snow manipulations. We found that snowmelt timing achieved by snow addition and snow removal manipulations (average 7.9days advance and 5.5days delay, respectively) were substantially lower than the temporal variation over natural spatial gradients within a given year (mean range 56days) or among years (mean range 32days). Differences between snow study approaches need to be accounted for when projecting snow dynamics and their impact on ecosystems in future climates.

Snow is an important driver of ecosystem processes in cold biomes. Snow accumulation determines ground temperature, light conditions, and moisture availability during winter. It also affects the growing season's start and end, and plant access to moisture and nutrients. Here, we review the current knowledge of the snow cover's role for vegetation, plant-animal interactions, permafrost conditions, microbial processes, and biogeochemical cycling. We also compare studies of natural snow gradients with snow experimental manipulation studies to assess time scale difference of these approaches. The number of tundra snow studies has increased considerably in recent years, yet we still lack a comprehensive overview of how altered snow conditions will affect these ecosystems. Specifically, we found a mismatch in the timing of snowmelt when comparing studies of natural snow gradients with snow manipulations. We found that snowmelt timing achieved by snow addition and snow removal manipulations (average 7.9 days advance and 5.5 days delay, respectively) were substantially lower than the temporal variation over natural spatial gradients within a given year (mean range 56 days) or among years (mean range 32 days). Differences between snow study approaches need to be accounted for when projecting snow dynamics and their impact on ecosystems in future climates.

본 연구는 병원 교육전담간호사가 신규간호사 교육 경험을 통해 인지한 필수 간호술기와 간호학 실습교육의 개선방안에 대해 포커스 그룹 인터뷰와 설문조사의 혼합연구방법을 이용하여 탐색하였다. 총 119개의 간호술기 중에서 교육전담간호사 전원이 매우 중요하다고 평가한 간호술기가 23개였다. 또한 교육전담간호사들은 신규간호사가 실무적응의 어려움을 보이는 원인을 무균술을 포함한 기본 원칙의 준수와 조작의 미숙, 대상자 상황 이해의 어려움, 낯선 상황에서의 미숙한 대처, 간호사로서 태도의 미흡으로 인식하고 있었다. 신규간호사의 임상실무역량을 높이기 위해서는 간호교육에서 간호전문직 의식을 고취시키기 위한 사고력 증진 교육 강화와 더불어 임상실무 역량을 향상시키기 위한 임상 실습의 교육 체계 개선과 프로그램 개발이 필요하다. 본 연구의 결과는 향후 임상의 요구와 대학의 현실을 반영하는 실습내용과 방법을 구성하는데 있어 유용한 기준으로 활용될 수 있을 것으로 기대 한다.

Background Coronavirus disease 2019 (COVID-19) is a highly contagious disease that causes respiratory failure. Tracheostomy is an essential procedure in critically ill COVID-19 patients; however, it is an aerosol-generating technique and thus carries the risk of infection transmission. We report our experience with percutaneous tracheostomy and its safety in a real medical setting. Methods During the COVID-19 outbreak, 13 critically ill patients were admitted to the intensive care unit (ICU) at Daegu Catholic University Medical Center between February 24 and April 30, 2020. Seven of these patients underwent percutaneous tracheostomy using Ciaglia Blue Rhino. The medical environment, percutaneous tracheostomy method, and COVID-19 reverse transcriptase-polymerase chain reaction (RT-PCR) results were retrospectively reviewed. After treatment, the COVID-19 infection status of healthcare personnel was investigated by RT-PCR. Results The ICU contained negative pressure cohort areas and isolation rooms, and healthcare personnel wore a powered air-purifying respirator system. We performed seven cases of percutaneous tracheostomy in the same way as in patients without COVID-19. Five patients (71.4%) tested positive for COVID-19 by RT-PCR at the time of tracheostomy. The median cycle threshold value for the RNA-dependent RNA polymerase was 30.60 (interquartile range [IQR], 25.50–36.56) in the upper respiratory tract and 35.04 (IQR, 28.40–36.74) in the lower respiratory tract. All healthcare personnel tested negative for COVID-19 by RT-PCR. Conclusions Percutaneous tracheostomy was performed with conventional methods in the negative pressure cohort area. It was safe to perform percutaneous tracheostomy in an environment of COVID-19 infection.

마르셀 뒤샹의 〈큰 유리〉(1915-1923)는 후기의 〈에탕 도네〉(1946-1966)와 더불어 장기간에 걸쳐 치밀하게 제작된 작가의 대표작으로 꼽힌다. 〈큰 유리〉의 도상과 의미에 대해서는 다양한 분석과 해석이 시도되어 왔으나, 복잡한 형상이나 난해한 내용으로 인해 여전히 쉽게 접근하기 어려운 것이 사실이다. 특히 〈큰 유리〉의 상단부에 위치한 ‘신부’ 영역은 하단부의 ‘독신자’ 영역에 비해 압축적이고 단순화된 형상들로 인해 그 내용과 의미를 파악하기가 매우 어렵다. 이에 본 연구는 〈큰 유리〉의 신부에 초점을 맞추어 신부란 무엇이며 어떤 방식으로 작용하는지를 집중적으로 탐구한다. 신부야말로 작품 전체에 내재한 에로스의 작동을 가능케 하는 욕망의 대상이자 근원이라 해도 지나치지 않을 것이기 때문이다. 신부의 정체와 작용을 분석하기 위해, 본고는 크게 세 가지 단계와 수준에서 신부의 의미를 탐구할 것이다. 우선, 1912년 뒤샹의 뮌헨 시기에 제작된 회화를 중심으로 ‘처녀’에서 ‘신부’로 이행하는 진행과정에서 나타나는 신부의 기계-생물 혼성체적 특성을 살펴본다. 다음으로, 뒤샹이 남긴 『그린 박스』와 그의 사후에 출판된 노트를 기반으로 신부 형상의 정체와 욕망 작동의 구조를 집중적으로 분석한다. 마지막으로, 뒤샹의 『화이트 박스』를 중심으로 그가 신부 영역 혹은 신부 자체를 ‘하이퍼스페이스’로 접근하였음을 밝히고 이를 시각화하기 위해 뒤샹이 시도한 표상 방식을 앙리 푸앵카레의 과학철학과 연결하여 논의한다. 이를 통해 본고는 뒤샹에게 ‘신부’란 ‘독신자’로 상징되는 지상의 모든 존재에게 삶의 원동력을 제공하는 에로스의 근원이자 그 존재들이 3차원의 한계를 넘어 끊임없이 희구하는 초월적인 영역임을 밝힌다.

Objectives:In order to improve the stability of the ANAMMOX process, a three-stage ANAMMOX process combined with denitritation/nitritation process was operated, and effect of internal recycle ratio on the nitrogen removal efficiency was investigated.Methods:For the treatment of supernatant from anaerobic digester, a three-stage ANAMMOX process which combined as anoxic/oxic reactor and subsequent ANAMMOX reactor was installed. The reactor was designed with a working volume of 2.5 m3. The internal recycle ratio was considered as the main operating parameter, and the performance of nitrogen removal in the ANAMMOX process was evaluated.Results and Discussion:As the internal recycle ratio was increased from 0 to 1.5Q, reduction of the nitrogen load increased to 23.5 ± 3.8%, and the nitrogen load reduced by internal recycle was 0.22 ± 0.04 kgN/m3/d. Since the ratio of NO2-N/NH3-N introduced in the ANAMMOX process is very important, considering this together, the most suitable internal recycle ratio was determined to be 1.5Q. As a result of introducing the effluent from the A/O process into the ANAMMOX process, the nitrogen removal rate could be stably maintained at 1.27 kg/m3/d.Conclusions:In the ANAMMOX process in conjunction with the A/O process including internal recycle, the A/O process represented an effect of reducing the influent nitrogen load and nitrite concentration, and the ANAMMOX process was able to effectively remove residual nitrogen.

Chimeric antigen receptor (CAR) T-cells have demonstrated promising efficacy, particularly in hematologic malignancies. A challenge for CAR T-cells in solid tumors is the immunosuppressive tumor microenvironment (TME), characterized by high levels of multiple inhibitory factors, including TGFβ. We report results from a first-in-human phase 1 trial of castration-resistant prostate cancer-directed CAR T-cells armored with a dominant-negative TGFβ receptor (NCT03089203). Primary endpoints were safety and feasibility; secondary objectives included assessing CAR T-cell distribution, bioactivity, and disease response. All pre-specified endpoints were met. Eighteen patients enrolled and thirteen subjects received therapy across four dose levels. Five of 13 patients developed grade ≥2 cytokine release syndrome (CRS), including one patient who experienced a marked clonal CAR T-cell expansion, >98% reduction in PSA, and death following grade 4 CRS with concurrent sepsis. Acute increases in inflammatory cytokines correlated with manageable high-grade CRS events. Three additional patients achieved PSA declines of ≥30%, with CAR T-cell failure accompanied by upregulation of multiple TME-localized inhibitory molecules following adoptive cell transfer. CAR T-cell kinetics revealed expansion in the blood and tumor trafficking. Thus, clinical application of TGFβ-resistant CAR T-cells is feasible and generally safe. Future studies should use superior multi-pronged approaches against the TME to improve outcomes.

Snow is an important driver of ecosystem processes in cold biomes. Snow accumulation determines ground temperature, light conditions and moisture availability during winter. It also affects the growing season’s start and end, and plant access to moisture and nutrients. Here, we review the current knowledge of the snow cover’s role for vegetation, plant-animal interactions, permafrost conditions, microbial processes and biogeochemical cycling. We also compare studies of natural snow gradients with snow manipulation studies, altering snow depth and duration, to assess time scale difference of these approaches. The number of studies on snow in tundra ecosystems has increased considerably in recent years, yet we still lack a comprehensive overview of how altered snow conditions will affect these ecosystems. In specific, we found a mismatch in the timing of snowmelt when comparing studies of natural snow gradients with snow manipulations. We found that snowmelt timing achieved by manipulative studies (average 7.9 days advance, 5.5 days delay) were substantially lower than those observed over spatial gradients (mean range of 56 days) or due to interannual variation (mean range of 32 days). Differences between snow study approaches need to be accounted for when projecting snow dynamics and their impact on ecosystems in future climates. This work was funded by the National Science Foundation (NSF grants ArcSEES-1233854, ARC 1023623, OPP-1722572, OPP-1820883, OPP-1806213, NNA-1928237).

Snow is an important driver of ecosystem processes in cold biomes. Snow accumulation determines ground temperature, light conditions and moisture availability during winter. It also affects the growing season’s start and end, and plant access to moisture and nutrients. Here, we review the current knowledge of the snow cover’s role for vegetation, plant-animal interactions, permafrost conditions, microbial processes and biogeochemical cycling. We also compare studies of natural snow gradients with snow manipulation studies, altering snow depth and duration, to assess time scale difference of these approaches. The number of studies on snow in tundra ecosystems has increased considerably in recent years, yet we still lack a comprehensive overview of how altered snow conditions will affect these ecosystems. In specific, we found a mismatch in the timing of snowmelt when comparing studies of natural snow gradients with snow manipulations. We found that snowmelt timing achieved by manipulative studies (average 7.9 days advance, 5.5 days delay) were substantially lower than those observed over spatial gradients (mean range of 56 days) or due to interannual variation (mean range of 32 days). Differences between snow study approaches need to be accounted for when projecting snow dynamics and their impact on ecosystems in future climates. publishedVersion

This paper is based on empirically revealed doubts on the universal preference of the golden ratio proportion. An empirical study has been conducted in order to examine differences about ‘preferences of proportions’ on the golden ratio between South Korean and Western preceding studies by Kimberly Elam’s “Geometry of Design: Studies in Proportion and Composition”. Proportions are determined by mathematical logic, however ‘preferred proportions’ arise from cultural influences and experience. The research was conducted with two hundred subjects between the ages of twenty to thirty in Korea, with questions that showed ten choices of different proportions of rectangles. The data of comparisons clearly revealed that Korean had a preference to root proportion (1:1.414). These results obviously contradict previous studies conducted in the Western culture showed preferences of the golden ratio (1:1.618) (Benjafield, 1979, 2010; Pittard, 2007). The aspect of the results will provide deeper insights of the influence of the design process in specifically on the design form. The paper continues to examine and introduce various Korean traditional and modern objects, architectural structures that exemplify the research results. The paper concludes that various examples of root proportions can be found in Korean design environment showing a Korean preference for root ratio reflecting the here presented results.

Background Previous randomized trials of vitamin C, hydrocortisone, and thiamine on sepsis were limited by short-term vitamin C administration, heterogeneous populations, and the failure to evaluate each component’s effect. The purpose of this study was to determine whether vitamin C alone for ≥ 5 days or in combination with corticosteroids and/or thiamine was associated with decreased mortality across the sepsis population and subpopulation. Methods Nationwide population-based study conducted using the Korean National Health Insurance Service database. A total of 384,282 adult patients with sepsis who were admitted to the intensive care unit were enrolled from January 2017 to December 2019. The primary outcome was hospital mortality, while the key secondary outcome was 90-day mortality. Results The mean [standard deviation] age was 69.0 [15.4] years; 57% were male; and 36,327 (9%) and 347,955 did and did not receive vitamin C, respectively. After propensity score matching, each group involved 36,327 patients. The hospital mortality was lower by − 0.9% in the treatment group (17.1% vs 18.0%; 95% confidence interval, − 1.3 to − 0.5%; p p Conclusions Intravenous vitamin C of ≥ 5 days was significantly associated with decreased hospital and 90-day mortality in sepsis patients. Vitamin C combined with corticosteroids and/or thiamine in specific sepsis subgroups warrants further study.

Additional file 1: Appendix 1. ICD-10 codes used for identification of infectious condition.

Additional file 2: Table S1. ICD-10-based classification of organ dysfunction. Table S2. Anatomical Therapeutic Chemical codes and charge codes for intravenous vitamin C, corticosteroids, and thiamine. Table S3. ICD-10 codes for different sites of infection. Table S4. Baseline patient characteristics in the unmatched cohort. Table S5. Primary and secondary outcomes according to ICU length of stay. Table S6. Secondary outcomes of patients who survived to hospital discharge. Table S7. Risk factors for hospital mortality. Table S8. Primary and secondary outcomes according to vitamin C duration. Table S9. Primary and secondary outcomes in patients who received vitamin C for ��� 5 days and in matched controls. Table S10. Primary and secondary outcomes according to ICU length of stay in patients who received vitamin C for ��� 5 days and in matched controls. Table S11. Primary and secondary outcomes by subpopulations. Table S12. Primary and secondary outcomes by subpopulation in patients who received vitamin C for ��� 5 days and in matched controls.

Additional file 1: Table S1. Review of surgical outcomes of urinary tract resection.

Additional file 3: Fig. S1. Survival from hospital admission to day 90 by subpopulations. Fig. S2. Survival from hospital admission to day 90 by sepsis subpopulations among patients who received vitamin C for ���5 days and matched controls. Fig. S3. Association between vitamin C monotherapy and hospital mortality compared with in combination with corticosteroids and/or thiamine in the sepsis subpopulations.

In end-of-life care settings, family caregivers (FC) play an essential role as primary communicators with clinicians concerning patient care preferences. However, few studies have examined FC-clinician communication quality and identified the effects of communication quality on FC outcomes with a specific focus on end-of-life care settings. Also, no studies have established the role of FC decision-making quality in the relationship between FC-clinician communication quality and FC outcomes. Therefore, this study examined FC-clinician communication quality and its influence on FC depression, anxiety, and quality of life in Korean hospital-based hospice and palliative care settings. FC decision-making quality was addressed by measuring decisional conflict and decision regret. Using a cross-sectional design, 200 Korean FCs completed a web-based online questionnaire. Participants completed the Quality of Communication Scale, Center for Epidemiological Studies-Depression, Zung's Self-rating Anxiety Scale, Decisional Conflict Scale, Decision Regret Scale, and Caregiver Quality of Life Index-Cancer. Descriptive, bivariate, multivariate multiple regression analyses, and structural equation modeling were performed. FCs rated communication quality with physicians during patient end-of-life care as 6.00 (SD=1.64) of 10.0 and nurses as 6.16 (SD=2.13) of 10.0. FCs' mean depression score was 32.19 (SD=8.51) of 60, and the mean anxiety score was 47.26 (SD=9.01) of 80. Their mean quality of life score was 67.69 (SD=15.96) of 140. Concerning FCs��� decision-making quality, the mean decisional conflict score was 49.31 (SD=18.09) of 100 and the mean decision regret score was 44.63 (SD=18.04) of 100. Multivariate regression analysis showed that FCs reporting better FC-physician communication quality experienced less depression and anxiety and better quality of life after adjusting for demographic, clinical, and treatment location covariates. The study findings highlight the need for interventions to enhance communication between FCs and physicians and other clinicians to improve critical caregiver outcomes. Structural equation modeling showed that decisional conflict mediated the effect of FC-physician communication quality on FC depression and that decision regret mediated the impact of FC-physician communication quality on FC quality of life. Additional research is required to develop strategies for supporting FCs in Korean end-of-life care settings.

Background There was no practical guideline for the management of patients with central nervous system tumor in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has developed the guideline for glioblastoma. Subsequently, the KSNO guideline for World Health Organization (WHO) grade II cerebral glioma in adults is established. Methods The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified by searching PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL databases using specific and sensitive keywords as well as combinations of keywords regarding diffuse astrocytoma and oligodendroglioma of brain in adults. Results Whenever radiological feature suggests lower grade glioma, the maximal safe resection if feasible is recommended globally. After molecular and histological examinations, patients with diffuse astrocytoma, isocitrate dehydrogenase (IDH)-wildtype without molecular feature of glioblastoma should be primarily treated by standard brain radiotherapy and adjuvant temozolomide chemotherapy (Level III) while those with molecular feature of glioblastoma should be treated following the protocol for glioblastomas. In terms of patients with diffuse astrocytoma, IDH-mutant and oligodendroglioma (IDH-mutant and 1p19q codeletion), standard brain radiotherapy and adjuvant PCV (procarbazine+lomustine+vincristine) combination chemotherapy should be considered primarily for the high-risk group while observation with regular follow up should be considered for the low-risk group. Conclusion The KSNO's guideline recommends that WHO grade II gliomas should be treated by maximal safe resection, if feasible, followed by radiotherapy and/or chemotherapy according to molecular and histological features of tumors and clinical characteristics of patients.