Caprylic Acid Inhibits High Mobility Group Box-1-Induced Mitochondrial Damage in Myocardial Tubes.

Myocardial damage significantly impacts the prognosis of patients with cancer; however, the mechanisms of myocardial damage induced by cancer and its treatment remain unknown. We previously reported that medium-chain fatty acids (MCFAs) improve cancer-induced myocardial damage but did not evaluate the differences in effect according to MCFA type. Therefore, this study investigated the role of inflammatory cytokines in cancer-induced myocardial damage and the effects of three types of MCFAs (caprylic acid [C8], capric acid [C10], and lauric acid [C12]). In a mouse model, the C8 diet showed a greater effect on improving myocardial damage compared with C10 and C12 diets. Myocardial tubes differentiated from H9C2 cardiomyoblasts demonstrated increased mitochondrial oxidative stress, decreased membrane potential and mitochondrial volume, and inhibited myocardial tube differentiation following treatment with high-mobility group box-1 (HMGB1) but not interleukin-6 and tumor necrosis factor-α cytokines. However, HMGB1 treatment combined with C8 improved HMGB1-induced mitochondrial damage, enhanced autophagy, and increased mitochondrial biogenesis and maturation. However, these effects were only partial when combined with beta-hydroxybutyrate, a C8 metabolite. Thus, HMGB1 may play an important role in cancer-related myocardial damage. C8 counteracts HMGB1's effects and improves cancer-related myocardial damage. Further clinical studies are required to investigate the effects of C8.

Independence in activities of daily living was achieved using aerobic exercise without overwork weakness during rehabilitation: a case report of Lambert-Eaton myasthenic syndrome.

[Purpose] Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease characterized by decreased transmitter secretion from neuromuscular junctions and nerve terminals. Such cases require physical therapy for independently performing daily activities; however, care must be taken to avoid overwork weakness. This study aimed to investigate the effects of aerobic exercise-based physical therapy in patients with LEMS. [Participants and Methods] We report a case of LEMS with decreased muscle endurance due to inactivity. The participant was subjected to physical therapy with an exercise modality-improved muscle endurance with low-intensity repetitions, while monitoring subjective exercise intensity over time. [Results] The participant achieved independence activities of daily living without developing overwork weakness. [Conclusion] Appropriate physical therapy is an important aspect in treating LEMS.

Significance of CD10 for Mucosal Immunomodulation by ß-Casomorphin-7 in Exacerbation of Ulcerative Colitis.

ß-Casomorphin-7 (BCM), a breakdown product of milk ß-casein, exhibits opioid activity. Opioids are known to affect the immune system, but the effects of BCM on ulcerative colitis (UC) are not clear. We examined the effects of BCM on mucosal immunity using a mouse dextran sulfate sodium-induced colitis model and an in vitro CD8+ T cell activation model. Human UC patients were examined to reveal the relationship between CD10 and mucosal immunity. Combined treatment of the colitis model with thiorphan (TOP) inhibited BCM degradation by suppressing CD10 in the intestinal mucosa, activating mouse mucosal CD8, and suppressing CD4 and Treg. In the CD8+ T cell in vitro activation assay using mouse splenocytes, BCM inhibited the oxidative phosphorylation (OXPHOS) of CD8+ T cells and induced the glycolytic pathway, promoting their activation. Conversely, in a culture system, BCM suppressed OXPHOS and decreased defensin α production in IEC6 mouse intestinal epithelial cells. In the mouse model, BCM reduced defensin α and butyrate levels in the colonic mucosa. During the active phase of human ulcerative colitis, the downward regulation of ileal CD10 expression by CpG methylation of the gene promoter was observed, resulting in increased CD8 activation and decreased defensin α and butyrate levels. BCM is a potential aggravating factor for UC and should be considered in the design of dietary therapy. In addition, decreased CD10 expression may serve as an indicator of UC activity and recurrence, but further clinical studies are needed.

Differential Effects of Three Medium-Chain Fatty Acids on Mitochondrial Quality Control and Skeletal Muscle Maturation.

Nutritional interventions are one focus of sarcopenia treatment. As medium-chain fatty acids (MCFAs) are oxidized in the mitochondria and produce energy through oxidative phosphorylation (OXPHOS), they are key parts of nutritional interventions. We investigated the in vitro effects of three types of MCFA, caprylic acid (C8), capric acid (C10), and lauric acid (C12), in skeletal muscle cells. Compared with C10 and C12, C8 promoted mitophagy through the phosphatase and tensin homolog (PTEN)-induced kinase 1-Parkin pathway and increased the expression of peroxisome proliferator-activated receptor gamma coactivator 1-α and dynamin-related protein 1 to reduce mitochondrial oxidative stress and promote OXPHOS. Furthermore, the expression of myogenic differentiation 1 and myosin heavy chain increased in myotubes, thus promoting muscle differentiation and maturation. These results suggest that C8 improves mitochondrial quality and promotes skeletal muscle maturation; in contrast, C10 and C12 poorly promoted mitochondrial quality control and oxidative stress and suppressed energy production. Future animal experiments are required to establish the usefulness of C8 for nutritional interventions for sarcopenia.

Cancerous Conditions Accelerate the Aging of Skeletal Muscle via Mitochondrial DNA Damage.

Skeletal muscle aging and sarcopenia result in similar changes in the levels of aging markers. However, few studies have examined cancer sarcopenia from the perspective of aging. Therefore, this study investigated aging in cancer sarcopenia and explored its causes in vitro and in vivo. In mouse aging, in vitro cachexia, and mouse cachexia models, skeletal muscles showed similar changes in aging markers including oxidative stress, fibrosis, reduced muscle differentiation potential, and telomere shortening. Furthermore, examination of mitochondrial DNA from skeletal muscle revealed a 5 kb deletion in the major arc; truncation of complexes I, IV, and V in the electron transport chain; and reduced oxidative phosphorylation (OXPHOS). The mouse cachexia model demonstrated high levels of high-mobility group box-1 (HMGB1) and tumor necrosis factor-α (TNFα) in cancer ascites. Continuous administration of neutralizing antibodies against HMGB1 and TNFα in this model reduced oxidative stress and abrogated mitochondrial DNA deletion. These results suggest that in cancer sarcopenia, mitochondrial oxidative stress caused by inflammatory cytokines leads to mitochondrial DNA damage, which in turn leads to decreased OXPHOS and the promotion of aging.

Reversible Adsorption of Ammonia in the Crystalline Solid of a CO2H-Functionalized Cyclic Oligophenylene.

Ammonia (NH3) is a viable candidate for the storage and distribution of hydrogen (H2) due to its exceptional volumetric and gravimetric hydrogen energy density. Therefore, it is desirable to develop NH3 storage materials that exhibit robust stability across numerous adsorption-desorption cycles. While porous materials with polymeric frameworks are often used for NH3 capture, achieving reversible NH3 uptake remains a formidable challenge, primarily due to the high reactivity of NH3. Here, we advocate the use of CO2H-functionalized cyclic oligophenylene 1a with high chemical stability as a novel single-molecule-based adsorbent for NH3. Simple reprecipitation of 1a selectively yielded microporous crystalline solid 1a (N). Crystalline 1a (N) adsorbs up to 8.27 mmol/g of NH3 at 100 kPa and 293 K. Adsorbed NH3 in the pore of 1a (N) has a packing density of 0.533 g/cm3 at 293 K, which is close to the density of liquid NH3 (0.681 g/cm3 at 240 K). Crystalline 1a (N) also exhibits reversible NH3 adsorption over at least nine cycles, sustaining its storage capacity (1st cycle: 8.27 mmol/g; 9th cycle: 8.25 mmol/g at 100 kPa and 293 K) and crystallinity. During each desorption cycle, NH3 was removed from 1a (N) under reduced pressure (∼65 Pa), leaving <3% of the total uptake, and 1a (N) was fully purged under dynamic vacuum conditions (∼5 × 10-4 Pa at 293 K for 1 h) before the subsequent adsorption cycles. Thus, microporous crystalline 1a (N) can reliably adsorb and desorb NH3 repeatedly, which avoids the need for heat-based activation between cycles.

Berberine Improves Cancer-Derived Myocardial Impairment in Experimental Cachexia Models by Targeting High-Mobility Group Box-1.

Cardiac disorders in cancer patients pose significant challenges to disease prognosis. While it has been established that these disorders are linked to cancer cells, the precise underlying mechanisms remain elusive. In this study, we investigated the impact of cancerous ascites from the rat colonic carcinoma cell line RCN9 on H9c2 cardiomyoblast cells. We found that the ascites reduced mitochondrial volume, increased oxidative stress, and decreased membrane potential in the cardiomyoblast cells, leading to apoptosis and autophagy. Although the ascites fluid contained a substantial amount of high-mobility group box-1 (HMGB1), we observed that neutralizing HMGB1 with a specific antibody mitigated the damage inflicted on myocardial cells. Our mechanistic investigations revealed that HMGB1 activated both nuclear factor κB and phosphoinositide 3-kinases-AKT signals through HMGB1 receptors, namely the receptor for advanced glycation end products and toll-like receptor-4, thereby promoting apoptosis and autophagy. In contrast, treatment with berberine (BBR) induced the expression of miR-181c-5p and miR-340-5p while suppressing HMGB1 expression in RCN9 cells. Furthermore, BBR reduced HMGB1 receptor expression in cardiomyocytes, consequently mitigating HMGB1-induced damage. We validated the myocardial protective effects of BBR in a cachectic rat model. These findings underscore the strong association between HMGB1 and cancer cachexia, highlighting BBR as a promising therapeutic agent for myocardial protection through HMGB1 suppression and modulation of the signaling system.

Vitamin K prophylaxis in neonates: comparing two different oral regimens.

OBJECTIVE: This prospective study compared PIVKA-II and PT-INR levels in infants who received two vitamin K (VK) prophylactic regimens. METHODS: A single institution administered 119 healthy newborns 2 mg of VK syrup. Infants were assigned to a 3-time regimen (n = 56) with VK at birth, five days (5D), and 1-month-old (1 M), or a 13-time regimen (n = 63) with VK at birth, 5D, and then weekly for 11 weeks. RESULTS: The 13-time regimen significantly lowered PIVKA-II and reduced PT-INR at 1 M in both breastfed (PIVKA-II: 18-16 mAU/mL, p = 0.02; PT-INR: 1.37-1.13, p < 0.01) and formula-fed infants (PIVKA-II: 18-15 mAU/mL, p = 0.01; PT-INR: 1.54-1.24, p < 0.01), compared to baseline measurements taken at 5D. The 3-time regimen did not significantly alter PIVKA-II levels and only improved PT-INR (2.00-1.50, p < 0.01) in formula-fed infants. CONCLUSION: The 13-time VK regimen significantly enhanced coagulation profiles more effectively than the 3-time regimen.

Factors influencing the reduction in quadriceps muscle thickness in the paretic limbs of patients with acute stroke.

BACKGROUND & AIMS: Muscle atrophy is an early event that occurs after stroke, but there are few reports on the changes in skeletal muscle thickness in acute stroke. This study investigated the factors contributing to reduced muscle thickness in patients with acute stroke. METHODS: In total, 51 patients with stroke and the National Institute of the Health Stroke Scale (NIHSS) > 3 were included in our study. They were admitted to our hospital between July 2017 and May 2020. The quadriceps muscle thickness was measured with an ultrasound device within 2 days after admission and 14 days later. The collected data included age, sex, body mass index, stroke type, neuromuscular electrical stimulation, NIHSS, serum albumin at admission, start of enteral nutrition, Functional Oral Intake Scale (FOIS), start of mobilization and ambulation, number of physical and occupational therapy units, C-reactive protein at admission and whether surgery had been performed. These data were retrospectively retrieved from medical documents. A dietician calculated energy intake, protein intake, and energy adequacy. Multiple regression analysis was used to identify the factors associated with reduced quadriceps muscle thickness. The independent variables were NIHSS, date of start of enteral feeding, protein intake, FOIS, date of mobilization, and date of start of ambulation training. RESULTS: The rate of change in quadriceps muscle thickness of the paretic limb was -15.3 % (interquartile range, -46.1-14.8 %). Multiple regression analysis showed that the factors responsible for the decrease in muscle thickness on the paretic side were FOIS (ß: 0.376; 95 % Cl, 0.999 to 4.541) and the start date of ambulation (ß: -0.378; 95 % Cl, -2.575 to -0.543), with a multiple correlation coefficient of 0.456. CONCLUSION: The FOIS and the start date of ambulation after acute stroke were related to the rate of reduction in muscle thickness on the paretic side.

Mass spectrometry-based proteomic analysis of proteins adsorbed by hexadecyl-immobilized cellulose bead column for the treatment of dialysis-related amyloidosis.

BACKGROUND: Dialysis-related amyloidosis (DRA) is a severe complication in end-stage kidney disease (ESKD) patients undergoing long-term dialysis treatment, characterized by the deposition of ß2-microglobulin-related amyloids (Aß2M amyloid). To inhibit DRA progression, hexadecyl-immobilized cellulose bead (HICB) columns are employed to adsorb circulating ß2-microglobulin (ß2M). However, it is possible that the HICB also adsorbs other molecules involved in amyloidogenesis. METHODS: We enrolled 14 ESKD patients using HICB columns for DRA treatment; proteins were extracted from HICBs following treatment and identified using liquid chromatography-linked mass spectrometry. We measured the removal rate of these proteins and examined the effect of those molecules on Aß2M amyloid fibril formation in vitro. RESULTS: We identified 200 proteins adsorbed by HICBs. Of these, 21 were also detected in the amyloid deposits in the carpal tunnels of patients with DRA. After passing through the HICB column and hemodialyzer, the serum levels of proteins such as ß2M, lysozyme, angiogenin, complement factor D and matrix Gla protein were reduced. These proteins acted in the Aß2M amyloid fibril formation. CONCLUSIONS: HICBs adsorbed diverse proteins in ESKD patients with DRA, including those detected in amyloid lesions. Direct hemoperfusion utilizing HICBs may play a role in acting Aß2M amyloidogenesis by reducing the amyloid-related proteins.

Relationship between ETCO2 and PaCO2 under Changing Capnogram in Ventilated Infants with NAVA: An Observational Study.

This observational study evaluated the validity of end-tidal CO2 (ETCO2) as a surrogate for arterial PCO2 (PaCO2) in infants on neurally adjusted ventilatory assist (NAVA), particularly considering the influence of variable spontaneous breathing on capnography waveforms. The study involved 16 infants, analyzing 50 paired ETCO2 and PaCO2 values. Deming regression analysis highlighted a notably stronger correlation for maximum ETCO2 (r2 = 0.6783, p <0.0001) compared to mean ETCO2 (r2 = 0.5686, p <0.0001) and demonstrated a significantly weaker association for minimum ETCO2 (r2 = 0.1838). These findings emphasize the superior predictive value of maximum ETCO2 in estimating PaCO2, advocating its reliable use in clinical monitoring, especially given the dynamic capnography associated with NAVA's variable pressures. The results suggest ETCO2's potential to enhance noninvasive respiratory management, reduce the frequency of blood sampling, and improve overall care for infants requiring mechanical ventilation.

Demonstration of the Formation of a Selenocysteine Selenenic Acid through Hydrolysis of a Selenocysteine Selenenyl Iodide Utilizing a Protective Molecular Cradle.

Selenocysteine selenenic acids (Sec-SeOHs) and selenocysteine selenenyl iodides (Sec-SeIs) have long been recognized as crucial intermediates in the catalytic cycle of glutathione peroxidase (GPx) and iodothyronine deiodinase (Dio), respectively. However, the observation of these reactive species remained elusive until our recent study, where we successfully stabilized Sec-SeOHs and Sec-SeIs using a protective molecular cradle. Here, we report the first demonstration of the chemical transformation from a Sec-SeI to a Sec-SeOH through alkaline hydrolysis. A stable Sec-SeI derived from a selenocysteine methyl ester was synthesized using the protective cradle, and its structure was determined by crystallographic analysis. The alkaline hydrolysis of the Sec-SeI at -50 °C yielded the corresponding Sec-SeOH in an 89% NMR yield, the formation of which was further confirmed by its reaction with dimedone. The facile and nearly quantitative conversion of the Sec-SeI to the Sec-SeOH not only validates the potential involvement of this process in the catalytic mechanism of Dio, but also highlights its utility as a method for producing a Sec-SeOH.

ERVK13-1/miR-873-5p/GNMT Axis Promotes Metastatic Potential in Human Bladder Cancer though Sarcosine Production.

N-methyl-glycine (sarcosine) is known to promote metastatic potential in some cancers; however, its effects on bladder cancer are unclear. T24 cells derived from invasive cancer highly expressed GNMT, and S-adenosyl methionine (SAM) treatment increased sarcosine production, promoting proliferation, invasion, anti-apoptotic survival, sphere formation, and drug resistance. In contrast, RT4 cells derived from non-invasive cancers expressed low GNMT, and SAM treatment did not produce sarcosine and did not promote malignant phenotypes. In T24 cells, the expression of miR-873-5p, which suppresses GNMT expression, was suppressed, and the expression of ERVK13-1, which sponges miR-873-5p, was increased. The growth of subcutaneous tumors, lung metastasis, and intratumoral GNMT expression in SAM-treated nude mice was suppressed in T24 cells with ERVK13-1 knockdown but promoted in RT4 cells treated with miR-873-5p inhibitor. An increase in mouse urinary sarcosine levels was observed to correlate with tumor weight. Immunostaining of 86 human bladder cancer cases showed that GNMT expression was higher in cases with muscle invasion and metastasis. Additionally, urinary sarcosine concentrations increased in cases of muscle invasion. Notably, urinary sarcosine concentration may serve as a marker for muscle invasion in bladder cancer; however, further investigation is necessitated.

Highly Electrophilic Intermediates in the Bypass Mechanism of Glutathione Peroxidase: Synthesis, Reactivity, and Structures of Selenocysteine-Derived Cyclic Selenenyl Amides.

Selenocysteine (Sec)-derived cyclic selenenyl amides, formed by the intramolecular cyclization of Sec selenenic acids (Sec-SeOHs), have been postulated to function as protective forms in the bypass mechanism of glutathione peroxidase (GPx). However, their chemical properties have not been experimentally elucidated in proteins or small-molecule systems. Recently, we reported the first nuclear magnetic resonance observation of Sec-SeOHs and their cyclization to the corresponding cyclic selenenyl amides by using selenopeptide model systems incorporated in a molecular cradle. Herein, we elucidate the structures and reactivities of Sec-derived cyclic selenenyl amides. The crystal structures and reactions toward a cysteine thiol or a 1,3-diketone-type chemical probe indicated the highly electrophilic character of cyclic selenenyl amides. This suggests that they can serve not only as protective forms to suppress the inactivation of Sec-SeOHs in GPx but also as highly electrophilic intermediates in the reactions of selenoproteins.

Timing of Elective Cesarean Section and Neonatal Outcomes in Term Singleton Deliveries: A Single-Center Experience.

OBJECTIVE: This study aimed to evaluate the timing of elective cesarean sections at 37 to 41 weeks from a tertiary hospital in Japan. The primary outcome was the rate of adverse neonatal outcomes, especially focusing on neonates delivered at 38 weeks of gestation. STUDY DESIGN: The study population was drawn from singleton pregnancies delivered following planned cesarean birth at the Fukuda Hospital from 2012 to 2019. Information on deliveries was obtained from the hospital database, which contains clinical, administrative, laboratory, and operating room databases. RESULTS: After excluding women with chronic conditions, maternal complications, indications for multiple births, or a neonate with an anomaly, 2,208 neonates remained in the analysis. Among adverse neonatal outcomes, the rate was significantly higher in neonates delivered at 37 weeks of gestation (unadjusted odds ratio [OR] = 13.22 [95% confidence interval [CI]: 6.28, 27.86], p < 0.001) or 38 weeks of gestation (unadjusted OR = 1.82 [95% CI: 1.04, 3.19], p = 0.036) compared with neonates delivered at 39 to 41 weeks. The adjusted risk of any adverse outcome was significantly higher at 380-1/7 weeks (adjusted OR = 2.40 [95% CI: 1.35, 4.30], p = 0.003) and 382-3/7 weeks (adjusted OR = 1.89 [95% CI: 1.04, 3.44], p = 0.038) compared with neonates delivered at 39 to 41 weeks, respectively. CONCLUSION: Our findings suggest that elective cesarean sections might be best scheduled at 39 weeks or later. When considering a cesarean at 38 weeks, it appears that 384/7 weeks of gestation or later could be a preferable timing in the context of reducing neonatal risks. However, as the composite outcome includes mostly minor conditions, the clinical significance of this finding needs to be carefully interpreted. KEY POINTS: · Timing of elective cesarean sections from 37 to 41 weeks was evaluated in a Japanese tertiary hospital.. · Neonates delivered at 37 and 38 weeks had higher adverse outcome rates compared with 39 to 41 weeks.. · Scheduling elective cesarean sections at least 384/7 weeks or later may reduce neonatal risk..

Modeling Selenoprotein Se-Nitrosation: Synthesis of a Se-Nitrososelenocysteine with Persistent Stability.

The Se-nitrosation in selenoproteins such as glutathione peroxidase and thioredoxin reductase to produce Se-nitrososelenocysteines (Sec-SeNOs) has been proposed to play crucial roles in signaling processes mediated by reactive nitrogen species and nitrosative-stress responses, although chemical evidence for the formation of Sec-SeNOs has been elusive not only in proteins but also in small-molecule systems. Herein, we report the first synthesis of a Sec-SeNO by employing a selenocysteine model system that bears a protective molecular cradle. The Sec-SeNO was characterized using 1H and 77Se nuclear magnetic resonance as well as ultraviolet/visible spectroscopy and found to have persistent stability at room temperature in solution. The reaction processes involving the Sec-SeNO provide experimental information that serves as a chemical basis for elucidating the reaction mechanisms involving the SeNO species in biological functions, as well as in selenol-catalyzed NO generation from S-nitrosothiols.

Role of creatine shuttle in colorectal cancer cells.

The creatine shuttle translocates the energy generated by oxidative phosphorylation to the cytoplasm via mitochondrial creatine kinase (MTCK) and creatine kinase B (CKB) in the cytoplasm. It is not apparent how the creatine shuttle is related to cancer. Here, we analyzed the expression and function of CKB and MTCK in colorectal cancer (CRC) and investigated the role of the creatine shuttle in CRC. Compared with normal mucosa, 184 CRC tissues had higher levels of CKB and MTCK, and these levels were associated with histological grade, tumor invasion, and distant metastasis. CK inhibitor dinitrofluorobenzene (DNFB) on CRC cell lines HT29 and CT26 inhibited cell proliferation and stemness to less than 2/3 and 1/20 of their control levels, respectively. In this treatment, the production of reactive oxygen species increased, mitochondrial respiration decreased, and mitochondrial volume and membrane potential decreased. In a syngeneic BALB/c mouse model using CT26 cells pretreated with DNFB, peritoneal metastasis was suppressed to 70%. Phosphorylation of EGFR, AKT, and ERK1/2 was inhibited in DNFB-treated tumors. High ATP concentrations prevented EGFR phosphorylation in HT29 cells following DNFB treatment, CKB or MTCK knockdown, and cyclocreatine administration. Despite not being immunoprecipitated, CKB and EGFR were brought closer together by EGF stimulation. These findings imply that blocking the creatine shuttle decreases the energy supply, suppresses oxidative phosphorylation, and blocks ATP delivery to phosphorylation signals, preventing signal transduction. These findings highlight the critical role of the creatine shuttle in cancer cells and suggest a potential new cancer treatment target.

Structural Interconversion Based on Intramolecular Boroxine Formation.

A novel structural interconversion unit based on intramolecular boroxine formation has been developed. A macrocyclic triboronic acid consisting of three phenylboronic acid units linked by covalent linkers preferentially underwent intramolecular rather than intermolecular boroxine formation, resulting in a quantitative formation of tricyclic boroxine. This structural transformation was accompanied by changes in the polarity, flexibility, and size of the molecule. Dynamic interconversion between the macrocyclic triboronic acid and the tricyclic boroxine was achieved by simple heating/cooling, whereas no boroxine formation occurred upon heating when three boronic acid units were not connected by linkers. Thermodynamic analysis revealed that the entropic advantage of the intramolecular boroxine formation process resulted in these unique features. The entropically stabilized tricyclic boroxine also shows high stability with respect to hydrolysis.

Ambulation status at an acute care hospital predicts pneumonia and mortality in stroke patients: A retrospective cohort study.

AIM: Higher post-stroke functional performance is associated with lower mortality in patients with stroke. This study aimed to investigate the relationship between ambulation ability in the acute phase of stroke, and pneumonia and mortality 1 year after stroke onset. METHODS: This retrospective cohort study included consecutive stroke patients between April 2008 and December 2018. Patients were divided into six groups according to their Functional Ambulation Category score at discharge (0 [unable to walk] to 5 [able to walk independently]). We observed pneumonia cases and all-cause mortality over 1 year, and investigated the association between Functional Ambulation Category score and pneumonia or mortality. Survival analysis was carried out using Kaplan-Meier curves, log-rank tests and Cox regression models. RESULTS: We analyzed 1727 consecutive patients (median age 77 years; 54% men). During the observation period, 144 patients (8.3%) experienced pneumonia and 157 (9.1%) died. Increasing ambulatory impairment showed stepwise relationships with the risk of pneumonia and mortality. Compared with patients with a Functional Ambulation Category score of 5, those with scores of 4 and 3 showed no significant association with pneumonia risk; a score ≤2 was significantly different. There was a stepwise relationship between increased gait disturbance and risk of death compared with the Functional Ambulation Category 5 group. CONCLUSIONS: Ambulation ability at discharge from an acute hospital is an important predictor of pneumonia incidence and survival in stroke patients at 1 year; these associations were observed even after controlling for clinical parameters, such as stroke severity and comorbidity. Geriatr Gerontol Int 2022; 22: 554-559.

Modeling of selenocysteine-derived reactive intermediates utilizing a nano-sized molecular cavity as a protective cradle.

In the biological functions of selenoproteins, various highly reactive species formed by oxidative modification of selenocysteine residues have been postulated to play crucial roles. Representative examples of such species are selenocysteine selenenic acids (Sec-SeOHs) and selenocysteine selenenyl iodides (Sec-SeIs), which have been widely recognized as important intermediates in the catalytic cycle of glutathione peroxidase (GPx) and iodothyronine deiodinase, respectively. However, examples of even spectroscopic observation of Sec-SeOHs and Sec-SeIs in either protein or small-molecule model systems remain elusive so far, most likely due to their notorious instability. For the synthesis of small-molecule model compounds of these reactive species, it is essential to suppress their very facile bimolecular decomposition such as self-condensation and disproportionation. Here we outline a novel method for the synthesis of stable small-molecule model compounds of the selenocysteine-derived reactive species, in which a nano-sized molecular cavity is used as a protective cradle to accommodate the reactive selenocysteine unit. Stabilization by the molecular cradle led to the successful synthesis of Sec-SeOHs, which are stable in solution at low temperatures, and a Sec-SeI, which can be isolated as crystals. The catalytic cycle of GPx was investigated using the NMR-observable Sec-SeOH models, and all the chemical processes proposed for the catalytic cycle of GPx, including the bypass process from Sec-SeOH to the corresponding cyclic selenenyl amide, were experimentally confirmed. Detailed protocols for the syntheses of selenopeptide derivatives bearing the molecular cradle and for the spectroscopic monitoring of their reactions are provided.