Cancer history and physical function in patients with cardiovascular disease.

Both cancer and cardiovascular disease (CVD) cause skeletal muscle mass loss, thereby increasing the likelihood of a poor prognosis. We investigated the association between cancer history and physical function and their combined association with prognosis in patients with CVD. We retrospectively reviewed 3,796 patients with CVD (median age: 70 years; interquartile range [IQR]: 61-77 years) who had undergone physical function tests (gait speed and 6-minute walk distance [6MWD]) at discharge. We performed multiple linear regression analyses to assess potential associations between cancer history and physical function. Moreover, Kaplan-Meier curves and Cox regression analyses were used to evaluate prognostic associations in four groups of patients categorized by the absence or presence of cancer history and of high or low physical function. Multiple regression analyses showed that cancer history was significantly and independently associated with a lower gait speed and 6MWD performance. A total of 610 deaths occurred during the follow-up period (median: 3.1 years; IQR: 1.4-5.4 years). The coexistence of low physical function and cancer history in patients with CVD was associated with a significantly higher mortality risk, even after adjusting for covariates (cancer history/low gait speed, hazard ratio [HR]: 1.93, P < 0.001; and cancer history/low 6MWD, HR: 1.61, P = 0.002). Cancer history is associated with low physical function in patients with CVD, and the combination of both factors is associated with a poor prognosis.

Leaf extract of Garcinia atroviridis promotes anti-heat stress and antioxidant effects in Caenorhabditis elegans.

Introduction: Garcinia atroviridis has been used for traditional medicines, healthy foods and tea. The chemical compositions and biological activities of fruit, stem bark and root have been widely studied. However, the phytochemical components and the biological activities in Garcinia atroviridis leaves (GAL) are limited. This research aims to study the phytochemical components and the stress resistance effects of GAL in Caenorhabditis elegans (C. elegans). Methods: To investigate the chemical components and antioxidant activities of GAL extract, the ethanol extract was characterized by liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF MS) analysis and C. elegans was used to evaluate the effects of GAL extracts on longevity and stress resistance. Results and discussion: The results revealed that the ethanol extract of GAL possesses free radical scavenging activities. Furthermore, GAL extract increased the lifespan of C. elegans by 6.02%, 15.26%, and 12.75% at concentrations of 25, 50, and 100 µg/mL, respectively. GAL extract exhibited improved stress resistance under conditions of heat and hydrogen peroxide-induced stress. The survival rates of GAL extract-treated worms were significantly higher than those of untreated worms, and GAL extract reduced reactive oxygen species (ROS) accumulation. Additionally, GAL extract treatment upregulated the expression of stress resistance-associated genes, including gst-4, sod-3, skn-1, and hsp16.2. GAL extract supplementation alleviated stress and enhanced longevity by inducing stress-related genes in C. elegans. The observed effects of GAL extracts may be attributed to the stimulation of oxidant enzymes mediated through DAF-16/FOXO and SKN-1/NRF2, as well as the enhancement of thermal defense in C. elegans. Collectively, this study provides the first evidence of the antioxidant activities of GAL and elucidates the underlying mechanisms of stress resistance.

Extraction and Fractionation of Human Gastric Mucins from Gastric Juice.

Mucin, a major component of the mucus, is considered to be one of the principal factors in the physiological defense mechanism of the gastrointestinal mucosa. Measuring the mucin content of human gastric mucus is a useful tool for the assessment of Helicobacter pylori (H. pylori) eradication or the involvement of mucus secretion in various gastroduodenal diseases. Here, we describe a methodology for the isolation of the mucin fraction from human gastric juice and the quantification of mucin.

Structural Elucidation of Sialylated O-Glycan Alditols Obtained from Mucins by Mass Spectrometry.

Acidic O-glycans having sialic acid and/or sulfate residue are abundantly expressed in intestinal mucins. However, structural elucidation of acidic O-glycans is a laborious and time-consuming task due to their large structural variations. Here, we describe a methodology of structural elucidation for sialylated O-glycan alditols from intestinal mucins using tandem mass spectroscopy. Methylesterification and mild periodate oxidation of sialylated O-glycan alditols assist mass analysis. This description includes the purification process of O-glycan alditols for structural analysis.

Mitochondria Play Essential Roles in Intracellular Protection against Oxidative Stress-Which Molecules among the ROS Generated in the Mitochondria Can Escape the Mitochondria and Contribute to Signal Activation in Cytosol?

Questions about which reactive oxygen species (ROS) or reactive nitrogen species (RNS) can escape from the mitochondria and activate signals must be addressed. In this study, two parameters, the calculated dipole moment (debye, D) and permeability coefficient (Pm) (cm s-1), are listed for hydrogen peroxide (H2O2), hydroxyl radical (•OH), superoxide (O2•-), hydroperoxyl radical (HO2•), nitric oxide (•NO), nitrogen dioxide (•NO2), peroxynitrite (ONOO-), and peroxynitrous acid (ONOOH) in comparison to those for water (H2O). O2•- is generated from the mitochondrial electron transport chain (ETC), and several other ROS and RNS can be generated subsequently. The candidates which pass through the mitochondrial membrane include ROS with a small number of dipoles, i.e., H2O2, HO2•, ONOOH, •OH, and •NO. The results show that the dipole moment of •NO2 is 0.35 D, indicating permeability; however, •NO2 can be eliminated quickly. The dipole moments of •OH (1.67 D) and ONOOH (1.77 D) indicate that they might be permeable. This study also suggests that the mitochondria play a central role in protecting against further oxidative stress in cells. The amounts, the long half-life, the diffusion distance, the Pm, the one-electron reduction potential, the pKa, and the rate constants for the reaction with ascorbate and glutathione are listed for various ROS/RNS, •OH, singlet oxygen (1O2), H2O2, O2•-, HO2•, •NO, •NO2, ONOO-, and ONOOH, and compared with those for H2O and oxygen (O2). Molecules with negative electrical charges cannot directly diffuse through the phospholipid bilayer of the mitochondrial membranes. Short-lived molecules, such as •OH, would be difficult to contribute to intracellular signaling. Finally, HO2• and ONOOH were selected as candidates for the ROS/RNS that pass through the mitochondrial membrane.

Trajectory of Abdominal Skeletal Muscle Changes During Cardiac Rehabilitation in Patients With Aortic Disease.

OBJECTIVE: This study focused on routine computed tomography imaging for aortic disease management and evaluated the trajectory of skeletal muscle changes through inpatient and outpatient cardiac rehabilitation. DESIGN: Prospective observational study included patients who underwent abdominal computed tomography three times (baseline, postacute care, and follow-up). The area and density of the all-abdominal and erector spine muscles and intramuscular adipose tissue were measured. A generalized linear model with patients as random effects was used to investigate skeletal muscle changes. RESULTS: Thirty-nine patients completed outpatient cardiac rehabilitation, and 60 were incomplete. Skeletal muscle area significantly decreased from baseline to the follow-up period only in the incomplete rehabilitation group. Skeletal muscle density significantly decreased from baseline to postacute care and increased at the follow-up period, but only patients who completed rehabilitation showed recovery up to baseline at the follow-up period. These trajectories were more pronounced in the erector spine muscle. Intramuscular adipose tissue showed a trend of gradual increase, but only the incomplete rehabilitation group showed a significant difference from baseline to the follow-up period. CONCLUSIONS: The density of skeletal muscle may reflect the most common clinical course; skeletal muscle area and intramuscular adipose tissue are unlikely to improve positively, and their maintenance seemed optimal.

The Association between the Level of Ankle-Brachial Index and the Risk of Poor Physical Function in Patients with Cardiovascular Disease.

AIMS: The progression of atherosclerosis and decline in physical function are poor prognostic factors in patients with cardiovascular disease (CVD). The ankle-brachial index (ABI) is a widely used indicator of the degree of progression of atherosclerosis, which may be used to identify patients with CVD who are at risk of poor physical function. This study examined the association between ABI and poor physical function in patients with CVD. METHODS: We reviewed the data of patients with CVD who completed the ABI assessment and physical function tests (6-min walking distance, gait speed, quadriceps isometric strength, and short physical performance battery). Patients were divided into five categories according to the level of ABI, and the association between ABI and poor physical function was examined using multiple logistic regression analysis. Additionally, r estricted cubic splines were used to examine the nonlinear association between ABI and physical function. RESULTS: A total of 2982 patients (median [interquartile range] age: 71[62-78] years, 65.8% males) were included in this study. Using an ABI range of 1.11-1.20 as a reference, logistic regression analysis showed that ABI ≤ 1.10 was associated with poor physical function. The restricted cubic spline analysis showed that all physical functions increased with an increase in ABI level. The increase in physical function plateaued at an ABI level of approximately 1.1. CONCLUSIONS: ABI may be used to identify patients with poor physical function. ABI levels below 1.1 are potentially associated with poor physical function in patients with CVD.

Association of sarcopenia defined by different skeletal muscle mass measurements with prognosis and quality of life in older patients with heart failure.

BACKGROUND: Diagnosing sarcopenia in heart failure (HF) patients is important, but how to assess skeletal muscle mass in HF patients with fluid retention is controversial. We aimed to examine the association between sarcopenia, defined by different skeletal muscle mass measurements, and clinical outcomes in older HF patients. METHODS: We included 546 older HF patients (≥ 65 years) who were assessed for sarcopenia at discharge (median age 77 years, 309 males). Sarcopenia was diagnosed using grip strength, usual gait speed, and skeletal muscle mass according to international criteria. We used mid-upper arm circumference (MUAC), mid-upper arm muscle circumference (MAMC), calf circumference (CC), and skeletal muscle mass index (SMI) assessed by bioelectrical impedance analysis to assess skeletal muscle mass and defined sarcopenia in each of these measurements. Prognostic outcomes were composite events (all-cause death and HF rehospitalization) and cardiovascular disease (CVD) events (CVD death and CVD rehospitalization). Quality of life (QOL) was assessed using the 36-item Short-Form Health Survey physical functioning (SF-36PF) score. RESULTS: The sarcopenia defined by MUAC [hazard ratio (HR): 2.50; 95 % confidence interval (95 % CI): 1.64-3.81; p < 0.001] or MAMC (HR: 1.98; 95 % CI: 1.35-2.92; p = 0.001) were associated with higher composite event rates than the non-sarcopenia. The sarcopenia defined by MUAC (HR: 1.88; 95 % CI: 1.25-2.83; p = 0.002) or MAMC (HR: 1.70; 95 % CI: 1.16-2.49; p = 0.007) were associated with higher CVD event rates than the non-sarcopenia. The sarcopenia defined by CC or SMI were not associated with prognoses. The sarcopenia defined by MUAC, MAMC, or CC were associated with low SF-36PF scores (all p < 0.05). CONCLUSIONS: These results suggest that a diagnosis of sarcopenia based on MUAC or MAMC rather than CC or SMI reflects prognosis and QOL in older HF patients.

Leg strength and incidence of heart failure in patients with acute coronary syndrome.

AIMS: The risk of developing heart failure (HF) after acute coronary syndrome (ACS) remains high. It is unclear whether skeletal muscle strength, in addition to existing risk factors, is a predictor for developing HF after ACS. We aimed to clarify the relationship between quadriceps isometric strength (QIS), a skeletal muscle strength indicator, and the risk of developing HF in patients with ACS. METHODS: We included 1,053 patients with ACS without a prior HF or complications of HF during hospitalization. The median (IQR) age was 67 (57-74) years. The patients were classified into two groups-high and low QIS-using the sex-specific median QIS. The endpoint was HF admissions. RESULTS: During a mean follow-up period of 4.4±3.7 years, 75 (7.1%) HF admissions were observed. After multivariate adjustment, a high QIS was associated with a lower risk of HF (hazard ratio [HR]: 0.52, 95% confidence interval [CI]: 0.32-0.87). HR (95% CI) per 5% body weight increment increase of QIS for HF incidents was 0.87 (0.80-0.95). Even when competing risks of death were taken into account, the results did not change. The inclusion of QIS was associated with increases in net reclassification improvement (0.26; 95% CI, 0.002-0.52) and an integrated discrimination index (0.01; 95% CI, 0.004-0.02) for HF. CONCLUSION: The present study showed that a higher level of QIS was strongly associated with a lower risk of developing HF after ACS. These findings suggest that skeletal muscle strength could be one of the factors contributing to the risk of developing HF after ACS.

The risk of developing heart failure (HF) after acute coronary syndrome (ACS) remains high. Basic attributes, coronary risk factors, and cardiac and renal function have been reported as risk factors for developing HF after ACS. However, the association between skeletal muscle strength and the development of HF after ACS is unclear. We included 1,053 patients with ACS without a prior HF or complications of HF during hospitalization and used quadriceps isometric strength (QIS) as a measure of skeletal muscle strength. We found that higher QIS was associated with a lower risk of developing HF after ACS. The results of our study suggest the benefit of assessing skeletal muscle strength in addition to basic attributes, coronary risk factors, and cardiac and renal function to assess the risk of developing HF after ACS.

LRRK2 negatively regulates glucose tolerance via regulation of membrane translocation of GLUT4 in adipocytes.

Epidemiological studies have shown that abnormalities of glucose metabolism are involved in leucine-rich repeat kinase 2 (LRRK2)-associated Parkinson's disease (PD). However, the physiological significance of this association is unclear. In the present study, we investigated the effect of LRRK2 on high-fat diet (HFD)-induced glucose intolerance using Lrrk2-knockout (KO) mice. We found for the first time that HFD-fed KO mice display improved glucose tolerance compared with their wild-type (WT) counterparts. In addition, high serum insulin and leptin, as well as low serum adiponectin resulting from HFD in WT mice were improved in KO mice. Using western blotting, we found that Lrrk2 is highly expressed in adipose tissues compared with other insulin-related tissues that are thought to be important in glucose tolerance, including skeletal muscle, liver, and pancreas. Lrrk2 expression and phosphorylation of its kinase substrates Rab8a and Rab10 were significantly elevated after HFD treatment in WT mice. In cell culture experiments, treatment with a LRRK2 kinase inhibitor stimulated insulin-dependent membrane translocation of glucose transporter 4 (Glut4) and glucose uptake in mouse 3T3-L1 adipocytes. We conclude that increased LRRK2 kinase activity in adipose tissue exacerbates glucose tolerance by suppressing Rab8- and Rab10-mediated GLUT4 membrane translocation.

Interleukin-13 Mediates Non-Steroidal Anti-Inflammatory-Drug-Induced Small Intestinal Mucosal Injury with Ulceration.

Non-steroidal anti-inflammatory drugs (NSAIDs), which are antipyretics and analgesics, cause gastrointestinal disorders, such as inflammation and ulcers. To prescribe NSAIDs more safely, it is important to clarify the mechanism of NSAID-induced gastrointestinal mucosal injury. However, there is a paucity of studies on small intestinal mucosal damage by NSAIDs, and it is currently unknown whether inflammation and ulceration also occur in the small intestine, and whether mediators are involved in the mechanism of injury. Therefore, in this study, we created an animal model in which small intestinal mucosal injury was induced using NSAIDs (indomethacin; IDM). Focusing on the dynamics of immune regulatory factors related to the injury, we aimed to elucidate the pathophysiological mechanism involved. We analyzed the pathological changes in the small intestine, the expression of immunoregulatory factors (cytokines), and identified cytokine secretion and expression cells from isolated lamina propria mononuclear cells (LPMCs). Ulcers were formed in the small intestine by administering IDM. Although the mRNA expression levels of IL-1ß, IL-6, and TNFα were decreased on day 7 after IDM administration, IL-13 mRNA levels increased from day 3 after IDM administration and remained high even on day 7. The IL-13 mRNA expression and the secretion of IL-13 were increased in small intestinal LPMCs isolated from the IDM-treated group. In addition, we confirmed that IL-13 was expressed in CD4-positive T cells. These results provided new evidence that IL-13 production from CD4-positive T cells in the lamina propria of the small intestine contributes to NSAID-induced mucosal injury.

Prognostic Utility of Skeletal Muscle Mass Metrics in Patients With Heart Failure.

BACKGROUND: Sarcopenia is associated with risks of various adverse outcomes, and the assessment of skeletal muscle mass is necessary for its diagnosis. However, heart failure (HF) is a syndrome characterised by fluid retention, which affects muscle mass measurements. Different measurement methods have been reported to have different prognostic implications. We investigated the association between skeletal muscle mass metrics measured with the use of bioelectrical impedance analysis (BIA) and anthropometric measures and prognosis in patients with HF. METHODS: The findings of 869 consecutive patients with HF were reviewed. We investigated the skeletal muscle mass index (SMI) measured with the use of BIA, the mid-upper arm circumference (MUAC), the arm muscle circumference (AMC), and the calf circumference (CC), and the patients were divided into 3 groups according to the sex-specific tertiles of the skeletal muscle mass metrics. The end points were all-cause death and readmission due to HF. RESULTS: The high MUAC and AMC groups showed significantly better prognoses than their respective low groups (combined events: high MUAC group hazard ratio [HR] 0.559, 95% confidence interval [CI] 0.395-0.789 [P < 0.01]; high AMC group HR 0.505, 95% CI 0.359-0.710 [P < 0.01]), although high SMI and high CC were not associated with better prognoses. CONCLUSIONS: Among patients with HF, MUAC and AMC are more associated with prognosis than SMI and CC, which are recommended in preexisting sarcopenia guidelines. MUAC and AMC may also be useful measures in sarcopenia assessments.

The plasma membrane of focal adhesions has a high content of cholesterol and phosphatidylcholine with saturated acyl chains.

Cellular functions, such as differentiation and migration, are regulated by the extracellular microenvironment, including the extracellular matrix (ECM). Cells adhere to ECM through focal adhesions (FAs) and sense the surrounding microenvironments. Although FA proteins have been actively investigated, little is known about the lipids in the plasma membrane at FAs. In this study, we examine the lipid composition at FAs with imaging and biochemical approaches. Using the cholesterol-specific probe D4 with total internal reflection fluorescence microscopy and super-resolution microscopy, we show an enrichment of cholesterol at FAs simultaneously with FA assembly. Furthermore, we establish a method to isolate the lipid from FA-rich fractions, and biochemical quantification of the lipids reveals that there is a higher content of cholesterol and phosphatidylcholine with saturated fatty acid chains in the lipids of the FA-rich fraction than in either the plasma membrane fraction or the whole-cell membrane. These results demonstrate that plasma membrane at FAs has a locally distinct lipid composition compared to the bulk plasma membrane.

Prognostic value of liver damage assessed through direct bilirubin levels and skeletal muscle weakness in patients with heart failure.

BACKGROUND: Patients with heart failure (HF) often exhibit signs of liver dysfunction such as high bilirubin concentrations, leading to physical dysfunction and poor prognosis. Nevertheless, the relationship between direct bilirubin (DB), a fractionated form of total bilirubin, and dynapenia remains unclear, as does their effect on prognosis. OBJECTIVES: This study investigated the association between DB concentrations and dynapenia in patients with HF. METHODS: This retrospective study included patients with HF who underwent assessments for DB concentration, and handgrip and leg strengths to evaluate dynapenia and muscle weakness, respectively. Multiple logistic regression analyses examined the associations of DB with muscle strength and dynapenia. Additionally, we examined the prognostic value of comorbid high DB concentrations (≥0.5 mg/dL) and dynapenia. The endpoint was all-cause mortality. RESULTS: Of 853 inpatients, high DB was identified in 147 and dynapenia in 377 (44.2%). Multiple regression analysis revealed that high DB was independently associated with decreased muscle strength (handgrip strength, P = 0.027; leg strength, P = 0.002). After adjusting for covariates, the high DB group (odds ratio: 1.800, 95% confidence interval [CI]: 1.203-2.695, P = 0.004) had a significantly higher risk of dynapenia than the low DB group. During the follow-up period, 189 patients died (median, 1.77 years; interquartile range, 0.64-3.81 years). The risk of death was significantly higher in the high DB and dynapenia group, even after adjusting for HF severity (hazard ratio: 2.610, 95% CI: 1.680-4.051, P<0.001). CONCLUSIONS: High DB is associated with muscle weakness, and when combined with dynapenia, DB predicts a poorer prognosis in patients with HF.

Evidence of Nrf2/Keap1 Signaling Regulation by Mitochodria-Generated Reactive Oxygen Species in RGK1 Cells.

It has been known that reactive oxygen species (ROS) are generated from the mitochondrial electron transport chain (ETC). Majima et al. proved that mitochondrial ROS (mtROS) caused apoptosis for the first time in 1998 (Majima et al. J Biol Chem, 1998). It is speculated that mtROS can move out of the mitochondria and initiate cellular signals in the nucleus. This paper aims to prove this phenomenon by assessing the change in the amount of manganese superoxide dismutase (MnSOD) by MnSOD transfection. Two cell lines of the same genetic background, of which generation of mtROS are different, i.e., the mtROS are more produced in RGK1, than in that of RGM1, were compared to analyze the cellular signals. The results of immunocytochemistry staining showed increase of Nrf2, Keap1, HO-1 and 2, MnSOD, GCL, GST, NQO1, GATA1, GATA3, GATA4, and GATA5 in RGK1 compared to those in RGM1. Transfection of human MnSOD in RGK1 cells showed a decrease of those signal proteins, suggesting mtROS play a role in cellular signals in nucleus.

Nrf2 Expression Is Decreased in LRRK2 Transgenic Mouse Brain and LRRK2 Overexpressing SH-SY5Y Cells.

Mutations in leucine rich-repeat kinase 2 (LRRK2) cause autosomal-dominant, late-onset Parkinson's disease (PD). Accumulating evidence indicates that PD-associated LRRK2 mutations induce neuronal cell death by increasing cellular reactive oxygen species levels. However, the mechanism of increased oxidative stress associated with LRRK2 kinase activity remains unclear. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that protects cells from oxidative stress by inducing the expression of antioxidant genes. In the present, it was found that decreased expression of Nrf2 and mRNA expression of its target genes in Lrrk2-transgenic mouse brain and LRRK2 overexpressing SH-SY5Y cells. Furthermore, knockdown of glycogen synthase kinase-3ß (GSK-3ß) recovered Nrf2 expression and mRNA expression of its target genes in LRRK2 overexpressing SH-SY5Y cells. We concluded that since Nrf2 is transcriptional factor for antioxidative responses, therefore, reduction of Nrf2 expression by LRRK2 may be part of a mechanism that LRRK2-induces vulnerability to oxidative stress in neuronal cells.

Prognostic impact of the coexistence of hepato-renal dysfunction and frailty in patients with heart failure.

BACKGROUND: Complex multi-organ interactions such as coexistence of hepato-renal dysfunction in heart failure (HF) adversely affects patient prognosis. However, the association between liver/kidney dysfunction and frailty and effects of their coexistence on HF prognosis remain unclear. METHODS: This retrospective cohort study included 922 patients with HF (median age, 72 years; interquartile range: 62-79 years). All patients underwent hepato-renal function testing using the model for end-stage liver disease, excluding international normalized ratio (MELD-XI) score and frailty score. Frailty was measured using a composite of four markers: handgrip strength, gait speed, serum albumin, and activities of daily living status, combined into a total frailty score (range 0-12). Patients were assigned to a frailty score <5 (without frailty) or ≥5 (frailty) group. The multivariable logistic regression model was used to analyze the association between MELD-XI score and frailty; the prognostic value of high MELD-XI score and frailty coexistence was investigated. The endpoint was all-cause mortality. RESULTS: After adjusting for covariates and dividing by the median MELD-XI score, the high MELD-XI score group [odds ratio: 1.663, 95 % confidence interval (CI): 1.200-2.304, p = 0.002] was significantly associated with frailty, compared with the low MELD-XI score group. One hundred and fifty deaths occurred during follow-up (median, 2.13 years; interquartile range, 0.93-4.09 years). Patients in the high MELD-XI score/frailty group had a significantly higher mortality risk, even after adjusting for HF severity (hazard ratio: 4.326, 95 % CI: 2.527-7.403, p < 0.001). CONCLUSIONS: Hepato-renal dysfunction is associated with frailty in patients with HF, which affects patient prognosis. BRIEF SUMMARY: This study showed that hepato-renal dysfunction in patients with HF, as assessed by the model for end-stage liver disease excluding international normalized ratio (MELD-XI) score, is associated with frailty, even after adjusting for factors involved in the frailty or severity of HF. Additionally, high MELD-XI score combined with frailty is associated with a poorer prognosis. These results suggest that hepato-renal dysfunction and frailty can be used for risk stratification in patients with HF.

SARC-F predicts poor motor function, quality of life, and prognosis in older patients with cardiovascular disease and cognitive impairment.

OBJECTIVES: We investigated whether SARC-F scores were associated with motor function, quality of life (QOL) related to physical function, and prognosis in older patients with cardiovascular disease (CVD) and cognitive impairment. METHODS: This was a retrospective cross-sectional cohort study. The study population consisted of 408 patients with CVD (≥60 years old) who completed the SARC-F questionnaire and Mini-Cog, a cognitive function test, at discharge. Sarcopenia was defined as a total SARC-F score ≥ 4 points. Patients who were cognitively-preserved (Mini-Cog score ≥ 3 points) were excluded. Patients completed the handgrip strength, leg strength, usual gait speed, 6-minute walking distance, short physical performance battery score, and 36-item Short-Form Health Survey Physical Functioning (SF-36PF) tests before discharge. Associations of SARC-F with physical function, QOL, and prognoses (i.e., composite of all-cause death and emergency CVD rehospitalization and the number of CVD rehospitalizations) were investigated. RESULTS: Sarcopenia (SARC-F score ≥ 4 points) was associated with poorer motor function test outcomes and SF-36PF scores (all P < 0.001). The correlations remained significant after adjusting for comorbidities (e.g., anemia, prior heart failure, and renal dysfunction). Sarcopenia was also associated with a poorer prognosis (hazard ratio: 1.574; 95 % confidence interval [CI], 1.011-2.445) and an increased risk of CVD rehospitalization (incidence rate ratio: 1.911; 95 % CI, 1.312-2.782) after adjusting for comorbidities. CONCLUSIONS AND IMPLICATIONS: In older patients with CVD and cognitive impairment, the SARC-F questionnaire may be a simple and inexpensive tool for identifying patients with decreased motor function and a poor prognosis.

Mitochondrial oxidative stress, mitochondrial ROS storms in long COVID pathogenesis.

Significance: This review discusses the coronavirus disease 2019 (COVID-19) pathophysiology in the context of diabetes and intracellular reactions by COVID-19, including mitochondrial oxidative stress storms, mitochondrial ROS storms, and long COVID. Recent advances: The long COVID is suffered in ~10% of the COVID-19 patients. Even the virus does not exist, the patients suffer the long COVID for even over a year, This disease could be a mitochondria dysregulation disease. Critical issues: Patients who recover from COVID-19 can develop new or persistent symptoms of multi-organ complications lasting weeks or months, called long COVID. The underlying mechanisms involved in the long COVID is still unclear. Once the symptoms of long COVID persist, they cause significant damage, leading to numerous, persistent symptoms. Future directions: A comprehensive map of the stages and pathogenetic mechanisms related to long COVID and effective drugs to treat and prevent it are required, which will aid the development of future long COVID treatments and symptom relief.

Voicing the story behind the cover.

In this selection, we celebrate the art of science by highlighting some of the submitted cover images from the past year. In this collection, our authors share the stories behind their inspiration for how to portray their science to captivate a broader audience.