Objective
Investigate the relationship between sedentary behavior and physical function in adults with knee osteoarthritis (OA), controlling for moderate–vigorous physical activity (MVPA) levels.
...Methods
Sedentary behavior was objectively measured by accelerometer on 1,168 participants ages 49–83 years in the Osteoarthritis Initiative with radiographic knee OA at the 48‐month clinic visit. Physical function was assessed using 20‐meter walk and chair stand testing. Sedentary behavior was identified by accelerometer activity counts/minute <100. The cross‐sectional association between sedentary quartiles and physical function was examined by multiple linear regression, adjusting for demographic factors (age, sex, race/ethnicity, education level), health factors (comorbidity, body mass index, knee pain, knee OA severity, presence of knee symptoms), and average daily MVPA minutes.
Results
Adults with knee OA spent two‐thirds of their daily time in sedentary behavior. The average gait speed among the most sedentary quartile was 3.88 feet/second, which was significantly slower than the speed of the less sedentary groups (4.23, 4.33, and 4.33 feet/second, respectively). The average chair stand rate among the most sedentary group was significantly lower (25.9 stands/minute) than the rates of the less sedentary behavior groups (28.9, 29.1, and 31.1 stands/minute, respectively). These trends remained significant in multivariable analyses adjusted for demographic factors, health factors, and average daily MVPA minutes.
Conclusion
Being less sedentary was related to better physical function in adults with knee OA independent of MVPA time. These findings support guidelines to encourage adults with knee OA to decrease time spent in sedentary behavior in order to improve physical function.
This prospective longitudinal study investigated the association between baseline objectively measured sedentary time and 2-year onset of physical frailty.
We studied 1333 Osteoarthritis Initiative ...participants 55 to 83 years of age who were at risk for physical frailty, as assessed via low gait speed (< 0.6 m per second) or inability to perform a single chair stand. Baseline sedentary time was assessed through accelerometer monitoring. Hazard ratios (HRs) for physical frailty onset were estimated with discrete survival methods that controlled for moderate physical activity, sociodemographic characteristics, baseline gait and chair stand functioning, and health factors.
The incidence of physical frailty in this high-risk group was 20.7 per 1000 person-years. Greater baseline sedentary time (adjusted HR = 1.36 per sedentary hour; 95% confidence interval CI = 1.02, 1.79) was significantly related to incident physical frailty after control for time spent in moderate-intensity activities and other covariates.
Our prospective data demonstrated a strong relationship between daily sedentary time and development of physical frailty distinct from insufficient moderate activity. Interventions that promote reductions in sedentary behaviors in addition to increases in physical activity may help decrease physical frailty onset.
To examine whether a JAK inhibitor regulates functional responses of human salivary gland epithelial cells (SGECs) and disease parameters in an animal model of Sjögren's syndrome (SS).
Common ...differentially expressed genes (DEGs) were analyzed among peripheral blood mononuclear cells from patients with primary SS and other data sets, using blood and SG tissue. Validation of expression in SGs was analyzed by focus score. Inhibition of messenger RNA expression of DEGs and BAFF by filgotinib was analyzed using reverse transcription-polymerase chain reaction in primary SGECs. SG organoid cultures were used to determine the association between DEGs and BAFF via knockdown using small interfering RNAs or to determine regulation of BAFF by JAK inhibitor. Filgotinib (1.5 mg/kg) was intraperitoneally injected into 8-week-old NOD/ShiLtJ mice 3 times per week to analyze manifestations of disease. Finally, STAT signaling was assessed in human and mouse SGECs.
Expression of the DEGs IFNG and BAFF increased in SGs from patients with primary SS, as assessed by focus score. There was a significant correlation between IFIT2 and BAFF expression. JAK inhibitor suppressed interferon (IFN)-induced transcription of DEGs and BAFF in human primary SGECs. Knockdown of DEGs or inhibition of JAK caused reduced secretion of BAFF in human SG organoid cultures. In addition, filgotinib-treated mice exhibited increased salivary flow rates and marked reductions in lymphocytic infiltration of SGs. JAK inhibitor regulated IFNα- and IFNγ-induced pSTAT-1
, pSTAT-3
, and protein inhibitor of activated STAT-3 (PIAS-3) in human SGECs as well as IFNγ-induced pSTAT-1
, pSTAT-3
, and PIAS-1 in mouse SGECs.
JAK inhibition controls aberrant activation of SGECs and may be a novel therapeutic approach for primary SS.
This article presents a low random noise, a low-power, and a high-speed 2-mega pixels (Mp) global-shutter (GS)-type CMOS image sensor (CIS) using an advanced dynamic random access memory (DRAM) ...technology. GS CIS is one of the alternatives to solve image distortion issues caused by a conventional rolling-shutter (RS) CIS operation, since a 2-D image data can be simultaneously sampled by the in-pixel analog memory. To achieve a high-performance GS CIS, we proposed a novel architecture for digital pixel sensor (DPS) which is a high-speed GS operation CIS with a pixel-wise analog-to-digital converter (ADC) and an in-pixel digital memory. The major technologies of the proposed DPS can be summarized as follows: 1) two large coupling capacitors with mature DRAM technology; 2) extremely narrow pitch Cu-to-Cu (C2C) bond; and 3) finally low-powered ADC with a near sub-threshold operation. A perfect auto-zero operation for ADC is implemented using two DRAM capacitors, and a large number of transistors have to be integrated in the single pixel for realizing pixel-level ADC. Thus, each pixel has two fine-pitch C2C interconnections. This makes it possible to realize wafer-level stacked unit pixel. The proposed DPS with low-power consuming analog circuits has been successfully designed and developed for extremely fast-readout speed of max. 1200 frames per second (fps) and high sensitivity for low-illumination conditions.
OBJECTIVE: To compare risks of lower-extremity amputation between patients with Charcot arthropathy and those with diabetic foot ulcers. RESEARCH DESIGN AND METHODS: A retrospective cohort of ...patients with incident Charcot arthropathy or diabetic foot ulcers in 2003 was followed for 5 years for any major and minor amputations in the lower extremities. RESULTS: After a mean follow-up of 37 ± 20 and 43 ± 18 months, the Charcot and ulcer groups had 4.1 and 4.7 amputations per 100 person-years, respectively. Among patients <65 years old at the end of follow-up, amputation risk relative to patients with Charcot alone was 7 times higher for patients with ulcer alone and 12 times higher for patients with Charcot and ulcer. CONCLUSIONS: Charcot arthropathy by itself does not pose a serious amputation risk, but ulcer complication multiplicatively increases the risk. Early surgical intervention for Charcot patients in the absence of deformity or ulceration may not be advisable.
Alzheimer's disease (AD) is a form of dementia characterized by progressive memory decline and cognitive dysfunction. With only one FDA-approved therapy, effective treatment strategies for AD are ...urgently needed. In this study, we found that microRNA-485-3p (miR-485-3p) was overexpressed in the brain tissues, cerebrospinal fluid, and plasma of patients with AD, and its antisense oligonucleotide (ASO) reduced Aβ plaque accumulation, tau pathology development, neuroinflammation, and cognitive decline in a transgenic mouse model of AD. Mechanistically, miR-485-3p ASO enhanced Aβ clearance via CD36-mediated phagocytosis of Aβ in vitro and in vivo. Furthermore, miR-485-3p ASO administration reduced apoptosis, thereby effectively decreasing truncated tau levels. Moreover, miR-485-3p ASO treatment reduced secretion of proinflammatory cytokines, including IL-1β and TNF-α, and eventually relieved cognitive impairment. Collectively, our findings suggest that miR-485-3p is a useful biomarker of the inflammatory pathophysiology of AD and that miR-485-3p ASO represents a potential therapeutic candidate for managing AD pathology and cognitive decline.
Single-cell sequencing, which is used to detect clinically important tumor subpopulations, is necessary for understanding tumor heterogeneity. Here, we analyzed transcriptomic data obtained from 34 ...single cells from human lung adenocarcinoma (LADC) patient-derived xenografts (PDXs). To focus on the intrinsic transcriptomic signatures of these tumors, we filtered out genes that displayed extensive expression changes following xenografting and cell culture. Then, we performed clustering analysis using co-regulated gene modules rather than individual genes to minimize read drop-out errors associated with single-cell sequencing. This combined approach revealed two distinct intra-tumoral subgroups that were primarily distinguished by the gene module G64. The G64 module was predominantly composed of cell-cycle genes. E2F1 was found to be the transcription factor that most likely mediates the expression of the G64 module in single LADC cells. Interestingly, the G64 module also indicated inter-tumoral heterogeneity based on its association with patient survival and other clinical variables such as smoking status and tumor stage. Taken together, these results demonstrate the feasibility of single-cell RNA sequencing and the strength of our analytical pipeline for the identification of tumor subpopulations.
To elucidate the epigenetic mechanisms of drug resistance, epigenetically reprogrammed H460 cancer cells (R-H460) were established by the transient introduction of reprogramming factors. Then, the ...R-H460 cells were induced to differentiate by the withdrawal of stem cell media for various durations, which resulted in differentiated R-H460 cells (dR-H460). Notably, dR-H460 cells differentiated for 13 days (13dR-H460 cells) formed a significantly greater number of colonies showing drug resistance to both cisplatin and paclitaxel, whereas the dR-H460 cells differentiated for 40 days (40dR-H460 cells) lost drug resistance; this suggests that 13dR-cancer cells present short-term resistance (less than a month). Similarly, increased drug resistance to both cisplatin and paclitaxel was observed in another R-cancer cell model prepared from N87 cells. The resistant phenotype of the cisplatin-resistant (CR) colonies obtained through cisplatin treatment was maintained for 2-3 months after drug treatment, suggesting that drug treatment transforms cells with short-term resistance into cells with medium-term resistance. In single-cell analyses, heterogeneity was not found to increase in 13dR-H460 cells, suggesting that cancer cells with short-term resistance, rather than heterogeneous cells, may confer epigenetically driven drug resistance in our reprogrammed cancer model. The epigenetically driven short-term and medium-term drug resistance mechanisms could provide new cancer-fighting strategies involving the control of cancer cells during epigenetic transition.
The present study assessed whether costotransverse foramen block (CTFB) is noninferior to thoracic paravertebral block (TPVB) for postoperative analgesia in video-assisted thoracoscopic surgery ...(VATS) pulmonary resection.
Single-center, double-blinded, randomized, non-inferiority trial.
Operating room and intensive care unit or ward in a tertiary hospital.
Patients aged 20 to 80 years with American Society of Anesthesiology physical status 1 to 3 scheduled for elective VATS pulmonary resection.
Sixty patients were randomly allocated 1:1 to receive CTFB or TPVB using 15 mL aliquots of 0.5% ropivacaine at the T4–5 and T6–7 intercostal levels immediately after the induction of general anesthesia.
The primary outcome was the area under the curve (AUC) of numeric rating scale (NRS, 0 to 10) during 24 h postoperatively (noninferiority limit was 24; NRS 1 per hour). The secondary outcomes included postoperative opioid consumption, rescue analgesic use, postoperative nausea and vomiting, pulmonary function, dermatomal spread of the blockade, and quality of recovery.
Forty-seven patients were included for final analysis. The difference between the mean 24-h AUCs of NRS in the CTFB (34.25 ± 16.30, n = 24) and TPVB (39.52 ± 17.13, n = 23) groups was −5.27 (95% confidence interval CI, −15.09 to 4.55), with the upper limit of 95% CI being far below the predefined noninferiority margin of 24. There was no significant difference in the dermatomal spread of the blockades between the groups, as both reached the upper and lower most levels of T3 and T7 (median). Additionally, there were no significant differences in other secondary outcomes between the two groups.
The analgesic effect of CTFB was noninferior to that of TPVB during 24 h postoperatively in VATS pulmonary resection. Moreover, CTFB may offer potential safety benefits by keeping the tip of the needle far from the pleura and vascular structure.
•Costotransverse foramen block (CTFB) targets the entrance to the paravertebral space rather than the space itself.•CTFB showed noninferior analgesic effect compared to thoracic paravertebral block (TPVB) after VATS pulmonary resection.•Considering the technical and safety advantages of CTFB, it is a good alternative to TPVB in VATS pulmonary resection.
•A sustainable thermolytic platform of swine manure using CO2.•Suppressed dehydrogenation by CO2 can be applicable in air pollution controls.•CO2 converted into fuel (CO) and changed the ...compositional matrix of pyrolysates.•Mechanistic roles of CO2 can be catalytically expedited.
Pyrolysis of swine manure (SM) was conducted as a case study to establish an environmentally sound management of livestock manure. To build a more renewable pyrolysis platform for SM, this study selected carbon dioxide (CO2) as the reaction medium. In addition, CO2 was used in pyrolysis of SM to restrict the formation of toxic compounds, such as benzene derivatives and polycyclic aromatic hydrocarbons (PAHs). A series of thermo-gravimetric analysis (TGA) tests was done to understand the thermolysis of SM in the CO2 environment. The TGA tests elucidated no occurrence of heterogeneous reactions between the SM sample and the CO2. Moreover, the TGA tests of SM suggested that SM contains more volatile matter (VM) than lignocellulosic biomass. Non-catalytic transesterification of SM lipids confirmed that the dried SM sample contained 8.85 ± 0.05 wt% of lipids. This study also confirmed that the mechanistic role of CO2 was realized through the gas phase reactions between volatile pyrolysates evolved from the thermolysis of SM and CO2. In summary, CO2 donates O, enhancing the generation of CO through homogeneous reactions. In parallel, this study confirmed that CO2 suppress dehydrogenation. Therefore, the identified gas phase reactions between volatile pyrolysates and CO2 led to the compositional modifications in the condensable pyrolysates. However, such mechanistic features arising from CO2 only initiated at ≥520 °C. To expedite the reaction kinetics of the homogeneous reaction triggered by CO2, steel slag (SS) was used as a catalyst. Hence, the reaction kinetics associated with the mechanistic role of CO2 were substantially enhanced (up to 80%) when SS was used as a catalyst. Therefore, all experimental findings strongly suggest that CO2 can be utilized as a raw material in a thermo-chemical process. More importantly, all observations suggest that CO2 lopping can also be achieved in a thermo-chemical process. Lastly, this study shows that the high Cu content in SM was effectively immobilized through pyrolysis. Conclusively, this study experimentally proved that CO2 could be promising for restricting the formation of toxic pollutant in the thermo-chemical treatment in that CO2 offers an innovative and strategic means for controlling the ratio of C to H. Note that aromaticity and toxicity of chemical compounds are highly contingent on the ratio of C to H.
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