The condition of muscle fiber atrophy and weakness that occurs in respiratory muscles along with systemic skeletal muscle with age is known as respiratory sarcopenia. The Japanese Working Group of ...Respiratory Sarcopenia of the Japanese Association of Rehabilitation Nutrition narratively reviews these areas, and proposes the concept and diagnostic criteria. We have defined respiratory sarcopenia as “whole-body sarcopenia and low respiratory muscle mass followed by low respiratory muscle strength and/or low respiratory function.” Respiratory sarcopenia can be caused by various factors such as aging, decreased activity, undernutrition, disease, cachexia, and iatrogenic causes. We have also created an algorithm for diagnosing respiratory sarcopenia. Respiratory function decreases with age in healthy older people, along with low respiratory muscle mass and strength. We have created a new term, “Presbypnea,” meaning a decline in respiratory function with aging. Minor functional respiratory disability due to aging, such as that indicated by a modified Medical Research Council level 1 (troubled by shortness of breath when hurrying or walking straight up hill), is an indicator of presbypnea. We also define sarcopenic respiratory disability as “a disability with deteriorated respiratory function that results from respiratory sarcopenia.” Sarcopenic respiratory disability is diagnosed if respiratory sarcopenia is present with functional disability. Cases of respiratory sarcopenia without functional disability are diagnosed as “at risk of sarcopenic respiratory disability.” Functional disability is defined as a modified Medical Research Council grade of 2 or more. Rehabilitation nutrition, treatment that combines rehabilitation and nutritional management, may be adequate to prevent and treat respiratory sarcopenia and sarcopenic respiratory disability.
Recently the Ni-hypersensitivity and toxicity of Ni have stimulated the development of Ni-free shape memory alloys. The β-Ti alloys are the most attractive candidates for biomedical shape memory ...alloys. Ti–Nb–X (X
=
Zr, Ta, Mo, Au, Pd, Pt, Al, Ga, Ge, O) and Ti–Mo–X (X
=
Ta, Nb, Zr, Au, Pd, Pt, Al, Ga, Ge) alloys have been developed and their shape memory effect and superelasticity were investigated systematically by the present authors for about 5 years. Although shape memory effect and superelasticity observed in the Ti–Nb alloys, the low critical stress for slip deformation caused the superelasticity not to reveal a large strain at room temperature. However, low temperature annealing and an aging treatment were effective in improving superelasticity. Additions of alloying elements such as Zr, Ta, Mo, Au, Pt and Al were also effective in stabilizing the superelasticity. In this paper, the basic characteristics of Ti–Nb, Ti–Nb–Zr, Ti–Nb–Ta and Ti–Nb–O are to be briefly reviewed based on the recent works of the present authors.
Shape memory and superelastic properties associated with the martensitic transformation from β to α″ martensite were investigated in Ti–(15–35)
at.% Nb alloys. The transformation strain and ...transformation temperature linearly decreased with increasing Nb content. The low critical stress for slip deformation resulted in only a small superelastic strain in solution-treated Ti–Nb binary alloys. Fine and dense ω precipitates formed during aging in the temperature range between 573 and 673
K were effective in increasing the critical stress for slip deformation in a Ti–26
at.% Nb alloy. An intermediate-temperature annealing at 873
K for 600
s without solution treatment was also effective in increasing the critical stress for slip deformation due to the fine subgrain structure. The higher critical stress for slip deformation resulted in a larger recovery strain and stable superelasticity. Excellent superelasticity was achieved by annealing at 873
K for 600
s followed by aging at 573
K due to the combined effect of work hardening and age hardening.
In the largest avascular low-nutrient intervertebral disc, resident cells would utilize autophagy, a stress-response survival mechanism by self-digestion and recycling wastes. Our goal was to ...elucidate the involvement of autophagy in disc homeostasis through RNA interference of autophagy-related gene 5 (Atg5).
In vitro, small interfering RNAs (siRNAs) targeting autophagy-essential Atg5 were transfected into rat disc cells. Cell viability with levels of autophagy including Atg5 expression, apoptosis, and senescence was assessed under serum starvation and/or pro-inflammatory interleukin-1 beta (IL-1β) stimulation. In vivo, time-course autophagic flux was monitored following Alexa Fluor® 555-labeled Atg5-siRNA injection into rat tail discs. Furthermore, 24-h temporary static compression-induced disruption of Atg5 siRNA-injected discs was observed by radiography, histomorphology, and immunofluorescence.
In disc cells, three different Atg5 siRNAs consistently suppressed autophagy with Atg5 protein knockdown (mean 44.4% 95% confidence interval: −51.7, −37.1, 51.5% −80.5, −22.5, 62.3% −96.6, −28.2). Then, Atg5 knockdown reduced cell viability through apoptosis and senescence not in serum-supplemented medium (93.6% −0.8, 21.4) but in serum-deprived medium (66.4% −29.8, −8.6) further with IL-1β (44.5% −36.9, −23.5). In disc tissues, immunofluorescence detected intradiscal signals for the labeled siRNA even at 56-d post-injection. Immunoblotting found 56-d autophagy suppression with prolonged Atg5 knockdown (33.2% −52.8, −5.3). With compression, Atg5 siRNA-injected discs presented radiographic height loss (−43.9, −0.8), histological damage (−5.5, −0.2), and immunofluorescent apoptosis (2.2, 22.2) and senescence (4.1, 19.9) induction compared to control siRNA-injected discs at 56 d.
This loss-of-function study suggests Atg5-dependent autophagy-mediated anti-apoptosis and anti-senescence. Autophagy could be a molecular therapeutic target for degenerative disc disease.
Abstract Context Transcatheter ablation of atrial fibrillation (AF) has undergone important development, with acceptable midterm results in terms of the safety and recurrence. A meta-analysis was ...performed to identify the periprocedural complications, midterm success rates and predictors of recurrence after AF ablation. Methods and results 4357 patients with paroxysmal AF, 1083 with persistent AF and 1777 with long standing AF were included. The pooled analysis showed that there was an in-hospital complication rate of tamponade requiring drainage of 0.99% (0.44–1.54; CI 99%), stroke with neurological persistent impairment of 0.22% (0.04–0.47; CI 99%), and stroke without of 0.36% (0.03–0.70; CI 99%) After a follow up of 22 (13–28) months and 1.23 (1.19–1.5; CI 99%) procedures per patient, the AF recurrence rate was 31.20% (24.87–34.81; CI 99%). The persistent AF patients exhibited a greater risk of recurrence after the first ablation (OR 1.78 1.14, 2.77 CI 99%), but a trend towards non significance was present in the patients with more than one procedure (OR 1.69 0.95, 3.00 CI 99%). The most powerful predictors of an AF ablation failure in the overall population were a recurrence within 30-days (OR 4.30; 2.00–10.80), valvular AF (OR 5.20; 2.22–9.50) and a left atrium diameter of more than 50 mm (OR 5.10 2.00–12.90; all CI 95%). Conclusions Persistent AF remains burdened from higher recurrence rates, however not so following redo-procedures. Three predictors, valvular AF, a left atrium diameter longer than 50 mm and recurrence within 30 days, could be appraised to drive selection of patients and therapeutic strategy.
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that integrates nutrients to execute cell growth. We hypothesized that mTOR is influential in the intervertebral disc—largest ...avascular, low-nutrient organ. Our objective was to identify the optimal mTOR inhibitor for treating human degenerative disc disease.
mTOR complex 1 (mTORC1) regulates p70/ribosomal S6 kinase (p70/S6K), negatively regulates autophagy, and is controlled by Akt. Akt is controlled by phosphatidylinositol 3-kinase (PI3K) and mTOR complex 2 (mTORC2). mTORC1 inhibitors—rapamycin, temsirolimus, everolimus, and curcumin, mTORC1&mTORC2 inhibitor—INK-128, PI3K&mTOR inhibitor—NVP-BEZ235, and Akt inhibitor—MK-2206—were applied to human disc nucleus pulposus (NP) cells. mTOR signaling, autophagy, apoptosis, senescence, and matrix metabolism were evaluated.
mTORC1 inhibitors decreased p70/S6K but increased Akt phosphorylation, promoted autophagy with light chain 3 (LC3)-II increases and p62/sequestosome 1 (p62/SQSTM1) decreases, and suppressed pro-inflammatory interleukin-1 beta (IL-1β)-induced apoptotic terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positivity (versus rapamycin, 95% confidence interval (CI) −0.431 to −0.194; temsirolimus, 95% CI −0.529 to −0.292; everolimus, 95% CI −0.477 to −0.241; curcumin, 95% CI −0.248 to −0.011) and poly (ADP-ribose) polymerase (PARP) and caspase-9 cleavage, senescent senescence-associated beta-galactosidase (SA-β-gal) positivity (versus rapamycin, 95% CI −0.437 to −0.230; temsirolimus, 95% CI −0.534 to −0.327; everolimus, 95% CI −0.485 to −0.278; curcumin, 95% CI −0.210 to −0.003) and p16/INK4A expression, and catabolic matrix metalloproteinase (MMP) release and activation. Meanwhile, dual mTOR inhibitors decreased p70/S6K and Akt phosphorylation without enhanced autophagy and suppressed apoptosis, senescence, and matrix catabolism. MK-2206 counteracted protective effects of temsirolimus. Additional disc-tissue analysis found relevance of mTOR signaling to degeneration grades.
mTORC1 inhibitors—notably temsirolimus with an improved water solubility—but not dual mTOR inhibitors protect against inflammation-induced apoptosis, senescence, and matrix catabolism in human disc cells, which depends on Akt and autophagy induction.
Since 1990, TiNi and TiNiX (X=Cu, Pd, Hf) thin films have been made by sputtering. The motivation for fabricating sputter-deposited TiNi-base shape memory alloy thin films originates from the ...great demand for the development of powerful microactuators which can drive micromachines, because actuation force and displacement are greatest in shape memory alloys amongst many actuator materials. Stable shape memory effect and superelasticity, which are equivalent to those of bulk alloys, have been achieved in the sputter-deposited TiNi thin films. Narrow transformation temperature hysteresis and high transformation temperatures were also achieved in TiNiCu and TiNi(Pd or Hf) thin films, respectively. In the meantime, unique microstructures consisting of nonequilibrium nanoscale precipitates and nonequilibrium compositions in the matrix have been found in Ti-rich TiNi thin films which were fabricated from amorphous condition by annealing at a considerably low temperature. Several micromachining processes have been proposed to fabricate some prototypes of microactuators utilizing TiNi thin films. The present paper will review the recent development of the above mentioned topics relating to sputter-deposited TiNi-base shape memory alloy thin films.
We previously found an inverse relationship between sialidase Neu1 expression and metastatic potential of marine cancer cells. To elucidate the mechanism underlying the cellular events, the human ...sialidase gene NEV1 was overexpressed or silenced in colon cancer HT-29 cells. When NEU1-overexpressing cells were injected transsplenically into mice, in vivo liver metastasis was significantly reduced. NEU1 suppressed cell migration, invasion and adhesion in vitro, whereas the silencing resulted in the opposite. One of the major molecular changes by NEU1 was decreased sialylation of integrin β4, assessed by PNA-and MAL-II-lectin blotting of immunoprecipitates with anti-integrin β4 antibody. The desialylation was accompanied by decreased phosphorylation of the integrin followed by attenuation of focal adhesion kinase and Erk1/2 pathway. Moreover, NEU1 caused downregulation of matrix metalloproteinase-7, overexpression of which is associated with cancer metastasis. Treatment of the cells with Ga1NAc-α-O-benzyl, an inhibitor of O-glycosylation, showed increased PNA-positive integrin β4 with its decreased phosphorylation, indicating that sialic acid removal from the integrin O-glycans results in the decreased phosphorylation. Biotinylation and immunofluorescence staining exhibited some NEU1 molecules to be at the cell surface accessible to the integrin. These results suggest that NEU1 is important in regulation of integrin β4-mediated signaling, leading to suppression of metastasis. doi:10.1038/onc.2008.471; published online 19 January 2009 Keywords: sialidase; integrin (34; sialic acid; metastasis; invasion; MMP-7
Shape memory characteristics of Ti–22Nb–(2–8)Zr(at.%) biomedical alloys were investigated by using tensile tests and X-ray diffraction (XRD) measurement. The alloy ingots were fabricated by an arc ...melting method. The ingots were cold-rolled by a reduction up to 95% in thickness at room temperature. All the alloys were solution-treated at 1173
K for 1.8
ks. The alloys subjected to the solution treatment exhibited large elongations ranging between 28 and 40%. The martensitic transformation temperature decreased by 38
K with 1
at.% increase of Zr content. The maximum recovered strain of 4.3% was obtained in the Ti–22Nb–4Zr(at.%) alloy. Ti–22Nb–(2–4)Zr(at.%) and Ti–22Nb–6Zr(at.%) alloys exhibited stable shape memory effect and superelastic behavior at room temperature, respectively.
Accurately estimating home range and understanding movement behavior can provide important information on ecological processes. Advances in data collection and analysis have improved our ability to ...estimate home range and movement parameters, both of which have the potential to impact species conservation. Fitting continuous-time movement model to data and incorporating the autocorrelated kernel density estimator (AKDE), we investigated range residency of forty-four jaguars fit with GPS collars across five biomes in Brazil and Argentina. We assessed home range and movement parameters of range resident animals and compared AKDE estimates with kernel density estimates (KDE). We accounted for differential space use and movement among individuals, sex, region, and habitat quality. Thirty-three (80%) of collared jaguars were range resident. Home range estimates using AKDE were 1.02 to 4.80 times larger than KDE estimates that did not consider autocorrelation. Males exhibited larger home ranges, more directional movement paths, and a trend towards larger distances traveled per day. Jaguars with the largest home ranges occupied the Atlantic Forest, a biome with high levels of deforestation and high human population density. Our results fill a gap in the knowledge of the species' ecology with an aim towards better conservation of this endangered/critically endangered carnivore-the top predator in the Neotropics.
PDF
