Objective
To examine the effect of different management methods on the effectiveness of care preventive programmes for community-dwelling older adults.
Methods
This study comprised two ...facilitator-led (FL) and one participant-led (PL) preventive care classes in Japan. All participants received the intervention for approximately 12 weeks. Functional assessments, occupational dysfunctions, and subjective health were measured before and after the interventions. A two-way mixed design analysis of covariance (ANCOVA) was adopted to examine the effect of the interventions, adjusted for previous experiences with preventive care services. The level of significance was set at P < 0.05.
Results
Fourteen participants in the PL group (76.64 ± 6.48 years, 92.9% women) and 29 participants in the FL group (76.55 ± 5.75 years, 75.9% women) were included in the statistical analysis. ANCOVA showed significant group × time interaction effects in the Five Times Sit-to-Stand Test (FTSST), the Timed Up & Go (TUG), occupational deprivation of the Classification and Assessment of Occupational Dysfunction Scale, and self-rated health. Simple main effect tests showed that the TUG decreased significantly in the PL group, while occupational deprivation and self-rated health scores improved significantly. In contrast, FTSST scores significantly improved in the FL group.
Conclusion
PL-type management may be more appropriate for preventing social isolation and withdrawal, while FL-type management may be more appropriate for preventing physical frailty. Selecting not only adequate programmes but also an appropriate management type that matches the service purpose can help provide more effective care preventive services.
In recent years, various large-scale proteomic studies have demonstrated that mitochondrial proteins are highly acylated, most commonly by addition of acetyl and succinyl groups. These acyl ...modifications may be enzyme catalysed but can also be driven non-enzymatically. The latter mechanism is promoted in mitochondria due to the nature of the mitochondrial microenvironment, which is alkaline and contains high concentrations of acyl-CoA species. Protein acylation may modify enzyme activity, typically inhibiting it. We posited that organismal ageing might be accompanied by an accumulation of acylated proteins, especially in mitochondria, and that this might compromise mitochondrial function and contribute to ageing. In this study, we used R. norvegicus, C. elegans and D. melanogaster to compare the acylation status of mitochondrial proteins between young and old animals. We observed a specific age-dependent increase in protein succinylation in worms and flies but not in rat. Rats have two substrate-specific mitochondrial deacylases, SIRT3 and SIRT5 while both flies and worms lack these enzymes. We propose that accumulation of mitochondrial protein acylation contributes to age-dependent mitochondrial functional decline and that SIRT3 and SIRT5 enzymes may promote longevity through regulation of mitochondrial protein acylation during ageing.
Mitochondria play a critical role in aging, however, the underlying mechanism is not well understood. We found that a mutation disrupting the C. elegans homolog of Miro GTPase (miro-1) extends life ...span. This phenotype requires simultaneous loss of miro-1 from multiple tissues including muscles and neurons, and is dependent on daf-16/FOXO. Notably, the amount of mitochondria in the miro-1 mutant is reduced to approximately 50% of the wild-type. Despite this reduction, oxygen consumption is only weakly reduced, suggesting that mitochondria of miro-1 mutants are more active than wild-type mitochondria. The ROS damage is slightly reduced and the mitochondrial unfolded protein response pathway is weakly activated in miro-1 mutants. Unlike previously described long-lived mitochondrial electron transport chain mutants, miro-1 mutants have normal growth rate. These results suggest that the reduction in the amount of mitochondria can affect the life span of an organism through activation of stress pathways.
To determine cellular distribution of cell adhesion molecule 1 (CADM1), an immunoglobulin superfamily member, in the human oxyntic gastric mucosa, and to explore possible involvement in the ...development and peritoneal dissemination of signet ring cell (SRC) gastric carcinoma, which often develops in the oxyntic mucosa.
Immunohistochemistry and double immunofluorescence were conducted on surgical specimens of normal and SRC-bearing stomachs and peritoneal metastatic foci of SRCs. KATO-III (lacking CADM1) and HSC-43 (expressing CADM1) SRC cell lines were cocultured on a Met-5A mesothelial or TIG-1 fibroblastic cell monolayer.
In the oxyntic gland, some neck and nearly all base glandular cells were CADM1-positive, and mucin 5AC-positive cells were CADM1-negative, while some mucin 6-positive neck cells were CADM1-positive. Foveolar-epithelial, parietal, and endocrine cells were CADM1-negative. CADM1 was negative in all SRC carcinomas that were confined within the submucosa (n = 11) and all but one of those invading deeper (n = 15). In contrast, peritoneal metastatic foci of SRCs were CADM1-positive in five out of eleven cases (P < 0.01). In the cocultures, exogenous CADM1 made KATO-III cells adhere more and grow faster on a Met-5A monolayer, not on TIG-1 monolayers. HSC-43 cells adhered more and grew faster on Met-5A than on TIG-1 monolayers, which were partly counteracted by a function-neutralizing anti-CADM1 antibody.
Nearly all chief cells and a part of mucous neck cells express CADM1. SRC gastric carcinoma appears to emerge as a CADM1-negative tumor, but CADM1 may help SRCs develop peritoneal dissemination through promoting their adhesion and growth in the serosal tissue.
Alveolar epithelial cell apoptosis and protease/antiprotease imbalance based proteolysis play central roles in the pathogenesis of pulmonary emphysema but molecular mechanisms underlying these two ...events are not yet clearly understood. Cell adhesion molecule 1 (CADM1) is a lung epithelial cell adhesion molecule in the immunoglobulin superfamily. It generates two membrane associated C terminal fragments (CTFs), αCTF and βCTF, through protease mediated ectodomain shedding.
To explore the hypothesis that more CADM1-CTFs are generated in emphysematous lungs through enhanced ectodomain shedding, and cause increased apoptosis of alveolar epithelial cells.
Western blot analyses revealed that CADM1-CTFs increased in human emphysematous lungs in association with increased ectodomain shedding. Increased apoptosis of alveolar epithelial cells in emphysematous lungs was confirmed by terminal nucleotide nick end labelling (TUNEL) assays. NCI-H441 lung epithelial cells expressing mature CADM1 but not CTFs were induced to express αCTF both endogenously (by shedding inducers phorbol ester and trypsin) and exogenously (by transfection). Cell fractionation, immunofluorescence, mitochondrial membrane potentiometric JC-1 dye labelling and TUNEL assays revealed that CADM1-αCTF was localised to mitochondria where it decreased mitochondrial membrane potential and increased cell apoptosis. A mutation in the intracytoplasmic domain abrogated all three abilities of αCTF.
CADM1 ectodomain shedding appeared to cause alveolar cell apoptosis in emphysematous lungs by producing αCTF that accumulated in mitochondria. These data link proteolysis to apoptosis, which are two landmark events in emphysema.
Epilepsy is a relatively common condition, but more than 30% of patients have refractory epilepsy that is inadequately controlled by or is resistant to multiple drug treatments. Thus, new ...antiepileptic drugs based on newly identified mechanisms are required. A previous report revealed the suppressive effects of transient receptor potential melastatin 8 (TRPM8) activation on penicillin G-induced epileptiform discharges (EDs). However, it is unclear whether TRPM8 agonists suppress epileptic seizures or affect EDs or epileptic seizures in
TRPM8
knockout (TRPM8KO) mice. We investigated the effects of TRPM8 agonist and lack of TRPM8 channels on EDs and epileptic seizures. Mice were injected with TRPM8 agonist 90 min after or 30 min before epilepsy-inducer injection, and electrocorticograms (ECoGs) were recorded under anesthesia, while behavior was monitored when awake. TRPM8 agonist suppressed EDs and epileptic seizures in wildtype (WT) mice, but not in TRPM8KO mice. In addition, TRPM8KO mice had a shorter firing latency of EDs, and EDs and epileptic seizures were deteriorated by the epilepsy inducer compared with those in WT mice, with the EDs being more easily propagated to the contralateral side. These findings suggest that TRPM8 activation in epileptic regions has anti-epileptic effects.
•Freezing was applied to a focal seizure model in Wistar rat, in which epileptiform discharges (EDs) were induced by penicillin G.•EDs were occasionally provoked again, even after ...freezing.•Time-frequency analysis of electrocorticograms (ECoGs) in a freezing procedure was conducted.•Relapse of EDs after freezing was associated with the remaining power of the delta band induced by insufficient freezing.•The therapeutic effect of freezing can be predicted by the delta band of the ECoG obtained intraoperatively.
Cryosurgery is an alternative technique for minimally invasive treatment of lesions. We have recently examined cryosurgery for epilepsy in animal models, and found that penicillin G (PG)-induced epileptiform discharges (EDs) mostly vanished after freezing. However, EDs were provoked again after insufficient freezing. Inadequate freezing is not visually detectable during and just after freezing and is not predictable beforehand. To manage this problem, we examined whether intraoperative monitoring of electrocorticograms (ECoGs) can predict recurrence of EDs after cryosurgery.
A palm-sized cryoprobe system was applied to focal seizures in a Wistar rat model in which EDs were induced in advance by intracerebral injection of PG. During stable induction of EDs, the cryoprobe was carefully inserted into the epileptic region and this region was immediately frozen. After the series of prefreezing, freezing, and postfreezing, rats in which PG-induced EDs relapsed within 3 h were defined as the ED-relapsed (EDR) group, and other rats were defined as the ED-vanished (EDV) group. Time-frequency analysis was conducted on the ECoGs in each group through each freezing series.
Relapse of PG-induced EDs on ECoG after the freezing series was associated with the remaining power of the delta band in the freezing period more strongly in the EDR group than in the EDV group.
Success or failure of the freezing procedure can be predicted by the specificity of the delta band of the ECoG obtained intraoperatively.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses its S1 spike protein to bind to angiotensin-converting enzyme 2 (ACE2) on human cells in the first step of cell entry. Tryptanthrin, ...extracted from leaves of the indigo plant, Polygonum tinctorium, using d-limonene (17.3 microg/ml), is considered to inhibit ACE2-mediated cell entry of another type of coronavirus, HCoV-NL63. The current study examined whether this extract could inhibit the binding of the SARS-CoV-2 spike protein to ACE2. Binding was quantified as cell-bound fluorescence intensity in live cell cultures in which canine kidney MDCK cells overexpressing ACE2 were incubated with fluorescein-labeled S1 spike protein. When indigo extract, together with S1 protein, was added at 8,650* and 17,300* dilutions, fluorescence intensity decreased in a dose- and S1 extract-dependent manner, without affecting cell viability. When 4.0-nM tryptanthrin was added instead of the indigo extract, fluorescence intensity also decreased, but to a lesser degree than with indigo extract. Docking simulation analyses revealed that tryptanthrin readily bound to the receptor-binding domain of the S1 protein, and identified 2- and 7-amino acid sequences as the preferred binding sites. The indigo extract appeared to inhibit S1-ACE2 binding at high dilutions, and evidently contained other inhibitory elements as well as tryptanthrin. This extract may be useful for the prevention or treatment of SARS-CoV-2 infection. Key words: natural product, coronavirus disease 2019 prevention, severe acute respiratory syndrome coronavirus 2 spike protein, tryptanthrin, indigo plant, d-limonene, docking simulation
OBJECTIVE To avoid ischemic complications, it is important to consider the arteries in resection planning for lesions such as a vascular intraparenchymal tumor and arteriovenous malformation. Here, ...the clinical application of laser speckle flow imaging (LSFI) as a complementary method for the management of mass lesion-related arteries during surgery was evaluated. METHODS LSFI was performed in 12 patients with mass lesion-related arteries and brain tumor or arteriovenous malformation. The portable LSFI device was centered over the surgical field, and the relative cerebral blood flow (CBF) before and after the temporary interruption of the arteries was measured through continuous recording. CBF fluctuations permitted the classification of 3 kinds of artery-a feeding artery (FA), a "passing through" artery (PA), and a combined FA and PA (FA+PA)-based on decreased relative CBF in the inner resection area and unchanged CBF in the surrounding area (FA), unchanged CBF in the inner area and decreased CBF in the surrounding area (PA), or decreased CBF in both areas (FA+PA). This information allowed the appropriate management of these arteries and avoidance of postoperative ischemic complications. RESULTS Good visualization of CBF in the surgical field and relative CBF measurements in the regions of interest were achieved in real time with excellent spatiotemporal resolution. In 11 patients (92%) and 20 regions of interest, a decline in CBF was observed after temporary interruption of the FA (n = 8), PA (n = 2), and FA+PA (n = 2) types. There was a significant average reduction in CBF of 15.3% ± 29.0%. There were no ischemic complications, and only 1 patient had a postoperative ischemic lesion caused by resection through an artery that could not be viewed by LSFI due to a positional problem. CONCLUSIONS LSFI permits noninvasive and rapid intraoperative real-time recognition of mass lesion-related vasculature. This information can be used to avoid ischemic complications as a procedure complementary to neurophysiological monitoring.
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