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This study aimed to examine the validity of the care-needs levels classified in Japan's long-term care insurance system (LTCI-CNLs) when compared with patients' self-perceived functioning, disability and physical performance among patients receiving home medical care.
This was a multicenter cross-sectional study in Japan. Patients who were receiving continuous home medical care and who could respond to the questionnaire were enrolled in this study. In addition to the LTCI-CNLs, the 12-item version of the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) and the SARC-F were used to measure functioning, disability and physical performance (sarcopenia). In addition, correlations and associations of the LTCI-CNLs with the WHODAS 2.0 and SARC-F were analyzed using Spearman correlations and linear mixed models.
Data from 181 patients were included in the analyses. The LTCI-CNLs varied, ranging from support level 1 (5.5%) to care-needs level 5 (10.5%), with care-needs level 2 being the most prevalent (24.9%). Moderate correlations of the LTCI-CNLs with the WHODAS 2.0 and SARC-F were found (ρ = 0.58 and 0.44, respectively). Although WHODAS 2.0 and SARC-F scores varied within each LTCI-CNL, predicted WHODAS 2.0 and SARC-F scores increased as LTCI-CNL increased. Dementia was not associated with WHODAS 2.0 or SARC-F.
The LTCI-CNLs was associated with self-reported functioning, disability and physical performance among home medical care patients. Future studies can use the LTCI-CNLs as an outcome variable for specific care approaches or as a proxy covariate for casemix status. Geriatr Gerontol Int 2021; 21 229-237.
The LTCI-CNLs was associated with self-reported functioning, disability and physical performance among home medical care patients. Future studies can use the LTCI-CNLs as an outcome variable for specific care approaches or as a proxy covariate for casemix status. Geriatr Gerontol Int 2021; 21 229-237.Trophoblasts are important parts of the placenta and exert vital roles in the maternal-foetal crosstalk, and sufficient trophoblasts migration and invasion is critical for embryo implantation and normal pregnancy. Macrophages, as the major components of decidual microenvironment at maternal-foetal interface, can interact with trophoblasts to participate in the regulation of normal pregnancy. Previously, our group have demonstrated that trophoblasts could induce macrophages polarization to M2 subtype by secreting interleukin-6 (IL-6); however, the understanding of macrophages regulating the migration and invasion of trophoblasts is limited. In the present study, we used the co-cultured model to further investigate the effects of macrophages on trophoblasts migration and invasion. Our results showed that co-culture with macrophages promoted epithelial-to-mesenchymal transition (EMT) of trophoblasts, thereby enhancing their migrative and invasive abilities. Further experiments revealed that M2 macrophage-derived G-CSF was a key factor, which promoted the EMT, migration and invasion of trophoblasts via activating PI3K/Akt/Erk1/2 signalling pathway. Clinically, G-CSF was highly expressed in placental villous tissues of normal pregnancy patients compared to patients with recurrent spontaneous abortion, and its expression level was significantly correlation with EMT markers. Taken together, these findings indicate the important role of M2 macrophages in regulating trophoblasts EMT, migration and invasion, contributing to a new insight in concerning the crosstalk between macrophages and trophoblasts in the establishment and maintenance of normal pregnancy.Fibrosis is a pathologic condition characterized by excessive deposition of extracellular matrix and chronic scaring that can affect every organ system. Organ fibrosis is associated with significant morbidity and mortality, contributing to as many as 45% of all deaths in the developed world. In the lung, many chronic lung diseases may lead to fibrosis, the most devastating being idiopathic pulmonary fibrosis (IPF), which affects approximately 3 million people worldwide and has a median survival of 3.8 years. Currently approved therapies for IPF do not significantly extend lifespan, and thus, there is pressing need for novel therapeutic strategies to treat IPF and other fibrotic diseases. At the heart of pulmonary fibrosis are myofibroblasts, contractile cells with characteristics of both fibroblasts and smooth muscle cells, which are the primary cell type responsible for matrix deposition in fibrotic diseases. Much work has centered around targeting the extracellular growth factors and intracellular signaling regulators of myofibroblast differentiation. Recently, metabolic changes associated with myofibroblast differentiation have come to the fore as targetable mechanisms required for myofibroblast function. In this review, we will discuss the metabolic changes associated with myofibroblast differentiation, as well as the mechanisms by which these changes promote myofibroblast function. We will then discuss the potential for this new knowledge to lead to the development of novel therapies for IPF and other fibrotic diseases.Due to climate warming, alpine ecosystems are changing rapidly. Ongoing upward migrations of plants and thus an increase of easily decomposable substrates will strongly affect the soil microbiome. To understand how belowground communities will respond to such changes, we set up an incubation experiment with permafrost and active soil layers from northern (NW) and southern (SE) slopes of a mountain ridge on Muot da Barba Peider in the Swiss Alps and incubated them with or without artificial root exudates (AREs) at two temperatures, 4°C or 15°C. The addition of AREs resulted in elevated respiration across all soil types. Bacterial and fungal alpha diversity decreased significantly, coinciding with strong shifts in microbial community structure in ARE-treated soils. These shifts in bacterial community structure were driven by an increased abundance of fast-growing copiotrophic taxa. Fungal communities were predominantly affected by AREs in SE active layer soils and shifted towards fast-growing opportunistic yeast. In contrast, in the colder NW facing active layer and permafrost soils fungal communities were more influenced by temperature changes. These findings demonstrate the sensitivity of soil microbial communities in high alpine ecosystems to climate change and how shifts in these communities may lead to functional changes impacting biogeochemical processes.A left ventricular assist device (LVAD) is used for patients with severe heart failure. We present a case of a 35-year-old man who had undergone LVAD implantation 2 years ago for dilated phase of hypertrophic cardiomyopathy. He had right lower abdominal pain and was diagnosed with acute appendicitis. Single-incision laparoscopic surgery for appendicitis was performed. We incised approximately 3 cm of the umbilicus carefully because the driveline of LVAD was passing just caudal to the umbilicus. LVAD is only available for patients waiting for cardiac transplantation in Japan, and the number of patients with LVAD has been increasing. Adequate anticoagulant therapy is necessary because device thrombosis often causes fatal complications, but during emergency cases, the surgeons have to be cautious of bleeding and injury to the driveline of LVAD.The COVID-19 pandemic has had an important impact on the academic world. It is known that university studies can influence the mental health of students, and especially those studying health sciences. In this study, we therefore sought to analyse whether the current pandemic has affected the mental well-being of final-year nursing students. This was a multi-centre study, with a descriptive, longitudinal, and prospective design. Mental well-being was evaluated using the General Health Questionnaire. A total of 305 participants were included in the study, of whom 52.1% had experienced the COVID-19 pandemic. Statistically significant differences were found between the two groups analysed in terms of age, access to university, average marks, mental well-being self-esteem, emotional exhaustion, and sense of coherence. In the case of mental well-being, a direct association was found with both the pandemic situation (OR = 2.32, P = 0.010) and emotional exhaustion scores (OR = 1.20, P less then 0.001), while an inverse association was found with sense of coherence scores (OR = 0.45, P less then 0.001). This study shows that the mental health of students is a significant factor and one that must be taken into consideration when training nursing staff at university. There is a need to promote healthy habits and provide appropriate coping strategies. It is also important to train and prepare students for pandemic situations as these can have an important impact on the mental health of both the members of the public who will be treated by these future nursing professionals and the students themselves.
Using brain network and graph theory methods to analyze the Alzheimer's disease (AD) and mild cognitive impairment (MCI) abnormal brain function is more and more popular. Plenty of potential methods have been proposed, but the representative signal of each brain region in these methods remains poor performance.
We propose a highly-available nodes approach for constructing brain network of patients with MCI and AD. With resting-state functional magnetic resonance imaging (rs-fMRI) data of 84 AD subjects, 81 MCI subjects, and 82 normal control (NC) subjects from the Alzheimer's Disease Neuroimaging Initiative Database, we construct connected weighted brain networks based on the different sparsity and minimum spanning tree. Support Vector Machine of Radial Basis Function kernel was selected as classifier.
Accuracies of 74.09% and 77.58% in classification of MCI and AD from NC, respectively. We also performed a hub node analysis and found 18 significant brain regions were identified as hub nodes.
The findings of this study provide insights for helping understanding the progress of the AD. The proposed method highlights the effectively representative time series of brain regions of rs-fMRI data for construction and topology analysis brain network.
The findings of this study provide insights for helping understanding the progress of the AD. The proposed method highlights the effectively representative time series of brain regions of rs-fMRI data for construction and topology analysis brain network.
This waiting-list randomized controlled trial examined the effectiveness of a self-management mHealth app in improving fatigue and quality of life (QoL) in cancer patients and survivors.
Persons with cancer-related fatigue (CRF) were recruited across four English speaking countries, via social media, and randomized into intervention (n = 519) and control (n = 280) groups. Whereas the intervention group received immediate access to the Untire app, the control group received access only after 12-weeks. Primary outcomes fatigue severity and interference, and secondary outcome QoL were assessed at baseline, 4, 8, and 12-weeks. We ran generalized linear mixed models for all outcomes to determine the effects of app access (yes/no), over 12-weeks, following the intention-to-treat principle.
Compared with the control group, the intervention group showed significantly larger improvements in fatigue severity (d = 0.40), fatigue interference (d = 0.35), and overall QoL on average (d = 0.32) (P's < .01), but not for overall QoL in the past week (P = .07). Sensitivity analyses indicated that participants with medium or high app use benefited most when compared with nonusers and control participants (P's ≤ .02). The intervention effect on fatigue interference was slightly stronger in younger participants (≤56 vs. >56). Effects did not depend on education and cancer status. Reliable change analyses indicated that significantly more people showed full recovery for fatigue in the intervention vs the control group (P's = .02).
The Untire app can be an effective mHealth solution for cancer patients and survivors with moderate to severe CRF.
The Untire app can be an effective mHealth solution for cancer patients and survivors with moderate to severe CRF.There is increasing concern about the prevalence of depression and self-harm among children adolescents in many countries. Governments who commission and fund psychological interventions to address these difficulties want to know what is effective. The techniques available for synthesising gold standard evidence are increasingly sophisticated, but there are many criticisms of being completely reliant on this approach. A precautionary approach, where public policy decision-makers acknowledge that where the evidence is limited, the benefits of certain interventions are thought to outweigh the risks, including the risk of doing nothing. This later element may be particularly important in the domain of depression and self-harm, as both are associated with elevated risk of death by suicide.
Dental implants allow functional and aesthetic reestablishment. Titanium (Ti) implants emerge as the preferred choice because Ti is considered an inert material, highly resistant to corrosion. However, virtually no material can be considered universally biocompatible and this includes titanium.
To report an unusual presentation of inflammatory reaction after a Ti dental implant.
The patient presented to a dermatology clinic to evaluate lesions on her face. She reported the placement of dental implants 2 years earlier, one of which evolved with inflammatory signs and instability a few days after the procedure. As anti-inflammatory and antibiotic therapy were fruitless, after 3 months the implant was removed, but the inflammation persisted. On physical examination, painful erythematous-papule-nodular lesions were found on the left mandibular and submandibular region.
Culture tests for microorganisms were negative and histopathological examination revealed a chronic fistula with a foreign body reaction. Using X-ray fluorescence, Ti particles were found along the fistula wall.
Professionals should be aware of complications arising from dental implants, including Ti implants. Detailed anamnesis and laboratory investigation can assure diagnosis for specific therapeutic approaches.
Professionals should be aware of complications arising from dental implants, including Ti implants. Detailed anamnesis and laboratory investigation can assure diagnosis for specific therapeutic approaches.The market trend towards plant-based protein has seen a significant increase in the last decade. This trend has been projected to continue in the coming years because of the strong factors of sustainability and less environmental impact associated with the production of plant-based protein compared to animal, aside from other beneficial health claims and changes in consumers' dietary lifestyles. In order to meet market demand, there is a need to have plant-based protein ingredients that rival or have improved quality and functionality compared to the traditional animal protein ingredients they may replace. In this review article, we present a detailed and concise summary of the functionality challenges of some plant protein ingredients with associated physical, chemical, and biological processing techniques (traditional and emerging technologies) that have been attempted to enhance them. We cataloged the differences between several studies that seek to address the functionality challenges of selected plant-based protein ingredients without overtly commenting on a general technique that addresses the functionality of all plant-based protein ingredients. Additionally, we elucidated the chemistry behind some of these processing techniques and how they modify the protein structure for improved functionality. Although, many food industries are shifting away from chemical modification of proteins because of the demand for clean label product and the challenge of toxicity associated with scale-up of this technique, so physical and biological techniques are widely being adopted to produce a functional ingredient such as texturized vegetable proteins, hydrolyzed vegetable protein, clean label protein concentrates, de-flavored protein isolates, protein flour, and grits.
Spigelian hernia is a rare lateral ventral hernia traditionally repaired through open incision with extensive dissection. Three laparoscopic techniques have been reported in the literature intraperitoneal onlay mesh (IPOM), transabdominal preperitoneal (TAPP), and total extraperitoneal (TEP). TEP is less popular than the other approaches. We evaluated TEP's safety and effectiveness and compared different laparoscopic techniques.
All patients with Spigelian hernia who had undergone extended TEP (eTEP) repair with mesh in our center from January 2007 to February 2020 were studied. A three-port technique with a preperitoneal space created by telescope at the midline was adopted. A systematic review on laparoscopic mesh repair was performed by searching for "Spigelian hernia" and "laparoscopic" from 1999 to 2019 in the MEDLINE database.
Seven patients underwent eTEP repair for Spigelian hernia. Five presented with abdominal mass and underwent preoperative imaging. Two were diagnosed incidentally during TEP for inguinal hernia. The mean operative duration was 65 minutes (range, 40-93 minutes). There were no open conversions or intraoperative complications. The mean length of hospital stay was 1.4 days (range, 1-3 days). The mean follow-up period was 44.3 months. One patient developed seroma. There was no recurrence or chronic pain. We identified 197 laparoscopic mesh repairs reported in 41 articles. IPOM (n = 91) was the most popular approach, followed by TAPP (n = 70) and TEP (n = 36). Laparoscopic mesh repair of Spigelian hernia is safe and offers excellent outcomes.
We found the eTEP approach safe and effective for Spigelian hernia repair. IPOM, TAPP, and TEP are comparable.
We found the eTEP approach safe and effective for Spigelian hernia repair. IPOM, TAPP, and TEP are comparable.
Late teens and early adulthood is the peak age of onset for mental disorders. Currently, there is a gap between primary mental health care and more intensive mental health services for young people in New South Wales (NSW), Australia. Two headspace Early Intervention Teams (hEITs) were developed to bridge this gap in Sydney Local Health District (SLHD), in Sydney, Australia. This study aims to explore clinician experiences of hEIT after the first 2 years of implementation.
Semistructured interviews were conducted with key clinicians working within hEIT or closely associated with hEIT. Nine interviews were conducted, transcribed and analysed using qualitative thematic analysis.
Four themes were identified (1) building a bridge between services, (2) filling a clinical gap, (3) service collaborations and their challenges and (4) difficulties of small team size.
There is evidence that clinicians value the service provided by hEIT. There are difficulties such as referral confusion, staff turnover and suggestions to increase staffing to improve the stability, skill diversity and viability of the service. Findings have implications for other collaborative youth mental health models.
There is evidence that clinicians value the service provided by hEIT. There are difficulties such as referral confusion, staff turnover and suggestions to increase staffing to improve the stability, skill diversity and viability of the service. Findings have implications for other collaborative youth mental health models.The synthesis of robust high-spin carbon radicals is an important topic in organic chemistry. Toward this end, several porphyrin-stabilized radicals have been systematically explored. A singly naphthalene-fused porphyrin radical was synthesized by a reaction sequence consisting of a Suzuki-Miyaura coupling of β-borylated porphyrin with 2-bromobenzaldehyde, addition of mesityl Grignard reagent, intramolecular Friedel-Crafts alkylation, and final oxidation with DDQ or tBuOK/O2 . This strategy was also used to synthesize doubly naphthalene-fused porphyrins and syn- and anti-fused-anthracene-bridged porphyrin dimers. While singly naphthalene-fused porphyrin radical has been shown to be a stable monoradical, doubly naphthalene-fused porphyrins and anti-fused-anthracene-bridged porphyrin dimers have been shown to be closed-shell molecules. Finally, the syn-dimer was characterized as a surprisingly stable radical (t1/2 =28 days under ambient air and at 80 °C) that is storable for more than several months, despite its high-spin triplet ground-state carbon diradical.
The Ehlers-Danlos syndromes (EDSs) are a group of heritable disorders of connective tissue associated with an increased prevalence of both structural and functional GI conditions.
We used 10years (2005-2014) of administrative claims data comprised of 4294 people with clinician-diagnosed EDS, aged 5-62years, and compared their frequency of GI drug prescription claims to their age-, sex-, state of residence-, and earliest claim date-matched controls. We categorized the GI medications into the following groups acid suppressants, anti-emetics, irritable bowel syndrome drugs, and visceral hypersensitivity (VHS) medications.
Compared to controls, a significantly higher proportion of persons with EDS had prescription claims for at least one GI drug group, as well as for drugs in each of the four GI drug groups included in our study. By age-group, 25.7% children and 45.1% adults with EDS had prescription claims for at least one GI drug group compared with only 7.4% and 21.0% of controls, respectively (p<0.0001). By gender, 44.0% of women and 25.3% of men with EDS had prescription claims for at least one class of GI drugs compared with 19.2% and 9.6% of controls, respectively (p<0.0001).
Predominant medication burden occurs among women with EDS, beginning peri-pubertally for anti-emetics and VHS drugs. High GI medication burden underscores previous evidence that GI dysmotility is common among persons with EDS.
Predominant medication burden occurs among women with EDS, beginning peri-pubertally for anti-emetics and VHS drugs. High GI medication burden underscores previous evidence that GI dysmotility is common among persons with EDS.Approaches to achieve stable perovskite nanocrystals (PNCs) of interest, in particular those with large structural anisotropy, through protective coating of the inorganic shell at a single-nanocrystal (NC) level are comparatively few and limited in scope. Reported here is a robust amphiphilic-diblock-copolymer-enabled strategy for crafting highly-stable anisotropic CsPbBr3 nanosheets (NSs) by in situ formation of a uniform inorganic shell (1st shielding) that is intimately ligated with hydrophobic polymers (2nd shielding). The dual-protected NSs display an array of remarkable stabilities (i.e., thermal, photostability, moisture, polar solvent, aliphatic amine, etc.) and find application in white-light-emitting diodes. In principle, by anchoring other multidentate amphiphilic polymer ligands on the surface of PNCs, followed by templated-growth of shell materials of interest, a rich variety of dual-shelled, multifunctional PNCs with markedly improved stabilities can be created for use in optics, optoelectronics, and sensory devices.Hutchinson-Gilford progeria syndrome (HGPS) causes premature aging in children, with adipose tissue, skin and bone deterioration, and cardiovascular impairment. In HGPS cells and mouse models, high levels of interleukin-6, an inflammatory cytokine linked to aging processes, have been detected. Here, we show that inhibition of interleukin-6 activity by tocilizumab, a neutralizing antibody raised against interleukin-6 receptors, counteracts progeroid features in both HGPS fibroblasts and LmnaG609G/G609G progeroid mice. Tocilizumab treatment limits the accumulation of progerin, the toxic protein produced in HGPS cells, rescues nuclear envelope and chromatin abnormalities, and attenuates the hyperactivated DNA damage response. In vivo administration of tocilizumab reduces aortic lesions and adipose tissue dystrophy, delays the onset of lipodystrophy and kyphosis, avoids motor impairment, and preserves a good quality of life in progeroid mice. This work identifies tocilizumab as a valuable tool in HGPS therapy and, speculatively, in the treatment of a variety of aging-related disorders.In the present study, we demonstrate the coaction of thioredoxin and glutathione (GSH) systems in mouse liver against iron overload-induced oxidative stress (OS). Mice were injected intraperitoneally with an iron dextran solution twice a week for 3 weeks. Iron accumulation in mouse liver was demonstrated spectroscopically. To confirm the iron overload model in the liver, the increased gene expression levels of hepcidin (Hamp), ferroportin (Fpn1), and ferritin (Fth1), which regulate iron trafficking, were observed by a quantitative polymerase chain reaction. In the case of iron overload, the GSH level and the reduced glutathione/oxidized glutathione ratio, which represents a marker of OS, decreased significantly. An increase in the malondialdehyde level, one of the final products of the lipid peroxidation process, was observed. The gene expression of the thioredoxin system, including thioredoxin (Trx1) and thioredoxin reductase (TrxR1), was examined. Though TrxR1 expression decreased, no changes were observed in Trx1. The enzyme activity and semiquantitative protein expression of TRXR1 increased. The activity of GSH reductase and GSH peroxidase increased in the iron overload group. The gene and protein expressions of thioredoxininteracting protein, which is an indicator of the commitment of the cell to apoptosis, were elevated significantly. The increased protein expression of Bcl-2-related X protein and CASPASE-3, which is an indicator of apoptosis, increased significantly. In conclusion, excess iron accumulation in mouse liver tissue causes OS, which affects the redox state of the thioredoxin and GSH systems, inducing cell apoptosis and also ferroptosis due to increased lipid peroxidation and the depletion of GSH level.Methamphetamine use disorder involves continued use of the drug despite negative consequences. Such 'compulsivity' can be measured by reversal learning tasks, which involve participants learning action-outcome task contingencies (acquisition-contingency) and then updating their behaviour when the contingencies change (reversal). Using these paradigms, animal models suggest that people with methamphetamine use disorder (PwMUD) may struggle to avoid repeating actions that were previously rewarded but are now punished (inflexibility). However, difficulties in learning task contingencies (reinforcement learning) may offer an alternative explanation, with meaningful treatment implications. We aimed to disentangle inflexibility and reinforcement learning deficits in 35 PwMUD and 32 controls with similar sociodemographic characteristics, using novel trial-by-trial analyses on a probabilistic reversal learning task. Inflexibility was defined as (a) weaker reversal phase performance, compared with the acquisition-contingency phases, and (b) persistence with the same choice despite repeated punishments. Conversely, reinforcement learning deficits were defined as (a) poor performance across both acquisition-contingency and reversal phases and (b) inconsistent postfeedback behaviour (i.e., switching after reward). Compared with controls, PwMUD exhibited weaker learning (odds ratio [OR] = 0.69, 95% confidence interval [CI] [0.63-0.77], p less then .001), though no greater accuracy reduction during reversal. Furthermore, PwMUD were more likely to switch responses after one reward/punishment (OR = 0.83, 95% CI [0.77-0.89], p less then .001; OR = 0.82, 95% CI [0.72-0.93], p = .002) but just as likely to switch after repeated punishments (OR = 1.03, 95% CI [0.73-1.45], p = .853). These results indicate that PwMUD's reversal learning deficits are driven by weaker reinforcement learning, not inflexibility.Reactivities of non-heme iron(IV)-oxo complexes are mostly controlled by the ligands. Complexes with tetradentate ligands such as [(TPA)FeO]2+ (TPA=tris(2-pyridylmethyl)amine) belong to the most reactive ones. Here, we show a fine-tuning of the reactivity of [(TPA)FeO]2+ by an additional ligand X (X=CH3 CN, CF3 SO3- , ArI, and ArIO; ArI=2-(t BuSO2 )C6 H4 I) attached in solution and reveal a thus far unknown role of the ArIO oxidant. The HAT reactivity of [(TPA)FeO(X)]+/2+ decreases in the order of X ArIO > MeCN > ArI ≈ TfO- . Hence, ArIO is not just a mere oxidant of the iron(II) complex, but it can also increase the reactivity of the iron(IV)-oxo complex as a labile ligand. The detected HAT reactivities of the [(TPA)FeO(X)]+/2+ complexes correlate with the Fe=O and FeO-H stretching vibrations of the reactants and the respective products as determined by infrared photodissociation spectroscopy. Hence, the most reactive [(TPA)FeO(ArIO)]2+ adduct in the series has the weakest Fe=O bond and forms the strongest FeO-H bond in the HAT reaction.The standard of age-related glomerulosclerosis is unclear. Both signal transducer and activator of transcription 3 (STAT3) and autophagy are involved in age-related kidney disease. Therefore, we aimed to explore the standard, as well as the potential mechanism(s). A total of 44 patients who underwent radical nephrectomy were enrolled. Pearson analysis was performed to investigate the parameters with ages. The patients were divided into the young- and aged-kidney groups. Kidney morphological changes were evaluated by histology staining, senescence was evaluated by senescence-associated-β-galactosidase (SA-β-gal) staining, and autophagosome was measured by transmission electron microscopy. Moreover, Western blot and/or immunohistochemistry were accomplished to assess the expression of p16, STAT3, and glycoprotein130 (GP130) and autophagy-related proteins. Furthermore, human glomerular mesangial cells were administrated with tocilizumab (TCZ) and/or IL-6, and then the above indexes were tested again. Sclerotic glomerular density and glomerular sclerosis rate were significantly higher in individuals more than 40 years old, and they were strongly correlated with ages. Moreover, the expression of p16, STAT3, GP130, and p62 was significantly increased, while LC3II and autophagosome were statistically decreased in the aged-kidney. Glomeruli were hardly to stain with SA-β-gal. For the in vitro experiments, we observed that IL-6 significantly increased p16, STAT3, GP130, and p62, induced higher SA-β-gal staining, while downregulated LC3II and autophagosome. Furthermore, TCZ statistically reversed the effects of IL-6 on the above expression of proteins. Glomerular sclerosis rate might be one standard for natural renal aging, and IL-6/STAT3-mediated autophagy may participate in the development of age-related glomerulosclerosis.Glue protein as secretion from fruit fly larva plays a significant role in metamorphosis as cementing material for pupation sites. However, the biochemical composition of this macromolecule remains obscure. This study takes the advantage of high-resolution proteomic analysis to unveil the protein compositions. A glue protein group is identified as chitin-binding motifs by bioinformatic analysis. Computational modeling analysis of representative proteins illustrates the binding site between protein and chitin. A biosynthetic approach is used to fabricate a glue protein by a modified Escherichia coli recombinant system. The as-biosynthesized biomimetic glue protein is applied as an extracellular matrix to investigate its biocompatibility and functionality. It is found that the purified recombinant protein shows enhanced performance to cellular viability. This finding provides a potential biomacromolecule candidate as an extracellular matrix for cell culture.
Maternal complications caused by the cesarean delivery inhibit the capability of preserving the uterus and subsequent fertility. However, successful restoration of the incisional scar continuously still remains a challenge. This work was to evaluate the repairing effect of Human Wharton's Jelly Mesenchymal Stem Cells (hWJ-MSC) on incisional scar of the uterine.
Eighteen rats were randomly assigned into two groups and nine for each one group injected with hWJ-MSC in phosphate buffer saline (PBS) and the other injected with PBS for comparison.
With hWJ-MSC in PBS injected, the uterine endometrium and myometrium with full-thickness injury were restored and the functionality was greatly improved in comparison with the group only with PBS injected.
The hWJ-MSC can repair the injured uterine effectively by promoting the uterine endometrium and myometrium cells proliferation and according to the chi-square analysis the pregnancy is improved.
The hWJ-MSC can repair the injured uterine effectively by promoting the uterine endometrium and myometrium cells proliferation and according to the chi-square analysis the pregnancy is improved.
The subepithelial connective tissue graft (SCTG) and flap combination is a highly predictable root coverage procedure, with low complication rates. To our knowledge, this article reports the first case of two late SCTG complications, epithelial cell discharge, and subsequent epidermal inclusion cyst (EIC) formation.
A 35-year-old male presented with a 3-mm deep Miller Class II recession defect on the mandibular right canine and mesial root of mandibular right first molar. A mild discomfort was reported at 8 weeks after envelope flap+SCTG in #27. At 4 months after the procedure, the patient presented with persistent discomfort and minimally compressible recipient site diffuse swelling with discharge, which was cytologically diagnosed as normal epithelial cells. One year postoperatively, enlargement of the lesion was seen, and excisional biopsy was performed simultaneously with SCTG in #30. The lesion was diagnosed as EIC. At 8 months follow-up, the site healed uneventfully, the patient remained asymptomatic, and the site exhibited scar formation and no recurrence of the lesion.
This report highlights epithelial cell discharge and EIC formation as a rare yet possible SCTG complication and emphasizes the importance of an excisional biopsy as the means to obtain a definitive diagnosis and manage this complication.
This report highlights epithelial cell discharge and EIC formation as a rare yet possible SCTG complication and emphasizes the importance of an excisional biopsy as the means to obtain a definitive diagnosis and manage this complication.Although recent genome-wide association studies have identified risk loci that strongly associates with autism spectrum disorder (ASD), how to pinpoint the causal genes remains a challenge. We aimed to pinpoint the potential causal genes and explore the possible susceptibility and mechanism. A convergent functional genomics (CFG) method was used to prioritize the candidate genes by combining lines of evidence, including Sherlock analysis, spatio-temporal expression patterns, expression analysis, protein-protein interactions, co-expression and association with brain structure. A higher score in the CFG approach suggested that more evidence supported this gene as an ASD risk gene. We screened genes with higher CFG scores for candidate functional single nucleotide polymorphisms (SNPs). A genotyping experiment (602 ASD children and 604 healthy sex-matched children) and the dual-luciferase reporter gene assay were followed to validate the effects of SNPs. We identified three genes (MAPT, ZNF285, and TIGD5) as candng ASD risk variants could be further investigated in future research Autism Res 2021, 14 631-644. © 2021 International Society for Autism Research and Wiley Periodicals LLC.Despite its environmental robustness Pseudomonas putida strain KT2440 is very sensitive to DNA damage and displays poor homologous recombination efficiencies. To gain an insight into this deficiency isogenic ∆recA and ∆lexA1 derivatives of prophage-free strain P. putida EM173 were generated and responses of the recA and lexA1 promoters to DNA damage tested with GFP reporter technology. Basal expression of recA and lexA1 of P. putida were high in the absence of DNA damage and only moderately induced by norfloxacin. A similar behaviour was observed when equivalent GFP fusions to the recA and lexA promoters of E. coli were placed in P. putida EM173. In contrast, all SOS promoters were subject to strong repression in E. coli, which was released only when cells were treated with the antibiotic. Replacement of P. putida's native LexA1 and RecA by E. coli homologues did not improve the responsiveness of the indigenous functions to DNA damage. Taken together, it seems that P. putida fails to mount a strong SOS response due to the inefficacy of the crucial RecA-LexA interplay largely tractable to the weakness of the corresponding promoters and the inability of the repressor to shut them down entirely in the absence of DNA damage.Benzo(a)pyrene [B(a)P], which is a carcinogen, is a substance most typically known in cigarette smoke and considered as an important intermediary of lung cancer. The enzyme CYP1A1 is crucial for the metabolic conversion of B(a)P into the intermediates that induce carcinogenesis. Stimulation of the aryl hydrocarbon receptor, which is regulated by B(a)P, is thought to induce numerous signaling cascades. Interruption in the mitogen-activated protein kinase (MAPK) pathway causes changes in cellular processes and may alter the AhR pathway. The aim of this investigation is to examine the potential ability of a flavonoid pinocembrin (PCB) to alleviate B(a)P toxicity and analyze the underlying molecular mechanisms. We found that PCB inhibited DNA adduct formation by attenuating CYP1A1 expression through the suppression of the AhR/Src/ERK pathways. PCB mitigated the B(a)P-stimulated DNA damage, inhibited Src and ERK1/2 expression, decreased CYP1A1 expression, and reduced the B(a)P-induced stimulation of NF-κB and MAPK signaling in lung epithelial cells. Finally, the activity of CYP1A1 and Src in lung tissues from mice supplemented with PCB was noticeably decreased and lower than that in lung tissues from mice supplemented with B(a)P alone. Collectively, these data suggest that PCB may alleviate the toxic effects of PAHs, which are important environmental pollutants.One can take advantage of the influence of a polymer conjugated with a protein to control the thermal stability and the deployment of the protein. Here, the structural properties are reported of the protein-polymer conjugate myoglobin (Mb)-poly(ethyl ethylene phosphate) (PEEP) in the native and unfolded conformations, in order to understand the respective roles of the protein and of the polymer size in the stability of the conjugate. The effect is also investigated of the grafting density of the linear biodegradable polyphosphoesters covalently attached to the protein. It is observed that, while the conjugation process at room temperature does not modify the secondary and tertiary structure of the Mb, the unfolding process, as a function of temperature, depends on the grafting density. Small angle neutron scattering reveals that, at room temperature, conjugation does not alter the size of the native protein and that the thickness of the polymer shell around the protein increases as a function of grafting density and of polymer molecular weight. The denatured form of all conjugates is described by an unfolded chain and a correlation length due to the presence of local stiffness.
Botulinum toxin (BT) injection into the laryngeal muscles has been a standard treatment for spasmodic dysphonia (SD). However, few high-quality clinical studies have appeared, and BT is used off-label in most countries.
We performed a multicenter, placebo-controlled, randomized, double-blinded, parallel-group comparison/open-label clinical trial to obtain approval for BT (Botox) therapy in Japan. Twenty-four patients (22 with adductor SD and two with abductor SD) were enrolled. The primary end point was the change in the number of aberrant morae (phonemes) at 4weeks after drug injection. The secondary end points included the change in the number of aberrant morae, GRBAS scale, Voice Handicap Index (VHI), and visual analog scale (VAS) over the entire study period.
In the adductor SD group, the number of aberrant morae at 4weeks after injection was reduced by 7.0±2.30 (mean±SE) in the BT group and 0.2±0.46 in the placebo group (p=0.0148). The improvement persisted for 12weeks following BT injections. The strain element in GRBAS scale significantly reduced at 2weeks after BT treatment. The VHI and VAS scores as subjective parameters also improved. In the abductor SD group, one patient responded to treatment. Adverse events included breathy hoarseness (77.3%) and aspiration when drinking (40.9%) but were mild and resolved in 4weeks.
Botulinum toxin injection was safe and efficacious for the treatment of SD. Based on these results, BT injection therapy was approved as an SD treatment in Japan.
Botulinum toxin injection was safe and efficacious for the treatment of SD. Based on these results, BT injection therapy was approved as an SD treatment in Japan.
To describe and compare the characteristics of women with placenta accreta spectrum (PAS) and their pregnancy outcomes according to the presence of placenta praevia and a prior caesarean section.
Prospective population-based study.
All 176 maternity hospitals of eight French regions.
Two hundred and forty-nine women with PAS, from a source population of 520114 deliveries.
Women with PAS were classified into two risk-profile groups, with or without the high-risk combination of placenta praevia (or an anterior low-lying placenta) and at least one prior caesarean. These two groups were described and compared.
Population-based incidence of PAS, characteristics of women, pregnancies, deliveries and pregnancy outcomes.
The PAS population-based incidence was 4.8/10000 (95% CI 4.2-5.4/10000). After exclusion of women lost to follow up from the analysis, the group with placenta praevia and a prior caesarean included 115 (48%) women and the group without this combination included 127 (52%). In the group wan delivery, and they have better maternal outcomes.Proteins of the ADF/cofilin family play a central role in the disassembly of actin filaments, and their activity must be tightly regulated in cells. Recently, the oxidation of actin filaments by the enzyme MICAL1 was found to amplify the severing action of cofilin through unclear mechanisms. Using single filament experiments in vitro, we found that actin filament oxidation by MICAL1 increases, by several orders of magnitude, both cofilin binding and severing rates, explaining the dramatic synergy between oxidation and cofilin for filament disassembly. Remarkably, we found that actin oxidation bypasses the need for cofilin activation by dephosphorylation. Indeed, non-activated, phosphomimetic S3D-cofilin binds and severs oxidized actin filaments rapidly, in conditions where non-oxidized filaments are unaffected. Finally, tropomyosin Tpm1.8 loses its ability to protect filaments from cofilin severing activity when actin is oxidized by MICAL1. Together, our results show that MICAL1-induced oxidation of actin filaments suppresses their physiological protection from the action of cofilin. We propose that, in cells, direct post-translational modification of actin filaments by oxidation is a way to trigger their disassembly.The outbreak of COVID-19 led to a reduction in the number of organ transplant interventions in most Countries. In April 2020, at the Tor Vergata University in Rome, Italy, two patients on the waiting list for kidney transplantation (KT) declined a deceased donor's kidney offer. Therefore, between April 20 and 25, 2020, we conducted a telephone survey among our 247 KT waitlist patients. Our aim was to explore (a) the COVID-19 diffusion among them and (b) their current willingness to be transplanted in case of a kidney offer from a deceased donor. Two hundred and forty-three patients participated in a phone interview. One patient had died from COVID-19. Eighty-five (35%) KT candidates would decline any kidney offer, in most cases until the end of the COVID-19 pandemic. Upon a multivariate analysis, female gender (OR = 2.25, 95% CI = 1.26-4.03, P = .006), high cardiovascular risk (OR = 2.33, 95% CI = 1.06-5.08, P = .034), a waiting list time less then 3 years (OR = 0.375, 95% CI = 0.15-0.95, P = .04), and the need to be transferred to another hospital for HD (OR = 2.56, 95% CI = 1.10-5.9, P = .03) were associated with such refusal. The COVID-19 pandemic led to a fear of transplantation in a third of the KT candidates. Proactive educational webinars could be a useful tool to remove, or at least lessen, any doubts on the part of KT candidates and to avoid losing the opportunity to quit dialysis.
Communities in southwest Madagascar have co-evolved with a hypervariable environment and climate. The paleoclimate record reflects major fluctuations in climatic conditions over the course of Holocene human settlement. Archeological evidence indicates short-term occupations of sites, suggesting that frequent residential mobility and flexible subsistence strategies have been central features of life on the southwest coast for millennia. Today, despite rapid changes linked to globalization and increasing market integration, mobility and subsistence flexibility remain key to the lives of communities of the region.
In this article, we advocate closer consideration of the social dimensions of the human niche, and their inextricable links to the biophysical world. Specifically, we explore the theoretical implications of applying a Niche Construction Theory framework to understanding the role of social memory in constructing the human niche of SW Madagascar. We look at how social memory facilitates mobility, resence and sustainability.There is intense interest in imaging intracellular metal ions because of their vital roles in many cellular processes. The challenge has been to develop chemical approaches that can detect metal ions in a cell-type-specific manner. Herein we report the design of an enzyme-activatable DNAzyme sensor technology that can distinguish metal-ion signals in tumor cells from those in normal cells both in vitro and in vivo. Specifically, the sensing activity of a traditional DNAzyme sensor was inhibited by engineering with a blocking sequence containing an abasic site that can be cleaved by cancer-specific enzymes and thus enables the selective recovery of metal-ion sensing capability in cancer cells. We demonstrated that the DNAzyme sensor not only enables cancer-cell-selective sensing and imaging of metal ions through an enzymically activated pathway, but also precise control over its metal-ion sensing activity in tumor-bearing mice. We envision the use of this biosensing technology to probe the biological roles of diverse metal ions in specific diseases.
The present study was performed to determine the clinical relevance of KLF7 in tongue squamous cell carcinoma (TSCC) and to characterize its potential function and mechanism of action.
KLF7 expression was measured by RT-qPCR in 21 tongue cancer samples. The clinical relevance of KLF7 was analyzed in another cohort of 127 TSCC samples from a public database. Then, we performed RNA sequencing analysis in KLF7-overexpressing TSCC (SCC9 and CAL27) cells to define significantly altered pathways. The possible changes in migration and adhesion were then analyzed in KLF7-overexpressing and knockdown TSCC cells.
Our results showed that KLF7 mRNA expression was upregulated in TSCC and was significantly associated with the T and N stages. Patients with high-KLF7 expression had worse overall survival. RNA sequencing and KEGG enriched pathway analysis showed that altered genes were enriched in extracellular matrix-receptor interactions and focal adhesions in both cell lines. KLF7-overexpressing TSCC cell lines showed enhanced migration capacity and cell adhesion ability, and knockdown of KLF7 expression decreased TSCC migration and adhesion ability.
We concluded that KLF7 was overexpressed in TSCC and has prognostic value. KLF7 promoted TSCC migration and increased cell adhesion.
We concluded that KLF7 was overexpressed in TSCC and has prognostic value. KLF7 promoted TSCC migration and increased cell adhesion.Large increases in treatment of Common Mental Disorders (CMD) have failed to reduce population prevalence and global burden. Preventive strategies are needed to lower CMD prevalence and burden. Giving prevention a real chance to prove its promise will require (a) full embedment in social institutions; (b) long-term structural funding; (c) targeting major CMD determinants early in life combining population-level and individual-level strategies; and, (d) integrated evaluation of short-term and long-term effects to guide implementation. Targeting life skills and resilience of children and parenting skills of their parents has the potential for long-term benefits for multiple outcomes including well-being, social, economic, and financial domains as well as mental health outcomes. However, the large investments may not occur without compelling proof of effectiveness, but evaluation of effectiveness cannot occur without long-term, structural investments. Overcoming this impasse requires a paradigm shift. Randomized controlled trials of initial efficacy need to be supplemented by evaluation strategies for long-term surveillance of community-based programs that guide implementation while assessing long-term effectiveness.
Apatinib has potential as an effective and safe second-line or higher treatment for patients with chemotherapy-refractory esophageal squamous cell carcinoma (ESCC). Clinical safety is of potential concern when administering apatinib to patients with uncontrolled esophageal lesions or severe invasion of trachea, bronchi, or major blood vessels. To the best of the authors' knowledge, this is the first prospective phase II study to investigate apatinib for patients with chemotherapy-refractory ESCC. Apatinib could provide an alternative option for ESCC after first-line or higher therapy in carefully selected patients.
The aim of this study was to evaluate the efficacy and adverse effects of the oral vascular endothelial growth factor receptor 2 (VEGFR-2) tyrosine kinase inhibitor apatinib in patients with chemotherapy-refractory esophageal squamous cell carcinoma (ESCC).
We enrolled patients with chemotherapy-refractory ESCC. All patients received continuous apatinib 500 mg once daily.
Between July 2017 and August 2018, 40 patients were recruited, of whom 5 (12.
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