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Takayasu's arteritis (TAK) is a granulomatous large-vessel vasculitis primarily affecting the aorta and its proximal branches. TAK can be a difficult disease to diagnose and manage given the rarity of the disease as well as current limitations in biomarkers, imperfect imaging modalities, and few randomized controlled trials.

In developing the American College of Rheumatology/Vasculitis Foundation guideline for the management of TAK, we performed an extensive systematic literature review to guide our recommendations. We included RCTs first. When RCTs were not available, we included observational studies that reported on patient-important outcomes for the intervention and comparison. When studies with comparative data were not available, we included case series that present patient-important outcomes for either the intervention or the comparison.

Three hundred forty-seven articles were included for full review to answer 27 population, intervention, comparison, and outcome questions related to TAK. Ten studies were evaluated that addressed the use of glucocorticoids (GCs), non-GC nonbiologic therapies, as well as biologics in treating TAK. A total of 33 studies, including 8 comparative studies, were included to determine the test accuracy of commonly available diagnostic tests for TAK.

This comprehensive systematic review synthesizes and evaluates the benefits and harms of different treatment options and the accuracy of commonly used tests for the management of TAK.

This comprehensive systematic review synthesizes and evaluates the benefits and harms of different treatment options and the accuracy of commonly used tests for the management of TAK.Benzalkonium bromide (BB) has been widely used as a skin antiseptic for wound management. However, BB had proinflammation and reactive oxygen species (ROS) induction effect, making its role in wound healing complex and unclear. A rat full-thickness skin defect wound model was established. The effects of BB, povidone iodine (PVP-I), chlorhexidine gluconate (CHG), and normal saline (NS) on wound healing and infection control were then evaluated based on wound healing rate (WHr) and bacterial killing. The wound tissues were sectioned for histopathological evaluation and nuclear factor E2 related factor 2 (Nrf2) expression determination. The ROS production, Nrf2 activation, and heme oxygenase 1 (HO-1) expression of the HaCat cells and the cytotoxicity treated with BB were further explored. Compared with NS, PVP-I, and CHG, BB showed the best wound infection control efficiency while delayed wound healing with the WHr of 91.42 ± 5.12% at day 20. The wound tissue of the BB group showed many inflammatory cells but feinistration may contribute to delayed wound healing.

Diabetes mellitus, chronic obstructive pulmonary disease, and chronic kidney disease are prevalent in patients with heart failure with reduced ejection fraction (HFrEF). We have analysed the impact of co-morbidities on quality of life (QoL) and outcome.

A total of 397 patients (58.8±11.0years, 73.6% with New York Heart Association functional class ≥3) with stable advanced HFrEF were followed for a median of 1106 (inter-quartile range 379-2606) days, and 68% of patients (270 patients) experienced an adverse outcome (death, urgent heart transplantation, and implantation of mechanical circulatory support). Chronic obstructive pulmonary disease was present in 16.4%, diabetes mellitus in 44.3%, and chronic kidney disease in 34.5% of patients; 33.5% of patients had none, 40.0% had one, 21.9% had two, and 3.8% of patient had three co-morbidities. Patients with more co-morbidities reported similar QoL (assessed by Minnesota Living with Heart Failure Questionnaire, 45.46±22.21/49.07±21.69/47.52±23.54/46.77±23.60 itively affect the prognosis both directly and indirectly through lower level of HF pharmacotherapy and increased myocardial stress and injury.

In stable advanced HFrEF patients, co-morbidities are not associated with impaired QoL, but negatively affect the prognosis both directly and indirectly through lower level of HF pharmacotherapy and increased myocardial stress and injury.

The object of this study was to analyze the benefits and harms of different treatment options and to analyze test accuracy used in the evaluation of patients with primary systemic polyarteritis nodosa (PAN).

A systematic search of published English-language literature was performed in Ovid Medline, PubMed, Embase, and the Cochrane Library from the inception of each database through August 2019. Articles were screened for suitability in addressing patient, intervention, comparison, and outcome questions, with studies presenting the highest level of evidence given preference.

Of 137 articles selected for data abstraction, we analyzed 21 observational studies and seven randomized controlled trials (RCTs). The results showed indirect evidence that a deep skin biopsy provides good diagnostic accuracy. A combined nerve and muscle biopsy should be obtained for patients with PAN with peripheral neuropathy. Cyclophosphamide with high-dose glucocorticoids (GCs) is effective as an induction treatment for newly diastudies. More high-quality RCTs are needed.Breast cancer constitutes a heterogeneous disease. The expression profiles of estrogen receptors (ERs), as well as the expression patterns of extracellular matrix (ECM) macromolecules, determine its development and progression. Hyaluronan (HA) is an ECM molecule that regulates breast cancer cells' properties in a molecular size-dependent way. Previous studies have shown that 200-kDa HA fragments modulate the functional properties, morphology, and expression of several matrix mediators of the highly metastatic ERα- /ERβ+ MDA-MB-231 cells. In order to evaluate the effects of HA fragments ( less then 10, 30 and 200-kDa) in ERβ-suppressed breast cancer cells, the shERβ MDA-MB-231 cells were used. These cells are less aggressive when compared with MDA-MB-231 cells. To this end, the functional properties, the morphology, and the expression of the molecules associated with breast cancer cells metastatic potential were studied. Notably, both cell proliferation and invasion were significantly reduced after treatment with 200-kDa HA. Moreover, as assessed by scanning electron microscopy, 200-kDa HA affected cellular morphology, and as assessed by qPCR, upregulated the epithelial marker Ε-cadherin. The expression profiles of ECM mediators, such as HAS2, CD44, and MMP7, were also altered. On the other hand, cellular migration and the expression levels of syndecan-4 (SDC-4) were not significantly affected in contrast to our observations regarding MDA-MB-231 cells. These novel data demonstrate that the molecular size of the HA determines its effects on ERβ-suppressed breast cancer cells and that 200-kDa HA exhibits antiproliferative effects on these cells. A deeper understanding of this mechanism may contribute to the development of therapeutic strategies against breast cancer.Rituximab (RTX) therapy for primary focal segmental glomerulosclerosis recurrence after kidney transplantation (KT) has been extensively debated. We aimed to assess the benefit of adding RTX to plasmapheresis (PP), corticosteroids, and calcineurin inhibitors (standard of care, SOC). We identified 148 adult patients who received KT in 12/2004-12/2018 at 21 French centers 109 received SOC (Group 1, G1), and 39 received immediate RTX along with SOC (Group 2, G2). In G1, RTX was introduced after 28 days of SOC in the event of failure (G1a, n = 19) or PP withdrawal (G1b, n = 12). Complete remission (CR) was achieved in 46.6% of patients, and partial remission (PR) was achieved in 33.1%. The 10-year graft survival rates were 64.7% and 17.9% in responders and nonresponders, respectively. Propensity score analysis showed no difference in CR+PR rates between G1 (82.6%) and G2 (71.8%) (p = .08). Following the addition of RTX (G1a), 26.3% of patients had CR, and 31.6% had PR. The incidence of severe infections was similar between patients treated with and without RTX. In multivariable analysis, infection episodes were associated with hypogammaglobulinemia less then 5 g/L. RTX could be used in cases of SOC failure or remission for early discontinuation of PP without increasing the risk of infection.

The incidence of thyroid cancer has increased annually, and has a heavy psychological and economic burden on society and individuals. Based thyroid cancer data from patients treated in Liaocheng People's Hospital from 2015 to 2018, with Chinese national and regional characteristics, in this study, we addressed the controversy of which initial thyroid surgical mode, lobectomy or total thyroidectomy, is most effective.

Clinical and pathological data from 2108 patients with thyroid cancer, who were initially diagnosed and treated surgically, were collected from the Department of Thyroid Surgery. Among them, there were 1001 cases who underwent open operation with total thyroidectomy+central lymph node dissection; meanwhile, 1107 cases were treated with neck lateral lymph node dissection at the same time.

The overall metastasis rate of all patients was 57.23%. Even the lymph node metastasis of papillary thyroid microcarcinoma (PTMC) was as high as 48.97%. When the mass rose above 2cm, the proportion of metas secondary surgery and effects on patient quality of life. When the tumor diameter exceeds 1cm, the risk of cervical lymph node metastasis is high, and we recommended lateral lymph node dissection.

The degree of malignancy of thyroid cancer depends on tumor genome evolution. Rates of neck lymph node metastasis are high, particularly among patients with risk factors for poor prognosis. It is recommended that initial treatment should comprise at least total thyroidectomy + central lymph node dissection in China, to avoid the risks associated with secondary surgery and effects on patient quality of life. When the tumor diameter exceeds 1 cm, the risk of cervical lymph node metastasis is high, and we recommended lateral lymph node dissection.

Limited data are available regarding cardiac expression of molecules involved in heart failure (HF) pathophysiology. The majority of the studies have focused on end-stage HF with reduced ejection fraction (HFrEF) without comparison with healthy subjects, while no data are available with regard to HF with preserved ejection fraction (HFpEF). HFpEF is a condition whose multiple pathophysiological mechanisms are still not fully defined, with many proposed hypotheses remaining speculative due to limited access to human heart tissue. This study aimed at evaluating cardiac expression levels of key genes of interest in human biopsy samples from patients affected with HFrEF and HFpEF in order to possibly point out distinct phenotypes.

Total RNA was extracted from left ventricular cardiac biopsies collected from stable patients with HFrEF (n=6) and HFpEF (n=7) and healthy subjects (n=9) undergoing elective cardiac surgery for valvular replacement, mitral valvuloplasty, aortic surgery, or coronary artery bypass. Reay a distinct molecular milieu of genes involved in somatotropic axis regulation, calcium handling, and adrenergic derangement at a myocardial level. The unique opportunity to compare these results with a control group, as reference population, may contribute to better understand HF pathophysiology and to identify novel potential therapeutic targets that could be modulated to improve ventricular function in patients with HF.

Dental students experience difficulties during the transition from preclinical to clinical curriculum. In order to help the students to adapt to the clinical education programme, a simulated practice using patient-based customised models was introduced in this study to prepare for their first clinical practice.

This study included 45 third-year predoctoral students (D3 students) who were about to perform the preparation of a single crown abutment on their first patient. After practicing abutment preparation using simulated models and providing the actual treatment to their own patient, the students were surveyed to investigate their perceptions on the simulated practice using the 3D-printed customised typodont model. The statistical analysis of the quantitative data and the thematic analysis of the qualitative data were conducted.

Regarding this simulation, more than 80% of the students gave positive feedback on their practice of (a) operative positions and postures, (b) finger rest, (c) occlusal reduction, (d) axial reduction and (e) proximal reduction. Student responses on the open-ended questions about how they perceived the usefulness of this simulation were categorised as "First clinical case," "Patient-based model" and "Realistic simulation environment." In addition, a number of improvements of the simulation were also suggested by the students including the typodont and the manikin.

This study gives insights into the significance of simulated practice using patient-based customised typodonts as a transitional education tool and its direction of development in the field of restorative treatments accompanied by irreversible tooth preparations.

This study gives insights into the significance of simulated practice using patient-based customised typodonts as a transitional education tool and its direction of development in the field of restorative treatments accompanied by irreversible tooth preparations.Cisplatin nephrotoxicity has been considered as serious side effect caused by cisplatin-based chemotherapy. Recent evidence indicates that renal tubular cell apoptosis and inflammation contribute to the progression of cisplatin-induced acute kidney injury (AKI). Hepatocyte nuclear factor 1β (HNF1β) has been reported to regulate the development of kidney cystogenesis, diabetic nephrotoxicity, etc However, the regulatory mechanism of HNF1β in cisplatin nephrotoxicity is largely unknown. In the present study, we examined the effects of HNF1β deficiency on the development of cisplatin-induced AKI in vitro and in vivo. HNF1β down-regulation exacerbated cisplatin-induced RPTC apoptosis by indirectly inducing NF-κB p65 phosphorylation and nuclear translocation. HNF1β knockdown C57BL/6 mice were constructed by injecting intravenously with HNF1β-interfering shRNA and PEI. The HNF1β scramble and knockdown mice were treated with 30 mg/kg cisplatin for 3 days to induce acute kidney injury. Cisplatin treatment caused increased caspase 3 cleavage and p65 phosphorylation, elevated serum urea nitrogen and creatinine, and obvious histological damage of kidney such as fractured tubules in control mice, which were enhanced in HNF1β knockdown mice. These results suggest that HNF1β may ameliorate cisplatin nephrotoxicity in vitro and in vivo, probably through regulating NF-κB signalling pathway.Developmental researchers commonly utilize multilevel models (MLMs) to describe and predict individual differences in change over time. In such growth model applications, researchers have been widely encouraged to supplement reporting of statistical significance with measures of effect size, such as R-squareds (R2 ) that convey variance explained by terms in the model. An integrative framework for computing R-squareds in MLMs with random intercepts and/or slopes was recently introduced by Rights and Sterba and it subsumed pre-existing MLM R-squareds as special cases. However, this work focused on cross-sectional applications, and hence did not address how the computation and interpretation of MLM R-squareds are affected by modeling considerations typically arising in longitudinal settings (a) alternative centering choices for time (e.g., centering-at-a-constant vs. person-mean-centering), (b) nonlinear effects of predictors such as time, (c) heteroscedastic level-1 errors and/or (d) autocorrelated level-1 err size when analyzing and predicting change using MLMs.Replacement of lost cranial bone (partly mesodermal and partly neural crest-derived) is challenging and includes the use of nonviable allografts. To revitalize allografts, bone marrow-derived mesenchymal stromal cells (mesoderm-derived BM-MSCs) have been used with limited success. We hypothesize that coating of allografts with induced neural crest cell-mesenchymal progenitor cells (iNCC-MPCs) improves implant-to-bone integration in mouse cranial defects. Human induced pluripotent stem cells were reprogramed from dermal fibroblasts, differentiated to iNCCs and then to iNCC-MPCs. BM-MSCs were used as reference. Cells were labeled with luciferase (Luc2) and characterized for MSC consensus markers expression, differentiation, and risk of cellular transformation. A calvarial defect was created in non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice and allografts were implanted, with or without cell coating. Bioluminescence imaging (BLI), microcomputed tomography (μCT), histology, immunofluorescence, and biomechanical tests were performed. Characterization of iNCC-MPC-Luc2 vs BM-MSC-Luc2 showed no difference in MSC markers expression and differentiation in vitro. In vivo, BLI indicated survival of both cell types for at least 8 weeks. At week 8, μCT analysis showed enhanced structural parameters in the iNCC-MPC-Luc2 group and increased bone volume in the BM-MSC-Luc2 group compared to controls. Histology demonstrated improved integration of iNCC-MPC-Luc2 allografts compared to BM-MSC-Luc2 group and controls. Human osteocalcin and collagen type 1 were detected at the allograft-host interphase in cell-seeded groups. The iNCC-MPC-Luc2 group also demonstrated improved biomechanical properties compared to BM-MSC-Luc2 implants and cell-free controls. Our results show an improved integration of iNCC-MPC-Luc2-coated allografts compared to BM-MSC-Luc2 and controls, suggesting the use of iNCC-MPCs as potential cell source for cranial bone repair.

An insight into students' motivation and confidence in the choice of entering and remaining in dental education is essential. The understanding of how choices are made can help universities in the planning of admission policies. This study aimed to evaluate the career choice influences, motivation and confidence in the choices made into dental education.

A mixed-method design was employed, using both quantitative and qualitative data. One hundred seventy-three questionnaires were distributed to all registered dental students, with a response rate of 85%. The questionnaire explored students' demographics and factors that influenced their career choice. Seven focus groups were facilitated with related data recorded and transcribed verbatim.

The quantitative data revealed the desire to help others, and socioeconomic factors were influential, whilst for parents' influence, the mother's influence was statistically significant. Qualitatively, results converged and complemented quantitative data; there was a balance between helping others and socioeconomic and familial influences. There was an increase in confidence in the choice made as students advanced in their dental education. The results indicate that informed awareness of the dental programme structure is essential before embarking on a dental career.

The factors that impacted on choice were helping others, socioeconomic factors and the influence on choice from family. They were generally satisfied with their choice and were confident in the choice they made. This confidence, however, was not reflected until the more advanced clinical stages of their dental education.

The factors that impacted on choice were helping others, socioeconomic factors and the influence on choice from family. They were generally satisfied with their choice and were confident in the choice they made. This confidence, however, was not reflected until the more advanced clinical stages of their dental education.The aim of the present study was to explore the potential mechanism underlying the involvement of CB2 in osteoporosis. Micro-CT was utilized to examine femur bone architecture. Also, real-time PCR and Western blot analysis were utilized to detect the effect of 2-AG on the expression of CB2 and Notch, or the interaction between CB2 and Notch 2. 2-AG treatment up-regulated BMD, Tb.Sp and SMI in OVX mice, whereas proportion of bone volume in total volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N) and bone mineral density (BMD) were decreased in 2-AG-treated OVX mice. Accordingly, 2-AG administration up-regulated Notch 1 expression in OVX mice but had no effect on CB2 and Notch 2 expression. Meanwhile, 2-AG administration promoted the differentiation of hBMSCs in OVX mice, while exhibiting no effect on the proliferation of hBMSCs. Furthermore, in the cellular models, 2-AG treatment also up-regulated Notch 1 expression but had no effect on CB2 and Notch 2 expression, while Notch 1 shRNA had no effect on CB2 and Notch 2 expression. 2-AG promoted cell proliferation and differentiation, which were inhibited by Notch 1 shRNA. NICD had no effect on CB2 level but increased Notch 1 expression, and CB2 shRNA decreased CB2 and Notch 1 expression. Finally, CB2 shRNA inhibited cell proliferation and differentiation, whereas NICD promoted proliferation and differentiation of hBMSCs. Our results provided further evidence for the association of CB2 gene with BMD and osteoporosis, and identified CB2 as a promising target for the treatment of osteoporosis.Using samples from the New England Centenarian Study (NECS), we sought to characterize the serum proteome of 77 centenarians, 82 centenarians' offspring, and 65 age-matched controls of the offspring (mean ages 105, 80, and 79 years). We identified 1312 proteins that significantly differ between centenarians and their offspring and controls (FDR less then 1%), and two different protein signatures that predict longer survival in centenarians and in younger people. By comparing the centenarian signature with 2 independent proteomic studies of aging, we replicated the association of 484 proteins of aging and we identified two serum protein signatures that are specific of extreme old age. The data suggest that centenarians acquire similar aging signatures as seen in younger cohorts that have short survival periods, suggesting that they do not escape normal aging markers, but rather acquire them much later than usual. For example, centenarian signatures are significantly enriched for senescence-associated secretory phenotypes, consistent with those seen with younger aged individuals, and from this finding, we provide a new list of serum proteins that can be used to measure cellular senescence. Protein co-expression network analysis suggests that a small number of biological drivers may regulate aging and extreme longevity, and that changes in gene regulation may be important to reach extreme old age. This centenarian study thus provides additional signatures that can be used to measure aging and provides specific circulating biomarkers of healthy aging and longevity, suggesting potential mechanisms that could help prolong health and support longevity.

Positron emission tomography/computed tomography (PET/CT) has been recognized for diagnosing and staging lung cancer, but the prognostic value of standardized uptake value (SUV) on

F-FDG PET/CT imaging in patients with advanced non-small cell lung cancer (NSCLC) remains controversial.

We performed a retrospective analysis of patients with advanced NSCLC who had undergone

F-FDG PET/CT before systemic treatment between June 2012 and June 2016. The relationship between the maximum SUV (SUVmax) of the pulmonary lesion and lesion size was evaluated via Spearman's correlation analysis. We collected patients' clinical and pathological data. Univariate and multivariate analyses were performed to analyze the factors influencing survival.

We included 157 patients with advanced NSCLC. Among these, 135 died, 13 survived, and nine were lost to follow-up (median follow-up period, 69 months). SUVmax was correlated with lesion size and was significantly greater for tumors ≥3 cm than for tumors <3 cm (10.2 ± 5.4 vs. 5.6 ± 3.3, t = -6.709, p = 0.000). Univariate analysis showed that survival was associated with gender, tumor size, epidermal growth factor receptor gene mutation or anaplastic lymphoma kinase rearrangement, SUVmax of the primary lung lesion, and treatment lines. Multivariate analysis showed a significant correlation between SUVmax of the primary lung lesion and survival. The mortality risk of patients with SUVmax ≤6 was 35% lower than that of patients with SUVmax >6 (HR = 0.651, 95% confidence interval, 0.436-0.972; Wald value, 4.400; p = 0.036).

The SUVmax of the primary lung lesion on PET/CT is significantly correlated with survival in treatment-naive patients with advanced NSCLC.

The SUVmax of the primary lung lesion on PET/CT is significantly correlated with survival in treatment-naive patients with advanced NSCLC.The successful removal of damaged myelin sheaths during Wallerian degeneration (WD) is essential for ensuring structural remodelling and functional recovery following traumatic peripheral nerve injury (PNI). Recent studies have established that autophagy involves myelin phagocytosis and cellular homoeostasis, and its disorder impairs myelin clearance. Based on the role of basic fibroblast growth factor (bFGF) on exerting neuroprotection and angiogenesis during nerve tissue regeneration, we now explicitly focus on the issue about whether the therapeutic effect of bFGF on supporting nerve regeneration is closely related to accelerate the autophagic clearance of myelin debris during WD. Using sciatic nerve crushed model, we found that bFGF remarkedly improved axonal outgrowth and nerve reconstruction at the early phase of PNI (14 days after PNI). More importantly, we further observed that bFGF could enhance phagocytic capacity of Schwann cells (SCs) to engulf myelin debris. Additionally, this enhancing effect is accomplished by autophagy activation and the increase of autophagy flux by immunoblotting and immune-histochemical analyses. Taken together, our data suggest that the action of bFGF on modulating early peripheral nerve regeneration is closely associated with myelin debris removal by SCs, which might result in SC-mediated autophagy activation, highlighting its insight molecular mechanism as a neuroprotective agent for repairing PNI.Prussian blue analogues (PBAs) are commonly believed to reversibly insert divalent ions, such as calcium and magnesium, rendering them as perspective cathode materials for aqueous magnesium-ion batteries. In this study, the occurrence of Mg2+ insertion into nanosized PBA materials is shown to be a misconception and conclusive evidence is provided for the unfeasibility of this process for both cation-rich and cation-poor nickel, iron, and copper hexacyanoferrates. Based on structural, electrochemical, IR spectroscopy, and quartz crystal microbalance data, the charge compensation of PBA redox can be attributed to protons rather than to divalent ions in aqueous Mg2+ solution. The reversible insertion of protons involves complex lattice water rearrangements, whereas the presence of Mg2+ ion and Mg salt anion stabilizes the proton (de)insertion reaction through local pH effects and anion adsorption at the PBA surface. The obtained results draw attention to the design of proton-based batteries operating in environmentally benign aqueous solutions with low acidity.Extracellular vesicles (EVs) released by tumor cells can directly or indirectly modulate the phenotype and function of the immune cells of the microenvironment locally or at distant sites. The uptake of circulating EVs and the responses by human monocytes in vitro may provide new insights into the underlying biology of the invasive and metastatic processes in cancer. Although a mixed population of vesicles is obtained with most isolation techniques, we predominantly isolated exosomes (small EVs) and microvesicles (medium EVs) from the SW480 colorectal cancer cell line (established from a primary adenocarcinoma of the colon) by sequential centrifugation and ultrafiltration, and plasma EVs were prepared from 22 patients with rectal adenoma polyps or invasive adenocarcinoma by size-exclusion chromatography. The EVs were thoroughly characterized. The uptake of SW480 EVs was analyzed, and small SW480 EVs were observed to be more potent than medium SW480 EVs in inducing monocyte secretion of cytokines. The plasma EVs were also internalized by monocytes; however, their cytokine-releasing potency was lower than that of the cell line-derived vesicles. The transcriptional changes in the monocytes highlighted differences between adenoma and adenocarcinoma patient EVs in their ability to regulate biological functions, whereas the most intriguing changes were found in monocytes receiving EVs from patients with metastatic compared with localized cancer.Endothelial tip cells are essential for VEGF-induced angiogenesis, but underlying mechanisms are elusive. The Ena/VASP protein family, consisting of EVL, VASP, and Mena, plays a pivotal role in axon guidance. Given that axonal growth cones and endothelial tip cells share many common features, from the morphological to the molecular level, we investigated the role of Ena/VASP proteins in angiogenesis. EVL and VASP, but not Mena, are expressed in endothelial cells of the postnatal mouse retina. Global deletion of EVL (but not VASP) compromises the radial sprouting of the vascular plexus in mice. Similarly, endothelial-specific EVL deletion compromises the radial sprouting of the vascular plexus and reduces the endothelial tip cell density and filopodia formation. Gene sets involved in blood vessel development and angiogenesis are down-regulated in EVL-deficient P5-retinal endothelial cells. Consistently, EVL deletion impairs VEGF-induced endothelial cell proliferation and sprouting, and reduces the internalization and phosphorylation of VEGF receptor 2 and its downstream signaling via the MAPK/ERK pathway. Together, we show that endothelial EVL regulates sprouting angiogenesis via VEGF receptor-2 internalization and signaling.Team job crafting, which refers to designing the task, relational, and cognitive aspects of a job, is thought to be beneficial for nurses working in the ward. There are no scales to assess team job crafting among nurses. This study aimed to develop and examine the reliability and validity of a scale to measure team job crafting. Based on literature reviews and interviews, potential items were created. A total of 293 nurses working on 19 wards in two hospitals in Japan were asked to complete a questionnaire twice. A series of exploratory factor analyses (EFAs) were conducted to select the final items. For convergent validity, multilevel correlations were calculated. Cronbach's α and intra-class correlation coefficients (ICCs) were calculated for reliability. A total of 190 participants responded to the baseline survey and 152 responded to the retest. The EFAs yielded a three-factor structure comprising 13 items. The three factors are task crafting considering the team's growth, cognitive crafting for members' respect and reflection of meaningfulness of work, and relational crafting for smooth information sharing. Cronbach's α ranged from .810 to .831, and test-retest ICCs ranged from 0.571 to 0.710. At the individual level, team job crafting had small-to-moderate correlations with individual levels of job crafting, job control, supervisor support, co-worker support, job satisfaction, workplace social capital, and work engagement. The ICC of the team job crafting scores of 0.125 indicated meaningful variation across wards. At the ward-level, nonsignificant but strong correlations were found with workplace social capital, job satisfaction, and psychological distress. This scale showed acceptable levels of reliability and validity. It would be useful in monitoring and improving team job crafting to increase team members' well-being and performance.Near-infrared spectroscopy is commonly used during carotid endarterectomy but its use in salvage oncological carotid resection has not previously been described. In comparison to other methods of determining the adequacy of contralateral cerebral circulation, near-infrared spectroscopy is simple, reliable, non-invasive and inexpensive.Histone post-translational modifications (PTMs) are key players in chromatin regulation. The identification of novel histone acylations raises important questions regarding their role in transcription. In this study, we characterize the role of an acylation on the lateral surface of the histone octamer, H3K122 succinylation (H3K122succ), in chromatin function and transcription. Using chromatin succinylated at H3K122 in in vitro transcription assays, we show that the presence of H3K122succ is sufficient to stimulate transcription. In line with this, we found in our ChIP assays H3K122succ enriched on promoters of active genes and H3K122succ enrichment scaling with gene expression levels. Furthermore, we show that the co-activators p300/CBP can succinylate H3K122 and identify sirtuin 5 (SIRT5) as a new desuccinylase. By applying single molecule FRET assays, we demonstrate a direct effect of H3K122succ on nucleosome stability, indicating an important role for histone succinylation in modulating chromatin dynamics. Together, these data provide the first insights into the mechanisms underlying transcriptional regulation by H3K122succ.Graft-versus-host disease (GVHD) is a major cause of toxicity after allogeneic hematopoietic cell transplantation (allo-HCT). While rapamycin (RAPA) is commonly used in GVHD prophylaxis in combination with a calcineurin inhibitor (CNI), the understanding of its mechanism of action on human T cells is still incomplete. Here, we performed an extensive analysis of RAPA effects on human T cells in a humanized mouse model of GVHD, in ex-vivo T cell cultures and in patients given RAPA plus tacrolimus as GVHD prophylaxis after nonmyeloablative allo-HCT. We demonstrate that RAPA mitigates GVHD by decreasing T cell engraftment and differentiation, inhibiting CD8+ T cell activation and increasing the long-term IL-2 secretion, thereby supporting regulatory T cell (Treg) proliferation. In contrast, graft-versus-leukemia effects were not abrogated, as RAPA-treated T cells had increased resistance to apoptosis and retained their effector function and proliferative capacity upon re-stimulation. Importantly, we found that RAPA impact on Treg and CD8+ T cells was closely dependent upon IL-2 signaling and that therapeutic options interfering with IL-2, such as calcineurin inhibitors, antagonize the IL-2-dependent promotion of Treg mediated by RAPA. Our results suggest that RAPA immunological efficacy could be improved in combination with drugs having possible synergistic effects such as the hypomethylating agent 5-azacytidine.

The aim of this study is to analyze the impact of the COVID-19 pandemic on the quality of life and the depression, anxiety, and stress levels of individuals above the age of eighteen.

This studyused the snowball method. Data were collected using the sociodemographic question form, the Depression, Anxiety, Stress Scale-21, and the SF-12 Life Quality Scale.

A statistically significant relationship (p < .05) was measured between age, gender, health condition, concomitant chronic and mental disease, fear of the COVID-19 pandemic, home confinement in this particular period, and the need for psychological support as well as mean scores of Depression, Anxiety, Stress Scale-21, and SF-12 Life Quality Scale.

Against the likelihood of facing new pandemics in the future, a guideline could be planned to protect and improve prospective the psychosocial wellness of individuals and society.

Against the likelihood of facing new pandemics in the future, a guideline could be planned to protect and improve prospective the psychosocial wellness of individuals and society.

To examine the performance and identify the optimal threshold of vibration perception threshold (VPT) for diagnosing diabetic polyneuropathy (DPN) in a Chinese population according to multiple definitions of DPN as gold standards.

VPT was determined in 421 Chinese individuals with type2 diabetes, who simultaneously completed a questionnaire of neuropathic symptoms, and underwent the assessment of signs of peripheral neuropathy and electromyography tests. Three definitions of DPN (i.e., clinician-diagnosed DPN, abnormal nerve conduction and confirmed DPN) were taken as reference gold standards.

Vibration perception threshold was a specific measure for all three groups of DPN outcomes, with the highest specificity noted for clinician-diagnosed DPN (85.1%). The specificity for abnormal nerve conduction and confirmed DPN was 77.0 and 76.6%, respectively. The sensitivity of VPT was 67.0% for clinician-diagnosed DPN, 66.5% for abnormal nerve conduction and 67.2% for confirmed DPN. The optimal cut-off threshold for abnormal nerve conduction, as well as confirmed DPN, was VPT>14.9V. The specificity and sensitivity of VPT>14.9V as the cut-off value for clinician-diagnosed DPN were 85.6 and 66.2%, respectively. When taking clinician-diagnosed DPN as the gold standard, the performance of VPT for diagnosing DPN was best with an area under the curve value of 0.804.

VPT measured using the neurothesiometer had relatively high specificity and best performance for diagnosing DPN when clinician-diagnosed DPN rather than abnormal nerve conduction was taken as the gold standard in a Chinese population. A VPT value of ≥15V might be equally applicable for diagnosing DPN in a Chinese population.

VPT measured using the neurothesiometer had relatively high specificity and best performance for diagnosing DPN when clinician-diagnosed DPN rather than abnormal nerve conduction was taken as the gold standard in a Chinese population. A VPT value of ≥15 V might be equally applicable for diagnosing DPN in a Chinese population.Reported herein is a molecular design strategy of deep-blue emitters for resolving the lack of highly efficient deep-blue organic light-emitting diodes (OLEDs) featuring CIEy (Commission Internationale de l'Eclairage) color coordinates matching the display requirements ( less then 0.1). The strategy is to combine weak spiro-donor and spiro-acceptor groups into a linear donor-π-acceptor type of thermally-activated delayed fluorescence molecule through a sterically bulky π-spacer. The strategy endows an emitter with deep-blue emission, a narrower emission bandwidth (51 nm in toluene), a high photoluminescence quantum yield (0.95 in toluene), weak concentration quenching, and efficient triplet-exciton utilization, which are all attractive characteristics for emitters of deep-blue OLEDs with lower CIEy coordinates. Owing to the rational design, the emitter has realized not only highly efficient doped deep-blue OLEDs with external quantum efficiencies (EQEs) up to 25.4 % and CIEy less than 0.1 but also so far the most efficient nondoped deep-blue OLED (EQE up to 22.5 %) with CIEy less than 0.1.

To evaluate the efficacy and safety of adding the once-weekly oral dipeptidyl peptidase-4 inhibitor omarigliptin to treatment of Japanese patients with type 2 diabetes and inadequate glycaemic control on insulin monotherapy.

In a 52-week clinical trial, Japanese patients on insulin monotherapy were randomized to once-weekly omarigliptin 25 mg (N = 123) or placebo (N = 61) for a 16-week, double-blind, placebo-controlled period. After Week 16, patients continued or switched to omarigliptin for a 36-week open-label period.

From a mean baseline of approximately 8.8%, the Week 16 least squares mean changes in HbA1c were -0.61% (omarigliptin) and 0.29% (placebo); the between-group difference was -0.90% (p < .001). At Week 52, the mean change from baseline in HbA1c was -0.57% in both the group on omarigliptin for 52 weeks and the group on omarigliptin for 36 weeks (switched from placebo at Week 16). During the first 16 weeks of treatment, the incidences of adverse events (AEs), serious AEs, drug-related AEs and discontinuation from trial medication because of an AE were similar in both groups. A slight increase in incidence of symptomatic hypoglycaemia was observed in the omarigliptin group (n = 13 [10.6%]) compared with placebo (n = 4 [6.6%]). No severe hypoglycaemia was reported during the study. No new safety signals emerged with treatment beyond Week 16 through Week 52.

The addition of once-weekly omarigliptin to insulin therapy for up to 52 weeks was generally well tolerated and provided clinically meaningful improvement in glycaemic control throughout the trial period. ClinicalTrials.gov NCT02906709.

The addition of once-weekly omarigliptin to insulin therapy for up to 52 weeks was generally well tolerated and provided clinically meaningful improvement in glycaemic control throughout the trial period. ClinicalTrials.gov NCT02906709.

To investigate the glucosuric, renal and haemodynamic effects of licogliflozin, a dual sodium-glucose co-transporter-1 and sodium-glucose co-transporter-2 inhibitor, in patients with chronic kidney disease (CKD).

This multiple-dose, parallel-group, phase II mechanistic study randomized 53 participants (aged 18-78 years, body mass index ≤ 50 kg/m

) with varying degrees of CKD or normal renal function to treatment with licogliflozin (50 mg once daily) or placebo for 7 days. The effects of licogliflozin on 24-h urinary glucose excretion (UGE

), renal function, haemodynamics, pharmacokinetics and safety were assessed.

Licogliflozin treatment for 7 days significantly (p < .01) increased UGE

from baseline in participants with normal renal function (adjusted mean change 41.8 [33.6, 49.9] g) or with mild (32.6 [24.1, 41.0] g), moderate A (35.7 [28.6, 42.9] g) or moderate B (20.3 [13.1, 27.5] g) CKD, but not in severe (6.2 [-0.71, 13.18] g) CKD. Licogliflozin reduced urinary electrolytes (sodium, potassium and chloride), blood pressure and urinary volume to varying extents among different groups. Significant increases in renin (p < .05), angiotensin II (p < .05) and aldosterone (p < .01) levels were observed. Adverse events were generally mild, and most commonly included diarrhoea (94%), flatulence (68%) and abdominal pain (21%).

Licogliflozin treatment results in significantly increased UGE and favourable changes in urinary electrolytes and haemodynamics in patients with varying degrees of CKD (estimated glomerular filtration rate ≥ 45 mL/min/1.73 m

).

Licogliflozin treatment results in significantly increased UGE and favourable changes in urinary electrolytes and haemodynamics in patients with varying degrees of CKD (estimated glomerular filtration rate ≥ 45 mL/min/1.73 m2 ).

The microbiome is a rapidly advancing biomedical frontier with relevance for psychiatric illness. The gut microbiota interact with the central nervous system bidirectionally through the gut-brain axis and generate substances that may influence host metabolism, including short-chain fatty acids such as butyrate. Understanding gut microbiota in bipolar disorder (BD) may suggest new disease markers and treatment approaches.

A PubMed search was performed on January 7, 2020 using terms "bipolar AND (microbiome OR microbiota)", for articles in English in which the study population included a distinct BD group and the gut microbiota/microbiome was assessed.

Thirteen articles met the inclusion criteria. In four of five studies that reported on group comparisons with respect to diversity, lower α-diversity was observed in BD relative to healthy controls (HC). The most convergent taxonomic finding was that in four studies, one particular clade distinguished gut microbiota between BD and HC family Ruminococcaceae, a hitherto unrecognized part of the pathophysiology underlying BD.

Aedes albopictus is a mosquito species and a vector of dengue virus and malaria parasites that represents a significant threat to global public health. Although mosquito populations have been effectively controlled through the use of synthetic insecticides, the emergence of widespread insecticide resistance in wild mosquito populations is a strong motivation to explore new insecticidal chemistries.

In this study, A. albopictus was treated with a series of novel pyrethroids containing 2-chlorobiphenyl and 2-chlorophenylpyridine via topical application. The relative antimosquito activity of each novel compound was determined, as measured by the LC

, and compared with the synthetic pyrethroid bifenthrin. The most antimosquito activity compound (SZ-B-11) was 4.69 times more active than bifenthrin. The novel compounds were also sensitive to wild A. albopictus. In addition, in silico toxicity assessment of aquatic organisms showed that the acute toxicity and chronic toxicity of SZ-B-11 were 31.96 times and 93prospects in agricultural production and environmental protection. © 2021 Society of Chemical Industry.A classical Lewis adduct derives from a covalent bond between a Lewis acid and a base. When the adduct formation is precluded by means of steric hindrance the association of the respective acid-base molecular system is defined as a frustrated Lewis pair (FLP). In this work, the archetypal FLP Mes3 P/B(C6 F5 )3 was characterized for the first time by resonance Raman spectroscopy, and the results were supported by density functional theory (DFT) calculations. The charge transfer nature of the lowest energy electronic transition, from phosphine to borane, was confirmed by the selective enhancement of the Raman bands associated to the FLP chromophore at resonance condition. Herein, we demonstrate the use of resonance Raman spectroscopy as a distinguished technique to probe the weak interaction involved in FLP chemistry.Malignant peripheral nerve sheath tumor (MPNST) is a highly malignant neoplasm arising from peripheral nerve or its attendant sheath and is derived from Schwann or pluripotent cells of neural crest origin. Patients with recurrent, unresectable, or advanced stage disease have limited treatment options, and current therapies are associated with little benefit. In this article, we report nine cases of MPNST treated with selinexor, an orally bioavailable, selective inhibitor of nuclear export, accompanied by tumor stabilization or regression.Hypertension is often associated with metabolic changes. The sustained increase in sympathetic activity is related to increased blood pressure and metabolic changes. Environmental stimuli may be related to increased sympathetic activity, blood pressure, and metabolic changes, especially in genetically predisposed individuals. The aim of this study was to evaluate the response of fatty acids to physical and mental stress in healthy volunteers and the hemodynamic, hormonal, and metabolic implications of these stimuli. Fifteen healthy individuals with a mean age of 31 ± 7 years, of both sexes, were evaluated. They were assessed at baseline and after combined physical and mental stress (isometric exercise test, Stroop color test). Blood samples were collected at baseline and after stimulation for glucose, insulin, fatty acid, and catecholamine levels. Blood pressure, heart rate, cardiac output, systemic vascular resistance, and distensibility of the large and small arteries were analyzed. The data obtained at baseline and after stimuli were from the same individual, being the control itself. Compared to baseline, after physical and mental stress there was a statistically significant increase (p less then .05) in free fatty acids, norepinephrine, diastolic blood pressure, peripheral vascular resistance, and distensibility of the large and small arteries. In conclusion, the combination of physical and mental stress raised fatty acids, norepinephrine, diastolic blood pressure, and peripheral vascular resistance in healthy individuals.

Changes in society, new public demands for dental care and contemporary educational insights have influenced dental education worldwide and demand a renewed perspective. Following this perspective, an innovative interprofessional dental Master curriculum was developed at Radboud University Nijmegen in the Netherlands.

The curriculum is based on five contemporary educational principles and the core of the curriculum consists of a Student Run Dental Clinic that is fully run by students under professional supervision.

In the Student Run Dental Clinic, Master dental students and Bachelor oral hygiene students are responsible for the care of approximately 750 patients. The students work within the same clinic for 3years and patients receive oral health care from the same students over a long period. The clinic is a longitudinal cross-disciplinary clinic with different dental subdisciplines. Entrustable professional activities (also known as EPAs), to our knowledge not yet widely used in dental education, were introduced to facilitate learning and assessment. Fourteen EPAs have been developed to stimulate interprofessional education and learning. Of these, five EPAs are identical for the dental and oral hygiene curriculum, leading to extended interprofessional education and learning in the Student Run Dental Clinic.

Preliminary results show that EPAs are generally well received by supervisors and students.

To monitor and investigate the exact effect of the interventions and underlying mechanisms, a research programme on interprofessional learning, practice-based learning and EPAs and entrustment in dental education was recently set up.

To monitor and investigate the exact effect of the interventions and underlying mechanisms, a research programme on interprofessional learning, practice-based learning and EPAs and entrustment in dental education was recently set up.

The field of nanotechnology offers great opportunities for cancer therapy.

This study aimed to compare the therapeutic impact of Zn oxide nanoparticles (ZnO NPs) and thymoquinone (TQ) alone or as cotherapy in Ehrlich ascites carcinoma (EAC) induced in mice.

This study was performed on 75 female albino mice divided intoGroup I EAC-bearing control group, Group II EAC treated with TQ, Group III EAC treated with low-dose ZnO NPs, Group IV EAC treated with high-dose ZnO NPs, Group V EAC treated with TQ and low-dose ZnO NPs. All groups were subjected to measurement of cell viability, ascites fluid volume, Bcl2 protein expression by Western blot analysis, cyclooxygenase 2 (COX2) gene expression by a real-time polymerase chain reaction, enzyme-linked immunosorbent assay levels of Beclin 1, interferon γ (INFγ), interleukin 13 (IL-13), and estimation of Zn concentrations in EAC cells and liver homogenate to evaluate its toxicity.

Cotherapy has an efficient anticancer effect by enhancing apoptosis and autophagy, resulting in reducing tumor cell viability and ascites fluid volume together with downregulation of Bcl2 protein expression.