Macdonaldseverinsen9318

The mammalian skeleton is a metabolically active organ that continuously undergoes bone remodeling, a process of tightly coupled bone resorption and formation throughout life. Recent studies have expanded our knowledge about the interactions between cells within bone marrow in bone remodeling. Macrophages resident in bone (BMMs) can regulate bone metabolism via secreting numbers of cytokines and exosomes. This review summarizes the current understanding of factors, exosomes, and hormones that involved in the communications between BMMs and other bone cells including mensenchymal stem cells, osteoblasts, osteocytes, and so on. We also discuss the role of BMMs and potential therapeutic approaches targeting BMMs in bone remodeling related diseases such as osteoporosis, osteoarthritis, rheumatoid arthritis, and osteosarcoma.The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that promotes cell responses to small molecules derived from the diet, microorganisms, metabolism and pollutants. The AhR signal regulates many basic cellular processes, including cell cycle progression, adhesion, migration, apoptosis and cell proliferation. Many studies have shown that AhR is associated with chronic kidney disease (CKD) and its complications. This article reviews the current knowledge about the role of AhR in CKD, showing that AhR mediates CKD complications, including cardiovascular disease, anemia, bone disorders, cognitive dysfunction and malnutrition, and that it influences drug metabolism in individuals with CKD. AhR enhances the intestinal barrier function to reduce the harmful effects of uremic toxins. Therefore, understanding the complex roles of AhR during CKD is important to be able to target this transcription factor safely and effectively for CKD prevention and treatment.To resolve the occurrence of unfulfillable detection in high-salts foods, we used fluorescence resonant energy transfer (FRET) sensors based on nanoparticle upconversion. In this study, we developed a novel FRET sensor for the detection of bisphenol A (BPA) in high-salt foods. We based this approach on the assembly of aptamer modified upconversion nanoparticles (DNA1-UCNPs) and complementary DNA modified metal organic frames (DNA2-MOFs), which possessed corresponding wavelength absorption. Targeting BPA signal transduction was performed using the BPA aptamer, via competitive recognition between the BPA analyte and complementary DNA sequences in a high-salt solution. Sensor adaption in high-salt samples was attributed to functional hydrophilic groups, modified in the MOFs, and the enhanced colloidal stability of these MOFs. The MOF-UCNP assembly displayed considerable analytical performance in terms of BPA detection, with a linear range of 0.1-100 nM, and a limit of detection (LOD) of 0.02 nM, in a 340 mM NaCl food sample (the energy drink, Gatorade). Thus, this method provides a solid basis for small molecules detection in high-salt foods.Reuse and discharge of treated wastewater can result in dissemination of microorganisms into the environment. Deployment of disinfection strategies is typically proposed as a last stage remediation effort to further inactivate viable microorganisms. In this study, we hypothesize that virulence traits, including biofilm formation, motility, siderophore, and curli production along with the capability to internalize into mammalian cells play a role in survival against disinfectants. Pathogenic E. coli PI-7 strain was used as a model bacterium that was exposed to diverse disinfection strategies such as chlorination, UV and solar irradiation. To this end, we used a random transposon mutagenesis library screening approach to generate 14 mutants that exhibited varying levels of virulence traits. In these 14 isolated mutants, we observed that an increase in virulence traits such as biofilm formation, motility, curli production, and internalization capability, increased the inactivation half-lives of mutants compared to wild-type E. coli PI-7. In addition, oxidative stress response and EPS production contributed to lengthening the lag phase duration (defined as the time required for exposure to disinfectant prior to decay). However, traits related to siderophore production did not help with survival against the tested disinfection strategies. Taken together, the findings suggested that selected virulence traits facilitate survival of pathogenic E. coli PI-7, which in turn could account for the selective enrichment of pathogens over the non-pathogenic ones after wastewater treatment. Further, the study also reflected on the effectiveness of UV as a more viable disinfection strategy for inactivation of pathogens.The cell envelope proteinase (CEP) of Lactococcus lactis is a large extracellular protease covalently linked to the peptidoglycan of the cell wall. Strains of L. lactis are typically auxotrophic for several amino acids and in order to grow to high cell densities in milk they need an extracellular protease. The structure of the entire CEP enzyme is difficult to determine experimentally due to the large size and due to the attachment to the cell surface. We here describe the use of a combination of structure prediction tools to create a structural model for the entire CEP enzyme of Lactococcus lactis. The model has implications for how the bacterium interacts with casein micelles during growth in milk, and it has implications regarding the energetics of the proteolytic system. Our model for the CEP indicates that the catalytic triad is activated through a structural change caused by interaction with the substrate. The CEP of L. lactis might become a useful model for the mode of action for enzymes belonging to the large class of S8 proteinases with a PA (protease associated) domain and a downstream fibronectin like domain.Anti-tumor drugs can effectively shrink the lesions of primary lung cancer; however, it has limited therapeutic effect on patients with brain metastasis (BM). A BM preclinical model based on a multi-organ microfluidic chip has been established proficiently in our previous work. In this study, the BM subpopulation (PC9-Br) derived from the parental PC9 cell line was isolated from the chip model and found to develop obvious resistance to antineoplastic drugs including chemotherapeutic agents (cisplatin, carboplatin, pemetrexed) and tyrosine kinase inhibitors (TKIs) which target epidermal growth factor receptor (EGFR); this suggested that the acquisition of drug-resistance by brain metastatic cells was attributable to the intrinsic changes in PC9-Br. Hence, we performed proteomic and revealed a greatly altered spectrum of BM protein expression compared with primary lung cancer cells. We identified the hyperactive glutathione (GSH) metabolism pathway with the overexpression of various GSH metabolism-related enzymes (GPX4, RRM2, GCLC, GPX1, GSTM4, GSTM1). Aldehyde dehydrogenases (ALDH1A1, ALDH3A1) were also found to be upregulated in BM. What's more, loss of EGFR and phosphorylated EGFR in PC9-Br gave reasons for the TKIs resistance. Collectively, our findings indicated potential mechanisms for the acquirement of drug resistance occurred in BM, providing new strategies to overcome therapeutic resistance in lung cancer BM.Bacterial cellulose (BC) is a natural biomaterial synthesized by bacteria. It possesses a unique structure of cellulose nanofiber-weaved three-dimensional reticulated network that endows it excellent mechanical properties, high water holding capability and outstanding suspension stability. It is also characterized with high purity, high degree of crystallinity, great biocompatibility and biodegradability. Due to these advantages, BC has gained great attentions in both academic and industrial areas. This critical review summarizes the up-to-date development of BC production and application from an industrial perspective. Firstly, a fundamental knowledge of BC's biosynthesis, structure and properties is described, and then recent developments in the industrial fermentation of BC are introduced. Subsequently, the latest commercial applications of BC in the areas of food, personal care, household chemicals, biomedicine, textile, composite resin are summarized. Finally, a brief discussion of future development of BC industry is presented at the end.As a key cytokine mediator of inflammation, interleukin-1β (IL-1β) binds to the IL-1 receptor (IL-1R) and activates various downstream signaling mediators, including NF-κB, which is required for immune vigilance and cellular protection. Toward the development of IL-1-targeting therapeutics which exhibit functional selectivity, the all-D-amino acid peptide 1 (101.10, H-D-Arg-D-Tyr-D-Thr-D-Val-D-Glu-D-Leu-D-Ala-NH2) was conceived as an allosteric IL-1R modulator that conserves NF-κB signaling while inhibiting other IL-1-activated pathways. Employing β-hydroxy-α-amino-γ-lactam (Hgl) stereoisomers to study the conformation about the Thr3 residue in 1, [(3R,4S)-Hgl3]-1 (2b), among all possible diastereomers, was found to exhibit identical in vitro and in vivo activity as the parent peptide and superior activity to the α-amino-γ-lactam (Agl) counterpart. Noting the relevance of the β-hydroxyl substituent and configuration for the activity of (3R,4S)-2b, fifteen different β-substituted-Agl3 analogs of 1 (e.g., 2c-q)rototypes to treat inflammatory events leading to prematurity and retinopathy of prematurity, which are leading causes of infant morbidity and blindness respectively.Monolithic perovskite/Silicon tandem solar cells have reached a certified efficiency of 29. 1% in recent years. In this review, we discuss material design for monolithic perovskite/Si tandem solar cells, with the focus on the top-cell development to improve their performance. Firstly, we introduce different types of transparent electrodes with high transmittance and low sheet-resistance used in tandem solar cells. We then discuss the development of the wide-bandgap perovskite absorber for top-cells, especially the strategies to obtain the perovskite layers with good efficiency and stability. In addition, as a special functional layer in tandem solar cells, the recombination layers play an important role in device performance, wherein different configurations are summarized. Furthermore, tandem device cost analysis is discussed. This review summarizes the progress of monolithic perovskite/Silicon tandem solar cells in a pragmatic perspective, which may promote the commercialization of this technology.Background Information communication technologies (ICT) are increasingly used in health promotion, but integration is challenging and involves complex processes. Large community health promotion events are often held but the experiences and processes have rarely been evaluated and published. No reports have described and systematically evaluated an ICT-supported health promotion event using digital games. Objective We evaluated the development and implementation of a large community family health promotion event with ICT integration to promote family happiness with collaboration between academia (The University of Hong Kong) and the social (family) service sector, and collected feedback from participants and social service workers. Methods We (i) conducted a systematic process evaluation, (ii) administered an on-site questionnaire survey on participant satisfaction and feedback, and (iii) collected post-event qualitative feedback from social workers on using new technologies, digital game design and overall e its kind, served as a capacity building and knowledge transfer platform for interdisciplinary co-sharing and co-learning of new technologies. It provided a solid foundation for further academic and social service partnerships and should be a useful model for similar community events and their evaluation. Further development and integration of ICT for health promotion among social service organizations with comprehensive evaluation are warranted.Background According to policy and theory, there is need for organizational workplace health promotion (WHP) to strengthen working conditions for all employees. However, earlier studies show it is hard to implement in practice. The aim was to critically analyze and identify interacting mechanisms and obstacles behind failures of organizational WHP projects from system perspectives. Methods A holistic case study was performed, to critically analyze data from an organizational WHP project approach at a public health care organization. The qualitative data was collected over 5 years and included interviews with key actors (n = 80), focus groups (n = 59 managers), structured observations (n = 250 hours), continuous field observations and documents (n = 180). Questionnaires to employees (n = 2,974) and managers (n = 140) was complementing the qualitative-driven mixed method approach. Results The analysis shows obstructing paradoxes of alignment and distribution of empowerment during the process of implementation into practice. The obstacles were interacting over system levels and were identified as Governance by logics of distancing and detaching, No binding regulation of WHP, Separated responsibility of results, Narrow focus on delegated responsibilities, Store-fronting a strategic model, Keeping poor organizational preconditions and support for developments and Isolate WHP from other organizational developments. Conclusions The following premises can be formulated regarding successful organizational WHP programs. Consider (1) the uncertainty a distributed empowerment to all system levels may create; (2) the distributed impact to define the target and allow broader areas to be included in WHP; and (3) the integration into other development processes and not reducing the organizational WHP to the form of a project.Introduction Green spaces support people mentally in their everyday life. Perceived restorativeness and Perceived Sensory Dimension (PSD) have been addressed as optimal environmental related characteristics with regards to psychological restoration. However, relatively little research has investigated how the perception of these characteristics, directly and indirectly, affects restoration experience, particularly in a sample of university students within the area of green outdoor campus landscapes. Methods This study hypothesizes these associations through application of partial least squares structural equation modeling (PLS-SEM), inputting data from a sample of university students in Malaysia. In the hypothesized model, we examine the degree of restoration that is enjoyed by subjects within landscapes through the effects of these characteristics. Indirect effects of perceived restorativeness via evaluation of mediation effects associated with perception of landscape characteristics and restoration experienmensions of PSD support perceived restorativeness and restoration experience more than others, and the wider psycho-social value of green spaces through the application of mediation effects and personal sensory dimensions in the development of mental health.Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2). TNBC constitutes about 15-30 percent of all diagnosed invasive breast cancer cases in the United States. African-American (AA) women have high prevalence of TNBC with worse clinical outcomes than European-American (EA) women. The contributing factors underlying racial disparities have been divided into two major categories based on whether they are related to lifestyle (non-biologic) or unrelated to lifestyle (biologic). Our objective in the present review article was to understand the potential interactions by which these risk factors intersect to drive the initiation and development of the disparities resulting in the aggressive TNBC subtypes in AA women more likely than in EA women. To reach our goal, we conducted literature searches using MEDLINE/PubMed to identify relevant articles published from tential interactions is essential to our understanding of disproportionately high burden and poor survival rates of AA women with TNBC.Objectives To determine the current tobacco smoking prevalence among Iranian adults, its geographical distribution in 2011, 2016, and time trend during 2004-2016. Methods We conducted a pooled analysis of the published reports of 2004, 2007, 2008, 2009, and the data of 2011 and 2016 of the STEPwise approach to chronic disease risk-factor surveillance (STEPS) surveys. Results The prevalence of current tobacco smoking and current daily cigarette smoking in 2016 was 14.1 and 9.7%, respectively. Only 0.2% of participants smoked water-pipe. Current tobacco smoking prevalence remained unchanged during 2004-2016 for both men and women. The prevalence of passive smoking at home or workplace was 27.4%. Current tobacco smoking prevalence and current daily cigarette smoking was significantly lower among women than men. Current tobacco smoking prevalence showed a geographical pattern throughout the country. In both 2011 and 2016, current tobacco smoking prevalence was higher among men who lived in the western provinces, especially the north-west, than those who lived in the eastern and southern provinces. Conclusions The current tobacco smoking prevalence among Iranian population has not changed significantly during 2004-2016 and does not conform to the international guidelines. Therefore, it remains crucial yet challenging that effective nationwide policies be implemented to reduce the use of tobacco products. One cannot hope for any reductions in smoking prevalence until a cocktail of interventions are built around strong commitment to government policy.In the absence of a consensus protocol to slow down the spread of SARS-CoV-2, policymakers need real-time indicators to support decisions in public health matters. The Effective Reproduction Number (R t ) represents the number of secondary infections generated per each case and can be dramatically modified by applying effective interventions. However, current methodologies to calculate R t from data remain somewhat cumbersome, thus raising a barrier between its timely calculation and application by policymakers. In this work, we provide a simple mathematical formulation for obtaining the effective reproduction number in real-time using only and directly daily official case reports, obtained by modifying the equations describing the viral spread. We numerically explore the accuracy and limitations of the proposed methodology, which was demonstrated to provide accurate, timely, and intuitive results. We illustrate the use of our methodology to study the evolution of the pandemic in different iconic countries, and to assess the efficacy and promptness of different public health interventions.Autoimmune Congenital Heart Block (CHB) is an immune-mediated disease due to transplacental passage of circulating anti-Ro/SSA and anti-La/SSB autoantibodies. It occurs in 2% of anti-Ro/SSA-exposed pregnancies, and recurrence rate is nine times higher in subsequent pregnancies. Aim of this review is to identify biomarkers of CHB and treatment strategies. The Ro-system is constituted by two polypeptides targeted by the anti-Ro52 and anti-Ro60 autoantibodies. The central portion of Ro52 (p200), more than the full amino-acid sequence of Ro-52, is recognized to be the fine specificity of anti-Ro associated to the highest risk of cardiac damage. If anti-p200 antibody should be tested, as biomarker of CHB, over standard commercial ELISAs is still debated. Recent studies indicate that type I-Interferon (IFN) can activate fibroblasts in fetal heart. In the mother the anti-Ro/La antibodies activate the type I IFN-signature, and maternal IFN-regulated genes correlate with a similar neonatal IFN-gene expression. Evaluation of maternal IFN-signature could be used as novel biomarker of CHB. The measurement of "mechanical" PR interval with weekly fetal echocardiogram (ECHO) from 16 to at least 24 weeks of gestation is strongly recommended for CHB prenatal diagnosis. However, ECHO screening presents some limitations due to difficult identification of first-degree block and possible occurrence of a complete block from a normal rhythm in few days. Maternal administration of Hydroxychloroquine from the tenth week of gestation, modulating toll-like receptor and autoantibody-dependent type I IFN activation on the fetus, has an important role in preventing CHB in pregnant women with high risk for recurrent CHB.Objective Human errors or protocol deviations during neonatal resuscitation are common. Excess workload has been proposed as a contributor to human error during medical tasks. We aim to characterize healthcare providers' perceived workload during neonatal resuscitation. Design Perceived workload was measured using a multi-dimensional retrospective National Aeronautics and Space Administration Task Load Index (NASA TLX) survey. The NASA TLX collects data on mental, physical, and temporal demand, performance, effort, and frustration. Each section is rated independently by participants on a scale of 0-20 (0 being lowest and 20 being highest). The Raw-TLX score is a composite score of all dimensions and presented on a scale of 0-100. Healthcare providers complete a paper and pencil survey after attending delivery room resuscitations within 3 months. Setting Level three neonatal intensive care unit at the Royal Alexandra Hospital, Edmonton, AB, Canada. Participants All neonatal healthcare providers who attended dend frustration 4 (1-10). Raw-TLX scores were higher when healthcare providers performed any intervention compared to no intervention [35 (22-49) vs. 8 (6-18), p = 0.0011]; intubation and no intubation was [55 (46-62) vs. 30 (17-46), p = 0.0001], and between performing chest compression vs. no chest compression [55 (49-64) vs. 33 (18-47), p = 0.001]. Conclusion Perceived workload of neonatal healthcare providers increases during higher acuity deliveries. Healthcare providers' workload during neonatal resuscitation can be measured using NASATLX and was inversely associated with 5-min Apgar score. Future studies assessing healthcare providers' perceived workload during neonatal resuscitation in different settings are warranted.Congenital adrenal hyperplasia includes autosomal recessive conditions that affect the adrenal cortex steroidogenic enzymes (cholesterol side-chain cleavage enzyme; 3β-hydroxysteroid dehydrogenase; 17α-hydroxylase/17,20 lyase; P450 oxidoreductase; 21-hydroxylase; and 11β-hydroxylase) and proteins (steroidogenic acute regulatory protein). These are located within the three major pathways of the steroidogenic apparatus involved in the production of mineralocorticoids, glucocorticoids, and androgens. Many countries have introduced newborn screening program (NSP) based on 17-OH-progesterone (17-OHP) immunoassays on dried blood spots, which enable faster diagnosis and treatment of the most severe forms of 21-hydroxylase deficiency (21-OHD). However, in several others, the use of this diagnostic tool has not yet been implemented and clinical diagnosis remains challenging, especially for males. Furthermore, less severe classic forms of 21-OHD and other rarer types of CAHs are not identified by NSP. The aim of this mini review is to highlight both the main clinical characteristics and therapeutic options of these conditions, which may be useful for a differential diagnosis in the neonatal period, while contributing to the biochemical evolution taking place in the steroidogenic field. Currently, chromatographic techniques coupled with tandem mass spectrometry are gaining attention due to an increase in the reliability of the test results of NPS for detecting 21-OHD. Furthermore, the possibility of identifying CAH patients that are not affected by 21-OHD but presenting elevated levels of 17-OHP by NSP and the opportunity to include the recently investigated 11-oxygenated androgens in the steroid profiles are promising tools for a more precise diagnosis and monitoring of some of these conditions.Allergic diseases have been linked to genetic and/or environmental factors, such as antibiotic use, westernized high fat and low fiber diet, which lead to early intestinal dysbiosis, and account for the rise in allergy prevalence, especially in western countries. Allergic diseases have shown reduced microbial diversity, including fewer lactobacilli and bifidobacteria, within the neonatal microbiota, before the onset of atopic diseases. Raised interest in microbiota manipulating strategies to restore the microbial balance for atopic disease prevention, through prebiotics, probiotics, or synbiotics supplementation, has been reported. We reviewed and discussed the role of prebiotics and/or probiotics supplementation for allergy prevention in infants. We searched PubMed and the Cochrane Database using keywords relating to "allergy" OR "allergic disorders," "prevention" AND "prebiotics" OR "probiotics" OR "synbiotics." We limited our evaluation to papers of English language including children aged 0-2 years old. Different products or strains used, different period of intervention, duration of supplementation, has hampered the draw of definitive conclusions on the clinical impact of probiotics and/or prebiotics for prevention of allergic diseases in infants, except for atopic dermatitis in infants at high-risk. This preventive effect on eczema in high-risk infants is supported by clear evidence for probiotics but only moderate evidence for prebiotic supplementation. However, the optimal prebiotic or strain of probiotic, dose, duration, and timing of intervention remains uncertain. Particularly, a combined pre- and post-natal intervention appeared of stronger benefit, although the definition of the optimal intervention starting time during gestation, the timing, and duration in the post-natal period, as well as the best target population, are still an unmet need.

To investigate the effect of splenectomy for correction of systemic hemodynamic disorders in hepatic cirrhosis patients with portal hypertension.

Hepatic cirrhosis patients with portal hypertension were enrolled from April 2015 to July 2018. Systemic hemodynamic parameters (heart rate, mean arterial pressure (MAP), cardiac output, and total peripheral vascular resistance (TPR)) were prospectively measured at baseline and 1 week, 1, 3, and 6 months, and 1, 2, and 3 years postoperatively. Paired analysis was conducted.

Sixty-nine patients were eligible, and 55 (79.7%) cases had a history of upper gastrointestinal bleeding. Child-Pugh classification was grade A in 41 (59.4%) cases, grade B in 26 (37.7%) cases, and grade C in 2 (2.9%) cases. The heart rate was significantly higher at 1 week postoperatively versus the baseline (

< 0.001). Meanwhile, the heart rate was significantly lower from 3 months to 2 years postoperatively versus the baseline (

< 0.05). The MAP was significantly higher at 6 months to 2 years postoperatively versus the baseline (

< 0.05). At 1 month postoperatively and 6 months to 2 years, the cardiac output was significantly lower versus the baseline (

< 0.05). At 1 month postoperatively and 6 months to 2 years, the TPR was significantly higher versus the baseline (

< 0.05).

Splenectomy corrects systemic hemodynamic disorder in hepatic cirrhosis patients with portal hypertension, and the effect is rapid and durable.

Splenectomy corrects systemic hemodynamic disorder in hepatic cirrhosis patients with portal hypertension, and the effect is rapid and durable.Compared to mono-species biofilm, biofilms formed by cross-kingdom pathogens are more refractory to conventional antibiotics, thus complicating clinical treatment and causing significant morbidity. Lemongrass essential oil and its bioactive component citral were previously demonstrated to possess strong antimicrobial efficacy against pathogenic bacteria and fungi. However, their effects on polymicrobial biofilms remain to be determined. In this study, the efficacy of lemongrass (Cymbopogon flexuosus) essential oil and its bioactive part citral against dual-species biofilms formed by Staphylococcus aureus and Candida species was evaluated in vitro. Biofilm staining and viability test showed both lemongrass essential oil and citral were able to reduce biofilm biomass and cell viability of each species in the biofilm. Microscopic examinations showed these agents interfered with adhesive characteristics of each species and disrupted biofilm matrix through counteracting nucleic acids, proteins and carbohydrates in the biofilm. Moreover, transcriptional analyses indicated citral downregulated hyphal adhesins and virulent factors of Candida albicans, while also reducing expression of genes involved in quorum sensing, peptidoglycan and fatty acids biosynthesis of S. aureus. Taken together, our results demonstrate the potential of lemongrass essential oil and citral as promising agents against polymicrobial biofilms as well as the underlying mechanisms of their activity in this setting.Orthohantaviruses (family Hantaviridae, order Bunyavirales) can cause two serious syndromes in humans hemorrhagic fever with renal syndrome (HFRS), associated with the Old World orthohantaviruses, and hantavirus cardiopulmonary syndrome (HCPS), associated with orthohantaviruses in the Americas. In Europe, four different orthohantaviruses (DOBV, PUUV, SEOV, and TULV) are associated with human disease. As disease severity and zoonotic source differ between orthohantavirus species, conclusive determination of the infecting species by either RT-PCR or comparative virus neutralization test (VNT) is of importance. Currently, the focus reduction neutralization test (FRNT) is considered the 'Gold Standard' for orthohantavirus VNTs, however this test is laborious and time-consuming. Consequently, more high-throughput alternatives are needed. In this study, we developed a comparative orthohantavirus microneutralization test (MNT) including all four human pathogenic orthohantavirus species circulating in Europe. The assvirus MNT to determine the infecting virus species in European HFRS patients. Identification of the causative species is needed for an adequate Public Health response and can support individual patient care. For many labs, the implementation of orthohantavirus neutralization tests has not been a straightforward procedure. This issue will be addressed by the rollout of the comparative MNT to multiple European laboratories to support patient diagnostics, surveillance and Public Health responses.

SARS-CoV-2 nucleic acid testing (NAT) has been routinely used for COVID-19 diagnosis during this pandemic; however, there have been concerns about its high false negative rate. We dissected its detection efficiency with a large COVID-19 cohort study.

We analyzed SARS-CoV-2 NAT positive rates of 4,275 specimens from 532 COVID-19 patients in Sichuan Province with different disease severities, statuses, and stages, as well as different types and numbers of specimens.

The total positive rate of the 4,275 specimens was 37.5%. Among seven specimen types, BALF generated a 77.8% positive rate, followed by URT specimens (38.5%), sputum (39.8%), and feces/rectal swabs (34.1%). Specimens from critical cases generated a 43.4% positive rate, which was significantly higher than that of other severities. With specimens from patients at stable status, the SARS-CoV-2 positive rate was 40.6%, which was significantly higher than that of improved status (17.1%), but lower than that of aggravated status (61.5%). Notably, the positive rate of specimens from COVID-19 patients varied significantly from 85 to 95% during 3 days before and after symptom onset, to 20% at around 18 days after symptom onset. In addition, the detection rate increased from 72.1% after testing one throat swab, to 93.2% after testing three consecutive respiratory specimens from each patient.

SARS-CoV-2 NAT detection rates vary with patient disease severity and status, specimen type, number of specimens, and especially disease progression. Sampling as close to symptom onset as possible, and consecutively collecting more than one respiratory specimen could effectively improve SARS-CoV-2 NAT detection efficiency.

SARS-CoV-2 NAT detection rates vary with patient disease severity and status, specimen type, number of specimens, and especially disease progression. Sampling as close to symptom onset as possible, and consecutively collecting more than one respiratory specimen could effectively improve SARS-CoV-2 NAT detection efficiency.

To investigate the association between clusters of conditions and psychological well-being across age groups.

This cross-sectional study used data collected in the Danish population-based Lolland-Falster Health Study. We included adults over the age of 18 years. Self-reported chronic conditions were divided into 10 groups of conditions. The primary outcome was psychological well-being (the WHO-5 Well-Being Index). Factor analysis constructed the clusters of conditions, and regression analysis investigated the association between clusters and psychological well-being.

Of 10,781 participants, 31.4% were between 18 and 49 years, 35.7% were between 50 and 64 years and 32.9% were above ≥65 years. 35.2% had conditions represented in 1 and 32.9% in at least 2 of 10 condition groups. Across age groups, living with one or more chronic conditions was associated with poorer psychological well-being. Two chronic condition patterns were identified; one comprised cardiovascular, endocrine, kidney, musculoskeletal and cancer conditions, the second mental, lung, neurological, gastrointestinal and sensory conditions. Both patterns were associated with poorer psychological well-being (Pattern 1 -4.5 (95% CI -5.3 to -3.7), Pattern 2 -9.1 (95% CI -13.8 to -8.2). For pattern 2, participants ≥65 years had poorer psychological well-being compared to younger (-12.6 (95% CI -14.2 to -11.0) vs -6.6 (95% CI -7.8 to -5.4) for 18-49 years and -8.7 (95% CI -10.1 to -7.3) for 50-64 years, interaction p ≤ 0.001).

Living with one or more chronic conditions is associated with poorer psychological well-being. Findings point toward a greater focus on supporting psychological well-being in older adults with both mental and somatic conditions.

Living with one or more chronic conditions is associated with poorer psychological well-being. Findings point toward a greater focus on supporting psychological well-being in older adults with both mental and somatic conditions.Hematogenous dissemination represents a common manifestation of squamous cell carcinoma of the head and neck, and the recommended therapeutic options usually consist of systemically administered drugs with palliative intent. However, mounting evidence suggests that patients with few and slowly progressive distant lesions of small size may benefit from various local ablation techniques, which have already been established as standard-of-care modalities for example in colorectal and renal cell carcinomas and in sarcomas. In principle, serving as radical approaches to eradicate cancer, these interventions can be curative. Their impact on local control and overall survival has been shown in numerous retrospective and prospective studies. The term oligometastatic refers to the number of distant lesions which should generally not surpass five in total, ideally in one organ. Currently, surgical resection remains the method of choice supported by the majority of published data. More recently, stereotactic (ablative) estations in this disease. At the same time, aggressive treatment of synchronous metastases early in the disease course should be weighed against the risk of futile interventions in a disease with already multimetastatic microscopic dissemination. Therefore, attentive treatment sequencing, meticulous appraisal of cancer extension, refinement of post-treatment surveillance, and understanding of tumor biology and kinetics are crucial in the management of oligometastases.Immunotherapy-based combinations have become standard of care in advanced renal cell carcinoma (RCC). Despite the potential for complete radiographic response, complete pathologic responses have been rarely reported. We present two cases of confirmed complete pathologic response to immunotherapy despite residual radiographic abnormalities. The first case describes a 68-year-old female with metastatic RCC who was treated with upfront pembrolizumab plus axitinib. She underwent nephrectomy after 15 doses of pembrolizumab with pathology revealing no evidence of viable tumor. To our knowledge, this is the first reported case of a complete pathologic response with pembrolizumab in metastatic RCC. The second case describes a 64-year-old female with metastatic RCC who was treated with second-line nivolumab after progression on cabozantinib. After 13 doses of nivolumab, she underwent nephrectomy with pathology revealing no evidence of viable tumor. These cases highlight the potential for scar tissue, fibrosis, and necrosis to persist radiographically after treatment with immunotherapy despite the absence of viable tumor cells.Allogeneic hematopoietic cell transplantation (allo-HCT) and chimeric antigen receptor T cell (CAR T) therapy are the main modalities of adoptive cellular immunotherapy that have widely permeated the clinical space. The advent of both technologies revolutionized treatment of many hematologic malignancies, both offering the chance at sustained remissions for patients who would otherwise invariably succumb to their diseases. The understanding and exploitation of the nonspecific alloreactivity of allo-HCT and the graft-versus-tumor effect is contrasted by the genetically engineered precision of CAR T therapy. Historically, those with relapsed and refractory hematologic malignancies have often been considered for allo-HCT, although outcomes vary dramatically and are associated with potential acute and chronic toxicities. Such patients, mainly with B-lymphoid malignancies, may now be offered CAR T therapy. Yet, a lack of prospective data to guide decisions thereafter requires individualized approaches on whether to proceed to allo-HCT or observe. The continued innovations to make CAR T therapy more effective and accessible will continue to alter such approaches, but similar innovations in allo-HCT will likely result in similarly improved clinical outcomes. In this review, we describe the history of the two platforms, dissect the clinical indications emphasizing their intertwining and competitive roles described in trials and practice guidelines, and highlight innovations in which they complement or inform one another.

Ovarian and uterine clear cell carcinomas (CCCs) are rare but associated with poor prognosis. This study explored RNA transcription patterns characteristic of these tumors.

RNA sequencing (RNA-seq) of 11 ovarian CCCs and five uterine CCCs was performed and compared to publicly available data from high grade serous ovarian cancers (HGSOCs). Ingenuity Pathway Analyses were performed. CIBERSORT analyses estimated relative fractions of 22 immune cell types in each RNA-seq sample. Sequencing data was correlated with PD-L1 immunohistochemical expression.

RNA-seq revealed 1,613 downregulated and 1,212 upregulated genes (corrected p < 0.05, |FC |≥10) in ovarian CCC

HGSOC. Two subgroups were identified in the ovarian CCC, characterized by ethnicity and expression differences in

. There were 3,252 differentially expressed genes between PD-L1+/- ovarian CCCs, revealing immune response, cell death, and DNA repair networks, negatively correlated with PD-L1 expression, whereas cellular proliferation networks rom each other and from other more common histologic subtypes. These insights may aid in devising novel therapeutics.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive softtissue sarcomas with dismal prognosis. Pathological and genetic markers maypredict more aggressive behavior in MPNSTs but have uncommonly been investigated, and feware used in daily practice. This study reviews the prognostic value of immunohistochemical markers and genetic alterations in MPNST.

A systematic search was performed in PubMed and Embase databases according to the PRISMA guidelines. Search terms related to 'MPNST' and 'prognostic' were used. Studies investigating the association of immunohistochemical markers or genetic alterations with prognosis were included. Qualitative synthesis was performed on all studies. A distinction was made between univariable and multivariable associations.

Forty-six studies were included after full-text screening. Sixty-seven different immunohistochemical markers were investigated. Absence of S100 and H3K27me3 and high Ki67 and p53 staining was most commonly independently associated with worse ay distinguish MPNSTs with worse outcomes. Genetic alterations and staining of other cell cycle regulatory and Ras pathway proteins may also help stratifying patients with worse outcomes. A combination of markers can increase the prognostic value.Primary CNS tumors are the leading cause of cancer-related death in pediatrics. It is essential to understand treatment trends to interpret national survival data. In Canada, children with CNS tumors are treated at one of 16 tertiary care centers. We surveyed pediatric neuro-oncologists to create a national standard of practice to be used in the absence of a clinical trial for seven of the most prevalent brain tumors in children. This allowed description of practice across the country, along with a consensus. This had a multitude of benefits, including understanding practice patterns, allowing for a basis to compare in future research and informing Health Canada of the current management of patients. This also allows all children in Canada to receive equivalent care, regardless of location.

Thymic squamous cell carcinoma (TSCC) is a rare neoplasm that has been sparsely cited in the literature. The aim of this study was to determine disease characteristics and prognostic factors of patients in a Surveillance, Epidemiology, and End Results (SEER) analysis.

Cases from 1990-2016 were retrieved from the SEER database and demographics, treatments, and survival outcomes were analyzed.

The TSCC accounted for 72.4% of the thymic carcinomas and 7.2% of thymic tumors. The 276 patients (165 men) selected for analysis had a median age of 65 (24-85) years, and 201 patients were diagnosed with Masaoka-Koga stage III/IV. The median survival of TSCC was 59 months with a 49.0% 5-year OS rate, a better prognosis than lymphoepithelioma-like carcinoma (32.1%) and undifferentiated carcinoma (33.3%). Multivariate analysis revealed the Masaoka-Koga stage (p = 0.003) and surgical types (complete resection, incomplete resection, and none; p < 0.001) were determinants of survival. Complete resection had the best prognosis with a 72.7% 5-year OS rate. Chemotherapy was an independent protective factor (HR = 0.555, 95% CI 0.347-0.886; p = 0.014) though poor survival was showed in univariate analysis. And the survival benefit of chemotherapy was validated in PSM analysis (3-year OS rate was 77.7% with chemotherapy

52.8% without chemotherapy; p = 0.014).

TSCC was frequently diagnosed in older patients with advanced Masaoka-Koga stage and had more favorable survival than other subtypes of thymic carcinomas. Complete resection is the preferred treatment. Masaoka-Koga stage and chemotherapy had a strong association with prognosis.

TSCC was frequently diagnosed in older patients with advanced Masaoka-Koga stage and had more favorable survival than other subtypes of thymic carcinomas. Complete resection is the preferred treatment. Masaoka-Koga stage and chemotherapy had a strong association with prognosis.

Invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) account for most breast cancers. However, the overall survival (OS) differences between ILC and IDC remain controversial. This study aimed to compare nonmetastatic ILC to IDC in terms of survival and prognostic factors for ILC.

This retrospective cohort study used data from the Surveillance, Epidemiology and End Results (SEER) Cancer Database (www.seer.cancer.gov). Women diagnosed with nonmetastatic ILC and IDC between 2006 and 2016 were included. A propensity score matching (PSM) method was used in our analysis to reduce baseline differences in clinicopathological characteristics and survival outcomes. Kaplan-Meier curves and log-rank test were used for survival analysis.

Compared to IDC patients, ILC patients were diagnosed later in life with poorly differentiated and larger lesions, as well as increased expression of estrogen receptors (ERs) and/or progesterone receptors (PRs). A lower rate of radiation therapy and chemotherapy was observed in ILC. After PSM, ILC, and IDC patients exhibited similar OS (HR=1.017, p=0.409, 95% CI 0.967-1.069). In subgroup analysis of HR-negative, AJCC stage III, N2/N3 stage patients, or those who received radiotherapy, ILC patients exhibited worse OS compared to IDC patients. Furthermore, multivariate analysis revealed a 47% survival benefit for IDC compared to ILC in HR-negative patients who received chemotherapy (HR=1.47, p=0.01, 95% CI 1.09-1.97).

Our results demonstrated that ILC and IDC patients had similar OS after PSM. However, ILC patients with high risk indicators had worse OS compared to IDC patients by subgroup analysis.

Our results demonstrated that ILC and IDC patients had similar OS after PSM. However, ILC patients with high risk indicators had worse OS compared to IDC patients by subgroup analysis.Multiple myeloma survival has significantly improved in recent years, due to novel agents that are available for treatment. The anti-CD38 monoclonal antibody Daratumumab is particularly efficient for patients with relapse/refractory disease, and many studies have shown its unprecedented efficacy also as a first treatment. However, to avoid the incidence of infusion reactions, long infusion schedules of 8 h at first dose and 4 h in the following doses are required, which can reduce the compliance of patients and health care professionals. A reduced infusion time of 90 min has been reported previously, but data are missing on the prolonged safety of this over time as well as the efficacy of this approach. In this work, we investigate the safety of 484 rapid Daratumumab infusions given early after the second dose over a 22 months period in 39 myeloma patients.Gliomas are one of the most aggressive primary brain tumors arising from neural progenitor cells. Delayed diagnosis, invasive biopsy, and diagnostic challenges stems the need for specific, minimally-invasive, and early diagnostic biomarkers. Tumor-associated (TA) autoantibodies are measurable in the biofluids long before the onset of the symptoms, suggesting their role in early diagnosis and clinical management of the patients. In the current study, cerebrospinal fluid (CSF) samples from patients with low-grade glioma (LGG) and the Glioblastoma multiforme (GBM) that characterizes advanced disease were compared with healthy control samples to identify putative TA autoantibodies, using protein microarrays. The CSF samples from LGGs (n = 10), GBM (n = 7) were compared with the control CSF samples (n = 6). Proteins showing significant antigenic response were cross-verified. Proteins NOL4 (a cancer-testis antigen) and KALRN showed an antigenic response in the CSF of GBM patients, whereas, UTP4 and CCDC28A showed an antigenic response in low grade gliomas when compared with the control samples. TA autoantibodies identified in this study from the CSF of the patients could supplement current screening modalities. Further validation of these TA autoantibodies on a larger clinical cohort could provide cues towards relevance of these proteins in early diagnosis of the disease.Most human tumors possess a high heterogeneity resulting from both clonal evolution and cell differentiation program. The process of cell differentiation is initiated from a population of cancer stem cells (CSCs), which are enriched in tumor-regenerating and tumor-propagating activities and responsible for tumor maintenance and regrowth after treatment. Intrinsic resistance to conventional therapies, as well as a high degree of phenotypic plasticity, makes CSCs hard-to-target tumor cell population. Reprogramming of CSC metabolic pathways plays an essential role in tumor progression and metastatic spread. Many of these pathways confer cell adaptation to the microenvironmental stresses, including a shortage of nutrients and anti-cancer therapies. A better understanding of CSC metabolic dependences as well as metabolic communication between CSCs and the tumor microenvironment are of utmost importance for efficient cancer treatment. In this mini-review, we discuss the general characteristics of CSC metabolism and potential metabolic targeting of CSC populations as a potent strategy to enhance the efficacy of conventional treatment approaches.Human hedgehog-interacting protein (HHIP), a negative regulator of hedgehog (HH) signaling pathway, has been reported to be dysregulated in many types of cancer, including gastric cancer. However, the inhibitory role of HHIP as well as the underlying molecular mechanism of HHIP regulation in gastric cancer haven't been fully elucidated yet. In this study, we demonstrated that HHIP overexpression significantly suppressed the proliferation and invasion of AGS cells evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and transwell assays, respectively. Interestingly, methylation-specific polymerase chain reaction (MS-PCR, MSP) showed that HHIP overexpression dramatically decreased its de novo promoter methylation levels in AGS cells. Furthermore, HHIP expression was higher in adjacent non-cancerous tissue compared to matched gastric cancer tissue. High HHIP level was negatively correlated with metastasis (p = 0.035) but not local recurrence (p = 0.58). Taken together, our study suggested that HHIP can modulate gastric cancer progression and metastasis via regulation of its de novo promoter methylation levels in a feedback manner. Lower HHIP levels is positively associated with gastric cancer metastasis, which not only indicates HHIP could be served as a protective marker for gastric cancer, but also suggests restoring HHIP expression might be a potential therapeutic strategy for clinical treatment.

Oxidized low-density lipoprotein (Ox-LDL) is a crucial pathogenic factor for vascular diseases, which can induce the proliferation of vascular smooth muscle cells (VSMCs). Genistein is the main component of soybean isoflavone. Genistein has a variety of pharmacological properties in the treatment of vascular diseases and a promising clinical application. Large-conductance calcium-activated potassium (BKCa) channels are the primary type of potassium channels in VSMCs, which regulate various biological functions of VSMCs. However, whether genistein exerts an antiproliferation effect on Ox-LDL-stimulated VSMCs remains unclear. The current study is aimed at elucidating the effect of genistein on the Ox-LDL-stimulated proliferation of VSMCs and its possible molecular mechanism, especially the electrophysiological mechanism related to BKCa channels.

Monoculture VSMC was obtained by an acute enzyme-dispersing method. The proliferation of cells was measured by CCK-8, cell cycle, and proliferating cell nuclear antigen (PCNA) expression.