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Background: With burnout rates highly prevalent in palliative care nurses, it is important to have a holistic understanding of the causes of burnout and strategies both to prevent burnout and to cope with burnout., Aim: To understand the causes of burnout and strategies used to prevent and cope with burnout in palliative care nurses. This would allow the implementation of strategies on a personal level and organisational level to mitigate the effects of burnout., Methods: A thematic analysis to explore palliative care nurses' experiences and their interpretations. In total, 11 in-depth interviews and one focus group discussion with 19 nurses were conducted. The study participants were recruited from three palliative care units within a health cluster in Singapore and had at least 1 year of experience working in palliative care., Results: Five themes were identified: (a) description of burnout and its attributes; (b) factors that contribute to burnout; (c) triggers that initiate burnout; (d) coping with burnout; and (e) resilience to burnout. The nurses were competent in recognising signs of burnout and understood the use of coping strategies to manage burnout. They were also able to develop resilience to burnout through meaning-making and personal experiences., Significance of Results: Helping palliative nurses find a deep purpose in their work builds resilience. Managers, organisation leaders, researchers and peers should look into ways to increase resilience in this group of nurses.

Introduction: Interleukin-17A (IL-17A) plays a crucial role in the pathogenesis of ankylosing spondylitis (AS), although not all patients respond to traditional IL-17A antibody treatments. QX002N injection, as a new monoclonal antibody targeting IL-17A, has shown potential in treating AS, offering a new treatment option for patients who do not respond well to existing therapies., Methods: A randomized, open, parallel, single-center, phase I study was conducted to assess the pharmacokinetics, safety, and immunogenicity of single doses of QX002N injection administered intravenously (IV) or subcutaneously (SC) to healthy Chinese volunteers. Blood samples were collected at specified time intervals, and then serum concentrations of QX002N were analyzed by enzyme-linked immunosorbent assay., Results: Pharmacokinetic analysis of the drug concentration-time data showed that the mean maximum observed serum QX002N concentration (C max ) was 110 and 33.9 µg/ml, respectively. The average area under the drug concentration-time curves from 0 to the time of the last quantifiable concentration (AUC last ) were 52,656 and 36,269 µg·h/ml, respectively and the average area under the drug concentration-time curves from 0 to infinity (AUC inf ) were 54,867 and 38,194 µg·h/ml, respectively. The absolute bioavailability of QX002N after SC injection was 69.6%., Conclusions: Immunogenicity was assessed and all the subjects in this study were Anti-drug antibody (ADA)-negative, which means no subjects appeared to develop immunogenicity to QX002N. All the results testify to the safety of QX002N injection, which is satisfactory after IV or SC dosing in healthy subjects., Trial Registration: www.chinadrugtirals.org.cn , CTR20220430., (© 2024. The Author(s).)

Aim: Novel long-acting drugs for type 2 diabetes mellitus may optimize patient compliance and glycaemic control. Exendin-4-IgG4-Fc (E4F4) is a long-acting glucagon-like peptide-1 receptor agonist. This first-in-human study investigated the safety, tolerability, pharmacokinetic, pharmacodynamic and immunogenicity profiles of a single subcutaneous injection of E4F4 in healthy subjects., Methods: This single-centre, randomized, double-blind, placebo-controlled phase 1 clinical trial included 96 subjects in 10 sequential cohorts that were provided successively higher doses of E4F4 (0.45, 0.9, 1.8, 3.15, 4.5, 6.3, 8.1, 10.35, 12.6 and 14.85 mg) or placebo (ChinaDrugTrials.org.cn: ChiCTR2100049732). The primary endpoint was safety and tolerability of E4F4. Secondary endpoints were pharmacokinetic, pharmacodynamic and immunogenicity profiles of E4F4. Safety data to day 15 after the final subject in a cohort had been dosed were reviewed before commencing the next dose level., Results: E4F4 was safe and well tolerated among healthy Chinese participants in this study. There was no obvious dose-dependent relationship between frequency, severity or causality of treatment-emergent adverse events. C max and area under the curve of E4F4 were dose proportional over the 0.45-14.85 mg dose range. Median T max and t 1/2 ranged from 146 to 210 h and 199 to 252 h, respectively, across E4F4 doses, with no dose-dependent trends. For the intravenous glucose tolerance test, area under the curve of glucose in plasma from time 0 to 180 min showed a dose-response relationship in the 1.8-10.35 mg dose range, with an increased response at the higher doses., Conclusion: E4F4 exhibited an acceptable safety profile and linear pharmacokinetics in healthy subjects. The recommended phase 2 dose is 4.5-10.35 mg once every 2 weeks., (© 2024 John Wiley & Sons Ltd.)

Vaccination plays a key role in preventing morbidity and mortality caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to evaluate the safety and immunogenicity of a SARS-CoV-2 messenger ribonucleic acid (mRNA) vaccine SYS6006. In the two randomized, observer-blinded, placebo-controlled phase 1 trials, 40 adult participants aged 18-59 years and 40 elderly participants aged 60 years or more were randomized to receive two doses of SYS6006 or placebo (saline). Adverse events (AEs) were collected through 30 days post the second vaccination. Immunogenicity was assessed by live-virus neutralizing antibody (Nab), spike protein (S1) binding antibody (S1-IgG), and cellular immunity. The result showed that 7/15, 9/15 and 4/10 adult participants, and 9/15, 8/15 and 4/10 elderly participants reported at least one AE in the 20-µg, 30-µg and placebo groups, respectively. Most AEs were grade 1. Injection-site pain was the most common AE. Two adults and one elder reported fever. No vaccination-related serious AE was reported. SYS6006 elicited wild-type Nab response with a peak geometric mean titer of 232.1 and 130.6 (adults), and 48.7 and 66.7 (elders), in the 20-µg and 30-µg groups, respectively. SYS6006 induced moderate-to-robust Nab response against Delta, and slight Nab response against Omicron BA.2 and BA.5. Robust IgG response against wild type and BA.2 was observed. Cellular immune response was induced. In conclusion, two-dose primary vaccination with SYS6006 demonstrated good safety and immunogenicity during a follow-up period of 51 days in immunologically naive population aged 18 years or more. (Trial registry: Chictr.org.cn ChiCTR2200059103 and ChiCTR2200059104).

Background: COVID-19 caused by SARS-CoV-2 is a great threat to public health. We present the safety and immunogenicity data from a phase I trial in China of an mRNA vaccine (LVRNA009)., Methods: In the single-centre, double-blind, placebo-controlled and dose-escalation study, 72 healthy unvaccinated adults aged 18-59 years were randomized (3:1) to receive LVRNA009 with one of three vaccine dosage (25, 50 and 100 μg) or placebo, to evaluate for the safety, tolerability and immunogenicity of LVRNA009., Results: All these participants received two injections 28 days apart. No adverse events higher than grade 2 were reported during the study. A total of 30 participants (42 %) reported solicited adverse reactions during the first 14 days after vaccinations. Of the events reported, fever (n = 11, 15 %) was the most common systemic adverse reaction, and pain at the injection site (n = 17, 24 %) was the most frequent solicited local adverse reaction. Anti-S-protein IgG and neutralising antibodies were observed to have been induced 14 days after the first dose, significantly increased 7 days after the second dose, and remained at a high level 28 days after the second dose. Specific T-cell responses peaked 7 days and persisted 28 days after second vaccination., Conclusion: LVRNA009 has demonstrated promising results in safety and tolerability at all three dose levels among Chinese adults. LVRNA009 at three dose levels could rapidly induce strong humoral and cellular immune responses, including binding and neutralising antibody production and IFN- γ secretion, which showed good immunogenicity., Clinical Trial Registration Number: Clinicaltrials.gov NCT05364047; Chictr.org.cn ChiCTR2100049349., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The production of textiles has undergone a considerable transformation, progressing from its primitive origins in hand-weaving to the implementation of contemporary automated systems. Weaving yarn into fabric is a crucial process in the textile industry that requires meticulous attention to output quality products, particularly in the tension control section. The efficiency of the tension controller in relation to the yarn tension significantly affects the quality of the resulting fabric, as proper tension control leads to strong, uniform, and aesthetically pleasing fabric, while poor tension control can cause defects and yarn breakage, leading to production downtime and increased costs. Maintaining the desired yarn tension during textile production is crucial, although it poses several problems, such as the continuous diameter change of the unwinder and rewinder sections leading to system change. Another problem faced by the industrial operation is maintaining proper tension on the yarn while changing the roll-to-roll operation velocity. In this paper, an optimized method for controlling yarn tension through the cascade control of tension and position, incorporating feedback controllers, feedforward, and disturbance observers, has been proposed to make the system more robust and suitable for industrial use. In addition, an optimum signal processor has been designed to obtain sensor data with reduced noise and minimal phase difference.

The information tranfered among individual animals can be shared by a network, which is consisted of the sender, the receiver, and the extra bystander of the communication signals. The bystanders can read and use the signal that is not sent directly to them and make use of it to interfere with the sender and the receiver, which is known as "audience effects" in the research area of animal behaviors. The processes of mate choice and mating of animals occur mainly in the network that is composed of the particular species. Increasing evidence show that the audience effects play an important role in regulating mating preference and mating strategy, resulting in changes in species evolution. Here, we review the role of audience effects on animal mate choice and evolution by clarifying the definition and functional explanations of audience effects, the factors contributing to audience effects, as well as the different impacts of audience effects on males and females. It would provide novel ideas to study the impacts of audience effects on mate choice and species evolution in the future.

Objective: To compare the clinical efficacy between Wei 's triple nine needling combined with esculin and digitalis glycosides eye drops and esculin and digitalis glycosides eye drops alone for presbyopia complicated with visual fatigue of liver depression and spleen deficiency., Methods: Forty-six cases (92 eyes) with presbyopia complicated with visual fatigue of liver depression and spleen deficiency were randomly divided into an observation group (23 cases) and a control group (23 cases, 2 cases dropped off). The cases in the observation group were treated with Wei 's triple nine needling and esculin and digitalis glycosides eye drops. The acupoints included Shangming (Extra), Chengqi (ST 1), Cuanzhu (BL 2) to Jingming (BL 1), Sizhukong (TE 23) to Taiyang (EX-HN 5), etc; the needling was given once every other day, three times a week, and the eye drops were given one drop each time, three times a day. The cases in the control group were only treated with the eye drops. Both groups were treated for 7 days as one course of treatment, and 2 courses of treatment were given. The visual fatigue core symptoms score, adjustment amplitude, adjustment lag and best average corrected visual acuity were observed in the two groups before treatment, 1 week and 2 weeks into treatment, respectively., Results: Compared before treatment, the visual fatigue core symptoms scores in the two groups were decreased after 1-week and 2-week treatment ( P <0.05); in the observation group, the adjustment amplitude was increased after 2-week treatment ( P <0.05), while in the control group, the adjustment amplitude was increased after 1-week and 2-week treatment ( P <0.05); in the observation group, the adjustment lag was decreased after 1-week and 2-week treatment ( P <0.05). After 2-week treatment, the visual fatigue core symptoms score in the observation group was lower than that in the control group, and the adjustment amplitude was higher than that in the control group ( P <0.05). There were no significant differences in adjustment lag and best average corrected visual acuity between the two groups after 1-week and 2-week treatment ( P >0.05)., Conclusion: Wei 's triple nine needling combined with esculin and digitalis glycosides eye drops could improve the visual fatigue and eye regulation ability in patients with presbyopia complicated with visual fatigue of liver depression and spleen deficiency, and the effect is better than esculin and digitalis glycosides eye drops alone.

Background: With more frail elderly living and likely to die in nursing homes, advance care planning (ACP) is critical in overall efforts to provide good palliative care. However, it is unclear how willing older, vulnerable residents in nursing homes are to take on an active role in care decisions., Aim: The objective of this pilot study was to examine nursing homes' healthcare professionals' and residents' views on ACP and the extent of similarities and differences in their views., Methods: Our sample of 24 healthcare professionals and 24 residents were identified and recruited through contacts established from existing collaborations with the nursing homes. Surveys were administered to the participants by a trained research assistant between April 2015 and August 2015., Results: Almost all the healthcare professionals (95.8%) would like to make an ACP for themselves in the future, while residents were divided in their choices (P<<0.01). Most residents (79.1%) felt that the most important guide for their surrogate in making decisions for them when they lose decision-making capacity should be based on their best interests. However, most healthcare professionals (75.0%) felt that it should be based on the resident's wishes and values., Conclusions: Healthcare professionals tended to overestimate the importance of patient autonomy compared to the residents. This study demonstrates that as much as advocacy and awareness are ongoing, nursing home residents' motivation to participate in ACP is lacking. The lack of motivation in ACP participation could be due to medical paternalism and familial determination, which have been a cultural norm for older Singaporeans. This study demonstrates there is a lack of cultural sensitivity in this group of healthcare professionals in approaching nursing home residents' end-of-life care decision-making.

Background: Many smokers have undiagnosed chronic obstructive pulmonary disease (COPD), and yet screening for COPD is not recommended. Smokers who know that they have airflow limitation are more likely to quit smoking. This study aims to identify the prevalence and predictors of airflow limitation among smokers in primary care., Methods: Current smokers ≥ 40 years old who were asymptomatic clinic attendees in a primary care setting were recruited consecutively for two months. We used a two-step strategy. Step 1: participants filled in a questionnaire. Step 2: Assessment of airflow limitation using a pocket spirometer. Multiple logistic regression was utilised to determine the best risk predictors for airflow limitation., Results: Three hundred participants were recruited. Mean age was 58.35 (SD 10.30) years old and mean smoking history was 34.56 pack-years (SD 25.23). One in two smokers were found to have airflow limitation; the predictors were Indian ethnicity, prolonged smoking pack-year history and Lung Function Questionnaire score ≤ 18. Readiness to quit smoking and the awareness of COPD were low., Conclusions: The high prevalence of airflow limitation and low readiness to quit smoking imply urgency with helping smokers to quit smoking. Identifying airflow limitation as an additional motivator for smoking cessation intervention may be considered. A two-step case-finding method is potentially feasible.

TRPV4 belongs to the 'Transient Receptor Potential' (TRP) superfamily. It has been identified to profoundly affect a variety of physiological processes, including nociception, heat sensation and inflammation. Unlike other TRP superfamily channels, its role in cancers are unknown until recently when we reported TRPV4 to be required for cancer cell softness that may promote breast cancer cell extravasation and metastasis. Here, we elucidated the molecular mechanisms mediated by TRPV4 in the metastatic breast cancer cells. TRPV4-mediated signaling was demonstrated to involve Ca 2+ -dependent activation of AKT and downregulation of E-cadherin expression, which was abolished upon TRPV4 silencing. Functionally, TRPV4-enhanced breast caner cell transendothelial migration requires AKT activity while a combination of transcriptional and post-translational regulation contributed to the TRPV4-mediated E-cadherin downregulation. Finally, mass spectrometry analysis revealed that TRPV4 is required for the expression of a network of secreted proteins involved in extracellular matrix remodeling. In conclusion, TRPV4 may regulate breast cancer metastasis by regulating cell softness through the Ca 2+ -dependent AKT-E-cadherin signaling axis and regulation of the expression of extracellular proteins.

Cigarette smoking enhances oxidative stress and airway inflammation in asthma, the mechanisms of which are largely unknown. Myeloid-derived regulatory cells (MDRC) are free radical producing immature myeloid cells with immunoregulatory properties that have recently been demonstrated as critical regulators of allergic airway inflammation. NO (nitric oxide)-producing immunosuppressive MDRC suppress T-cell proliferation and airway-hyper responsiveness (AHR), while the O2(•-) (superoxide)-producing MDRC are proinflammatory. We hypothesized that cigarette smoke (CS) exposure may impact MDRC function and contribute to exacerbations in asthma. Exposure of bone marrow (BM)-derived NO-producing MDRC to CS reduced the production of NO and its metabolites and inhibited their potential to suppress T-cell proliferation. Production of immunoregulatory cytokine IL-10 was significantly inhibited, while proinflammatory cytokines IL-6, IL-1β, TNF-α and IL-33 were enhanced in CS-exposed BM-MDRC. Additionally, CS exposure increased NF-κB activation and induced BM-MDRC-mediated production of O2(•-), via NF-κB-dependent pathway. Intratracheal transfer of smoke-exposed MDRC-producing proinflammatory cytokines increased NF-κB activation, reactive oxygen species and mucin production in vivo and exacerbated AHR in C57BL/6 mice, mice deficient in Type I IFNR and MyD88, both with reduced numbers of endogenous MDRC. Thus CS exposure modulates MDRC function and contributes to asthma exacerbation and identifies MDRC as potential targets for asthma therapy.

The urokinase-type plasminogen activator receptor (uPAR) is a glycosylphosphatidylinositol-linked membrane protein with no cytosolic domain that localizes to lipid raft microdomains. Our laboratory and others have documented that lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) exhibit a hypermotile phenotype. This study was undertaken to elucidate the molecular mechanism whereby uPAR ligation with its cognate ligand, urokinase, induces a motile phenotype in human lung fibroblasts. We found that uPAR ligation with the urokinase receptor binding domain (amino-terminal fragment) leads to enhanced migration of fibroblasts on fibronectin in a protease-independent, lipid raft-dependent manner. Ligation of uPAR with the amino-terminal fragment recruited α5β1 integrin and the acylated form of the Src family kinase, Fyn, to lipid rafts. The biological consequences of this translocation were an increase in fibroblast motility and a switch of the integrin-initiated signal pathway for migration away from the lipid raft-independent focal adhesion kinase pathway and toward a lipid raft-dependent caveolin-Fyn-Shc pathway. Furthermore, an integrin homologous peptide as well as an antibody that competes with β1 for uPAR binding have the ability to block this effect. In addition, its relative insensitivity to cholesterol depletion suggests that the interactions of α5β1 integrin and uPAR drive the translocation of α5β1 integrin-acylated Fyn signaling complexes into lipid rafts upon uPAR ligation through protein-protein interactions. This signal switch is a novel pathway leading to the hypermotile phenotype of IPF patient-derived fibroblasts, seen with uPAR ligation. This uPAR dependent, fibrotic matrix-selective, and profibrotic fibroblast phenotype may be amenable to targeted therapeutics designed to ameliorate IPF.

Objective: By studying the process of reverse osmosis system for traditional Chinese medicine materials physicochemical parameters affecting the osmotic pressure of its relevance, new compound system reverse osmosis process design methods were explored., Method: Three concentrations materials for high, middle and low were dubbed with Sini decoction as a model drug, and pretreated by 50 thousand relative molecular weight cut-off ultrafiltration membrane. The viscosity, turbidity, conductivity, salinity, TDS, pH value and osmotic pressure of each sample were determined after the reverse osmosis to study the physical and chemical parameters between their respective correlations with the osmotic pressure, and characterized by HPLC chromatograms showing changes before and after the main chemical composition of samples of reverse osmosis., Result: Conductivity-osmotic pressure, salinity-osmotic pressure of the linear correlation coefficient, TDS-osmotic pressure between the three sets of parameters were 0.963 8, 0.932 7, 0.973 7, respectively. Reverse osmosis concentrate and its characteristic spectrum ultrafiltrate HPLC similarity were up to 0. 968 or more, except the low concentrations., Conclusion: There is a significant correlation between the three physicochemical parameters (conductivity, salinity, TDS) and osmotic pressure of each sample system, and there is also significant linear correlation between salinity, conductivity, TDS. The original chemical composition of Sini decoction material concentrate was completely remained after the process of reverse osmosis.

Chemoresistance due to heterogeneity of the tumor microenvironment (TME) hampers the long-term efficacy of first-line therapies for lung cancer. Current combination therapies for lung cancer provide only modest improvement in survival, implicating necessity for novel approaches that suppress malignant growth and stimulate long-term antitumor immunity. Oxidative stress in the TME promotes immunosuppression by tumor-infiltrating myeloid-derived suppressor cells (MDSC), which inhibit host protective antitumor immunity. Using a murine model of lung cancer, we demonstrate that a combination treatment with gemcitabine and a superoxide dismutase mimetic targets immunosuppressive MDSC in the TME and enhances the quantity and quality of both effector and memory CD8(+) T-cell responses. At the effector cell function level, the unique combination therapy targeting MDSC and redox signaling greatly enhanced cytolytic CD8(+) T-cell response and further decreased regulatory T cell infiltration. For long-term antitumor effects, this therapy altered the metabolism of memory cells with self-renewing phenotype and provided a preferential advantage for survival of memory subsets with long-term efficacy and persistence. Adoptive transfer of memory cells from this combination therapy prolonged survival of tumor-bearing recipients. Furthermore, the adoptively transferred memory cells responded to tumor rechallenge exerting long-term persistence. This approach offers a new paradigm to inhibit immunosuppression by direct targeting of MDSC function, to generate effector and persistent memory cells for tumor eradication, and to prevent lung cancer relapse., (©2013 AACR)

Matrix stiffening and myofibroblast resistance to apoptosis are cardinal features of chronic fibrotic diseases involving diverse organ systems. The interactions between altered tissue biomechanics and cellular signaling that sustain progressive fibrosis are not well defined. In this study, we used ex vivo and in vivo approaches to define a mechanotransduction pathway involving Rho/Rho kinase (Rho/ROCK), actin cytoskeletal remodeling, and a mechanosensitive transcription factor, megakaryoblastic leukemia 1 (MKL1), that coordinately regulate myofibroblast differentiation and survival. Both in an experimental mouse model of lung fibrosis and in human subjects with idiopathic pulmonary fibrosis (IPF), we observed activation of the Rho/ROCK pathway, enhanced actin cytoskeletal polymerization, and MKL1 cytoplasmic-nuclear shuttling. Pharmacologic disruption of this mechanotransduction pathway with the ROCK inhibitor fasudil induced myofibroblast apoptosis through a mechanism involving downregulation of BCL-2 and activation of the intrinsic mitochondrial apoptotic pathway. Treatment with fasudil during the postinflammatory fibrotic phase of lung injury or genetic ablation of Mkl1 protected mice from experimental lung fibrosis. These studies indicate that targeting mechanosensitive signaling in myofibroblasts to trigger the intrinsic apoptosis pathway may be an effective approach for treatment of fibrotic disorders.

To improve the conventional BCG vaccine in cake appearance and integrity, a new formulation with corresponding freeze drying cycle was developed for a recombinant BCG vaccine. The new formulation contains mannitol as a bulking agent, and trehalose, sucrose and sodium glutamate as stabilizers. The formulation and freeze drying cycle were tested with different super cooling rates and secondary drying temperatures, with or without an annealing process. Thermodynamic behavior was characterized using differential scanning calorimetry (DSC). Varying the secondary drying temperature and presence/absence of an annealing step caused marked differences in cake thermodynamic profiles irrespective of different cooling rates. The annealing process allowed efficient crystallization of the mannitol. Failure to crystallize the bulking agent had the potential to depress the Tg' and compromise storage stability in the final lyophile by crystallizing from the solid during storage, even when the secondary drying temperature was as high as 40°C. The improved formulation and freeze drying cycle resulted in good recovery of 53.2% during lyophilization and a higher survival rate of 61.7% in an accelerated stability study than the conventional BCG formulation and cycle. In summary, full crystallization was necessary for the mannitol bulking formulation. The freeze dried rBCG vials obtained using the formulation and drying cycle developed here met the requirements of BCG vaccine in good cake appearance, high viability post freeze drying and heat stability during storage., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

A powder vaccine intended for aerosol delivery was formulated by spray drying the Ad35-vectored tuberculosis (TB) AERAS-402 vaccine with mannitol-based stabilizers. Thermodynamic properties, water absorption, particle size distribution and morphology of the powders were evaluated. Virus survival during spray drying and storage was determined by medium Tissue Culture Infectious Dose (TCID(50)). A mannitol-based powder (mannitol-cyclodextrin-trehalose-dextran, MCTD) had a narrow size distribution with a median volume diameter around 3.2-3.5microm (suitable for pulmonary vaccination of humans) and good aerosolization characteristics. The spray dry powders generated from mannitol-based formulations were hydrophobic, which benefits virus survival during both production and storage at 4 degrees C, 25 degrees C and 37 degrees C as compared to the hygroscopic formulations (trehalose, sucrose, dextran, PVP, leucine). In conclusion, this study demonstrates that it is possible to produce in a one-step spray drying process a stable dry powder formulation of a TB vaccine suitable for mass vaccination.

Fibroblasts from patients with pulmonary fibrosis express higher levels of the receptor for urokinase, and the extent of fibrosis in some animal models exhibits a dependence on the urokinase receptor. Recent observations have identified the urokinase receptor as a trans-interacting receptor with consequences on signaling and cell responses that vary depending on its interacting partner, the relative levels of expression, and the state of cellular transformation. We undertook this study to define the urokinase-type plasminogen activator cellular receptor (u-PAR)-integrin interactions and to determine the functional consequences of such interactions on normal human lung fibroblast attachment and migration. u-PAR colocalizes in lammelipodia/filopodia with relevant integrins that mediate fibroblast attachment and spreading on the provisional matrix proteins vitronectin, fibronectin, and collagens. Inhibitory antibody studies have revealed that human lung fibroblasts utilize alpha(v)beta(5) to attach to vitronectin, predominantly alpha(5)beta(1) (and alpha(v)beta(3)) to attach to fibronectin, and alpha(1)beta(1), alpha(2)beta(1), and alpha(3)beta(1) to attach to collagen. Blocking studies with alpha-integrin subunit decoy peptides and u-PAR neutralizing antibodies indicate that u-PAR modulates the integrin-mediated attachment to purified provisional matrix proteins, to anti-integrin antibodies, or to fibroproliferative lesions from fibrotic lungs. Furthermore, these decoy peptides blunt fibroblast spreading and migration. We show that u-PAR can interact with multiple alpha-integrins but with a preference for alpha(3). Taken together, these data demonstrate that u-PAR may interact with multiple integrins in normal human lung fibroblasts thereby promoting attachment, spreading, and migration. Modulation of fibroblast invasion would be expected to lead to amelioration of fibroproliferative diseases of the lung.

Purpose: The purpose of this study was to compare five different abutment-crown combinations for single implant-supported restorations regarding their capabilities to withstand loads., Materials and Methods: Fifty implants were placed into resin blocks, and the restorations were connected to the implants. The five tested restorations were: (1) metal-ceramic crowns cemented to titanium abutments, (2) In-Ceram crowns cemented to titanium abutments, (3) Celay feldspathic crowns cemented to titanium abutments, (4) In-Ceram crowns cemented to milled ceramic abutments, and (5) Celay feldspathic crowns cemented to milled ceramic abutments. The specimens were loaded at 0- and 45-degree angles to the long axis, and the load values at the moment of failure were recorded using a universal testing machine., Results: The fracture strengths under vertical loading were greater than those under oblique loading. The fracture strengths of metal-ceramic crowns cemented to the titanium abutments were higher than those of all-ceramic crowns cemented on the milled ceramic abutments, regardless of loading direction. There were no differences in the fracture strengths of the ceramic crowns between the two different abutment types under oblique loading., Conclusion: All-ceramic crowns on the milled ceramic abutments were weaker than the metal-ceramic crowns on the titanium abutments under oblique loading.

Purpose: This article reviews recent research on the esthetics of the smile, covering the attractiveness of the smile, the effect of aging on the smile, oral condition and the smile, personality and smile, and smile exercises., Material and Methods: The subjects were Koreans with normal occlusion. Photographs of a full smile were taken and the esthetic quality of the subjects' smiles was estimated. Smile scores were correlated with oral condition, personality, the practice of smile exercises, and elements of the smile, such as the position of the lip in a smile. The personality of the subjects was assessed by means of a Sixteen Personality Factor Questionnaire. Gibson's smile exercises were used to investigate the effect of smile exercise., Results: In an attractive smile, the full shape of the maxillary anterior teeth was shown between the upper and lower lip, the upper lip curved upward or was straight, the maxillary anterior incisal curve was parallel to the lower lip, and teeth were displayed to the first molar. The amount of maxillary incisal exposure gradually decreased with age, accompanied by a gradual increase in mandibular incisal exposure. Personality traits such as warmth, calmness, extroversion, and low anxiety were closely related to an attractive smile. Smile exercises were an effective means of improving the esthetic level of the smile if patients exercised continuously., Conclusion: An attractive smile is important for esthetic treatment. The lip position, oral condition, personality traits, and smile exercise affect the esthetics of the smile.

The effect of drinking Chinese green tea on the risk of stomach cancer was evaluated in a population-based case-control study conducted in Shanghai, China, from October 1991 to December 1993. Eligible cases were incident cases of primary stomach cancer diagnosed during the study period among residents of Hongkou district and Nanhui county aged under 80 years. Controls were selected from the same street or commune where the case resided and were matched to the cases on age (within three years) and gender. A total of 711 cases and 711 matched controls, more than 90 percent of the eligible subjects, completed the interview. Information was obtained on the types of tea used, age when habitual tea drinking started, frequency of new batches of tea leaves used per day, number of cups brewed from each batch, total duration of drinking for each batch, strength and temperature of the tea consumed. Statistical analysis was based on modelling through conditional logistic regression. After adjusting for age, gender, place of residence, education, birthplace, alcohol consumption, and cigarette smoking, the odds ratio (OR) comparing drinkers of green tea with nondrinkers was 0.71 (95 percent confidence interval = 0.54-0.93). The adjusted OR decreased with increasing number of new batches of the green tea consumed each day (P value trend = 0.006). With the largest series of stomach cancer cases to date, this study found green-tea consumption associated with lower risk of stomach cancer. Among drinkers of green tea, the risk of stomach cancer did not depend on the age when habitual green-tea drinking started. Green tea may disrupt gastric carcinogenesis at both the intermediate and the late stages.