Noninvasive Detection of Skin Cancer by Imprint Desorption Electrospray Ionization Mass Spectrometry Imaging.

We report a technique for the noninvasive detection of skin cancer by imprint desorption electrospray ionization mass spectrometry imaging (DESI-MSI) using a transfer agent that is pressed against the tissue of interest. By noninvasively pressing a tape strip against human skin, metabolites, fatty acids, and lipids on the skin surface are transferred to the tape with little spatial distortion. Running DESI-MSI on the tape strip provides chemical images of the molecules on the skin surface, which are valuable for distinguishing cancer from healthy skin. Chemical components of the tissue imprint on the tape strip and the original basal cell carcinoma (BCC) section from the mass spectra show high consistency. By comparing MS images (about 150-µm resolution) of same molecules from the tape strip and from the BCC section, we confirm that chemical patterns are successfully transferred to the tape stripe. We also used the technique to distinguish cherry angiomas from normal human skin by comparing the molecular patterns from a tape strip. These results demonstrate the potential of the imprint DESI-MSI technique for the noninvasive detection of skin cancers as well as other skin diseases before and during clinical surgery.

Have farmers had enough of experts?

The exponential rise of information available means we can now, in theory, access knowledge on almost any question we ask. However, as the amount of unverified information increases, so too does the challenge in deciding which information to trust. Farmers, when learning about agricultural innovations, have historically relied on in-person advice from traditional 'experts', such as agricultural advisers, to inform farm management. As more farmers go online for information, it is not clear whether they are now using digital information to corroborate in-person advice from traditional 'experts', or if they are foregoing 'expert' advice in preference for peer-generated information. To fill this knowledge gap, we sought to understand how farmers in two contrasting European countries (Hungary and the UK) learnt about sustainable soil innovations and who influenced them to innovate. Through interviews with 82 respondents, we found farmers in both countries regularly used online sources to access soil information; some were prompted to change their soil management by farmer social media 'influencers'. However, online information and interactions were not usually the main factor influencing farmers to change their practices. Farmers placed most trust in other farmers to learn about new soil practices and were less trusting of traditional 'experts', particularly agricultural researchers from academic and government institutions, who they believed were not empathetic towards farmers' needs. We suggest that some farmers may indeed have had enough of traditional 'experts', instead relying more on their own peer networks to learn and innovate. We discuss ways to improve trustworthy knowledge exchange between agricultural stakeholders to increase uptake of sustainable soil management practices, while acknowledging the value of peer influence and online interactions for innovation and trust building.

Gender differences in self-perceived changes among Japanese workers with depression.

BACKGROUND: The number of patients living with depression continues to increase in Japan. The economic effects of depression include loss of productivity due to both absenteeism and presenteeism. Gender differences have been reported in prevalence, onset pathways and subjective symptoms of depression. AIMS: To understand how workers with major depressive disorder (MDD) perceive problems in the workplace and examine gender differences in their self-perceived levels of functioning at work, noticed during the initial stages of depression. METHODS: This is a cross-sectional study of Japanese workers with MDD. Participants' self-perceived changes in the level of functioning at work were surveyed after the diagnosis during the first visit. The relationship between gender and changes in the level of functioning at work as initially perceived by the participants themselves was analysed using the chi-square test, supplemented by a residual analysis. RESULTS: We administered the survey to 147 workers with MDD. In terms of gender differences in initial self-perceived changes in the level of functioning at work, the proportion of men reporting reduced work efficiency was significantly higher than that of women, while the proportion of women reporting deterioration in relationships with colleagues and superiors was significantly higher than that of men. CONCLUSIONS: The findings suggest that greater attention to reduced work efficiency by men and to deterioration in work relationships by women with MDD should be essential components of self-care. Managers need to pay attention to the level of functioning and provide adequate social support for employees.

Probing the Mechanism of LAL-32, a Gold Nanoparticle-Based Antibiotic Discovered through Small Molecule Variable Ligand Display.

The unrelenting rise of antimicrobial-resistant bacteria has necessitated the search for novel antibiotic solutions. Herein we describe further mechanistic studies on a 2.0-nm-diameter gold nanoparticle-based antibiotic (designated LAL-32). This antibiotic exhibits bactericidal activity against the Gram-negative bacterium Escherichia coli at 1.0 µM, a concentration significantly lower than several clinically available antibiotics (such as ampicillin and gentamicin), and acute treatment with LAL-32 does not give rise to spontaneous resistant mutants. LAL-32 treatment inhibits cellular division, daughter cell separation, and twin-arginine translocation (Tat) pathway dependent shuttling of proteins to the periplasm. Furthermore, we have found that the cedA gene imparts increased resistance to LAL-32, and shown that an E. coli cedA transposon mutant exhibits increased susceptibility to LAL-32. Taken together, these studies further implicate cell division pathways as the target for this nanoparticle-based antibiotic and demonstrate that there may be inherently higher barriers for resistance evolution against nanoscale antibiotics in comparison to their small molecule counterparts.

The combination of Bifidobacterium breve with non-digestible oligosaccharides suppresses airway inflammation in a murine model for chronic asthma.

Over the last decade, there has been a growing interest in the use of interventions that target the intestinal microbiota as a treatment approach for asthma. This study is aimed at exploring the therapeutic effects of long-term treatment with a combination of Bifidobacterium breve with non-digestible oligosaccharides on airway inflammation and remodeling. A murine ovalbumin-induced chronic asthma model was used. Pulmonary airway inflammation; mRNA expression of pattern recognition receptors, Th-specific cytokines and transcription factors in lung tissue; expression of Foxp3 in blood Th cells; in vitro T cell activation; mast cell degranulation; and airway remodeling were examined. The combination of B. breve with non-digestible oligosaccharides suppressed pulmonary airway inflammation; reduced T cell activation and mast cell degranulation; modulated expression of pattern recognition receptors, cytokines and transcription factors; and reduced airway remodeling. The treatment induced regulatory T cell responses, as shown by increased Il10 and Foxp3 transcription in lung tissue, and augmented Foxp3 protein expression in blood CD4+CD25+Foxp3+ T cells. This specific combination of beneficial bacteria with non-digestible oligosaccharides has strong anti-inflammatory properties, possibly via the induction of a regulatory T cell response, resulting in reduced airway remodeling and, therefore, may be beneficial in the treatment of chronic inflammation in allergic asthma.

Proteins associated with pancreatic cancer survival in patients with resectable pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with a dismal prognosis. However, while most patients die within the first year of diagnosis, very rarely, a few patients can survive for >10 years. Better understanding the molecular characteristics of the pancreatic adenocarcinomas from these very-long-term survivors (VLTS) may provide clues for personalized medicine and improve current pancreatic cancer treatment. To extend our previous investigation, we examined the proteomes of individual pancreas tumor tissues from a group of VLTS patients (survival ≥10 years) and short-term survival patients (STS, survival <14 months). With a given analytical sensitivity, the protein profile of each pancreatic tumor tissue was compared to reveal the proteome alterations that may be associated with pancreatic cancer survival. Pathway analysis of the differential proteins identified suggested that MYC, IGF1R and p53 were the top three upstream regulators for the STS-associated proteins, and VEGFA, APOE and TGFß-1 were the top three upstream regulators for the VLTS-associated proteins. Immunohistochemistry analysis using an independent cohort of 145 PDAC confirmed that the higher abundance of ribosomal protein S8 (RPS8) and prolargin (PRELP) were correlated with STS and VLTS, respectively. Multivariate Cox analysis indicated that 'High-RPS8 and Low-PRELP' was significantly associated with shorter survival time (HR=2.69, 95% CI 1.46-4.92, P=0.001). In addition, galectin-1, a previously identified protein with its abundance aversely associated with pancreatic cancer survival, was further evaluated for its significance in cancer-associated fibroblasts. Knockdown of galectin-1 in pancreatic cancer-associated fibroblasts dramatically reduced cell migration and invasion. The results from our study suggested that PRELP, LGALS1 and RPS8 might be significant prognostic factors, and RPS8 and LGALS1 could be potential therapeutic targets to improve pancreatic cancer survival if further validated.

(Un)ethical behavior in organizations.

This review spotlights research related to ethical and unethical behavior in organizations. It builds on previous reviews and meta-analyses of the literature on (un)ethical behavior in organizations and discusses recent advances in the field. The review emphasizes how this research speaks to the influence of the organizational context on (un)ethical behavior, proceeding from a more macro to a more micro view on (un)ethical behavior and covering ethical infrastructures, interpersonal influences, individual differences, and cognitive and affective processes. The conclusion highlights opportunities for future research.

Dual role of Toll-like receptors in asthma and chronic obstructive pulmonary disease.

During the last decade, significant research has been focused on Toll-like receptors (TLRs) in the pathogenesis of airway diseases. TLRs are pattern recognition receptors that play pivotal roles in the detection of and response to pathogens. Because of the involvement of TLRs in innate and adaptive immunity, these receptors are currently being exploited as possible targets for drug development. Asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory airway diseases in which innate and adaptive immunity play an important role. To date, asthma is the most common chronic disease in children aged 5 years and older. COPD is prevalent amongst the elderly and is currently the fifth-leading cause of death worldwide with still-growing prevalence. Both of these inflammatory diseases result in shortness of breath, which is treated, often ineffectively, with bronchodilators and glucocorticosteroids. Symptomatic treatment approaches are similar for both diseases; however, the underlying immunological mechanisms differ greatly. There is a clear need for improved treatment specific for asthma and for COPD. This review provides an update on the role of TLRs in asthma and in COPD and discusses the merits and difficulties of targeting these proteins as novel treatment strategies for airway diseases. TLR agonist, TLR adjuvant, and TLR antagonist therapies could all be argued to be effective in airway disease management. Because of a possible dual role of TLRs in airway diseases with shared symptoms and risk factors but different immunological mechanisms, caution should be taken while designing pulmonary TLR-based therapies.

Chemo-attractant N-acetyl proline-glycine-proline induces CD11b/CD18-dependent neutrophil adhesion.

BACKGROUND: Chronic inflammation in lung diseases contributes to lung tissue destruction leading to the formation of chemotactic collagen fragments such as N-acetylated proline-glycine-proline (N-ac-PGP). In the current study, we investigate whether N-ac-PGP influences ß(2)-integrin activation and function in neutrophilic firm adhesion to endothelium. METHODS: Human polymorphonuclear leukocytes (PMNs) were isolated from fresh human blood. Subsequently, a transmigration assay was performed to evaluate the active migration of PMNs towards N-ac-PGP. Furthermore, the effect of the tripeptide on ß(2)-integrin activation was assessed by performing the adhesion assay using fibrinogen as a ligand. To determine whether this effect was due to conformational change of ß(2)-integrins, antibodies against CD11b and CD18 were used in the adhesion assay and the expression pattern of CD11b was determined. RESULTS: Human neutrophils transmigrated through an endothelial cell layer in response to basolateral N-ac-PGP. N-ac-PGP induced also a neutrophil adherence to fibrinogen. Using functional blocking antibodies against CD11b and CD18, it was demonstrated that CD11b/CD18 (Mac-1) was responsible for the N-ac-PGP-induced firm adhesion of neutrophils to fibrinogen. Pertussis toxin decreased the Mac-1 activation indicating the involvement of G-proteins. N-ac-PGP most likely activated Mac-1 by initiating a conformational change, since the expression pattern of Mac-1 on the cell surface did not change significantly. CONCLUSIONS: Chemo-attractant N-acetyl proline-glycine-proline induces CD11b/CD18-dependent neutrophil adhesion. GENERAL SIGNIFICANCE: This is the first study to describe that the chemo-attractant N-ac-PGP also activates Mac-1 on the surface of neutrophils, which can additionally contribute to neutrophilic transmigration into the lung tissue during lung inflammation.

Nanoscale structure-activity relationships, mode of action, and biocompatibility of gold nanoparticle antibiotics.

The emergence of resistance to multiple antimicrobial agents by pathogenic bacteria has become a significant global public health threat. Multi-drug-resistant (MDR) Gram-negative bacteria have become particularly problematic, as no new classes of small-molecule antibiotics for Gram-negative bacteria have emerged in over two decades. We have developed a combinatorial screening process for identifying mixed ligand monolayer/gold nanoparticle conjugates (2.4 nm diameter) with antibiotic activity. The method previously led to the discovery of several conjugates with potent activity against the Gram-negative bacterium Escherichia coli. Here we show that these conjugates are also active against MDR E. coli and MDR Klebsiella pneumoniae. Moreover, we have shown that resistance to these nanoparticles develops significantly more slowly than to a commercial small-molecule drug. These results, combined with their relatively low toxicity to mammalian cells and biocompatibility in vivo, suggest that gold nanoparticles may be viable new candidates for the treatment of MDR Gram-negative bacterial infections.

Bifidobacterium breve and Lactobacillus rhamnosus treatment is as effective as budesonide at reducing inflammation in a murine model for chronic asthma.

BACKGROUND: Asthma is estimated to affect as many as 300 million people worldwide and its incidence and prevalence are rapidly increasing throughout the world, especially in children and within developing countries. Recently, there has been a growing interest in the use of potentially beneficial bacteria for allergic diseases. This study is aimed at exploring the therapeutic effects of long-term treatment with two different beneficial bacterial strains (Bifidobacterium breve M-16 V and Lactobacillus rhamnosus NutRes1) and a glucocorticoid (budesonide), as a reference treatment, on inflammatory response in a murine model for chronic allergic asthma. METHODS: To mimic the chronic disease in asthmatic patients, we used the murine ovalbumin-induced asthma model combined with prolonged allergen exposure. Airway function; pulmonary airway inflammation; airway remodelling, mRNA expression of pattern recognition receptors, Th-specific cytokines and transcription factors in lung tissue; mast cell degranulation; in vitro T cell activation; and expression of Foxp3 in blood Th cells were examined. RESULTS: Lactobacillus rhamnosus reduced lung resistance to a similar extent as budesonide treatment in chronically asthmatic mice. Pulmonary airway inflammation, mast cell degranulation, T cell activation and airway remodelling were suppressed by all treatments. Beneficial bacteria and budesonide differentially modulated the expression of toll-like receptors (TLRs), nod-like receptors (NLRs), cytokines and T cell transcription factors. Bifidobacterium breve induced regulatory T cell responses in the airways by increasing Il10 and Foxp3 transcription in lung tissue as well as systemic by augmenting the mean fluorescence intensity of Foxp3 in blood CD4+ T cells. CONCLUSION: These findings show that Bifidobacterium breve M-16 V and Lactobacillus rhamnosus NutRes1 have strong anti-inflammatory properties that are comparable to budesonide and therefore may be beneficial in the treatment of chronic asthma.

Nominal Differences in Acute Symptom Presentation and Recovery Duration of Sport-Related Concussion Between Male and Female Collegiate Athletes in the PAC-12.

BACKGROUND: Sport-related concussion (SRC) is a heterogenous injury that often presents with varied symptoms and impairment. Recently, research has focused on identifying subtypes, or clinical profiles of concussion to be used in assessing and treating athletes with SRC. The purpose of this study was to investigate sex differences in clinical profiles, recovery duration, and initial symptom severity after SRC in a cohort of collegiate athletes in the Pacific-12 Conference (Pac-12). METHODS: This prospective cohort study examined post-SRC symptoms, recovery, and return-to-play times using data from the Pac-12 CARE Affiliated Program and Pac-12 Health Analytics Program. Clinical profiles reported by student-athletes were defined by the number (> 50%) of specific symptoms frequently reported for each profile. Generalized linear mixed models were used to examine associations among sex, clinical profiles, time-to-recovery, and return-to-play times. RESULTS: 479 concussion incidents met inclusion criteria. The probabilities of initial presentation of each clinical profile, initial injury severity scores, and recovery times within a profile did not differ between sexes (p = 0.33-0.98). However, both males and females had > 0.75 probabilities of exhibiting cognitive and ocular profiles. Initial injury severity score was a strong nonlinear predictor of initial number of clinical profiles (p < 0.0001), which did not differ between sexes. The number of clinical profiles was also a nonlinear predictor of time-to-recovery (p = 0.03) and return-to-play times (p < 0.0001). CONCLUSIONS: Initial symptom severity was strongly predictive of the number of acute clinical profiles experienced post-SRC. As the number of clinical profiles increased, time-to-recovery and time to return-to-play also increased. Factors other than sex may be better associated with acute symptom presentation post-concussion as no sex differences were found in reported clinical profiles or recovery. Understanding the number and type of clinical profiles experienced post-SRC may help inform concussion diagnostics and management.

Differential regulation of inflammation and immunity in mild and severe experimental asthma.

This study aimed at exploring innate and adaptive immunity in allergic asthma by investigation of mRNA expression of pattern recognition receptors, T-cell-specific cytokines, and transcription factors. Mouse models for mild and severe asthma, with similar pathological characteristics observed in humans, were used to study the involved inflammatory markers as a first step in the development of phenotype-directed treatment approaches. In the mild model, mice were sensitized to ovalbumin-Imject Alum and challenged with ovalbumin. In the severe model, mice were sensitized to trinitrophenyl-conjugated ovalbumin and challenged with trinitrophenyl-ovalbumin/IgE immune complex. Pulmonary airway inflammation and mRNA expression of Toll-like receptors (TLRs), NOD-like receptors (NLRs), T cell cytokines, and transcription factors in lung tissue were examined. Different mRNA expression profiles of TLRs, NLRs, T cell cytokines, and transcription factors were observed. In the mild model, Il10 showed the largest increase in expression, whereas in the severe model, it was Inf γ with the largest increase. Expression of Tbet was also significantly increased in the severe model. Inflammation and immunity are differentially regulated in mild and severe experimental asthma. This preclinical data may help in directing clinical research towards a better understanding and therapy in mild and severe asthmatic patients.

Effect of the 2018 NCAA Kickoff Rule Change on Concussion Rates in Collegiate Football: Results From a Division 1 Conference.

Background: Kickoff plays in American football are associated with an increased risk of concussion compared with other play types. In 2018, the National Collegiate Athletic Association (NCAA) Football Rules Committee altered the kickoff rules so a fair catch inside the 25-yard line results in a touchback, with the ensuing drive starting on the 25-yard line. The intention was to decrease the number of kickoff returns with a corresponding decrease in the rate of concussions on kickoff plays. Purpose: To determine whether the 2018 rule changes had the intended effects in an NCAA Division 1 Conference. Study Design: Cohort study; Level of evidence, 3. Methods: The study population included football athletes in the NCAA Pacific-12 (Pac-12) Conference. Data on the total number of plays, punts, kickoffs, touchbacks, and fair catches were obtained for all in-conference games from the 2016 to 2021 seasons. The number of game concussions and the play type were provided by each conference institution. Incidence of concussions occurring during kickoff plays before (2016-2017) and after (2018-2021) the rule change were compared with a difference-in-difference analysis using Poisson general linear models. Results: There were 242 concussions in 108,774 total plays in the study period, with an overall concussion rate of 2.2 per 1000 plays. The percentage of touchbacks increased significantly from 45% to 51% (P < .001) and the percentage of fair catches increased from 1% to 7% (P < .001) from before to after the rule change. Kickoffs accounted for 6% of plays both before and after the rule change and 11% of concussions before and 14% after the change. The mean annual concussion rate (per 1000 plays) on kickoffs was 3.42 before and 5.31 after the rule change (rate difference: 1.89; 95% confidence interval, -1.22 to 5.01). Conclusion: Touchbacks and fair catches increased after the kickoff rule change, but there was not a corresponding decrease in concussions during kickoff plays as anticipated. Concussions occurring during other football plays remained stable.

Impact of oral iron challenges on circulating non-transferrin-bound iron in healthy Guatemalan males.

INTRODUCTION: Oral iron as a supplement has been associated with adverse health consequences, especially in the context of young children with active malaria. A potential aggravating role of non-transferrin-bound iron (NTBI) has been proposed. MATERIAL AND METHODS: NTBI responses in both a fasting and post-oral iron dosing situation were related to serum iron concentration and ferritin status. Fasting and 1, 2, and 3 h postdose serum samples were obtained in conjunction with oral ferrous sulfate supplementation in aqueous solution of 0, 15, 30, 60, 120 and 240 mg Fe in a cohort of 8 healthy Guatemalan men over a 9-week metabolic protocol. Hemoglobin, serum ferritin, percent transferrin saturation, serum iron and NTBI were all measured. RESULTS: Circulating levels of serum iron and NTBI increased in a graded fashion in response to oral iron, with the relative increment for NTBI slightly greater than that of iron. Detectable NTBI was occasionally measured in fasting specimens, more frequently in subjects with high ferritin status. Post-iron NTBI responses, by contrast, were higher in normal-ferritin subjects in absolute terms, and rose with increasing postabsorptive serum iron responses. DISCUSSION: The appearance and response of circulating NTBI were consistent with recognized principles of iron regulation.

Autoimmune retinopathy with associated anti-retinal antibodies as a potential immune-related adverse event associated with immunotherapy in patients with advanced cutaneous melanoma: case series and systematic review.

OBJECTIVE: To demonstrate the spectrum of autoimmune retinopathy (AIR) associated with immunotherapy for advanced cutaneous melanoma. METHODS AND ANALYSIS: Retrospective chart review on patients with advanced cutaneous melanoma who developed AIR after initiating immunotherapy. Complete ophthalmic examination and relevant ancillary testing were performed on each patient. The presence of AIR-associated anti-retinal antibodies was confirmed by western blot and/or immunohistochemical staining. Ophthalmic and systemic outcomes after treatment for AIR were followed over time. A systematic review of AIR associated with immunotherapy for cutaneous or non-ocular mucosal melanoma was carried out in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Case 1 developed photopsia and nyctalopia with electroretinographic findings characteristic for melanoma-associated retinopathy 1 week after initiating ipilimumab/nivolumab immunotherapy. Case 2 experienced new severe bilateral visual field loss associated with anti-retinal and anti-optic nerve antibodies while on maintenance nivolumab immunotherapy. Case 3 developed decreased visual acuity due to acute exudative polymorphous vitelliform maculopathy within 2 weeks of initiating ipilimumab/nivolumab immunotherapy. All patients had concurrent extraocular immune-related adverse events in addition to the presence of anti-retinal antibodies on serological testing. 14 published cases of AIR associated with immunotherapy for cutaneous or non-ocular mucosal melanoma were identified and reviewed. CONCLUSIONS: Immune checkpoint inhibition can trigger the development of AIR with varied clinical manifestations in patients with advanced cutaneous melanoma. This study highlights the need for close monitoring in cutaneous melanoma patients receiving immunotherapy who develop new visual symptoms with or without funduscopic changes, as well as the potential role for screening of patients prior to initiating immunotherapy.

Analysis of LKB1 mutations and other molecular alterations in pancreatic acinar cell carcinoma.

Acinar cell carcinoma is a rare non-ductal neoplasm of the pancreas with poorly defined molecular genetic features. Recently, biallelic inactivation of LKB1 was described in an acinar cell carcinoma of a Peutz-Jeghers patient carrying a heterozygous germline LKB1 mutation, and inhibition of mTOR signaling resulted in partial remission of the tumor. To explore the potential of mTOR inhibitors in sporadic acinar cell carcinoma, the LKB1 gene was investigated in five sporadic acinar cell carcinomas by sequence analysis, methylation analysis and mRNA expression. In addition, microsatellite instability and methylation of a number of tumor suppressor genes were investigated and KRAS, TP53, CDKN1A, SMAD4 and CTNNB1 were studied by mutation analysis and immunohistochemistry. No mutations, deletions or promoter hypermethylation of LKB1 were found in any of the sporadic acinar cell carcinomas, and mRNA expression of LKB1 was not altered. Amplifications at chromosome 20q and 19p were found in 100 and 80% of the cases, respectively. In addition, hypermethylation of one or more tumor suppressor genes was found in 80% of cases. One case harbored a TP53 mutation, and expression of SMAD4 and CTNNB1 was altered in one case each. No KRAS mutations or microsatellite instability were found. To conclude, no evidence for a role for LKB1 in tumorigenesis of sporadic pancreatic acinar cell carcinoma was found. However, copy number variations and hypermethylation were found in a majority of cases. Molecular pathways involved in acinar cell carcinoma-tumorigenesis differ from those involved in ductal pancreatic neoplasms. Further studies are needed to increase our understanding of molecular pathogenesis of acinar cell carcinoma, which may eventually result in development of new therapeutic targets.

Cigarette smoke induces ß2-integrin-dependent neutrophil migration across human endothelium.

BACKGROUND: Cigarette smoking induces peripheral inflammatory responses in all smokers and is the major risk factor for neutrophilic lung disease such as chronic obstructive pulmonary disease. The aim of this study was to investigate the effect of cigarette smoke on neutrophil migration and on ß2-integrin activation and function in neutrophilic transmigration through endothelium. METHODS AND RESULTS: Utilizing freshly isolated human PMNs, the effect of cigarette smoke on migration and ß2-integrin activation and function in neutrophilic transmigration was studied. In this report, we demonstrated that cigarette smoke extract (CSE) dose dependently induced migration of neutrophils in vitro. Moreover, CSE promoted neutrophil adherence to fibrinogen. Using functional blocking antibodies against CD11b and CD18, it was demonstrated that Mac-1 (CD11b/CD18) is responsible for the cigarette smoke-induced firm adhesion of neutrophils to fibrinogen. Furthermore, neutrophils transmigrated through endothelium by cigarette smoke due to the activation of ß2-integrins, since pre-incubation of neutrophils with functional blocking antibodies against CD11b and CD18 attenuated this transmigration. CONCLUSION: This is the first study to describe that cigarette smoke extract induces a direct migratory effect on neutrophils and that CSE is an activator of ß2-integrins on the cell surface. Blocking this activation of ß2-integrins might be an important target in cigarette smoke induced neutrophilic diseases.

How to transition to reduced-meat diets that benefit people and the planet.

Overwhelming evidence shows that overconsumption of meat is bad for human and environmental health and that moving towards a more plant-based diet is more sustainable. For instance, replacing beef with beans in the US could free up 42% of US cropland and reduce greenhouse gas emissions by 334 mmt, accomplishing 75% of the 2020 carbon reduction target. We summarise the evidence on how overconsumption of meat affects social, environmental and economic sustainability. We highlight the social, environmental and economic effectiveness of a range of dietary interventions that have been tested to date. Because meat eating is embedded within complex cultural, economic, and political systems, dietary shifts to reduce overconsumption are unlikely to happen quickly and a suite of sustained, context-specific interventions is likely to work better than brief, one-dimensional approaches. We conclude with key actions needed by global leaders in politics, industry and the health sector that could help aide this dietary transformation to benefit people and the planet.

Insulin secretion by anomers of d-glucose.

Isolated rat islets were incubated for 5 minutes in the media containing either the alpha or beta anomer of D-glucose (2 milligrams per milliliter). The amounts of secreted insulin and changes of anomers ratio were concomitantly determined. In spite of rapid mutarotation, significantly greater stimulation of insulin secretion was observed by alpha-D-glucose as compared with beta-D-glucose.