The value of lost productivity from workplace bullying in Ireland.

BACKGROUND: Workplace bullying is a pervasive problem with significant personal, social and economic costs. Estimates of the resulting lost productivity provide an important societal perspective on the impact of the problem. Understanding where these economic costs fall is relevant for policy. AIMS: We estimated the value of lost productivity to the economy from workplace bullying in the public and private sectors in Ireland. METHODS: We used nationally representative survey data and multivariable negative binomial regression to estimate the independent effect of workplace bullying on days absent from work. We applied the human capital approach to derive an estimate of the annual value of lost productivity due to bullying by sector and overall, in 2017. RESULTS: Bullying was independently associated with an extra 1.00 (95% CI: 0.38-1.62) days absent from work over a 4-week period. This differed for public and private sector employees: 0.69 (95% CI: -0.12 to 1.50) versus 1.45 (95% CI: 0.50-2.40) days respectively. Applying official data, we estimated the associated annual value of lost productivity to be €51.8 million in the public sector, €187.6 million in the private sector and €239.3 million overall. CONCLUSIONS: The economic value of lost productivity from workplace bullying in Ireland is significant. Although bullying is more prevalent in the public sector, it has a larger effect on absence in the private sector. Given this, along with the greater overall share of employees, productivity losses from bullying are considerably larger in the private sector in Ireland.

Influenza vaccine uptake and attitudes of healthcare workers in Ireland.

BACKGROUND: Influenza vaccination uptake by Irish healthcare workers remains sub-optimal despite local initiatives to increase it. AIMS: To investigate hospital workers' attitudes to influenza vaccination and how this influenced their decisions about vaccination. METHODS: A questionnaire survey of Irish hospital workers, measuring uptake of and attitudes to influenza vaccination. RESULTS: There were 747 responders, of whom 361 (48%) reported having received influenza vaccination. Attitudes predicting vaccination uptake included a belief that vaccination would protect family members (P < 0.0005, CI 1.191-1.739), a perception of susceptibility to 'flu (P < 0.0005, CI 1.182-1.685), a belief that all healthcare workers should be vaccinated (P < 0.005, CI 1.153-1.783), perceived ease of getting 'flu vaccination at work (P < 0.0005, CI 1.851-2.842) and encouragement by line managers (P < 0.05, CI 1.018-1.400). Attitudes negatively associated with vaccination uptake included fear of needles (P < 0.05, CI 0.663-0.985) and a belief that vaccination would cause illness (P < 0.0005, CI 0.436-0.647). Medical staff were significantly more likely to be vaccinated. Healthcare students were least likely to be vaccinated (P < 0.0005). CONCLUSION: Addressing specific barriers to influenza vaccination in healthcare workers may improve uptake.

The Prevalence of Respiratory Symptoms in Irish Dairy Farmers.

Work-related respiratory disease is a significant risk in the farming community. We assessed respiratory symptoms using a validated work-related respiratory questionnaire in 126 dairy farmers (19-75 years; 91.3% male). The prevalence of cough symptoms was 34.4%. Thirty-seven farmers (29.4%) complained of upper airway symptoms while forty (31.7%) complained of eye problems. Cumulated symptoms scores did not indicate higher than normal rates of chronic lung disease. Only 10 farmers (7.9%) were taking medication for lung conditions. Only 7 (5.6%) were current smokers. The rate of respiratory symptoms did not relate to the herd size or the method of animal feeding used by the farmers. The incidence of respiratory symptoms remains high among Irish dairy farmers. While the exact reason for this is unknown it may be related to continuing work- related dust exposure.

A study of workaholism in Irish academics.

BACKGROUND: Workaholism is recognized as a health risk for academics given the open-ended nature of academic work; however, current prevalence rates of workaholism in the academic setting are unknown. AIMS: To assess the prevalence of workaholism within academics and determine the impact of workaholism on psychological well-being, work-life conflict, work-life fit, job satisfaction and perceived work effort. METHODS: Academics in three Irish universities completed a survey including measures of workaholism, psychological well-being, work-life conflict and job satisfaction. Analysis of variance tests were used to compare workaholism types on the outcome measures. RESULTS: A total of 410 academics completed the survey and were categorized by workaholism type: workaholics (27%), enthusiastic workaholics (23%), relaxed workers (27%) and uninvolved workers (23%). Workaholics reported poorer functioning across all the outcome measures in comparison to the other three groups. CONCLUSIONS: This study demonstrates the high levels of workaholism within academia and highlights the negative impact of workaholism on work-related outcomes and psychological well-being. These findings are significant given the highly intensive nature of academic work today and reducing resources within this sector.

Suppression of bone turnover by B-cell depletion in patients with rheumatoid arthritis.

UNLABELLED: The role of B cells in inflammatory bone formation and resorption is controversial. We investigated this in patients with rheumatoid arthritis (RA) treated with rituximab, a B-cell depleting antibody. We found a significant suppression in bone turnover, possibly a direct effect or as a consequence of a reduction in inflammation and disease activity. INTRODUCTION: RA is the most prevalent inflammatory joint disease, in which B cells play an important role. However, the role of B cells in bone turnover is controversial and RA subjects treated with rituximab, a B-cell depleting monoclonal antibody, provide an ideal model for determining the role of B cells in inflammatory bone resorption. METHODS: Serum from 46 RA patients, collected pre- and post-rituximab therapy, was analysed for biomarkers of bone turnover (procollagen type I amino-terminal propeptide [P1NP], osteocalcin, ß-isomerised carboxy-terminal telopeptide of type 1 collagen [ßCTX] and osteoprotegerin [OPG]). RESULTS: A significant decrease in bone resorption was observed 6 months after rituximab (median change ßCTX -50 ng/L, 95%CI -136, -8 p < 0.001, this equates to -37%; 95%CI -6, -49), mirrored by a reduction in disease activity. Similarly, there was a significant increase in P1NP, a marker of bone formation (median change P1NP 5.0 µg/L, 95%CI -1.0, 11.2, p = 0.02; 13%; 95%CI -3, 39), but no significant change in osteocalcin or OPG levels. The percentage change from baseline of ßCTX in a subgroup of patients (not on prednisolone or bisphosphonate) was significantly correlated with the percentage reduction in DAS28 score (r (s) = 0.570, p = 0.014). CONCLUSIONS: In conclusion, we have found that B-cell depletion increases bone formation and decreases bone resorption in RA patients; this may be a direct effect on osteoblasts and osteoclasts, respectively, and be at least partially explained by the decreased inflammation and disease activity.

Inhibition of spontaneous metastasis in a rat prostate cancer model by oral administration of modified citrus pectin.

BACKGROUND: Prostate cancer is the most common cancer diagnosed in U.S. men and remains incurable once it has metastasized. Many stages of the metastatic cascade involve cellular interactions mediated by cell surface components, such as carbohydrate-binding proteins, including galactoside-binding lectins (galectins). Modified citrus pectin (pH-modified), a soluble component of plant fiber derived from citrus fruit, has been shown to interfere with cell-cell interactions mediated by cell surface carbohydrate-binding galectin-3 molecules. PURPOSE: The aim of this study was to determine whether modified citrus pectin, a complex polysaccharide rich in galactosyl residues, could inhibit spontaneous metastasis of prostate adenocarcinoma cells in the rat. METHODS: The ability of modified citrus pectin to inhibit the adhesion of Dunning rat prostate cancer MAT-LyLu cells to rat endothelial cells was measured by 51Cr-labeling. Modified citrus pectin inhibition of MAT-LyLu cell anchorage-independent growth was measured by colony formation in agarose. The presence of galectin-3 in rat MAT-LyLu cells and human prostate carcinoma was demonstrated by immunoblotting and immunohistochemistry. One million MAT-LyLu cells were injected subcutaneously into the hind limb of male Copenhagen rats on day 0. Rats were given 0.0%, 0.01%, 0.1%, or 1.0% (wt/vol) modified citrus pectin continuously in their drinking water (from day 4 until necropsy on day 30). The number of MAT-LyLu tumor colonies in the lungs were counted. RESULTS: Compared with 15 or 16 control rats that had lung metastases on day 30, seven of 14 rats in the 0.1% and nine of 16 rats in the 1.0% modified citrus-pectin group had statistically significant (two-sided; P < .03 and P < .001, respectively) reductions in lung metastases. The lungs of the 1.0% modified citrus pectin-treated rats had significantly (two-sided; P < .05) fewer metastatic colonies than control groups (9 colonies +/- 4 [mean +/- SE] in the control group compared with 1 colony +/- 1 in the treated group). Modified citrus pectin had no effect on the growth of the primary tumors. In vitro, modified citrus pectin inhibited MAT-LyLu cell adhesion to rat endothelial cells in a time- and dose-dependent manner as well as their colony formation in semisolid medium. CONCLUSIONS: We present a novel therapy in which oral intake of modified citrus pectin acts as a potent inhibitor of spontaneous prostate carcinoma metastasis in the Copenhagen rat. IMPLICATIONS: Further investigations are warranted to determine the following: 1) the role of galectin-3 in normal and cancerous prostate tissues and 2) the ability of modified citrus pectin to inhibit human prostate metastasis in nude mice.

Purification of B16-F1 melanoma autocrine motility factor and its receptor.

Tumor autocrine motility factor (AMF) is a cytokine which stimulates both random and directed cell migration by self-producing cells. AMF has been detected in and purified from serum-free conditioned medium of murine B16-F1 melanoma cells. Under nonreducing conditions AMF migrates in sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a single band of Mr 55,000, whereas under reducing conditions it migrates as a single polypeptide of Mr 64,000. Two-dimensional polyacrylamide gel electrophoresis of the purified AMF resolved two polypeptides with isoelectric points of 6.35 (major) and 6.4 (minor). No carbohydrate side chains were detected in the B16-F1 AMF. Purified AMF stimulated B16-F1 cell migration in a dose-dependent fashion and bound directly in a protein-protein-binding assay to the AMF receptor, a cell surface glycoprotein of Mr 78,000 [glycoprotein (gp) 78]. The involvement of gp78 in AMF-stimulated function was demonstrated by motility assays. These results suggest that AMF is the natural ligand for the gp78-AMF receptor.

Molecular cloning and chromosomal mapping of a human galactoside-binding protein.

A human galactoside-binding protein with an Mr of 31,000 was cloned from the human HT-1080 fibrosarcoma complementary DNA library. A partial complementary DNA clone containing the complete coding region was characterized and the deduced sequence encodes a polypeptide of 242 amino acids with the characteristics of a carbohydrate-binding protein. The gene coding for the human galactoside-binding protein was mapped to the chromosomal band 1p13. The deduced amino acid sequence of the human galactoside-binding protein revealed 95 residues at the amino terminus, homologous to the predicted amino acid sequence of the second exon of the human L-myc gene.

The NH2 terminus of galectin-3 governs cellular compartmentalization and functions in cancer cells.

Galectin-3 is a member of the beta-galactoside-binding protein family shown to be involved in tumor progression and metastasis. It has a unique primary structure consisting of three domains: a 12-amino acid leader sequence containing a casein kinase I serine phosphorylation site, which is preceded by a collagenase-sensitive Pro-Gly-rich motif, and a COOH-terminal half encompassing the carbohydrate-binding site. To study the functional role of the unusual leader sequence of galectin-3, a mutant cDNA that causes an 11-amino acid deletion in the NH2-terminal region was generated and expressed in galectin-3-null BT-549 human breast carcinoma cells. Deletion of the NH2 terminus resulted in abolition of the secretion of truncated galectin-3, loss of nuclear localization, and reduced carbohydrate-mediated functions compared with the wild-type protein. When green fluorescent protein was fused to the galectin-3 leader sequence and transiently transfected into BT-549 cells, the uniform cellular distribution of native green fluorescent protein was changed mainly to a nuclear pattern. To further investigate whether the functional changes observed in a galectin-3 with the 11 NH2-terminal amino acids deleted were due to loss of phosphorylation at Ser6, two point mutations were created at this serine: Ser6-->Ala and Ser6-->Glu. No obvious difference was observed in cellular localization between wild-type and Ser6-mutated transfectants. These results suggest a structural role for the NH2 terminus leader motif of galectin-3 in determining its cellular targeting and biological functions independent of phosphorylation.

Increased calmodulin levels in psoriasis and low Ca++ regulated mouse epidermal keratinocyte cultures.

Calcium has been shown to regulate the proliferation of epidermal keratinocytes in vitro. We became interested in the role of the calcium binding protein, calmodulin, in hyperproliferative, low calcium regulated keratinocytes in vitro and in the in vivo hyperproliferative state, psoriasis. Calmodulin levels were measured by radioimmune assay in neonatal mouse keratinocytes grown in 0.02 mM calcium (hyperproliferative) and 1.2 mM calcium (normal) media, and in cells that had been grown in low calcium medium and then switched to normal calcium. On a whole culture basis the normal cells had more calmodulin than the low calcium cells. However, when low calcium monolayers were compared to the normal basal monolayer, the low calcium hyperproliferative cells had more calmodulin. Cells that were switched from 0.02 mM calcium to 1.2 mM calcium showed increasing calmodulin levels over time. Psoriatic plaques contained 2-3 times more calmodulin than the skin of normal controls when examined on a per micrograms of DNA, per micrograms of protein, and per gram of wet weight basis. Adjacent uninvolved psoriatic skin also had significantly elevated calmodulin levels in all data bases except per microgram of protein/cm2. These data suggest that increased calmodulin levels are associated with epidermal hyperproliferation and/or with the state of differentiation.

Specificity and inhibition of the epidermal cell detachment induced by pemphigus IgG in vitro.

IgG isolated from sera of patients with pemphigus vulgaris (PV) has been shown to induce cell detachment when added to primary epidermal cell cultures (PECC). We studied the specificity of this phenomenon. IgG fractions were purified from the sera of five patients with PV and control IgG fractions from the sera of normal donors and patients with bullous pemphigoid (BP), systemic lupus erythematosus (SLE), and anti-AB blood group sera (anti-AB). IgG fractions were added to PECC either at initial plating (0 hours), at media change (48 hours), or sequentially at both times, and cell detachment was quantitated at 72 and 96 hours. Significant cell detachment occurred only when PV IgG was added to the growth media sequentially at 0 and 48 hours (p = 0.001), and this effect was dose-dependent for either dose. Substitution of an unrelated IgG (BP, SLE, or anti-AB) at either time points reduced cell detachment to near control values. Furthermore, cell detachment was inhibited by the addition of the proteinase inhibitors alpha 2 macroglobulin (70% inhibition of detachment), aprotinin (63% inhibition), soybean and lima bean trypsin inhibitor (62 and 64%, respectively), and pepstatin (49%), but not by the inhibitors chymostatin, leupeptin, or antipain. These data confirm that PV IgG induces increased cell detachment in PECC and shows that this effect is specific for PV IgG, is dose-dependent, and may be inhibited by certain proteinase inhibitors.

Galectin-3 regulates p21 stability in human prostate cancer cells.

Galectin-3 (Gal-3) is a multifunctional protein involved in cancer through regulation of cell adhesion, cell growth, apoptosis and metastasis, while p21 (Cip1/WAF1) is a negative regulator of the cell cycle, involved in apoptosis, transcription, DNA repair and metastasis. The results presented here demonstrate for the first time that the level of Gal-3 protein is associated with the level of p21 protein expression in human prostate cancer cells and the effects of Gal-3 on cell growth and apoptosis were reversed by modulating p21 expression level. Furthermore, Gal-3 regulates p21 expression at the post-translational level by stabilizing p21 protein via the carbohydrate-recognition domain. This is the first report suggesting a molecular function not yet described for Gal-3 as the regulator of p21 protein stability. This study provides a unique insight into the relationship of these two molecules during prostate cancer progression, and may provide a novel therapeutic target.

Calpain activation through galectin-3 inhibition sensitizes prostate cancer cells to cisplatin treatment.

Prostate cancer will develop chemoresistance following a period of chemotherapy. This is due, in part, to the acquisition of antiapoptotic properties by the cancer cells and, therefore, development of novel strategies for treatment is of critical need. Here, we attempt to clarify the role of the antiapoptotic molecule galectin-3 in prostate cancer cells using siRNA and antagonist approaches. The data showed that Gal-3 inhibition by siRNA or its antagonist GCS-100/modified citrus pectin (MCP) increased cisplatin-induced apoptosis of PC3 cells. Recent studies have indicated that cisplatin-induced apoptosis may be mediated by calpain, a calcium-dependent protease, as its activation leads to cleavage of androgen receptor into an androgen-independent isoform in prostate cancer cells. Thus, we examined whether calpain activation is associated with the Gal-3 function of regulating apoptosis. Here, we report that Gal-3 inhibition by siRNA or GCS-100/MCP enhances calpain activation, whereas Gal-3 overexpression inhibits it. Inhibition of calpain using its inhibitor and/or siRNA attenuated the proapoptotic effect of Gal-3 inhibition, suggesting that calpain activation may be a novel mechanism for the proapoptotic effect of Gal-3 inhibition. Thus, a paradigm shift for treating prostate cancer is suggested whereby a combination of a non-toxic anti-Gal-3 drug together with a toxic chemotherapeutic agent could serve as a novel therapeutic modality for chemoresistant prostate cancers.

Bacterial vaginosis: a public health problem for women.

Bacterial vaginosis (BV) remains a moderately prevalent condition with clearly observed links to adverse reproductive, gynecological, and other outcomes in women, including human immunodeficiency virus infection. Because of inconsistent findings from clinical studies concerning BV's etiologic role, no definitive policies with respect to screening and treatment have yet been established. Of concern is the high, unexplained prevalence of BV among African-American women, who are also at extremely high risk for preterm birth. The complexity of the sociodemographic picture challenges the field of public health to continue to explore the role of BV and its relationship to a whole host of social and biomedical conditions that may contribute to adverse health outcomes among society's most vulnerable members. Future decisions about screening and treatment, currently based on the biomedical model, may need to take into consideration issues of social context and expanded views of causality if we are to better understand and eliminate those factors that place individual women at risk of adverse outcomes, as well as the conditions that underlie racial and ethnic disparities in health.

A simple method for preparing neocyte-enriched leukocyte-poor blood for transfusion-dependent patients.

Recent treatment for patients with thalassemia and chronic anemia involves transfusion of young red cells (YRBCs) or "neocytes." We developed a technique enabling YRBCs to be separated based on their buoyant density in autologous plasma during centrifugation. Following this procedure, measurement of pyruvate kinase (PK), an age-dependent red cell enzyme, showed neocyte enrichment in the top one-third of the RBC layer corresponding to a mean of 47.5 percent of the total PK present in the unfractionated unit. To provide a neocyte transfusion preparation with an acceptable hemoglobin content, the top one-third fraction from each of three bags of blood was pooled. Leukocytes were removed from this "neocyte unit" by an initial sedimentation with 6 percent hydroxyethyl starch (HES) followed by filtration through a filter (IG 500, Imugard). This process resulted in removal of 99.3 +/- 0.5 percent (mean +/- SD) of the leukocytes with a mean RBC recovery of 89.5 +/- 5.5 percent and a final hemoglobin content of 53.4 +/- 2.3 g. Tests for plasma-free hemoglobin and HES in the supernatant of the final transfusion product gave acceptable mean values of 28 mg per dl and 3.0 mg per ml. Autologous mean RBC survival of Cr51-labeled YRBC fractions was 41.8 +/- 2.9 days (n = 5). This technique yields neocyte enrichment superior to that achieved using a cell processor (model 2991, IBM) and has the added advantage of being less costly to prepare ($45.00 [1984] U.S. per YRBC unit as compared to an estimated $135.00 [1984] U.S., IBM) and more economical in terms of blood use.

Structure-function relationship of a recombinant human galactoside-binding protein.

A galactoside-binding lectin (hL-31) containing a collagen-like sequence was identified in human tumor cells. It was found to be the homologue of the IgE-binding protein, the macrophage cell-surface Mac-2 antigen, and the murine CBP35, RL-29, and mL-34 lectins. Here we report on the expression in Escherichia coli and functional analysis of recombinant hL-31 (rhL-31). The rhL-31 was purified in one step through an asialofetuin affinity column. The rhL-31 was reactive to anti-lectin antibodies and retained its lactose-dependent hemagglutination of trypsin-treated glutaraldehyde-fixed rabbit erythrocytes. The rhL-31 elutes from an affinity column as a 31-kDa monomer and undergoes homodimerization at relatively high protein concentrations, comparable to those used to mediate hemagglutination. Electron microscopy showed that the rhL-31 appears as a Y-shaped structure. Lactoperoxidase-catalyzed iodination of murine tumor cell-surface proteins followed by collagenase treatment revealed that the lectin is probably a peripheral membrane protein whereby both the amino and the carboxy termini are exposed on the outer cell membrane. These results point to the membrane disposition and orientation of the lectin and suggest a mechanism for a structure-function relationship of lectin activity.