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SETTING: The COVID-19 pandemic has impacted all of us in many areas of life due to mitigation measures, delays in medical care, or the disease itself. When it concerns issues as complex and universal as COVID-19, the public should also have a say in how to deal with managing its impact. DESIGN: In a widely distributed online questionnaire, members of the Austrian public were invited to contribute experiences, ideas and opinions on the level of risk they were willing to accept regarding COVID-19. The huge variety of responses were categorised by social scientists into groups used in a workshop to draw up recommendations for responding to future challenges to the healthcare system from an interdisciplinary point of view. RESULTS: The results of the survey indicated that while members of the public are primarily afraid of illnesses caused by COVID-19, they also fear the psychological burden and effects at the societal level. CONCLUSION: Our study has shown that there is a significant public desire to have a say in issues which directly impact citizens.

CONTEXTE: La pandémie de COVID-19 a eu un impact sur chacun d'entre nous dans de nombreux domaines de la vie en raison des mesures d'atténuation, des retards dans les soins médicaux ou de la maladie elle-même. Lorsqu'il s'agit de questions aussi complexes et universelles que la COVID-19, le public devrait également avoir son mot à dire sur la façon de gérer son impact. MÉTHODE: Dans un questionnaire en ligne largement diffusé, les membres du public autrichien ont été invités à faire part de leurs expériences, idées et opinions sur le niveau de risque qu'ils étaient prêts à accepter concernant le COVID-19. La grande variété des réponses a été classée par des spécialistes en sciences sociales dans des groupes utilisés lors d'un atelier pour élaborer des recommandations visant à répondre aux futurs défis du système de santé d'un point de vue interdisciplinaire. RÉSULTATS: Les résultats de l'enquête ont indiqué que si les membres du public craignent avant tout les maladies causées par le COVID-19, ils craignent également le fardeau psychologique et les effets au niveau de la société. CONCLUSION: Notre étude a montré qu'il existe un désir significatif du public d'avoir son mot à dire sur les questions qui ont un impact direct sur les citoyens.

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PURPOSE: Middle managers in health care today are expected to continuously and efficiently decide and act in administration, finance, care quality, and work environment, and strategic communication has become paramount. Since dialogical communication is considered to promote a healthy work environment, the purpose of this paper is to investigate the ways in which health care managers experienced observing subordinates' dialogue training. DESIGN/METHODOLOGY/APPROACH: A qualitative study using semi-structured interviews and documents from eight middle managers in a dialogue programme intervention conducted by dialogue trainers. Focus was on fostering and assisting workplace dialogue. Conventional qualitative content analysis was used. FINDINGS: Managers' experiences were both enriching and demanding, and consisted of becoming aware of communication, meaning perceiving interaction between subordinates as well as own silent interaction with subordinates and trainer; Discovering communicative actions for leadership, by gaining self-knowledge and recognizing relational leadership models from trainers--such as acting democratically and pedagogically--and converting theory into practice, signifying practising dialogue-promoting conversation behaviour with subordinates, peers, and superiors. RESEARCH LIMITATIONS/IMPLICATIONS: Only eight managers participated in the intervention, but data afforded a basis for further research. PRACTICAL IMPLICATIONS: Findings stressed the importance of listening, and of support from superiors, for well-functioning leadership communication at work. ORIGINALITY/VALUE: Studies focusing on health care managers' communication and dialogue are few. This study contributes to knowledge about these activities in managerial leadership.

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PURPOSE: Leadership can positively affect the work environment and health. Communication and dialogue are an important part in leadership. Studies of how dialogue is valued and handled in first-line leadership have not so far been found. The aim of this study is to develop a theoretical understanding of how first-line leaders at hospitals in western Sweden value and handle dialogue in the organisation. DESIGN/METHODOLOGY/APPROACH: The study design was explorative and based on grounded theory. Data collection consisted of interviews and observations. A total of 11 first-line leaders at two hospitals in western Sweden were chosen as informants, and for four of them observation was also used. FINDINGS: One core category emerged in the analysis: leaders' communicative actions, which could be strategically or understanding-oriented, and experienced as equal or unequal and performed equitably or inequitably, within a power relationship. Four different types of communicativeactions emerged: collaborative, nurturing, controlling, and confrontational. Leaders had strategies for creating arenas and relationships for dialogue, but dialogue could be constrained by external circumstances or ignorance of the frameworks needed to conduct and accomplish dialogue. PRACTICAL IMPLICATIONS: First-line leaders should be offered guidance in understanding the consequences of consciously choosing and strengthening the communication component in leadership. ORIGINALITY/VALUE: The positive valuation of dialogue was not always manifest in practical action. One significant consequence of not using dialogue was that information with impact on organisational efficiency and finances was communicated upwards in the management system.

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IGF-binding protein-3 (IGFBP-3) potentiates IGF-I action in the non-transformed mammary epithelial cell line, MAC-T, via a mechanism that is independent of its ability to bind IGF-I. The goal of the present study was to determine if IGFBP-3 might enhance IGF action by influencing intracellular signaling events downstream of the IGF receptor. IGF-I stimulated a time-dependent activation of Akt in which phosphorylation of Ser(473) was detectable by 1 min and maximal at 15 min. In contrast, no activation of extracellular signal-regulated kinase (ERK)1/2 by IGF-I was observed although basal phosphorylation was readily detectable. In MAC-T cells constitutively expressing IGFBP-3 (+BP3), phosphorylation of Akt following stimulation with IGF-I was enhanced relative to mock-transfected cells (Mock). The enhancement was detectable within 1 min of IGF-I treatment and persisted for up to 10 h. The increased phosphorylation observed by Western blotting corresponded to a 1.7-fold increase in Akt kinase activity. The enhanced Akt response was elicited by factors that activate the IGF receptor but exhibit reduced affinity for IGFBP-3, such as Long R(3)IGF-I, B chain IGF-I and insulin. In contrast, [Leu(60)]IGF-I, which binds IGFBP-3 but has reduced affinity for the IGF receptor, failed to induce comparable activation, suggesting that an association between IGF-I and IGFBP-3 is not required for the effect. The enhanced Akt activation could not be mimicked by addition of exogenous IGFBP-3. Akt phosphorylation was also enhanced by transforming growth factor-alpha in +BP3 cells, indicating that the effect was not specific to IGF-I. Similar to Akt, phosphorylation of p70S6 kinase (p70(S6K)) by IGF-I was also enhanced in +BP3 cells relative to Mock cells at both 15 min and 10 h. However, this was largely an effect of lower basal activation of p70(S6K) in +BP3 cells. These data indicate that endogenous IGFBP-3 potentiates IGF action in MAC-T cells by enhancing signaling via the phosphatidylinositol 3-kinase pathway at a point that is downstream of IGF receptor activation. Further studies will delineate specific mechanisms by which IGFBP-3 may influence intracellular events that regulate growth in mammary epithelial cells.

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We previously showed that moderate iron deficiency is associated with increased susceptibility to chemically induced breast carcinogenesis. Epidemiological and experimental data suggest that breast cancer risk may be modulated by the developmental and proliferative state of the mammary epithelium. The adverse effects of iron deficiency on organ growth are well documented. However, the role of iron in mammary gland development has not been examined. Therefore, we studied the effect of iron deficiency on mammary gland development and epithelial cell kinetics in female Sprague-Dawley rats. Weanling rats were fed experimental diets that provide 6 (severe), 12 (moderate) or 35 (control) mg Fe/kg diet. After 6 wk of treatment, hematocrit and blood hemoglobin were lower in iron-restricted rats than in controls, with significant differences from controls observed in rats receiving 6 mg Fe/kg diet (P < 0.05). Liver iron was reduced 90 and 80% in severe and moderate groups, respectively, compared with controls. Puberty onset and 17-beta-estradiol levels were unaltered by iron status, but plasma progesterone was significantly lower in iron-restricted groups (P < 0.05). Microscopic examination of mammary gland whole mounts revealed an increased density of terminal end buds in thoracic glands from iron-restricted rats, indicative of decreased differentiation, although the differences were not statistically significant compared with controls (P = 0.21). Mammary epithelial cell proliferation, determined in contralateral glands by measuring 5-bromo-2'-deoxyuridine incorporation, did not differ between rats receiving 12 and 35 mg Fe/kg diet. In conclusion, these results suggest that alveolar development of the mammary gland and the proliferative capacity of the mammary epithelium are refractory to iron deficiency during early postpubertal growth of the rat.

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IGF-I is mitogenic for the bovine mammary epithelial cell line MAC-T. In addition, IGF-I specifically upregulates IGFBP-3 synthesis in these cells. To investigate this effect on cell growth and IGF-I responsiveness, cell lines were developed that constitutively express IGFBP-3. MAC-T cells transfected with IGFBP-3 (+BP3) or vector alone (Mock) grew similarly over 7 days in 10 or 1% fetal calf serum. Basal DNA synthesis was lower (70%) in +BP3 cells compared to Mock cells. However, DNA synthesis was increased by IGF-I (1-50 ng/ml) relative to untreated controls to a greater extent in +BP3 cells compared to Mock cells. IGF-I (20 ng/ml) increased DNA synthesis 11- and threefold in +BP3 and Mock cells, respectively. Additionally, +BP3 cells were more sensitive to the lower concentrations of IGF-I (1-5 ng/ml). In contrast, preincubation of Mock cells with exogenous IGFBP-3 did not enhance responsiveness or sensitivity to IGF-I. Basal DNA synthesis was unaffected by either an IGF neutralizing antibody or exogenous IGFBP3, indicating the differences observed between +BP3 and Mock cells were not attributable to sequestration of endogenous IGF-I by IGFBP-3. There were no differences between +BP3 and Mock cells in IGF-I receptor number or affinity. DNA synthesis was also increased in +BP3 cells, compared to controls, in response to 5 microg/ml insulin and 2.5 ng/ml Long R(3)IGF-I, indicating that the potentiated response did not require an interaction with IGFBP-3. These results suggest that IGF-I regulation of IGFBP-3 represents a regulatory loop, the function of which is to increase IGF-I bioactivity, using a mechanism that does require an IGF-I-IGFBP-3 interaction.

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Closed-loop steady-state recycling (SSR) is a cyclic, one-column process that is similar to simulated moving bed (SMB) chromatography in several respects. Both processes are cyclic. In both SMB and SSR, fractions are collected from the leading and trailing portions of the circulating chromatographic profile, and fresh sample is injected into the interior of the profile. However, SMB is a continuous process whereas SSR is a discontinuous, repetitive process. This paper presents a model for the closed-loop SSR process and its experimental validation in a case of practical importance. For this last purpose, we used the closed-loop SSR separation of the enantiomers of a racemic pharmaceutical intermediate. The experimental determination of the competitive adsorption equilibria was performed by frontal analysis in a system composed of a chiral HPLC column as the stationary phase and pure acetonitrile as the mobile phase. All the adsorption data were well correlated by the Langmuir model. The Langmuir model was used to calculate overloaded band profiles corresponding to the separation of racemic mixtures at both analytical and preparative scales. Theoretical band profiles were calculated using the equilibrium-dispersive model. With proper corrections for the contributions of the sources of extra-column band broadening, the model properly predicts the experimental band profiles obtained in the closed-loop SSR setup and demonstrates that a cyclic steady-state develops after the completion of a finite number of cycles. The results also show that the extra-column effects must be accounted for in order to model the closed-loop SSR process accurately.

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Since cell proliferation is indispensable for the growth and development of the breast, and estrogens are considered to play a major role in promoting cell proliferation, while progesterone influences its differentiation, the present work was designed with the purpose of verifying the relationship between cells containing steroid hormone receptors and proliferating cells in the normal human breast. Twelve breast samples were analyzed for their content of lobules type 1 (Lob1), Lob2, Lob3, and Lob4, and the number of cells containing estrogen receptor alpha (ER-alpha), progesterone receptor (PgR), or expressing Ki67 antibody was determined by double immunocytochemical technique with specific antibodies. The highest percentage of ER-alpha, PgR, and Ki67 positive cells was found in Lob1, with a progressive reduction in the more differentiated Lob2 and Lob3. ER-alpha and PgR positive cells were found exclusively in the breast epithelium and were negative for Ki67, while cells positive for Ki67 did not express receptors. These findings were compared with the distribution of ER-alpha and PgR in the autoradiographs of mammary gland of young virgin rats inoculated with 3H-thymidine for determination of the DNA labeling index (DNA-LI). Both the DNA-LI and the percentage of ER-alpha and PgR positive cells were maximal in the epithelium of terminal end buds, and these values were reduced in alveolar buds and lobules. ER-alpha and PgR positive cells did not proliferate, and those cells that had incorporated 3H-thymidine were negative for both receptors. Our results led us to conclude that the content of ER-alpha and PgR in the normal mammary tissue varies with the degree of lobular development, in parallel with cell proliferation. However, the expression of receptors occurs in cells other than the proliferating cells, indicating that they represent at least two separate cell populations. These findings open new avenues towards the understanding of the mechanisms through which estrogens and progesterone affect the proliferative activity of breast epithelial cells, and their role in the initiation of the cascade of events that leads a normal cell to cancer.

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BACKGROUND: Previous studies have suggested that endothelins, a family of 21 amino acid peptides with potent vasoconstrictive and mitogenic properties, are involved in the pathogenesis of acute and chronic renal failure. In addition, endothelin seems to play an important role in mediating the nephrotoxic side effects of cyclosporine A (CsA) and tacrolimus. The present study investigated the production of endothelin-1 (ET-1) and endothelin-3 (ET-3) by bipolar differentiated rabbit proximal tubule cells (PT-1 cells), and the modulatory effect of CsA, tacrolimus, hepatocyte growth factor (HGF) and epidermal growth factor (EGF) on ET-1 and ET-3 release. METHODS: ET-1 and ET-3 mRNA was detected by RT-PCR, immunoreactive endothelin was localized to PT-1 cells by immunofluorescence staining with antibodies against ET-1 and ET-3. ET-1 and ET-3 release into the culture medium was determined by specific radioimmunoassays after solid phase extraction. RESULTS: PT-1 cells exhibited a time-dependent increase of ET-1 release up to an incubation period of 36 hours, whereas ET-3 release already reached a steady state level after four hours. PT-1 cells, cultured on filter membranes, released a significantly higher amount of immunoreactive ET-1 into the basolateral compartment than into the apical compartment. ET-3 release did not differ significantly between the basolateral and the apical compartment. Supplementation of the cell culture medium with 10% fetal calf serum induced a marked increase of the basolateral and apical ET-1 release, whereas ET-3 release was only slightly increased. CsA and tacrolimus (0.5 to 5000 microgram/liter) induced a significant, dose-dependent increase of ET-1 and ET-3 release by PT-1 cells with a maximum stimulation at a CsA concentration of 500 microgram/liter (P < 0.001) and a tacrolimus concentration of 50 microgram/liter (P < 0.001). HGF and EGF (10-10 to 10-8 mol/liter) exerted a significant (P < 0.001) dose-dependent inhibitory effect on ET-1 release, whereas ET-3 release was not significantly reduced. Coincubation of PT-1 cells with CsA or tacrolimus and HGF or EGF also resulted in a marked reduction of ET-1 release. CONCLUSIONS: The present data suggest that ET-1 and ET-3 release by cultured rabbit proximal tubule cells are regulated differently, and that the stimulatory effect of CsA and tacrolimus on ET-1 release is antagonized by HGF and EGF.

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Closed-loop recycling with periodic intra-profile injection (CLRPIPI) is a binary chromatographic separation technique. It is similar to simulated moving bed chromatography in that sample is injected into the interior of the circulating chromatographic profile. Although the CLRPIPI process is repetitive, it is different from SMB in that CLRPIPI is not continuous. It is shown that the CLRPIPI process reaches a steady state and that high purity fractions can be collected.

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Despite the advent of dual chamber ICDs, differentiation of VT (SMVT) with 1:1 VA conduction will remain a challenge. In this study, VA conduction capability and prevalence of inducible sustained monomorphic (SM) VT with 1:1 VA conduction was assessed in 305 ICD recipients. SMVT with a mean cycle length (CL) of 304 +/- 61 ms was induced in 161 (53%) patients. Twenty-six percent of the patients maintained 1:1 VA conduction to CL < or = 400 ms during incremental ventricular pacing, regardless of presenting tachyarrhythmia or presence of inducible SMVT. Among ten patients who had inducible SMVT with possible 1:1 VA conduction (based on SMVT CL comparable to the shortest CL associated with 1:1 retrograde conduction during ventricular pacing), all seven with available intracardiac tracings had documented 1:1 VA conduction during the induced SMVT--representing 4.4% of the patients with inducible SMVT (95% CI 1.2%-7.6%), and 2.3% of the entire ICD cohort (95% CI 0.6%-4.0%). We conclude that about one-fifth of ICD recipients possess 1:1 VA conduction to CL < or = 400 ms and that inducible SMVT with 1:1 VA conduction can be demonstrated in a small but nonnegligible proportion of ICD recipients. These data are relevant to the design of tachyarrhythmia-discrimination algorithms for dual chamber ICDs.

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The implantable cardioverter defibrillator has played an increasingly greater role in the management of episodes of sudden cardiac-related death related to ventricular tachycardia or ventricular fibrillation. This study reviews the cases of 142 patients who underwent insertion of an implantable cardioverter defibrillator, 104 who received a device alone (group I) and 38 who underwent insertion of the device in combination with other cardiac surgical procedures (group II). The overall operative mortality was 3.5% and this did not differ between the two groups. The complication rate was higher for group II than for group I patients, and consisted primarily of an increased incidence of atrial arrhythmias (53% versus 13%; p < 0.001). Late complications included three device infections requiring removal of the defibrillator. The late mortality did not differ between the two groups and was primarily related to congestive heart failure. Sudden cardiac-related death was an uncommon late event, with an actuarial freedom from sudden cardiac-related death of 98%, 97%, and 87% at 1, 2, and 5 years, respectively. The morbidity and mortality rate are low in association with the insertion of an implantable cardioverter defibrillator, even when this is combined with other cardiac surgical procedures. Its insertion is also associated with a low subsequent rate of sudden cardiac-related death.

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Immunocytochemical and morphometric analyses were combined to demonstrate the presence of neuron subpopulations in the rat vestibular ganglion. Monoclonal antibodies reacting with neurofilament proteins (NF), calbindin-D 28K (CaBP) and calretinin (CaR) were used. Three subpopulations were identified: (1) CaBP- and CaR-positive neurons were the largest neurons (16%) and they were also highly NF-immunoreactive; (2) exclusively NF-positive neurons; (3) unlabelled neurons, representing about two-thirds of the population.

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Erucic acid (C22:l fatty acid) has been found to be useful in the treatment of adrenoleukodystrophy (ALD). It appears to work by reducing the blood levels of very-long-chain fatty acids (VLCFAs) which destroy the myelin sheaths of the nerves. Erucic acid was purified by reversed-phase high-performance liquid chromatography (HPLC) on columns packed with YMC C18 (10-20 microns, 120 A). Using ethanol-water as the mobile phase, the recovery of erucic acid was 69% and the purity was more than 97% as measured by gas chromatography. The amount of saturated VLCFAs was found to be within the limits specified for ALD treatment. The production rate (yield per 8 h shift) was low, however. Using methanol-water instead of ethanol-water as the mobile phase, a ninefold increase in the production rate was achieved. The recovery of erucic acid was 65% and the purity of erucic acid was 98%. All other purity specifications were met. By performing a low-temperature crystallization after the preparative HPLC step, the production rate was increased a further 142%. This represents a 22-fold increase in production rate over the ethanol-water method. The crystalline erucic acid was found to be 99% pure. All other purity requirements were met. The yield for the combined process (HPLC plus crystallization) decreased to 55%, however.

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Mixed-chain, multispecies, egg yolk-derived lecithin was isolated and purified on a silica column with isocratic elution. A method development column (20 x 0.46 cm I.D.) packed with YMC 15-30 microns, 120 A spherical silica and a mobile phase consisting of 5 mM ammonium acetate in acetonitrile-2-propanol-methanol-water (80:13:5:12) was used to separate the lecithin from other phospholipids. The mobile phase conditions for the method development system was adopted for two types of preparative HPLC systems: a Separations Technology SepTech NovaPrep 5000 system with a 20 x 1.93 cm I.D. column and a ST/800A system with a 20 x 5.00 cm I.D. Annular Expansion (A/E) column. The maximum load was 50 microliters of crude solution (2 mg) for the method development column, 0.90 ml (35 mg) for the 20 x 1.93 cm I.D. column and 6.0 ml (240 mg) for the 20 x 5.00 cm I.D. A/E column. The flow-rates were 2, 35 and 235 ml/min, respectively. The fractions collected from the preparative systems were analyzed for purity by analytical-scale high-performance liquid chromatography and by thin-layer chromatography with selective detection with molybdenum blue for phospholipids and detection of all organic compounds by sulfuric acid. Purity of the recovered lecithin was greater than 99%.

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High levels of catecholamines have been found in plasma from the umbilical cord of newborn infants, suggesting a release of catecholamine from the fetus during parturition. Plasma catecholamine levels are also elevated in mothers at delivery.

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