High proportion of healthcare-associated urinary tract infection in the absence of prior exposure to urinary catheter: a cross-sectional study.

BACKGROUND: Exposure to urinary catheters is considered the most important risk factor for healthcare-associated urinary tract infection (UTI) and is associated with significant morbidity and substantial extra-costs. In this study, we assessed the impact of urinary catheterisation (UC) on symptomatic healthcare-associated UTI among hospitalized patients. METHODS: A nationwide period prevalence survey of healthcare-associated infections was conducted during 1 May to 30 June 2004 in 49 Swiss hospitals and included 8169 adult patients (4313 female; 52.8%) hospitalised in medical, surgical, intermediate, and intensive care wards. Additional data were collected on exposure to UC to investigate factors associated with UTI among hospitalised adult patients exposed and non-exposed to UC. RESULTS: 1917 (23.5%) patients were exposed to UC within the week prior to survey day; 126 (126/8169; 1.5%) developed UTI. Exposure to UC preceded UTI only in 73 cases (58%). By multivariate logistic regression analysis, UTI was independently associated with exposure to UC (odds ratio [OR], 3.9 [95% CI, 2.6-5.9]), female gender (OR, 2.1 [95% CI, 1.4-3.1]), an American Society of Anesthesiologists' score > 2 points (OR, 3.2 [95% CI, 1.1-9.4], and prolonged hospital stay >20 days (OR, 1.9 [95% CI, 1.4-3.2]. Further analysis showed that the only significant factor for UTI with exposure to UC use was prolonged hospital stay >40 days (OR, 2.9 [95% CI, 1.3-6.1], while female gender only showed a tendency (OR, 1.6 [95% CI, 1.0-2.7]. In the absence of exposure to UC, the only significant risk factor for UTI was female gender (OR, 3.3 [95% CI, 1.7-6.5]). CONCLUSIONS: Exposure to UC was the most important risk factor for symptomatic healthcare-associated UTI, but only concerned about half of all patients with UTI. Further investigation is warranted to improve overall infection control strategies for UTI.

Cross-neutralization of four paramyxoviruses by a human monoclonal antibody.

Broadly neutralizing antibodies reactive against most and even all variants of the same viral species have been described for influenza and HIV-1 (ref. 1). However, whether a neutralizing antibody could have the breadth of range to target different viral species was unknown. Human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV) are common pathogens that cause severe disease in premature newborns, hospitalized children and immune-compromised patients, and play a role in asthma exacerbations. Although antisera generated against either HRSV or HMPV are not cross-neutralizing, we speculated that, because of the repeated exposure to these viruses, cross-neutralizing antibodies may be selected in some individuals. Here we describe a human monoclonal antibody (MPE8) that potently cross-neutralizes HRSV and HMPV as well as two animal paramyxoviruses: bovine RSV (BRSV) and pneumonia virus of mice (PVM). In its germline configuration, MPE8 is HRSV-specific and its breadth is achieved by somatic mutations in the light chain variable region. MPE8 did not result in the selection of viral escape mutants that evaded antibody targeting and showed potent prophylactic efficacy in animal models of HRSV and HMPV infection, as well as prophylactic and therapeutic efficacy in the more relevant model of lethal PVM infection. The core epitope of MPE8 was mapped on two highly conserved anti-parallel β-strands on the pre-fusion viral F protein, which are rearranged in the post-fusion F protein conformation. Twenty-six out of the thirty HRSV-specific neutralizing antibodies isolated were also found to be specific for the pre-fusion F protein. Taken together, these results indicate that MPE8 might be used for the prophylaxis and therapy of severe HRSV and HMPV infections and identify the pre-fusion F protein as a candidate HRSV vaccine.

Novel nuclear ribonucleoprotein structural components in the dormouse adrenal cortex during hibernation.

Adrenocortical cell nuclei of the dormouse Muscardinus avellanarius were investigated by electron microscopic immunocytochemistry in hibernating, arousing and euthermic individuals. While the basic structural constituents of the cell nucleus did not significantly modify in the three groups, novel structural components were found in nuclei of hibernating dormice. Lattice-like bodies (LBs), clustered granules (CGs), fibrogranular material (FGM) and granules associated with bundles of nucleoplasmic fibrils (NF) all contained ribonucleoproteins (RNPs), as shown by labeling with anti-snRNP (small nuclear RNP), anti-m3G-capped RNA and anti-hnRNP (heterogeneous nuclear RNP) antibodies. Moreover, the FGM also showed immunoreactivity for the proliferation associated nuclear antigen (PANA) and the non-snRNP splicing factor SC-35. All these nuclear structural components disappeared early during arousal and were not found in euthermic animals. These novel RNP-containing structures, which have not been observed in other tissues investigated so far in the same animal model, could represent storage and/or processing sites for pre-mRNA during the extreme metabolic condition of hibernation, to be quickly released upon arousal. NFs, which had been sometimes found devoid of associated granules in nuclei of brown adipose tissue from hi-bernating dormice, were present in much higher amounts in adrenocortical cell nuclei; they do not contain RNPs and their role remains to be elucidated. The possible roles of these structures are discussed in the frame of current knowledge of morpho-functional relationships in the cell nucleus.

Invasive Candida infections in the ICU

Invasive candidiasis, including candidemia and deep-seated Candida infections, is a severe opportunistic infection with an overall mortality in ICU patients comparable to that of severe sepsis/septic shock. With an incidence ranging from 5 to 10 cases per 1000 ICU admissions, invasive candidiasis represents 510% of all ICU-acquired infections. Although a high proportion of critically ill patients is colonised with Candida spp., only 540% develop an invasive infection. The occurrence of this complication is difficult to predict and an early diagnosis remains a major challenge. Indeed, blood cultures are positive in a minority of cases and often late in the course of infection. New non-culture based laboratory techniques may contribute to early diagnosis and management of invasive candidiasis. Recent data suggest that prediction rules based on risk factors, clinical and microbiological parameters or monitoring of Candida colonisation may efficiently identify critically ill patients at high risk of invasive candidiasis who may benefit of preventive or pre-emptive antifungal therapy. In many cancer centres, exposure to azoles antifungals has been associated with an epidemiological shift from Candida albicans to non-albicans Candida species with reduced antifungal susceptibility or intrinsic resistance. This trend has not been observed in recent surveys on candidemia in non-immunocompromised ICU patients. Prophylaxis, pre-emptive or empirical antifungal treatment are possible approaches for prevention or early management of invasive candidiasis. However, the selection of high-risk patients remains critical for an efficient management aimed at reducing the number needed to treat and thus avoiding unnecessary treatments associated with the emergence of resistance, drug toxicity and costs.

Pre-pregnancy and pregnancy predictors of obesity.

Obesity has progressively become a global epidemic that constitutes one of the biggest current health problems worldwide. Pregnancy is a risk factor for excessive weight gain. Factors that may predict development of obesity in later life mainly include gestational weight gain, pre-pregnancy nutritional status, age, parity and race. Change in lifestyle factors, such as eating habits, enrollment in physical activity, smoking and duration of lactation, in addition to the above factors, may also contribute to the development of obesity but are still not fully understood. Women who retain more body weight after pregnancy have, in general, larger pregnancy body weight gain, higher pre-pregnancy body mass index, marked weight changes in previous pregnancies, lactate slightly less and stop smoking during pregnancy to a larger extent. In addition, irregular eating habits and decreased leisure time activity after delivery influence postpartum weight retention. Taking into consideration the epidemic of obesity, with all its adverse long-term consequences, there is an increasing need to promote counseling before, during and after pregnancy on the role of diet and physical activity in reproductive health.

Surfactant protein A, exposure to endotoxin, and asthma in garbage collectors and in wastewater workers.

Endotoxin causes an inflammation at the bronchial and alveolar level. The inflammation-induced increase in permeability of the bronchoalveolar epithelial barrier is supposed to cause a leakage of pneumoproteins. Therefore, their concentrations are expected to increase in the bloodstream.This study aimed at examining the association between occupational exposure to endotoxin and a serum pneumoprotein, surfactant protein A, to look for nonoccupational factors capable of confounding this association, and examine the relation between surfactant protein A and spirometry. There were 369 control subjects, 325 wastewater workers, and 84 garbage collectors in the study. Exposure to endotoxin was assessed through personal sampling and the Limulus amebocytes lysate assay. Surfactant protein A was determined by an in house sandwich enzyme-linked immunosorbent assay (ELISA) in 697 subjects. Clinical and smoking history were ascertained and spirometry carried out according to American Thoracic Society criteria. Multiple linear regression was used for statistical analysis. Exposure was fairly high during some tasks in wastewater workers but did not influence surfactant protein A. Surfactant protein A was lower in asthmatics. Interindividual variability was large. No correlation with spirometry was found. Endotoxin has no effect on surfactant protein A at these endotoxin levels and serum surfactant protein A does not correlate with spirometry. The decreased surfactant protein A secretion in asthmatics requires further study.

The cooperative induction of hypoxia-inducible factor-1 alpha and STAT3 during hypoxia induced an impairment of tumor susceptibility to CTL-mediated cell lysis.

Hypoxia is an essential component of tumor microenvironment. In this study, we investigated the influence of hypoxia (1% PO(2)) on CTL-mediated tumor cell lysis. We demonstrate that exposure of target tumor cells to hypoxia has an inhibitory effect on the CTL clone (Heu171)-induced autologous target cell lysis. Such inhibition correlates with hypoxia-inducible factor-1alpha (HIF-1alpha) induction but is not associated with an alteration of CTL reactivity as revealed by granzyme B polarization or morphological change. Western blot analysis indicates that although hypoxia had no effect on p53 accumulation, it induced the phosphorylation of STAT3 in tumor cells by a mechanism at least in part involving vascular endothelial growth factor secretion. We additionally show that a simultaneous nuclear translocation of HIF-1alpha and phospho-STAT3 was observed. Interestingly, gene silencing of STAT3 by small interfering RNA resulted in HIF-1alpha inhibition and a significant restoration of target cell susceptibility to CTL-induced killing under hypoxic conditions by a mechanism involving at least in part down-regulation of AKT phosphorylation. Moreover, knockdown of HIF-1alpha resulted in the restoration of target cell lysis under hypoxic conditions. This was further supported by DNA microarray analysis where STAT3 inhibition resulted in a partly reversal of the hypoxia-induced gene expression profile. The present study demonstrates that the concomitant hypoxic induction of phospho-STAT3 and HIF-1alpha are functionally linked to the alteration of non-small cell lung carcinoma target susceptibility to CTL-mediated killing. Considering the eminent functions of STAT3 and HIF-1alpha in the tumor microenvironment, their targeting may represent novel strategies for immunotherapeutic intervention.

Assessment of the occurrence of nanoparticles in Swiss industry and evaluation of the appropriatenesss of the measurement devices to determine the workforce exposure

Abstract : The occupational health risk involved with handling nanoparticles is the probability that a worker will experience an adverse health effect: this is calculated as a function of the worker's exposure relative to the potential biological hazard of the material. Addressing the risks of nanoparticles requires therefore knowledge on occupational exposure and the release of nanoparticles into the environment as well as toxicological data. However, information on exposure is currently not systematically collected; therefore this risk assessment lacks quantitative data. This thesis aimed at, first creating the fundamental data necessary for a quantitative assessment and, second, evaluating methods to measure the occupational nanoparticle exposure. The first goal was to determine what is being used where in Swiss industries. This was followed by an evaluation of the adequacy of existing measurement methods to assess workplace nanopaiticle exposure to complex size distributions and concentration gradients. The study was conceived as a series of methodological evaluations aimed at better understanding nanoparticle measurement devices and methods. lt focused on inhalation exposure to airborne particles, as respiration is considered to be the most important entrance pathway for nanoparticles in the body in terms of risk. The targeted survey (pilot study) was conducted as a feasibility study for a later nationwide survey on the handling of nanoparticles and the applications of specific protection means in industry. The study consisted of targeted phone interviews with health and safety officers of Swiss companies that were believed to use or produce nanoparticles. This was followed by a representative survey on the level of nanoparticle usage in Switzerland. lt was designed based on the results of the pilot study. The study was conducted among a representative selection of clients of the Swiss National Accident Insurance Fund (SUVA), covering about 85% of Swiss production companies. The third part of this thesis focused on the methods to measure nanoparticles. Several pre- studies were conducted studying the limits of commonly used measurement devices in the presence of nanoparticle agglomerates, This focus was chosen, because several discussions with users and producers of the measurement devices raised questions about their accuracy measuring nanoparticle agglomerates and because, at the same time, the two survey studies revealed that such powders are frequently used in industry. The first preparatory experiment focused on the accuracy of the scanning mobility particle sizer (SMPS), which showed an improbable size distribution when measuring powders of nanoparticle agglomerates. Furthermore, the thesis includes a series of smaller experiments that took a closer look at problems encountered with other measurement devices in the presence of nanoparticle agglomerates: condensation particle counters (CPC), portable aerosol spectrometer (PAS) a device to estimate the aerodynamic diameter, as well as diffusion size classifiers. Some initial feasibility tests for the efficiency of filter based sampling and subsequent counting of carbon nanotubes (CNT) were conducted last. The pilot study provided a detailed picture of the types and amounts of nanoparticles used and the knowledge of the health and safety experts in the companies. Considerable maximal quantities (> l'000 kg/year per company) of Ag, Al-Ox, Fe-Ox, SiO2, TiO2, and ZnO (mainly first generation particles) were declared by the contacted Swiss companies, The median quantity of handled nanoparticles, however, was 100 kg/year. The representative survey was conducted by contacting by post mail a representative selection of l '626 SUVA-clients (Swiss Accident Insurance Fund). It allowed estimation of the number of companies and workers dealing with nanoparticles in Switzerland. The extrapolation from the surveyed companies to all companies of the Swiss production sector suggested that l'309 workers (95%-confidence interval l'073 to l'545) of the Swiss production sector are potentially exposed to nanoparticles in 586 companies (145 to l'027). These numbers correspond to 0.08% (0.06% to 0.09%) of all workers and to 0.6% (0.2% to 1.1%) of companies in the Swiss production sector. To measure airborne concentrations of sub micrometre-sized particles, a few well known methods exist. However, it was unclear how well the different instruments perform in the presence of the often quite large agglomerates of nanostructured materials. The evaluation of devices and methods focused on nanoparticle agglomerate powders. lt allowed the identification of the following potential sources of inaccurate measurements at workplaces with considerable high concentrations of airborne agglomerates: - A standard SMPS showed bi-modal particle size distributions when measuring large nanoparticle agglomerates. - Differences in the range of a factor of a thousand were shown between diffusion size classifiers and CPC/SMPS. - The comparison between CPC/SMPS and portable aerosol Spectrometer (PAS) was much better, but depending on the concentration, size or type of the powders measured, the differences were still of a high order of magnitude - Specific difficulties and uncertainties in the assessment of workplaces were identified: the background particles can interact with particles created by a process, which make the handling of background concentration difficult. - Electric motors produce high numbers of nanoparticles and confound the measurement of the process-related exposure. Conclusion: The surveys showed that nanoparticles applications exist in many industrial sectors in Switzerland and that some companies already use high quantities of them. The representative survey demonstrated a low prevalence of nanoparticle usage in most branches of the Swiss industry and led to the conclusion that the introduction of applications using nanoparticles (especially outside industrial chemistry) is only beginning. Even though the number of potentially exposed workers was reportedly rather small, it nevertheless underscores the need for exposure assessments. Understanding exposure and how to measure it correctly is very important because the potential health effects of nanornaterials are not yet fully understood. The evaluation showed that many devices and methods of measuring nanoparticles need to be validated for nanoparticles agglomerates before large exposure assessment studies can begin. Zusammenfassung : Das Gesundheitsrisiko von Nanopartikel am Arbeitsplatz ist die Wahrscheinlichkeit dass ein Arbeitnehmer einen möglichen Gesundheitsschaden erleidet wenn er diesem Stoff ausgesetzt ist: sie wird gewöhnlich als Produkt von Schaden mal Exposition gerechnet. Für eine gründliche Abklärung möglicher Risiken von Nanomaterialien müssen also auf der einen Seite Informationen über die Freisetzung von solchen Materialien in die Umwelt vorhanden sein und auf der anderen Seite solche über die Exposition von Arbeitnehmenden. Viele dieser Informationen werden heute noch nicht systematisch gesarnmelt und felilen daher für Risikoanalysen, Die Doktorarbeit hatte als Ziel, die Grundlagen zu schaffen für eine quantitative Schatzung der Exposition gegenüber Nanopartikel am Arbeitsplatz und die Methoden zu evaluieren die zur Messung einer solchen Exposition nötig sind. Die Studie sollte untersuchen, in welchem Ausmass Nanopartikel bereits in der Schweizer Industrie eingesetzt werden, wie viele Arbeitnehrner damit potentiel] in Kontakt komrrien ob die Messtechnologie für die nötigen Arbeitsplatzbelastungsmessungen bereits genügt, Die Studie folcussierte dabei auf Exposition gegenüber luftgetragenen Partikel, weil die Atmung als Haupteintrittspforte iïlr Partikel in den Körper angesehen wird. Die Doktorarbeit besteht baut auf drei Phasen auf eine qualitative Umfrage (Pilotstudie), eine repräsentative, schweizerische Umfrage und mehrere technische Stndien welche dem spezitischen Verständnis der Mëglichkeiten und Grenzen einzelner Messgeräte und - teclmikeri dienen. Die qualitative Telephonumfrage wurde durchgeführt als Vorstudie zu einer nationalen und repräsentativen Umfrage in der Schweizer Industrie. Sie zielte auf Informationen ab zum Vorkommen von Nanopartikeln, und den angewendeten Schutzmassnahmen. Die Studie bestand aus gezielten Telefoninterviews mit Arbeit- und Gesundheitsfachpersonen von Schweizer Unternehmen. Die Untemehmen wurden aufgrund von offentlich zugànglichen lnformationen ausgewählt die darauf hinwiesen, dass sie mit Nanopartikeln umgehen. Der zweite Teil der Dolctorarbeit war die repräsentative Studie zur Evalniernng der Verbreitnng von Nanopaitikelanwendungen in der Schweizer lndustrie. Die Studie baute auf lnformationen der Pilotstudie auf und wurde mit einer repräsentativen Selektion von Firmen der Schweizerischen Unfall Versicherungsanstalt (SUVA) durchgeüihxt. Die Mehrheit der Schweizerischen Unternehmen im lndustrieselctor wurde damit abgedeckt. Der dritte Teil der Doktorarbeit fokussierte auf die Methodik zur Messung von Nanopartikeln. Mehrere Vorstudien wurden dnrchgefîihrt, um die Grenzen von oft eingesetzten Nanopartikelmessgeräten auszuloten, wenn sie grösseren Mengen von Nanopartikel Agglomeraten ausgesetzt messen sollen. Dieser F okns wurde ans zwei Gründen gewählt: weil mehrere Dislcussionen rnit Anwendem und auch dem Produzent der Messgeràte dort eine Schwachstelle vermuten liessen, welche Zweifel an der Genauigkeit der Messgeräte aufkommen liessen und weil in den zwei Umfragestudien ein häufiges Vorkommen von solchen Nanopartikel-Agglomeraten aufgezeigt wurde. i Als erstes widmete sich eine Vorstndie der Genauigkeit des Scanning Mobility Particle Sizer (SMPS). Dieses Messgerät zeigte in Präsenz von Nanopartikel Agglorneraten unsinnige bimodale Partikelgrössenverteilung an. Eine Serie von kurzen Experimenten folgte, welche sich auf andere Messgeräte und deren Probleme beim Messen von Nanopartikel-Agglomeraten konzentrierten. Der Condensation Particle Counter (CPC), der portable aerosol spectrometer (PAS), ein Gerät zur Schàtzung des aerodynamischen Durchniessers von Teilchen, sowie der Diffusion Size Classifier wurden getestet. Einige erste Machbarkeitstests zur Ermittlnng der Effizienz von tilterbasierter Messung von luftgetragenen Carbon Nanotubes (CNT) wnrden als letztes durchgeiührt. Die Pilotstudie hat ein detailliiertes Bild der Typen und Mengen von genutzten Nanopartikel in Schweizer Unternehmen geliefert, und hat den Stand des Wissens der interviewten Gesundheitsschntz und Sicherheitsfachleute aufgezeigt. Folgende Typen von Nanopaitikeln wurden von den kontaktierten Firmen als Maximalmengen angegeben (> 1'000 kg pro Jahr / Unternehrnen): Ag, Al-Ox, Fe-Ox, SiO2, TiO2, und ZnO (hauptsächlich Nanopartikel der ersten Generation). Die Quantitäten von eingesetzten Nanopartikeln waren stark verschieden mit einem ein Median von 100 kg pro Jahr. ln der quantitativen Fragebogenstudie wurden l'626 Unternehmen brieflich kontaktiert; allesamt Klienten der Schweizerischen Unfallversicherringsanstalt (SUVA). Die Resultate der Umfrage erlaubten eine Abschätzung der Anzahl von Unternehmen und Arbeiter, welche Nanopartikel in der Schweiz anwenden. Die Hochrechnung auf den Schweizer lndnstriesektor hat folgendes Bild ergeben: ln 586 Unternehmen (95% Vertrauensintervallz 145 bis 1'027 Unternehmen) sind 1'309 Arbeiter potentiell gegenüber Nanopartikel exponiert (95%-Vl: l'073 bis l'545). Diese Zahlen stehen für 0.6% der Schweizer Unternehmen (95%-Vl: 0.2% bis 1.1%) und 0.08% der Arbeiternehmerschaft (95%-V1: 0.06% bis 0.09%). Es gibt einige gut etablierte Technologien um die Luftkonzentration von Submikrometerpartikel zu messen. Es besteht jedoch Zweifel daran, inwiefern sich diese Technologien auch für die Messurrg von künstlich hergestellten Nanopartikeln verwenden lassen. Aus diesem Grund folcussierten die vorbereitenden Studien für die Arbeitsplatzbeurteilnngen auf die Messung von Pulverri, welche Nan0partike1-Agg10merate enthalten. Sie erlaubten die ldentifikation folgender rnöglicher Quellen von fehlerhaften Messungen an Arbeitsplätzen mit erhöhter Luft-K0nzentrati0n von Nanopartikel Agglomeratenz - Ein Standard SMPS zeigte eine unglaubwürdige bimodale Partikelgrössenverteilung wenn er grössere Nan0par'til<e1Agg10merate gemessen hat. - Grosse Unterschiede im Bereich von Faktor tausend wurden festgestellt zwischen einem Diffusion Size Classiîier und einigen CPC (beziehungsweise dem SMPS). - Die Unterschiede zwischen CPC/SMPS und dem PAS waren geringer, aber abhängig von Grosse oder Typ des gemessenen Pulvers waren sie dennoch in der Grössenordnung von einer guten Grössenordnung. - Spezifische Schwierigkeiten und Unsicherheiten im Bereich von Arbeitsplatzmessungen wurden identitiziert: Hintergrundpartikel können mit Partikeln interagieren die während einem Arbeitsprozess freigesetzt werden. Solche Interaktionen erschweren eine korrekte Einbettung der Hintergrunds-Partikel-Konzentration in die Messdaten. - Elektromotoren produzieren grosse Mengen von Nanopartikeln und können so die Messung der prozessbezogenen Exposition stören. Fazit: Die Umfragen zeigten, dass Nanopartikel bereits Realitàt sind in der Schweizer Industrie und dass einige Unternehmen bereits grosse Mengen davon einsetzen. Die repräsentative Umfrage hat diese explosive Nachricht jedoch etwas moderiert, indem sie aufgezeigt hat, dass die Zahl der Unternehmen in der gesamtschweizerischen Industrie relativ gering ist. In den meisten Branchen (vor allem ausserhalb der Chemischen Industrie) wurden wenig oder keine Anwendungen gefunden, was schliessen last, dass die Einführung dieser neuen Technologie erst am Anfang einer Entwicklung steht. Auch wenn die Zahl der potentiell exponierten Arbeiter immer noch relativ gering ist, so unterstreicht die Studie dennoch die Notwendigkeit von Expositionsmessungen an diesen Arbeitsplätzen. Kenntnisse um die Exposition und das Wissen, wie solche Exposition korrekt zu messen, sind sehr wichtig, vor allem weil die möglichen Auswirkungen auf die Gesundheit noch nicht völlig verstanden sind. Die Evaluation einiger Geräte und Methoden zeigte jedoch, dass hier noch Nachholbedarf herrscht. Bevor grössere Mess-Studien durgefîihrt werden können, müssen die Geräte und Methodem für den Einsatz mit Nanopartikel-Agglomeraten validiert werden.

Characterizing emission and breathing-zone concentrations following exposure cases to fluororesin-based waterproofing spray mists.

Measurements and simulations were performed to assess workers' exposure to solvent vapors and aerosols during the waterproofing of a tiled surface. This investigation followed two recent incidents in the same company where workers experienced acute respiratory illness after spraying a stain-repellent resin containing fluorinated polymers on stone-tiled walls and floors. Because the waterproofing activity had been done for years at the tile company without encountering any exposure problems prior to these cases, it was strongly suspected that the incidents were linked to a recent change in the composition of the coating mixture. Experimental measurements and simulations indicated that the emission rate of particles smaller than 10 microm may be estimated at 0.66 mg/sec (SD 0.10) for the old resin and at 0.37 mg/sec (SD 0.04) for the new one. The measurement of the solvent emission rate from surfaces coated with the two resins indicated that shortly after spraying, the emission was in the range of 18 to 20 mg/sec x m2 and was similar for both products. Solvent and overspray emission rates were introduced in a two-zone compartment model. The results obtained in the near-field indicate significant exposure to overspray mist (7 and 34 mg/m3 for new resin) and solvent vapors (80 to 350 ppm for the new resin). It was also shown that the introduction of the new resin tended to significantly decrease the levels of solvents and particulates in the workers' breathing zone. These results strongly suggest that cases of acute respiratory illness are related to the specific toxicity of the fluorinated polymer itself. The fact that the same polymer is used in various commercial products raises concern regarding other possible occupational and domestic exposures.

Impact of targeted antifungal prophylaxis in heart transplant recipients at high risk for early invasive fungal infection.

BACKGROUND: Invasive fungal infection (IFI) is associated with high mortality after heart transplantation (HTx). After two undiagnosed fatal cases of early disseminated fungal infections in our heart transplant program, a retrospective analysis was conducted to identify risk factors for the development of IFI and implement a new antifungal prophylaxis policy. METHODS: Clinical characteristics of HTx recipients hospitalized in our center (2004-2010) were recorded (Period 1), and risk factors associated with IFI were investigated using Cox regression analysis. From October 2010 to October 2012 (Period 2), targeted caspofungin prophylaxis was administered to all recipients at high risk for IFI, based on the results of the Period 1 analysis. RESULTS: During Period 1, 10% (6/59) of the patients developed IFI at a median onset of 9 days after transplantation. By multivariate analysis, the use of posttransplant extracorporeal membrane oxygenation (ECMO) was the strongest predictor for fungal infection (OR, 29.93; 95% CI, 1.51-592.57, P=0.03), whereas renal replacement therapy (RRT) and Aspergillus colonization were significant predictors only by univariate analysis. During Period 2, only 4% (1/26) of the patients developed IFI. In patients at high risk for IFI, antifungal prophylaxis was administered to 17% (4/23) in Period 1 versus 100% (13/13) in Period 2 (P<0.01). By survival analysis, antifungal prophylaxis was associated with a reduction in 90-day IFI incidence (HR, 0.14; 95% CI, 0.03-0.84, P=0.03) and 30-day mortality (HR, 0.25; 95% CI, 0.09-0.8, P=0.02). CONCLUSION: Extracorporeal membrane oxygenation was identified an important risk factor for IFI after HTx, and its use may require targeted administration of antifungal prophylaxis in the immediate posttransplant period.

Bone metabolism and risk of secondary hyperparathyroidism 12 months after gastric banding in obese pre-menopausal women.

OBJECTIVE: To evaluate, during the first postoperative year in obese pre-menopausal women, the effects of laparoscopic gastric banding on calcium and vitamin D metabolism, the potential modifications of bone mineral content and bone mineral density, and the risk of development of secondary hyperparathyroidism. SUBJECTS: Thirty-one obese pre-menopausal women aged between 25 and 52 y with a mean body mass index (BMI) of 43.6 kg/m(2), scheduled for gastric banding were included. Patients with renal, hepatic, metabolic and bone disease were excluded. METHODS: Body composition and bone mineral density (BMD) were measured at baseline, 6 and 12 months after gastric banding using dual-energy X-ray absorptiometry. Serum calcium, phosphate, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, bilirubin, urea, creatinine, uric acid, proteins, parathormone, vitamin D(3), IGF-1, IGF-BP3 and telopeptide, as well as urinary telopeptide, were measured at baseline and 1, 3, 6, 9 and 12 months after surgery. RESULTS: After 1 y vitamin D3 remained stable and PTH decreased by 12%, but the difference was not significant. Serum telopeptide C increased significantly by 100% (P<0.001). There was an initial drop of the IGF-BP3 during the first 6 months (P<0.05), but the reduction was no longer significant after 1 y. The BMD of cortical bone (femoral neck) decreased significantly and showed a trend of a positive correlation with the increase of telopeptides (P<0.06). The BMD of trabecular bone, at the lumbar spine, increased proportionally to the reduction of hip circumference and of body fat. CONCLUSION: There is no evidence of secondary hyperparathyroidism 1 y after gastric banding. Nevertheless biochemical bone markers show a negative remodelling balance, characterized by an increase of bone resorption. The serum telopeptide seems to be a reliable parameter, not affected by weight loss, to follow up bone turnover after gastroplasty.

Pregnancy outcome following exposure to topical retinoids: a multicenter prospective study.

Concerns have been raised about the use of topical retinoids since the publication of isolated cases of characteristic retinoid embryopathy, originally described after oral use. A collaborative study of the European Network of Teratology Information Services was carried out to evaluate the rate of congenital malformations following first-trimester topical retinoid exposure. A population of 235 exposed pregnant women was compared with 444 controls. No significant differences were observed between groups with regard to the rates of spontaneous abortion (odds ratio [95% confidence interval], 1.5 [0.8-2.7]), minor birth defects (1.3 [0.4-3.7]), and major birth defects (1.8 [0.6-5.4]). No child showed features of retinoid embryopathy. The rate of elective termination in the exposed group was increased 3-fold (3.4 [1.5-7.8]). In conclusion, these results do not suggest an increased risk of retinoid embryopathy. However, according to current knowledge, topical retinoids cannot be advised for use during pregnancy because their risk/benefit ratio remains questionable.

Risk-benefit balance assessment of SSRI antidepressant use during pregnancy and lactation based on best available evidence.

INTRODUCTION: Psychiatric disorders are among the leading causes of disability in Western societies. Selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed antidepressant drugs during pregnancy and the postpartum period. Over the last decade, conflicting findings regarding the safety of SSRI drugs during pregnancy and lactation have questioned whether such treatments should be used during this period. AREAS COVERED: We discuss the main criteria that should be considered in the risk/benefit assessment of SSRI treatment in pregnant and/or breastfeeding patients (i.e., risks associated with SSRI use and with untreated depression as well as therapeutic benefits of SSRI and some alternative treatment strategies). For each criterion, available evidence has been synthesized and stratified by methodological quality as well as discussed for clinical impact. EXPERT OPINION: Currently, it is impossible for most of the evaluated outcomes to distinguish between the effects related to the mother's underlying disease and those inherent to SSRI treatment. In women suffering from major depression and responding to a pharmacological treatment, introduction or continuation of an SSRI should be encouraged in order to prevent maternal complications and to preserve maternal-infant bonding. The choice of the right drug depends above all on individual patient characteristics such as prior treatment response, diagnoses and comorbid conditions.

Exposure to stallion accelerates the onset of mares' cyclicity.

Horses (Equus caballus) belong to the group of seasonally polyestrous mammals. Estrous cycles typically start with increasing daylight length after winter, but mares can differ greatly in the timing of onset of regular estrus cycles. Here, we test whether spatial proximity to a stallion also plays a role. Twenty-two anestrous mares were either exposed to one of two stallions (without direct physical contact) or not exposed (controls) under experimental conditions during two consecutive springs (February to April). Ovarian activity was monitored via transrectal ultrasound and stallion's direct contact time with each mare was determined three times per week for one hour each. We found that mares exposed to a stallion ovulated earlier and more often during the observational period than mares that were not exposed to stallions. Neither stallion identity nor direct contact time, mare age, body condition, size of her largest follicle at the onset of the experiment, or parasite burden significantly affected the onset of cyclicity. In conclusion, the timing of estrous cycles and cycle frequency, i.e., crucial aspects of female reproductive strategy, strongly depend on how the mares perceive their social environment. Exposing mares to the proximity of a stallion can therefore be an alternative to, for example, light programs or elaborated hormonal therapies to start the breeding season earlier and increase the number of estrous cycles in horses.