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Human African trypanosomiasis or sleeping sickness, caused by the protozoan parasite Trypanosoma brucei, is characterized by the manipulation of the host's immune response to ensure parasite invasion and persistence. Uncovering key molecules that support parasite establishment is a prerequisite to interfere with this process. We identified Q586B2 as a T. brucei protein that induces IL-10 in myeloid cells, which promotes parasite infection invasiveness. Q586B2 is expressed during all T. brucei life stages and is conserved in all Trypanosomatidae. Deleting the Q586B2-encoding Tb927.6.4140 gene in T. brucei results in a decreased peak parasitemia and prolonged survival, without affecting parasite fitness in vitro, yet promoting short stumpy differentiation in vivo. Accordingly, neutralization of Q586B2 with newly generated nanobodies could hamper myeloid-derived IL-10 production and reduce parasitemia. In addition, immunization with Q586B2 delays mortality upon a challenge with various trypanosomes, including Trypanosoma cruzi. Collectively, we uncovered a conserved protein playing an important regulatory role in Trypanosomatid infection establishment., (© 2024. The Author(s).)

Binaural reproduction aims at recreating a realistic sound scene at the ears of the listener using headphones. Unfortunately, externalization for frontal and rear sources is often poor (virtual sources are perceived inside the head, instead of outside the head). Nevertheless, previous studies have shown that large head-tracked movements could substantially improve externalization and that this improvement persisted once the subject had stopped moving his/her head. The present study investigates the relation between externalization and evoked response potentials (ERPs) by performing behavioral and EEG measurements in the same experimental conditions. Different degrees of externalization were achieved by preceding measurements with 1) head-tracked movements, 2) untracked head movements, and 3) no head movement. Results showed that performing a head movement, whether the head tracking was active or not, increased the amplitude of ERP components after 100 ms, which suggests that preceding head movements alters the auditory processing. Moreover, untracked head movements gave a stronger amplitude on the N1 component, which might be a marker of a consistency break in regards to the real world. While externalization scores were higher after head-tracked movements in the behavioral experiment, no marker of externalization could be found in the EEG results., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Surgical patients are asked to adhere to preoperative fasting guidelines to minimize gastric contents. Large fluid volumes or solid content can still be present as shown with gastric ultrasound. It has been suggested that additional rating of patients' satiety, measured as the feeling of hunger and thirst, could help clinicians to better judge emptying of the stomach., Methods: We performed a prospective observational study in fasted elective surgical patients. The primary objective was to investigate the correlation between hunger measured on a 0-10 numeric rating scale and total gastric fluid volume measured with gastric ultrasonography. Secondary objectives included the correlation between 1) thirst and total gastric fluid volume and 2) hunger, thirst, and the Perlas grading scale score., Results: We included 515 patients. The exam was inconclusive in 14 individuals (2.7%). The Spearman correlation coefficient between gastric fluid volumes and hunger was 0.11 (95% confidence interval [CI], 0.02 to 0.20) (P = 0.01). The correlation between gastric fluid volumes and thirst was 0.11 (95% CI, 0.02 to 0.20) (P = 0.02). Between antral grades and numeric rating scale, the correlation coefficient was 0.00 (95% CI, -0.09 to 0.09) (P = 1.00) for thirst and 0.00 (95% CI, -0.08 to 0.09) (P = 0.94) for hunger. Ten patients (2.0%) had solid content, 24 presented a grade 2 antrum (4.8%)., Conclusion: This study suggests that the correlation between total gastric fluid volume and satiety sensation is very weak. Satiety did not reliably predict total gastric fluid volume., Study Registration: ClinicalTrials.gov (NCT04884373); registered 13 May 2021., (© 2023. Canadian Anesthesiologists' Society.)

Background: Breast cancer screening programs were introduced in many countries worldwide following randomized controlled trials in the 1980s showing a reduction in breast cancer-specific mortality. However, their effectiveness remains debated and estimates vary. A breast cancer screening program was introduced in 2001 in Flanders, Belgium where high levels of opportunistic screening practices are observed. The effectiveness of this program was estimated by measuring its effect on breast cancer-specific mortality., Methods: We performed a case-referent study to investigate the effect of participation in the Flemish population-based mammography screening program (PMSP) on breast cancer-specific mortality from 2005 to 2017. A multiple logistic regression model assessed the association between breast cancer-specific death and screening program participation status in the four years prior to (pseudo)diagnosis (yes/no), with adjustment for potential confounders (individual socio-economic position and calendar year of diagnosis) and stratified for age. In addition, we performed different sensitivity analyses., Results: We identified 1571 cases and randomly selected 6284 referents. After adjustment, women who participated in PMSP had a 51 % lower risk of breast cancer-specific mortality compared to those who did not (adjusted odds ratio [aOR] =0.49, 95 % CI: 0.44-0.55). Sensitivity analyses did not markedly change the estimated associations. Correction for self-selection bias reduced the effect size, but the estimate remained significant., Conclusion: Our results indicate that in a context of high opportunistic screening rates, participation in breast cancer screening program substantially reduces breast cancer-specific mortality. For policy, these results should be balanced against the potential harms of screening, including overdiagnosis and overtreatment., Competing Interests: Declarations of interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Exacerbated IL-22 activity induces tissue inflammation and immune disorders such as psoriasis. However, because IL-22 is also essential for tissue repair and defense at barrier interfaces, targeting IL-22 activity to treat psoriasis bears the risk of deleterious effects at mucosal sites such as the gut. We previously showed in vitro that IL-22 signaling relies on IL-22 receptor alpha (IL-22Rα) Y-dependent and -independent pathways. The second depends on the C-terminal Y-less region of IL-22Rα and leads to a massive signal transducer and activator of transcription 3 (STAT3) activation. Because STAT3 activation is associated with the development of psoriasis, we hypothesized that the specific inhibition of the noncanonical STAT3 activation by the Y-less region of IL-22Rα could reduce psoriasis-like disease while leaving intact its tissue defense functions in the gut. We show that mice expressing a C-terminally truncated version of IL-22Rα (ΔCter mut/mut mice) are protected from the development of psoriasis-like dermatitis lesions induced by imiquimod to a lesser extent than Il22ra -/- mice. In contrast, only Il22ra -/- mice lose weight after Citrobacter rodentium infection. Altogether, our data suggest that specific targeting of the noncanonical STAT3 activation by IL-22 could serve to treat psoriasis-like skin inflammation without affecting IL-22‒dependent tissue repair or barrier defense at other sites., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Release of virus-blocking Wolbachia-infected mosquitoes is an emerging disease control strategy that aims to control dengue and other arboviral infections. Early entomological data and modelling analyses have suggested promising outcomes, and wMel Wolbachia releases are now ongoing or planned in 12 countries. To help inform government, donor, or philanthropist decisions on scale-up beyond single city releases, we assessed this technology's cost-effectiveness under alternative programmatic options., Methods: Using costing data from existing Wolbachia releases, previous dynamic model-based estimates of Wolbachia effectiveness, and a spatially explicit model of release and surveillance requirements, we predicted the costs and effectiveness of the ongoing programme in Yogyakarta City and three new hypothetical programmes in Yogyakarta Special Autonomous Region, Jakarta, and Bali., Results: We predicted Wolbachia to be a highly cost-effective intervention when deployed in high-density urban areas with gross cost-effectiveness below $1500 per DALY averted. When offsets from the health system and societal perspective were included, such programmes even became cost saving over 10-year time horizons with favourable benefit-cost ratios of 1.35 to 3.40. Sequencing Wolbachia releases over 10 years could reduce programme costs by approximately 38% compared to simultaneous releases everywhere, but also delays the benefits. Even if unexpected challenges occurred during deployment, such as emergence of resistance in the medium-term or low effective coverage, Wolbachia would remain a cost-saving intervention., Conclusions: Wolbachia releases in high-density urban areas are expected to be highly cost-effective and could potentially be the first cost-saving intervention for dengue. Sites with strong public health infrastructure, fiscal capacity, and community support should be prioritised.

Background: Wolbachia-infected mosquitoes reduce dengue virus transmission, and city-wide releases in Yogyakarta city, Indonesia, are showing promising entomological results. Accurate estimates of the burden of dengue, its spatial distribution and the potential impact of Wolbachia are critical in guiding funder and government decisions on its future wider use., Methods: Here, we combine multiple modelling methods for burden estimation to predict national case burden disaggregated by severity and map the distribution of burden across the country using three separate data sources. An ensemble of transmission models then predicts the estimated reduction in dengue transmission following a nationwide roll-out of wMel Wolbachia., Results: We estimate that 7.8 million (95% uncertainty interval [UI] 1.8-17.7 million) symptomatic dengue cases occurred in Indonesia in 2015 and were associated with 332,865 (UI 94,175-754,203) lost disability-adjusted life years (DALYs). The majority of dengue's burden was due to non-severe cases that did not seek treatment or were challenging to diagnose in outpatient settings leading to substantial underreporting. Estimated burden was highly concentrated in a small number of large cities with 90% of dengue cases occurring in 15.3% of land area. Implementing a nationwide Wolbachia population replacement programme was estimated to avert 86.2% (UI 36.2-99.9%) of cases over a long-term average., Conclusions: These results suggest interventions targeted to the highest burden cities can have a disproportionate impact on dengue burden. Area-wide interventions, such as Wolbachia, that are deployed based on the area covered could protect people more efficiently than individual-based interventions, such as vaccines, in such dense environments.

Background: The zoonotic tapeworm Taenia saginata, although causing only minor discomfort in humans, is responsible for considerable economic losses in the livestock sector due to condemnation or downgrading of infected beef carcasses. An overview of current knowledge on the distribution and prevalence of this parasite in West and Central Africa is lacking., Methods: We conducted a systematic review, collecting information on published and grey literature about T. saginata taeniosis and bovine cysticercosis from 27 countries/territories in West and Central Africa, published between January 1st, 1990 and December 31st, 2017., Results: The literature search retrieved 1672 records, of which 51 and 45 were retained for a qualitative and quantitative synthesis, respectively. Non-specified human taeniosis cases were described for Nigeria, Cameroon, Senegal, Burkina Faso, Democratic Republic Congo, Guinea, and Ivory Coast (seven out of 27 countries/territories), while T. saginata taeniosis specifically was only reported for Cameroon. Most prevalence estimates for taeniosis ranged between 0-11%, while three studies from Nigeria reported prevalence estimates ranging between 23-50%. None of the studies included molecular confirmation of the causative species. The presence of bovine cysticercosis was reported for Benin, Burkina Faso, Cameroon, Central African Republic, Chad, Democratic Republic Congo, Ghana, Guinea, Ivory Coast, Mali, Niger, Nigeria, Senegal, and Tristan da Cunha (14 out of 27 countries/territories). Prevalence estimates ranged between 0-29%., Conclusions: Our systematic review has revealed that human taeniosis and bovine cysticercosis are seriously understudied in West and Central Africa. The high prevalence estimates of both conditions suggest an active dissemination of this parasite in the region, calling for a concerted One Health action from public health, veterinary health and food surveillance sectors.

Para-Phenylenediamine (PPD) is an aromatic amine used in hair dyes and in temporary black henna tattoos, which is a frequent cause of allergic contact dermatitis (ACD). ACD is a skin inflammatory reaction characterized by modifications such as spongiosis, exocytosis and acanthosis. The aim of this study is to characterize the expression and the role of IL-20-related cytokines, including IL-19, IL-20, IL-22 and IL-24, in ACD. The expression of IL19, IL20, IL22 and IL24 is increased in affected skin from PPD allergic patients compared with uninvolved skin. In addition, the expression of these cytokines positively correlates with clinical symptoms. To assess their role in ACD, we set up a mouse model of PPD-induced allergic contact dermatitis and we showed that, in contrast to Il22-deficient mice, Il22ra1-, Il20rb- and Il24-deficient mice are partially protected against development of PPD-induced contact hypersensitivity. These mice have decreased ear thickening and less acanthosis compared with WT mice after PPD treatment. In addition, the absence of IL-22R, IL-20R2 or IL-24 affects the recruitment of neutrophils into the skin but not the total IgE production. Taken together, these results demonstrate the implication of IL-24 via the IL-20R type II receptor in the inflammatory process of ACD.

Background: Allergic contact dermatitis has been described as a type IV reaction caused by antigen-specific T cells. Central roles for CD8 + cytotoxic T cells as effector cells and CD4 + T cells as regulatory cells have been suggested. T helper (Th) 2 and Th1 cytokines have been implicated; however, the nature of the allergen influences the Th response., Objective: To determine the types of T cells and cytokines expressed in patients allergic to p-phenylenediamine (PPD)., Methods: Serial skin biopsies of areas with positive patch test reactions in 29 PPD-sensitized patients were collected. T cell markers and cytokine expression were analysed by flow cytometry and quantitative reverse transcription polymerase chain reaction in both skin and peripheral blood mononuclear cells (PBMCs) of sensitized patients., Results: We observed increased expression of T cell markers and Th2/Th9-associated cytokines in both skin and stimulated PBMCs of PPD-allergic patients. Moreover, interleukin (IL)-9 was mainly produced by Th9 cells, in both skin and PBMCs. Further investigations showed that Il9r-deficient mice were more affected in a PPD contact hypersensitivity model than wild-type mice., Conclusion: We did not confirm the preclinical presence of CD8 + T cells. However, the expression of different T cell markers positively correlated with patch test reactions. IL-9 expression was strongly upregulated and directly related to patch test severity. In addition, we showed that IL-9 has an anti-inflammatory role in a mouse model of PPD contact hypersensitivity., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Expression of the chemokine receptor Ccr6 is shared by most IL-22-producing cells, and Ccr6-deficient mice showed decreased IL-22 production and skin inflammation upon IL-23 intradermal injections. To determine whether this observation might be extended to another psoriasis model, we applied imiquimod on Ccr6-deficient mice. Although epidermal IL-22 production was decreased because of a deficient recruitment of γδ T cells in these mice, they were not protected against psoriatic lesions. When primary epidermis or dermis tissue culture cells from nontreated mice were stimulated ex vivo with IL-1α/IL-2/IL-23, we observed that Ccr6 is crucial for Il22 expression from epidermal but not dermal cultures. Taking advantage of Ccr6-LacZ-knock-in mice, we showed that Ccr6 is necessary for the homing of Ccr6-positive cells, probably a γδ T-cell subset, which represents the main potential IL-22 source in the epidermis. Similar results were observed in Rag1 -/- epidermis and dermis primary cultures, in which a subset of innate lymphoid cells expressing Ccr6 represents the main potential source of IL-22. Taken together, our data show that Ccr6 is not required for the development of skin lesions induced by imiquimod despite its effect on epidermal homing of IL-22-producing cells., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Binaural reproduction aims at recreating a realistic audio scene at the ears of the listener using headphones. In the real acoustic world, sound sources tend to be externalized (that is, perceived to be emanating from a source out in the world) rather than internalized (that is, perceived to be emanating from inside the head). Unfortunately, several studies report a collapse of externalization, especially with frontal and rear virtual sources, when listening to binaural content using non-individualized Head-Related Transfer Functions (HRTFs). The present study examines whether or not head movements coupled with a head tracking device can compensate for this collapse. For each presentation, a speech stimulus was presented over headphones at different azimuths, using several intermixed sets of non-individualized HRTFs for the binaural rendering. The head tracker could either be active or inactive, and the subjects could either be asked to rotate their heads or to keep them as stationary as possible. After each presentation, subjects reported to what extent the stimulus had been externalized. In contrast to several previous studies, results showed that head movements can substantially enhance externalization, especially for frontal and rear sources, and that externalization can persist once the subject has stopped moving his/her head.

IL-22 has a detrimental role in skin inflammatory processes, for example in psoriasis. As transcription factor, AhR controls the IL-22 production by several cell types (i.e. Th17 cells). Here, we analyzed the role of Ahr in IL-22 production by immune cells in the inflamed skin, using an imiquimod-induced psoriasis mouse model. Our results indicate that IL-22 is expressed in the ear of imiquimod-treated Ahr(-/-) mice but less than in wild-type mice. We then studied the role of AhR on three cell populations known to produce IL-22 in the skin: γδ T cells, Th17 cells, and ILC3, and a novel IL-22-producing cell type identified in this setting: CD4(-) CD8(-) TCRβ(+) T cells. We showed that AhR is required for IL-22 production by Th17, but not by the three other cell types, in the imiquimod-treated ears. Moreover, AhR has a role in the recruitment of γδ T cells, ILC3, and CD4(-) CD8(-) TCRβ(+) T cells into the inflamed skin or in their local proliferation. Taken together, AhR has a direct role in IL-22 production by Th17 cells in the mouse ear skin, but not by γδ T cells, CD4(-) CD8(-) TCRβ(+) T cells and ILCs., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

When presented with a spatially discordant auditory-visual stimulus, subjects sometimes perceive the sound and the visual stimuli as coming from the same location. Such a phenomenon is often referred to as perceptual fusion or ventriloquism, as it evokes the illusion created by a ventriloquist when his voice seems to emanate from his puppet rather than from his mouth. While this effect has been extensively examined in the horizontal plane and to a lesser extent in distance, few psychoacoustic studies have focused on elevation. In the present experiment, sequences of a man talking were presented to subjects. His voice could be reproduced on different loudspeakers, which created disparities in both azimuth and elevation between the sound and the visual stimuli. For each presentation, subjects had to indicate whether the voice seemed to emanate from the mouth of the actor or not. Results showed that ventriloquism could be observed with larger audiovisual disparities in elevation than in azimuth.

Background: A few case reports suggest that incretin-based therapies could improve psoriasis in patients with type 2 diabetes, the mechanism(s) of which remain unclear., Objectives: To determine the effects after 16-20 weeks of treatment with a glucagon-like peptide (GLP)-1 analogue on clinical severity and histopathological aspects of psoriasis in patients with type 2 diabetes, and to examine the presence of γδ T cells and the expression of interleukin (IL)-17 in psoriasis before and after treatment., Methods: Seven patients with type 2 diabetes and psoriasis were followed. Psoriasis Area and Severity Index (PASI) was measured at baseline (T0) and after 7 ± 1 (T1) and 18 ± 2 (T2) weeks' treatment with exenatide/liraglutide. The histopathological pattern of psoriasis, and flow cytometry and immunological data (γδ T-cell percentage and IL-17 expression) were obtained from psoriatic and control sites., Results: The mean PASI decreased from 12·0 ± 5·9 to 9·2 ± 6·4 (P = 0·04). Histological analysis showed a reduction in epidermal thickness after treatment. The dermal γδ T-cell percentage was higher in psoriatic lesions than in control specimens (P = 0·03), as was IL-17 expression (P = 0·018). A reduction of γδ T cells from 6·7 ± 4·5% to 2·7 ± 3·8% (P = 0·05) was demonstrated in the six patients with improved/unchanged PASI. A correlation between PASI and γδ T-cell percentage evolution during therapy (T2-T0) was noted (r = 0·894, P = 0·007). IL-17 was reduced in the four patients with the highest PASI reductions., Conclusions: The administration of a GLP-1 analogue improved clinical psoriasis severity in patients with type 2 diabetes. This favourable outcome was associated with a decrease of dermal γδ T-cell number and IL-17 expression. Further studies are needed to establish long-term efficacy in (diabetic) patients with psoriasis., (© 2014 British Association of Dermatologists.)

Background: Delayed allergic hypersensitivity reactions have classically been described as type IV reactions, which are caused by T cells; however, the respective roles of CD4(+) and CD8(+) cells are yet to be defined. A central role for CD8(+) cytotoxic T cells as effector cells has been suggested., Objectives: To determine the type of T cell involved in corticosteroid allergy., Methods: We analysed the kinetics of T cell recruitment and the cytokine production profile in positive patch tests of 27 corticosteroid-sensitized patients, as compared with control sites and control subjects. Skin biopsies, collected at 8, 24 and 48 hr following drug application, were embedded in paraffin for histological and immunohistological staining, and, in some cases, also deep-frozen for gene expression analyses., Results: CD3(+) T cells were rapidly recruited in concert with the positivity of the patch test sites. High levels of interleukin (IL)-4, IL-5 and, to a lesser extent, interferon-γ suggested that both Th2 and Th1 cytokines were implicated. IL-4 was also produced by γδ T cell receptor (TCR) lymphocytes., Conclusions: This study showed that, in allergic contact dermatitis caused by corticosteroids, the inflammatory infiltrate is composed of CD3(+) T cells with a predominant Th2 cytokine profile, among which IL-4 is also produced by γδ TCR lymphocytes., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: When calculating life expectancy, it is usually assumed that deaths are uniformly distributed within each of the age intervals. As most of the infant deaths are neonatal deaths, this calls for a better assessment for that age group., Methods: The Flemish unified death and birth certificates database for all calendar years between 1999 and 2008 was used. A Kaplan-Meier survival analysis on a yearly basis was performed to assess the mean time-to-event and to compare survival curves between both genders., Results: Over the last years, a slight though not steady decrease of the infant mortality rate is observed. In 2008, the probability among live births of dying before their first anniversary is 4.6‰ in boys and 3.5‰ in girls. The large majority (about 85%) of these have died in their year of birth. The mean survival time of deaths in their year of birth was found to centre around 1 month (about 30 days), which results in a 'mean proportion of the calendar year lived' (k1) close to 0.09. Among those who died in the year after their year of birth yet before their first anniversary, no such concentration in time of the deaths is observed. Differences between the gender groups are small and generally not statistically significant., Conclusion: Statistics Belgium, the federal statistics office, imputes a value for k1 equal to 0.1 for infant deaths in their year of birth when calculating life expectancy. Our data fully support this value. We think such refinement is generally feasible in calculating life expectancy.

Psoriasis is a common chronic autoimmune skin disease of unknown cause that involves dysregulated interplay between immune cells and keratinocytes. IL-22 is a cytokine produced by the TH1, TH17, and TH22 subsets that are functionally implicated in the psoriatic pathology. We assessed the role of IL-22 in a mouse model where psoriasiform skin inflammation is triggered by topical application of the TLR7/8 agonist imiquimod. At the macroscopic level, scaly skin lesions induced by daily applications of imiquimod in wild-type mice were almost totally absent in IL-22-deficient mice or in mice treated with a blocking anti-IL-22 Ab. At the microscopic level, IL-22-deficient mice showed a dramatic decrease in the development of pustules and a partial decrease in acanthosis. At the molecular level, the absence or inhibition of IL-22 strongly decreased the expression of chemotactic factors such as CCL3 and CXCL3 and of biomarkers such as S100A8, S100A7, and keratin 14, which reflect the antimicrobial and hyperproliferative responses of keratinocytes. IL-22 also played a major role in neutrophil infiltration after imiquimod treatment. IL-23 was required for IL-22 production, and γδ TCR lymphocytes represented the major source of IL-22 in lymph nodes from imiquimod-treated mice. However, T cells were not absolutely required for IL-22 production because imiquimod-induced IL-22 expression in the skin is still preserved in Rag2(-/-) mice. Taken together, our data show that IL-22 is required for psoriasis-like lesions in the mouse imiquimod model and is produced by both T cells and innate immune cells.

Objectives: To assess the proportion of parenteral treatment of the total outpatient antibiotic use in Europe, and to identify the antibiotic groups and individual antibiotics most commonly administered in this way., Methods: Within the European Surveillance of Antimicrobial Consumption (ESAC; www.esac.ua.ac.be), using the anatomic therapeutic chemical (ATC) and defined daily dose (DDD) classification, data on outpatient use of antibacterials for systemic use (ATC J01), aggregated at the level of the active substance and expressed in DDD per 1000 inhabitants per day (DID; WHO version 2007), were extracted for 2006 by route of administration and by country. Parenteral use was expressed as a percentage of the total outpatient use in DID., Results: In 20 European countries, the total outpatient antibiotic use ranged from 27.91 DID in France to 9.58 DID in Russia. The proportion of outpatient parenteral antibiotic treatment ranged from 6.75% in Russia to 0.001% in Iceland. The three most commonly used antibiotic groups for parenteral treatment in Europe were the cephalosporins (J01D; 44.58%), the aminoglycosides (J01G; 25.27%) and the penicillins (J01C; 17.78%). Four antibiotics [gentamicin (J01GB03) 18.53%; ceftriaxone (J01DD04) 17.85%; cefazolin (J01DB04) 13.16%; and lincomycin (J01FF02) 5.47%] represented more than half of the use., Conclusions: In all 20 European countries studied together, 2.04% of outpatient antibiotics were used for parenteral treatment. However, as for the total outpatient antibiotic use and the use of different antibiotic groups and antibiotics, there is a striking variation in the proportions of parenteral antibiotic use in Europe. More in-depth data on outpatient antibiotic use are needed to explain this variation.

Background: The ESAC project, granted by DG SANCO of the European Commission, is an international network of surveillance systems, aiming to collect comparable and reliable data on antibiotic use in Europe. Data on outpatient antibiotic use were collected from 34 countries using the ATC/DDD methodology., Methods: For the period 1997-2003, data on outpatient use of systemic antibiotics aggregated at the level of the active substance were collected and expressed in DDD (WHO, version 2004) per 1000 inhabitants per day (DID). Outpatient antibiotic (ATC J01) use in 25 European countries, able to deliver valid data, was analysed., Results: Total outpatient antibiotic use in 2003 varied by a factor of 3 between the country with the highest (31.4 DID in Greece) and the country with the lowest (9.8 DID in the Netherlands) use. General use patterns in individual countries as well as trends during the period 1997-2003 are described in this paper, while major antibiotic classes (penicillins, cephalosporins, macrolides/lincosamides/streptogramins and quinolones) will be analysed in detail in separate papers., Conclusion: The ESAC project established for the first time a credible alternative to industry sources for the collection of internationally comparable data on antibiotic use in Europe, based on cooperation between regulatory authorities, scientific societies, health insurers and professional organizations. These data provide a tool for assessing public health strategies aiming to optimize antibiotic prescribing.

Background: Data on outpatient penicillin use in Europe were collected from 25 countries within the ESAC project, funded by DG SANCO of the European Commission, using the WHO ATC/DDD methodology., Methods: For the period 1997-2003, data on outpatient use of systemic penicillins aggregated at the level of the active substance were collected and expressed in DDD (WHO, version 2004) per 1000 inhabitants per day (DID). Of the 'Penicillins' (J01C), outpatient use of narrow-spectrum penicillins (J01CE), broad-spectrum penicillins (J01CA), penicillinase-resistant penicillins (J01CF) and combinations with beta-lactamase inhibitors (J01CR) in 25 European countries was analysed in detail., Results: Total outpatient penicillin use in 2003 varied by a factor of 4 between the country with the highest (15.27 DID in Slovakia) and lowest use (3.86 DID in the Netherlands). Narrow-spectrum penicillins, broad-spectrum penicillins and combinations with beta-lactamase inhibitors were used most in 4, 12 and 9 countries, respectively. Penicillin use increased by more than 1 DID in nine countries, whereas it decreased by more than 1 DID in two countries (Czech Republic, France). An increase of the use of combinations with beta-lactamase inhibitors by more than 10% in 10 countries coincided with an equal decrease of broad-spectrum penicillins in seven countries and narrow-spectrum penicillins in three countries., Conclusion: Penicillins represent the most widely used antibiotic class in all 25 participating countries; albeit with considerable variation of their use patterns. A distinct shift from narrow-spectrum penicillins to broad-spectrum penicillins, and specifically their combinations with beta-lactamase inhibitors, was observed during the period 1997-2003.

In coronary surgery patients the use of a volatile anesthetic regimen with sevoflurane was associated with a better recovery of myocardial function and less postoperative release of troponin I. In the present study we investigated whether these cardioprotective properties were also apparent in the cardiac surgical setting of aortic valve replacement (AVR) surgery for the correction of aortic stenosis. Thirty AVR surgery patients were randomly assigned to receive either target-controlled infusion of propofol or inhaled anesthesia with sevoflurane. Cardiac function was assessed perioperatively using a pulmonary artery catheter. Perioperatively, a high-fidelity pressure catheter was positioned in the left ventricle. Postoperative concentrations of cardiac troponin I were followed for 48 h. After cardiopulmonary bypass (CPB), stroke volume and dP/dt(max) were significantly higher in the patients with sevoflurane. Post-CPB, the effects of an increase in cardiac load on dP/dt(max) were similar to pre-CPB in the sevoflurane group (1.0 % +/- 5.4% post-CPB versus 1.3% +/- 8.6% pre-CPB) but more depressed in the propofol group (-8.2% +/- 4.4% post-CPB versus 0.1% +/- 4.9% pre-CPB). The rate of relaxation was significantly slower post-CPB in the propofol group. Postoperative levels of troponin I were significantly lower in the sevoflurane group. Our data indicate that the use of a volatile anesthetic regimen in AVR surgery was associated with better preservation of myocardial function and a reduced postoperative release of troponin I.

Background: Data on outpatient quinolone use in Europe were collected from 25 countries within the ESAC project, funded by DG SANCO of the European Commission, using the WHO ATC/DDD methodology., Methods: For the period 1997-2003, data on outpatient use of systemic quinolones aggregated at the level of the active substance were collected and expressed in DDD (WHO, version 2004) per 1000 inhabitants per day (DID). Because a new DDD for levofloxacin was published in the ATC 2004 index (0.5 g instead of 0.25 g) all data were recalculated accordingly. Quinolone use was analysed in detail, using a classification into three generations based on their pharmacokinetic and in vitro potency profiles, which determines the area of clinical use., Results: Total outpatient quinolone use in 2003 varied by a factor of 12 between the country with the highest (3.10 DID in Portugal) and lowest (0.25 DID in Denmark) quinolone use. The second-generation quinolones represented more than 50% of the quinolone use (mainly ciprofloxacin) except for Croatia, where the first-generation was used most (mainly norfloxacin). In 22 countries, the use of second and/or third-generation quinolones increased at the expense of the use of first-generation quinolones. The new so-called respiratory quinolones (levofloxacin and moxifloxacin) represented more than 10% of quinolone use in 12 countries, with extreme seasonal variation in all these countries except for one., Conclusion: There has been a substantial change in the use pattern of quinolones between 1997 and 2003, since the introduction of quinolones that are effective for the treatment of respiratory tract infections. These quinolones are not the first-line antibiotics for this indication and therefore quinolone use should in general still be limited and not show substantial seasonal variation.

Background: Data on outpatient cephalosporin use in Europe were collected from 25 countries within the ESAC project, funded by DG SANCO of the European Commission, using the WHO ATC/DDD methodology., Methods: For the period 1997-2003, data on outpatient use of systemic cephalosporins aggregated at the level of the active substance were collected and expressed in DDD (WHO, version 2004) per 1000 inhabitants per day (DID). Use was analysed in detail, using the new ATC codes J01DB, J01DC, J01DD and J01DE, introduced in the 2005 issue of the WHO ATC index and assigned to the four cephalosporin generations., Results: Total outpatient cephalosporin use in 2003 varied by a factor of 270 between the country with the highest (6.18 DID in Greece) and lowest (0.02 DID in Denmark) use. First-, second- and third-generation cephalosporins were used most in 6, 16 and 3 countries, respectively. We observed fourth-generation use (mainly cefepime) in ambulatory care in 11 countries. From 1997 to 2003 cephalosporin use decreased in 13 countries, in France by more than 1 DID. A relative increase of second-generation (mainly cefuroxime) or third-generation use (mainly cefpodoxime or cefixime) by more than 10% in 12 countries coincided with an equally large decrease of first-generation use in eight countries (mainly cefadroxil, cefalexin or cefatrizine). In six countries, first-generation use increased, second-generation use decreased or both occurred., Conclusion: The new ATC codes allow a more detailed description of outpatient cephalosporin use. The variation in antibiotic use in Europe is most extreme for this class of antibiotics, suggesting that in many countries in Europe these antibiotics are prescribed inappropriately.

Background: Data on outpatient macrolide, lincosamide and streptogramin (MLS) use in Europe were collected from 25 countries within the ESAC project, funded by DG SANCO of the European Commission, using the WHO ATC/DDD methodology., Methods: For the period 1997-2003, data on outpatient use of systemic MLS aggregated at the level of the active substance were collected and expressed in DDD (WHO, version 2004) per 1000 inhabitants per day (DID). Macrolide use was analysed in detail, using a classification based on their mean plasma elimination half-life., Results: Total outpatient MLS use in 2003 varied by a factor of 11 between the country with the highest (9.36 DID in Greece) and lowest (0.85 DID in Sweden) use. MLS use showed high seasonal variation. Short-, intermediate- and long-acting macrolides were used most in 6, 18 and 1 countries, respectively (mainly erythromycin, clarithromyin and azithromycin, respectively). Lincosamide use was observed in all countries (mainly clindamycin) and substantial streptogramin use only in France (pristinamycin). From 1997 to 2003, MLS use increased in 14 countries and was most pronounced in Greece (increase of >5 DID). Except for Sweden, a relative increase of intermediate- (mainly clarithromycin) and/or long-acting (mainly azithromycin) macrolide use was observed, at the expense of short-acting macrolide (mainly erythromycin) use., Conclusion: The observed differences between European countries in the levels of MLS use and the extreme seasonal variations in their use suggest that this class of antibiotics is prescribed inappropriately in many countries. The MLS classification developed here facilitates a more comprehensive description of macrolide use in Europe. These data (collected as part of ESAC) could promote investigations that lead to a deeper understanding of the link between macrolide use and resistance.

In the present study we evaluated whether the sitting position during initiation of small-dose combined spinal-epidural anesthesia (CSE) would induce less hypotension as compared with the lateral position. Sixty women undergoing elective cesarean delivery were randomly assigned to receive a spinal injection consisting of 6.6 mg hyperbaric bupivacaine with sufentanil 3.3 microg in either the lateral or the sitting position. After securing the epidural catheter, patients were turned to a 15 degrees left lateral supine position. Ephedrine 5 mg IV was administered prophylactically and subsequently in case of nausea/vomiting and/or hypotension, defined as a systolic blood pressure less than 95 mm Hg or a 25% decrease from baseline values. Although the incidence of ephedrine supplementation was not different, females in the sitting group required less ephedrine (P = 0.012) and there were fewer problems with identifying the epidural space (P = 0.01). However, more patients in this group required epidural supplementation (35% versus 3%; P = 0.007). In the lateral group, blocks extended more cephalad than with the sitting position (P = 0.014). Apgar scores did not differ, but umbilical artery pH values were significantly higher in patients of the sitting group (7.31 +/- 0.04 versus 7.26 +/- 0.03; P = 0.02). We conclude that performing a CSE technique for cesarean delivery in the sitting position was technically easier and induced less severe hypotension.

Occurrence of atrial fibrillation is a common complication after coronary surgery. This study aimed to identify the perioperative factors that are associated with its occurrence with specific attention to the possible influence of the choice of the anesthetic regimen after elective coronary surgery. A retrospective chart analysis was performed in 460 patients who underwent elective coronary artery surgery with cardiopulmonary bypass using the standard institutional anesthetic, surgical and postoperative protocols. The only difference in management was the choice of the primary anesthetic regimen. 110 patients had a total intravenous anesthesia with propofol, 90 patients had a total intravenous anesthesia with midazolam, 150 patients were anesthetized with sevoflurane and 110 patients with desflurane. The primary outcome variable was the incidence of atrial fibrillation within the first 24 postoperative hours. Atrial fibrillation occurred in 64 of the 460 patients included (13.9%). Multiple logistic regression analysis identified increased age (> 70 years), EuroSCORE > 4, prolonged CPB time (> 100 min) and need for prolonged inotropic support (> 6 hours) as the significant independent risk factors for the occurrence of postoperative atrial fibrillation. The incidence of postoperative atrial fibrillation differed among the different anesthetic groups with the lowest incidence in the sevoflurane group (propofol: 17/110; midazolam: 15/90; sevoflurane: 9/150; desflurane: 23/110) (p = 0.004). This finding should be further confirmed in a prospective sufficiently powered multicenter study.

Background: The present multicenter study aimed to survey the patients' experiences in relation to the diagnosis and non-surgical treatment of periodontitis according to current treatment routine., Methods: Patients (N = 268) treated for plaque-related periodontitis were enrolled in two groups: group 1 received primary probing of pocket depths (PD 1) and/or primary scaling and root planing (SRP 1); group 2 consisted of patients who were scheduled in the different centers for recall PD/scaling/subgingival instrumentation. Data collection included a full periodontal status, anesthesia employed, procedure time, and patient self-completed questionnaires to assess their previous and current experience of pain and discomfort during anesthesia and periodontal treatment., Results: Ninety percent of the patients received infiltration anesthesia during primary SRP, compared to only 2% during recall scaling/instrumentation and none during PD. Many patients (40% in SRP group 1 and 52% in the recall scaling/instrumentation group) were most bothered by the scaling procedure, while others (35% in the primary SRP patients) by the anesthetic injection. Painful experiences during previous primary PD and present SRP were highly correlated (r = 0.6)., Conclusions: From these results, it is evident that subgingival instrumentation causes pain and discomfort, an aspect that should be considered in periodontal therapy. Unfortunately, the use of local infiltration anesthesia to reduce pain is in itself a cause of discomfort. Attractive alternatives for anesthetic applications are much needed.

Background: Periodontal scaling procedures commonly require some kind of anesthesia. From the patient's perspective, the choice of anesthetic method is a trade-off between the degree of anesthesia and accepting the side effects. The present study evaluates the preferences for a novel non-injection anesthetic product (a gel, containing lidocaine 25 mg/g plus prilocaine 25 mg/g and thermosetting agents) versus injection anesthesia (lidocaine 2% adrenaline) in conjunction with scaling and/or root planing (SRP)., Methods: In a multicenter, crossover, randomized, open study patients were asked, after they had experienced both products, if they preferred anesthetic gel or injection anesthesia. In addition, the adequacy of anesthesia and occurrence of post-procedure problems were assessed. The patients were also asked about their willingness to return if they were offered anesthetic gel at their next visit and their maximum willingness to pay (WTP) for this option., Results: One-hundred seventy (170) patients at eight centers in Belgium were included in the study. There were 157 per protocol (PP) patients. A vast majority of the PP patients (70%) preferred the anesthetic gel to injection anesthesia (22%). The most common reason was less post-procedure numbness. Eighty percent (80%) of the patients expressed satisfactory anesthesia with the gel and 96% with injection anesthesia (P <0.001). Post-procedure problems were significantly less with the gel than with injection (P <0.001): numbness 15% versus 66%, unpleasant sensations such as soreness and pain 44% versus 63%, and problems connected with daily activities 19% versus 69%. The majority of patients (60%) who preferred gel were also willing to pay for it. A conservative estimate of the median WTP was $10.00. Furthermore, anesthetic gel would make almost every second patient (45%) more or much more willing to return for the next treatment., Conclusions: The data suggest that a somewhat less profound anesthesia with gel is clearly preferred by the patients because of the low incidence of post-procedure problems as compared to conventional injection anesthesia. The median WTP is likely in excess of the acquisition cost of the product, which indicates a favorable cost-benefit ratio for the individual patient.

We demonstrate the recording of holograms and their nondestructive readout in a photorefractive polymer, using two-photon absorption. Sensitivity is provided by the excitation of the electroactive chromophore with femtosecond pulses, followed by charge injection into the photoconducting poly(N -vinylcarbazole) matrix. The holograms can be fully erased with a pulsed laser source but are insensitive to cw laser beams with the same wavelength. Studies of the field and intensity dependence of the diffraction efficiency indicate that the holograms are formed through the photorefractive effect.

We have constructed an all-optical tracking novelty filter based on the dynamic holographic properties of an efficient and fast infrared-sensitive photorefractive polymer. The photorefractive polymer was used in a two-beam coupling geometry. The polymer had a gain coefficient of 175 cm(-1) at a wavelength of 780 nm and an applied field of 72 V/microm. In contrast to what has been observed in photorefractive crystals, the gain coefficient and the filter contrast are largely independent of the writing beam's intensity ratio. We show images of a swinging pendulum observed through the novelty filter.

Leishmaniasis in Colombia has traditionally been seen as a health risk for adult males, as they become infected when they enter the vector's biotopes to tap natural resources. National health statistics seem to confirm this theory. However, during field studies, the Program for the Study and Control of Tropical Diseases (PECET) observed both equal proportions of men and women with active leishmaniasis and delayed hypersensitivity skin tests and equal proportions of males and females having had contact with the parasite from early childhood. Several factors that have not been analyzed in depth in Colombia thus far appear to distort the disease's epidemiological pattern in the country, and gender-linked differences in access to health care appear to exist. As a consequence, no relief is provided for this source of human suffering, and socioeconomic repercussions for households are significant. Preventive measures by the Colombian Ministry of Health (MOH) systematically underestimate the magnitude of intra- and peridomiciliary transmission, and female patients are excluded from active case detection. Further research should be devoted to this phenomenon. The MOH should be encouraged to improve leishmaniasis control programs, especially with regard to active case detection, training, and teaching, so that quicker diagnosis can be performed. Meanwhile, the MOH should retrain its health personnel.

In a nonblinded, therapeutic trial conducted in Colombia, 1.25-1.5 grams of mefloquine base given as a single oral dose or as 250 mg a day for 5-6 consecutive days was not efficacious in the treatment of New World cutaneous leishmaniasis. The drug had cured only 30.8 % of patients with leishmaniasis skin lesions by the 10th week after start of therapy as compared with a 27.9% complete cicatrization rate in historical controls treated with placebo tablets and an 86.3% cicatrization rate in historical controls who received meglumine antimoniate, 20 mg/ kg/day intramuscularly for 20 days, with no upper limit to daily dose. It is concluded that a single course treatment with mefloquine is not indicated as monotherapy in the treatment of Colombian cutaneous leishmaniasis primarily due to L. panamensis.

Photorefractive polymers with high diffraction efficiency in the visible and near-infrared regions of the electromagnetic spectrum have been developed. These polymers, which have a large dynamic range because of their high orientational birefringence, incorporate a dye designed to have a large dipole moment and a high linear polarizability anisotropy. Such polymers have enabled demonstrations of imaging through scattering media, using a holographic time-gating technique at a wavelength that is compatible with the transparency of biological tissues and with the emission of low-cost semiconductor laser diodes.

The overall aim was to evaluate whether a trackball could be used for communication by people who cannot speak due to severe motor impairment. The precision of trackball control by isolated jaw movements or a combination of jaw and head movements was evaluated in 18 healthy physical-education students, free of overt symptoms of craniomandibular dysfunction. The participants were asked to operate a trackball using the chin to type a standard text of four short sentences. There were two experimental situations: nine participants performed the typewriting task with their heads fixed; the other nine performed this task with free head movements. Trackball operation moved to the cursor over an alphabetical keyboard displayed on a computer screen and character selection was made by depression of the left-hand click button using the chin. Participants were asked to perform the task as quickly and accurately as possible. Result showed that those with free head movement typed the test significantly faster than those restricted to using only their jaw muscles. The mean time per character selection was 2.4 s (SD 0.3) for the group with free head movement and 2.7 s (SD 0.3) for the group using only jaw muscles. Group scores were not significantly different with regard to accuracy. It is suggested that a chin-operated trackball could be used for communication applications both with and without neck movements.

Background: Hundreds of thousands of cases of cutaneous leishmaniasis occur each year worldwide. Available therapies are parenteral, moderately toxic, and costly., Objective: To determine the efficacy of and tolerance for oral allopurinol as monotherapy for cutaneous leishmaniasis., Design: Randomized, controlled trial., Setting: Outpatient clinics in 11 regions of Colombia in which cutaneous leishmaniasis is endemic., Patients: 187 otherwise healthy adults with cutaneous leishmaniasis. Eighty-four percent of patients were infected with or were from regions with Leishmania panamensis; 16% were infected or were from regions with L. braziliensis., Intervention: Patients were randomly assigned to one of three treatment groups. The first group received allopurinol, three 100-mg tablets four times daily (20 mg/kg of body weight per day) for 28 days. The second group received three placebo tablets four times daily for 28 days. The third group received Glucantime, 20 mg of intramuscular antimony/kg per day for 20 days., Measurement: Complete cure was defined as complete clinical reepithelialization of all lesions at 3 months and no relapse during 12 months of follow-up., Results: Of 182 patients whose data could be analyzed, 157 (86%) were evaluated. In the allopurinol group, 18 of 55 (33% [95% CI, 21% to 47%]) patients were cured; in the placebo group, 17 of 46 patients (37% [CI, 23% to 52%]) were cured (difference, 4% [CI, -14% to 22%]; P = 0.68); and in the Glucantime group, 52 of 56 patients (93% [CI, 83% to 98%]) were cured (P < 0.001 compared with the allopurinol and placebo groups combined). In most cases, therapy was considered to have failed because the lesion did not reepithelialize by 1.5 months after the end of therapy. Three cases of relapse (two in the allopurinol group and one in the placebo group) at the nasal mucosa (mucosal leishmaniasis) had occurred by the end of 12 months of follow-up., Conclusions: Allopurinol monotherapy has no effect on Colombian cutaneous disease primarily caused by L. panamensis and therefore is unlikely to be effective against cutaneous leishmaniasis in other endemic regions.

Hyper-Rayleigh scattering has been used to determine the nonlinear optical properties of a chromophore-containing protein in solution. Because the technique of hyper-Rayleigh scattering allows the measurement of hyperpolarizabilities in an isotropic solution without the application of an electric field, this method is ideally suited for the study of proteins that carry a net charge. The observed orientational correlation between the nonlinear optical chromophores in incompletely solubilized protein molecules suggests that guidelines from protein structures can be used for the engineering of supramolecular structures with high optical nonlinearity.

A method to protect the cornea in case of lagophthalmos is presented, consisting in weighting the upper eyelid with dermis graft, combined with a weakening of the levator palpebrae. The technique is described, and the method is discussed versus other methods of upper lid loading.

A simplified technique of skin transplantation is proposed: local anaesthesia of donor site; use of a regular razor-blade for skin harvesting and use of donor site for preservation of residual skin grafts.