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Background Fibroblasts found in keloid tissues are known to present an altered sensitivity to microenvironmental stimuli. However, the impact of changes in extracellular matrix stiffness on phenotypes of normal fibroblasts (NFs) and keloid fibroblasts (KFs) is poorly understood. Objectives Investigation the impact of matrix stiffness on NFs and KFs mainly via detecting yes-associated protein (YAP) expression. Methods We used fibronectin-coated polyacrylamide hydrogel substrates with a range from physiological to pathological stiffness values with or without TGF-β (fibrogenic inducer). Atomic force microscopy was used to measure the stiffness of fibroblasts. Cellular mechanoresponses were screened by immunocytochemistry, Western blot and Luminex assay. Results KFs are stiffer than NFs with greater expression of α-SMA. In NFs, YAP nuclear translocation was induced by increasing matrix stiffness as well as by stimulation with TGF-β. In contrast, KFs showed higher baseline levels of nuclear YAP that was not responsive to matrix stiffness or TGF-β. TGF-β1 induced p-SMAD3 in both KFs and NFs, demonstrating the pathway was functional and not hyperactivated in KFs. Moreover, blebbistatin suppressed α-SMA expression and cellular stiffness in KFs, linking the elevated YAP signaling to keloid phenotype. Conclusions These data suggest that whilst normal skin fibroblasts respond to matrix stiffness in vitro, keloid fibroblasts have elevated activation of mechanotransduction signaling insensitive to the microenvironment. This elevated signaling appears linked to the expression of α-SMA, suggesting a direct link to disease pathogenesis. These findings suggest changes to keloid fibroblast phenotype related to mechanotransduction contribute to disease and may be a useful therapeutic target.

Olivier Subilia et Aurélien Witzig, spécialistes en droit du travail, ne sont pas favorables à la création d'un statut spécial pour les travailleurs de plateforme, type Uber. Le premier estime que ces travailleurs conservent en principe la liberté d'un indépendant, tandis que le second considère qu'ils peuvent, selon les circonstances, être économiquement dépendants ou subordonnés.

Resume Introduction Les complications ophtalmologiques de la toxoplasmose congenitale, notamment sous forme de retinochoroidite, sont particulierement redoutees. Tout enfant dont la toxoplasmose congenitale est confirmee beneficie d’un traitement systematique et d’un suivi ophtalmologique regulier, avec realisation de multiples fond d’yeux. L’objectif de notre etude est d’evaluer la prise en charge et le suivi d’une cohorte de patients alsaciens presentant une toxoplasmose congenitale, ainsi que le retentissement psychologique de cette pathologie sur les parents, a l’aide d’un questionnaire standardise. Materiel et methodes Notre etude retrospective a collige les dossiers de 35 enfants atteints de toxoplasmose congenitale, nes entre 1990 et 2011 en Alsace, suivis au niveau ophtalmologique. Un questionnaire standardise concernant le vecu des grossesses et le suivi post-natal ont ete soumis aux parents. Resultats A la naissance, une retinochoroidite a ete retrouvee chez 2 enfants sur 35, et seulement 1 enfant a developpe une chorioretinite depistee au cours du suivi ulterieur (duree de suivi entre 1 et 22 ans). Des anomalies cerebrales ont ete notees chez 3 enfants a la naissance, aucun d’entre eux n’ayant presente d’atteinte oculaire a ce jour. Un score moyen de 15 sur 23 a ete retrouve par notre questionnaire standardise, traduisant une angoisse importante vis-a-vis de la toxoplasmose congenitale. Discussion L’anxiete parentale face a la toxoplasmose congenitale, mise en evidence par notre questionnaire standardise, est manifeste. Un suivi oriente par un examen pediatrique complet a la naissance, incluant un fond d’œil, et une information precise sur les signes fonctionnels de toxoplasmose oculaire pourrait permettre d’ameliorer les modalites du depistage, sans engendrer de consequences sur la fonction visuelle.

Background/Aims: To compare the efficacy of intravitreal injections of dexamethasone implants (IVD) with those of bevacizumab (IVB) for the treatment of macular oedema associated with branch retinal vein occlusion. Methods: A total of 19 patients (19 eyes) were included in this prospective pilot study. Initially, 8 eyes received three IVBs (group 1) and 11 received one IVD (group 2). All the patients underwent a 1-, 3-, 4- and 6-month follow-up visit. A repeated IVB (group 1) or IVD (group 2) was proposed at 4 months when necessary. Results: The mean visual acuity was significantly better 1 month after treatment in group 2, while the mean central macular thickness was also significantly lower in group 2. However, there was no longer any difference between the two groups at 3, 4 and 6 months, neither in terms of visual acuity nor in terms of retinal thickness. More than three IVBs were needed in 3 of 10 patients in group 1 while two IVDs were required in 10 of 11 patients in group 2. Conclusion: There was no significant difference between the two treatment regimens at the 6-month follow-up visit. A more rapid functional and anatomical efficacy was noted with IVD during the first month; however, reinjection at 4 months seemed more frequent with IVD than with IVB treatment.

Panton–Valentine leukocidin (PVL) is a pore-forming toxin associated with current outbreaks of community-associated methicillin-resistant strains and implicated directly in the pathophysiology of Staphylococcus aureus -related diseases. Humanized heavy chain-only antibodies (HCAb) were generated against S. aureus PVL from immunized transgenic mice to neutralize toxin activity. The active form of PVL consists of the two components, LukS-PV and LukF-PV, which induce osmotic lysis following pore formation in host defense cells. One anti–LukS-PV HCAb, three anti–LukF-PV HCAbs with affinities in the nanomolar range, and one engineered tetravalent bispecific HCAb were tested in vitro and in vivo, and all prevented toxin binding and pore formation. Anti–LukS-PV HCAb also binds to γ-hemolysin C (HlgC) and inhibits HlgC/HlgB pore formation. Experiments in vivo in a toxin-induced rabbit endophthalmitis model showed that these HCAbs inhibit inflammatory reactions and tissue destruction, with the tetravalent bispecific HCAb performing best. Our findings show the therapeutic potential of HCAbs, and in particular, bispecific antibodies.

Ophthalmologic complications of congenital toxoplasmosis, such as retino-choroiditis, are particularly feared. Any child with confirmed congenital toxoplasmosis is systematically treated and followed regularly with multiple fundus examinations. The goal of our study is to describe the management and monitoring of a cohort of patients with congenital toxoplasmosis in Alsace, and the impact of this disease in terms of parental anxiety using a standardized questionnaire.Our study recorded 35 children with congenital toxoplasmosis, born between 1990 and 2011 in Alsace. All patients were followed by an ophthalmologist. A standardized questionnaire concerning the experience of pregnancy and post-natal follow-up was administered to the parents.At birth, retinochoroiditis was detected in 2 of the 35 children, and only one child developed chorioretinitis detected during follow-up monitoring (follow-up ranged from 1 to 22 years). Brain abnormalities were noted in 3 children at birth; none of them have presented with chorioretinitis to this day. An average score of 15 out of 23 was found by our standardized questionnaire, reflecting significant anxiety due to congenital toxoplasmosis.Parental anxiety due to congenital toxoplasmosis is obvious, as demonstrated by our standardized questionnaire. Follow-up, directed by comprehensive pediatric examination at birth, including fundus examination, and good information on functional signs of ocular toxoplasmosis may improve screening, so as to avoid impact on visual function.

Purpose Ophthalmologic complications of congenital toxoplasmosis, such as retino-choroiditis, are particularly feared. Any child with confirmed congenital toxoplasmosis is treated and regularly followed with many fundus examinations. The aim of our study is to describe the management and monitoring of a cohort of patients with congenital toxoplasmosis in Alsace, and the impact of this disease in terms of parental anxiety using a standardized questionnaire. Methods Our study recorded 35 children with congenital toxoplasmosis, born between 1990 and 2011 in Alsace. All patients were followed by an ophthalmologist. A standardized questionnaire concerning the experience of pregnancy and post-natal follow up were submitted to parents. Results At birth, a retinochoroiditis was detected in 2 children, and only one child developed the disease during routine monitoring. Brain abnormalities were noted in 3 children at birth, none of them presented with retinochoroiditis to this day. An average score of 15 out of 23 was found by our standardized questionnaire, reflecting significant anxiety due to congenital toxoplasmosis. Conclusion Parental anxiety due to congenital toxoplasmosis is obvious. A directed follow-up by a complete pediatric examination at birth, including eye fundus, and good information on functional signs of ocular toxoplasmosis may improve the screening without impact on visual function.

Staphylococcus aureus is a frequent cause of acute endophthalmitis, and infection with this virulent bacterium is often associated with a poor visual outcome. In this study, we investigated the bactericidal efficacy and the safety of intravitreal daptomycin (DAP), a lipopeptide antibiotic with broad-spectrum activity against Gram-positive bacteria, compared with those of intravitreal vancomycin (VAN) in a methicillin-resistant S. aureus endophthalmitis rabbit model. The pharmacokinetics and pharmacodynamics of daptomycin in the infected eyes were also studied. Rabbits were randomly divided into three treatment groups ( n = 8) and one untreated group ( n = 4), to compare the effect of single intravitreal injections of 0.2 mg and 1 mg of daptomycin (DAP 0.2 and DAP 1 groups, respectively) with that of 1 mg of intravitreal vancomycin (VAN 1 group). Vitreal aspirates were regularly collected and grading of ocular inflammation was regularly performed until euthanasia on day 7. In the DAP 0.2 group, 62.5% of the eyes were sterilized and the mean bacterial count presented a reduction of 1 log unit. In the DAP 1 and VAN 1 groups, the infection was eradicated (100% and 87.5% of eyes sterilized, respectively), with a 4-log-unit reduction of the mean bacterial count. The bactericidal efficacy in the DAP 1 group was not inferior to that in the VAN 1 group and was superior to that of the other regimens in limiting the ocular inflammation and preserving the architecture of the ocular structures ( P < 0.05). The elimination half-life ( t 1/2β ) of daptomycin was independent of the administered dose (38.8 ± 16.5 h and 40.9 ± 6.7 h, respectively, for the DAP 0.2 and DAP 1 groups) and was significantly longer than the t 1/2β of vancomycin (20.5 ± 2.0 h for the VAN 1 group) ( P < 0.05). This antibiotic could therefore be considered for the treatment of intraocular infections caused by Gram-positive bacteria.

PURPOSE To evaluate the efficacy of intravitreal administration of linezolid (LZD) in a rabbit model of Staphylococcus aureus endophthalmitis. METHODS Of 40 rabbits studied, 36 of them received 10(2) colony-forming units (CFU) of S. aureus in their right eye before being randomly assigned to the following groups: four groups of 8 animals received 24 hours after the bacterial inoculation, 1, 10, 30 mg of LZD (LZD 1, LZD 10, and LZD 30) or 1 mg of vancomycin (V1), respectively. Four other animals had a sham injection in their infected eye. The 4 remaining animals were used as negative controls. Clinical, bacterial, and histologic assessments were conducted at different endpoints. Animals were euthanized at day 8. The safety profile of intravitreal LZD was assessed by electroretinography in 5 more animals by comparing the recordings in eyes injected with 30 mg of LZD and contralateral control eyes injected with a solution of sterile saline water. RESULTS At day 5, the mean inflammatory clinical scores of Nussenblatt were 7.0 ± 1.0, 3.6 ± 0.7, and 3.1 ± 0.8, in the LZD 1, LZD 10, and LZD 30 groups and 3.4 ± 1.7 and 7.5 ± 0 in the V1 and BSS+ groups, respectively (P < 0.05, ANOVA). The corresponding mean bacterial counts in the vitreous (log 10 CFU/mL) were 6.2 ± 6.5, 3.5 ± 3.8, 0, 3.8 ± 4.2, and 7.8 ± 4.9, respectively (P < 0.05, ANOVA). A 30 mg dose of LZD sterilized all the eyes at day 5 and displayed the lowest (best) histologic score (1.5 ± 0.6). Residual LZD concentrations 24 hours after the administration were between 0.1 and 7.2 mg/L LZD 30 group. The half-time of linezolid in the vitreous was 2 hours. There were no differences in the electroretinogram recordings between control eyes and eyes injected with 30 mg of linezolid at days 1 and 14 after the intravitreal injection. CONCLUSIONS This is the first evidence of the effectiveness of linezolid for the treatment of experimental staphylococcal endophthalmitis. High ocular concentrations of LZD were needed to obtain a satisfactory bactericidal effect. Linezolid displayed a concentration-dependent killing activity in the eye. Such doses of intravitreal linezolid appeared to be safe for the retinal function.

Ce travail s’intéresse à ce que les parents racontent de leur expérience lorsque leur enfant est hospitalisé aux soins intensifs de pédiatrie. Ce questionnement est issu d’un stage dans ce contexte précis, où les infirmières rencontrées exprimaient de la difficulté à comprendre réellement ce que les parents vivaient de manière intime et la raison de certaines de leurs réactions. Comment l’infirmière peut-elle adapter son savoir, savoir-être et savoir-faire au quotidien face à ce que vivent les parents ? Les auteurs se sont basé sur des résultats de recherches scientifiques enrichissant et rendant fiables les savoirs cliniques. Les huit articles issus dans les bases de données Medline, Cinhal, Ovid et Health Source, rendent compte du phénomène sous trois angles différents : 1. L’expérience brute des parents lors de l’hospitalisation de leur enfant 2. La manière dont les parents vivent leur relation avec l’infirmière 3. Ce que vivent les parents sur le long terme, c’est-à-dire une année après l’événement Ces trois approches ont permis de dégager quelques résultats surprenants. Par exemple, il semblerait que la mère soit capable intuitivement d’évaluer la gravité de l’état de santé de son enfant, ce qui rend son évaluation indispensable à l’infirmière au quotidien. Une autre découverte des auteurs réside dans le fait que l’expérience des parents reste vive encore une année après, et qu’au vu du lien très fort qui s’établit avec les soins intensifs de pédiatrie, il serait tout à fait intéressant que les infirmières des soins intensifs assument leur suivi sur le long terme si la demande existe. D’autres résultats ont permis de déduire des recommandations pour une pratique clinique en harmonie avec ce que vivent les parents.

Choroidal metastases are, with melanoma, the most frequent malignant eye neoplasms. Breast carcinoma for women and lung carcinoma for men most commonly metastasize to the eye. We report a rare case of choroidal metastasis from follicular thyroid carcinoma.A 75-year-old man, with metastatic follicular thyroid carcinoma, presented a decline in visual acuity of the left eye lasting one month. The best corrected visual acuity was 3/10 in his left eye. Biomicroscopic examination of the anterior segment did not reveal anything abnormal. Funduscopic examination showed an amelanotic choroidal mass located at the posterior pole with serous retinal detachment. Tomoscintigraphy with computed tomography confirmed the thyroid origin by uptake of radioiodine in the choroidal mass. External radiotherapy was then proposed.Although it is exceptional, diagnosis of choroidal metastases should be considered in any decline in visual acuity in patients with thyroid cancer. The treatment is difficult because metastases from thyroid cancer are very poorly sensitive to radiotherapy and chemotherapy.

We report a case of a 72-year-old man who presented with bilateral panuveitis in a context of unclassified arthritis. The recurrence of uveitis associated with ear chondritis led to the diagnosis of relapsing polychondritis. Ocular symptoms are frequent in the course of relapsing polychondritis, but uveitis is a rare symptom and could compromise the visual outcome.

Physicians may be asked to provide care to victims of violence. Adequate diagnostic and therapeutic management must be provided. Establishing a detailed medical testimony can substantially influence the judiciary or administrative procedure's outcome. This paper provides guidelines for writing a medical testimony and describes the criteria that physicians need to consider in order to serve at best the interests of their patient within a mutually trustful relationship.

As the end of this century approaches, the pressure of migration is increasing. It is difficult to limit with restrictive measures the number of refugees and persons seeking asylum in Europe in each country, medical screening programs are organised for arriving refugees and asylum seekers. In Switzerland, they are screened for tuberculosis and hepatitis B. They are offered standard vaccinations and immunized for hepatitis B according to screening results. The prevalence of tuberculosis in asylum seekers is 414 per 100,000, 227 per 100,000 of bacteriologically active tuberculosis. Anti-HBc antibody is present in 22% of women and 39% of men. The frequency increases with age and varies greatly according to origin. Initially, refugees were screened for intestinal parasites. Over a quarter were carriers, a large majority asymptomatic. Increasing numbers of asylum seekers come from countries affected by war and insecurity. Systematic screening carried out in Geneva for previous exposure to violence revealed that 61% reported major trauma, 18% reported torture and 37% complained of symptoms such as nightmares, insomnia, flashbacks, etc. The authors discuss issues related to medical screening programs, and their relative usefulness in an increasingly mobile world where the distinction between travellers and migrants is not always clear.

Many asylum seekers and refugees arriving in Switzerland have been exposed to major trauma such as war, incarceration or torture. A growing number of Swiss doctors treat patients who are victims of violence and torture, and may need to draw up medical reports on sequelae of such trauma. These are often difficult to detect, as patients do not bring up the subject spontaneously. A request for a medical report offers an opportunity to recognize and explore the patient's past traumatic experiences and can be a first step in the therapeutic process. The experience gained in this field at the Travel and Migration Medicine Unit, Geneva, is reported in this article. Analysis of 82 cases treated between June 1991 and December 1993 documents the types of trauma alleged and illustrates the patients' complaints and the clinical signs observed.

Introduction Choroidal metastases are, with melanoma, the most frequent malignant eye neoplasms. Breast carcinoma for women and lung carcinoma for men most commonly metastasize to the eye. We report a rare case of choroidal metastasis from follicular thyroid carcinoma. Observation A 75-year-old man, with metastatic follicular thyroid carcinoma, presented a decline in visual acuity of the left eye lasting one month. The best corrected visual acuity was 3/10 in his left eye. Biomicroscopic examination of the anterior segment did not reveal anything abnormal. Funduscopic examination showed an amelanotic choroidal mass located at the posterior pole with serous retinal detachment. Tomoscintigraphy with computed tomography confirmed the thyroid origin by uptake of radioiodine in the choroidal mass. External radiotherapy was then proposed. Discussion Although it is exceptional, diagnosis of choroidal metastases should be considered in any decline in visual acuity in patients with thyroid cancer. The treatment is difficult because metastases from thyroid cancer are very poorly sensitive to radiotherapy and chemotherapy.

We report a case of a 72-year-old man who presented with bilateral panuveitis in a context of unclassified arthritis. The recurrence of uveitis associated with ear chondritis led to the diagnosis of relapsing polychondritis. Ocular symptoms are frequent in the course of relapsing polychondritis, but uveitis is a rare symptom and could compromise the visual outcome.

The authors report on three cases of severe P. falciparum malaria successfully treated by iv quinine and exchange transfusion. Serum concentrations of Tumor Necrosis Factor (TNF) were determined before and during treatment. After an initial decrease, serum levels of TNF remained markedly elevated during the first 48 hours despite exchange transfusion. Though exchange transfusion accelerates the elimination of parasites from the blood, it seems to have no immediate effects on reducing serum levels of cytokines such as TNF.