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Environmentally responsive hydrogel composites embedded with submicron-sized spherical silica particles for the modulation of the mid-infrared radiation derived from the Bragg reflection are therein designed for personalized body thermoregulation.

Purpose:Androgen deprivation regenerates the thymus in adults, expanding of T-cell receptor V β repertoire in blood and lymphoid organs and tumor-infiltrating lymphocytes in human prostate tumors. In melanoma murine models, androgen receptor promotes metastases and androgen blockade potentiates antitumor vaccine efficacy. This phase I study evaluated the safety, efficacy, and pharmocodynamics of androgen deprivation with the gonadotropin releasing hormone (GnRH) agonist triptorelin combined with nivolumab in male patients with melanoma resistant to anti–PD-1.Patients and Methods:Adult male patients with advanced melanoma who progressed under anti–PD-1 containing regimens received triptorelin 3.75 mg every 4 weeks, nivolumab 3 mg/kg every 2 weeks, and bicalutamide 50 mg once daily during the first 28 days. Tumor response was first assessed after 3 months; adverse events (AE) were monitored throughout the study. T-cell receptor excision circles (TREC), a biomarker of thymus activity, were explored throughout the study.Results:Of 14 patients, 4 were locally advanced and 10 had distant metastases. There were no grade 4 or 5 AEs. Five grade three AEs were reported in 4 patients. According to RECIST v1.1, best overall response was partial response (PR) in one patient with a pancreas metastasis, stable disease (SD) in 5 patients, and progressive disease in 8 patients. According to iRECIST, a second PR occurred after an initial pseudoprogression, TRECs increased in 2 patients, one with PR who also had an increase in TILs, and the second with SD.Conclusions:This combination was well tolerated. Disease control was obtained in 42.8% (RECIST) and 50% (iRECIST). The evidence for thymus rejuvenation was limited.

Recognition of radiographers' work has received limited research attention to date, notably its link with wellbeing at work (i.e., job and career satisfaction) and emotional exhaustion. This research focuses on these links and examines more precisely the mediational psychological mechanism (i.e., professional identification) that could explain these relationships.This was a cross-sectional, quantitative study with data obtained through an online survey. The sample comprised 713 radiographers working in France. Structural equation modeling was used to test the mediational model.Results of structural equation analysis suggest that radiographers who perceive more professional recognition from their supervisors, colleagues and patients are those who identify most with their profession and who are most satisfied by their job and their career; they also show lower levels of emotional exhaustion. These results underline the crucial role of recognition in the workplace for these professionals.Recognition is one of the basic needs of an individual, and satisfying this need is a crucial issue for organizations. This paper focuses on the importance of recognition for radiographers, notably to protect their psychological health and increase their well-being at work and in their professional career.Health organizations and supervisors should be aware of the importance of recognizing radiographers' work in order to improve their psychological health, enhance their perceived quality of life at work, and have a positive perception of their career and their work.

Resume Objectif: Le nombre de femmes victimes d’agression sexuelle reste eleve, malgre les campagnes de prevention et d’information. Ces victimes peuvent etre des adolescentes, des femmes en âge de procreer ou des femmes menopausees. Dans le cadre des examens de victimes d’agression sexuelle, la diversite morpho-anatomique de l’appareil genital feminin impose une connaissance des variations physiologiques existantes par les praticiens prenant en charge ces victimes. Notre travail avait pour objectif de decrire et de caracteriser l’examen genital des femmes ayant une activite sexuelle consentie. Methode: Notre cohorte etait constituee de 196 femmes âgees de 14 a 81 ans, examinees dans le cadre de consultations de gynecologie medicale de deux maternites francaises. Resultats: Les lesions traumatiques genitales d’allure recente etaient retrouvees chez 12,8% des femmes dont le dernier rapport sexuel datait de moins de 5 jours. Les hymens intacts, indemnes de dechirure traumatique malgre une activite sexuelle reguliere, etaient presents chez 10,7% de ces femmes. Conclusion: Ainsi, dans de nombreux cas, l’examen genital seul ne permet ni d’affirmer, ni d’infirmer l’existence d’un rapport sexuel anterieur, qu’il soit ou non consenti. Le developpement de travaux sur les donnees de l’anatomie genitale feminine, permettrait d’optimiser la prise en charge medico-legale des victimes d’agression sexuelle.

Previous therapies and outcome

Age, localisation primary, stage, TNM

Washout, response to protocol therapy, AEs

Representativeness of Study Participants

Purpose:Androgen deprivation regenerates the thymus in adults, expanding of T-cell receptor V β repertoire in blood and lymphoid organs and tumor-infiltrating lymphocytes in human prostate tumors. In melanoma murine models, androgen receptor promotes metastases and androgen blockade potentiates antitumor vaccine efficacy. This phase I study evaluated the safety, efficacy, and pharmocodynamics of androgen deprivation with the gonadotropin releasing hormone (GnRH) agonist triptorelin combined with nivolumab in male patients with melanoma resistant to anti–PD-1.Patients and Methods:Adult male patients with advanced melanoma who progressed under anti–PD-1 containing regimens received triptorelin 3.75 mg every 4 weeks, nivolumab 3 mg/kg every 2 weeks, and bicalutamide 50 mg once daily during the first 28 days. Tumor response was first assessed after 3 months; adverse events (AE) were monitored throughout the study. T-cell receptor excision circles (TREC), a biomarker of thymus activity, were explored throughout the study.Results:Of 14 patients, 4 were locally advanced and 10 had distant metastases. There were no grade 4 or 5 AEs. Five grade three AEs were reported in 4 patients. According to RECIST v1.1, best overall response was partial response (PR) in one patient with a pancreas metastasis, stable disease (SD) in 5 patients, and progressive disease in 8 patients. According to iRECIST, a second PR occurred after an initial pseudoprogression, TRECs increased in 2 patients, one with PR who also had an increase in TILs, and the second with SD.Conclusions:This combination was well tolerated. Disease control was obtained in 42.8% (RECIST) and 50% (iRECIST). The evidence for thymus rejuvenation was limited.

Immunohistology: Response at time of biopsy, tissue, date biopsies, previous CPI and protocol CPI, elapse times, TILs and macrophages phenotypes.

Correction for ‘Environmentally responsive hydrogel composites for dynamic body thermoregulation’ by M. Garzón Altamirano et al., Soft Matter, 2023, 19, 2360–2369, https://doi.org/10.1039/D2SM01548J.

The number of women victims of sexual assault remains high, despite prevention and information campaigns. These victims can be adolescent girls, women of childbearing age or postmenopausal women. As part of examinations of victims of sexual assault, the morpho-anatomical diversity of the female genitalia requires knowledge of the physiological variations existing by the practitioners caring for these victims. Our work aimed to describe and characterize the genital examination of women with consented sexual activity.Our cohort consisted of 196 women aged 14 to 81, examined in the context of medical gynecology consultations in two French maternity hospitals.Recent genital traumatic injuries were found in 12.8% of women whose last sexual intercourse was less than 5days old. Intact hymens, free from traumatic tearing despite regular sexual activity, were present in 10.7% of these women.Thus, in many cases, genital examination alone cannot confirm or deny the existence of prior sexual intercourse, whether or not it was consented to. The development of work on data on female genital anatomy would make it possible to optimize the medico legal care of victims of sexual assault.

Introduction Des facteurs cliniques et biologiques associés à des formes graves de l’infection à SARS-CoV-2 ont été publiés dans le monde entier. Dans notre département, un cluster urbain composé principalement d’une population gitane a rapidement émergé. L’objectif de l’étude est de décrire ce cluster et de mettre en évidence les facteurs associés aux formes graves de COVID-19. Matériels et méthodes Du 11/03 au 17/04/2020, une étude rétrospective observationnelle a été menée dans notre centre hospitalier. Étaient inclus les patients avec un diagnostic de COVID-19 confirmé par PCR ou présumé sur un faisceau d’argument cliniques, biologiques et radiologiques. Ils appartenaient à un cluster défini par la localisation géographique de leur lieu de résidence. Les données anamnestiques, cliniques et biologiques ont été recueillies et analysées à partir des dossiers médicaux. Résultats Quatre-vingt-dix-sept patients ont été inclus, dont 61 (62,9 %) avaient une PCR positive. L’âge médian était de 52 ans (IQR : 43–70), 31 (32 %) étaient des hommes. Soixante-quatorze patients (79,6 %) étaient obèses (IMC > 30), 46 (47,4 %) étaient diabétiques et 56 (57,7 %) avaient une HTA. La fièvre, la toux et la dyspnée étaient les symptômes les plus fréquemment rapportés par respectivement 80 (82,5 %), 79 (81,4 %) et 71 (73,2 %) patients. Quatre-vingt-un (83,5 %) étaient lymphopéniques avec un taux médian de 1150c/mm3 (IQR : 800–1410). La CRP médiane était de 80 mg/L (IQR : 36–149). Trois quarts des patients ont eu une TDM thoracique, 100 % étaient évocateurs de COVID-19 dont 24 (34,7 %) avec une atteinte supérieure à 50 % du parenchyme. Une antibiothérapie a été administrée chez 45 patients (46,4 %). L’hydroxychloroquine et les corticoïdes ont été principalement prescrits en réanimation pour respectivement 16 (16,5 %) et 18 (18,6 %) patients. La durée médiane des symptômes avant hospitalisation était de 7 jours (IQR : 4–10), 67 (69,1 %) patients ont été hospitalisés plus de 5 jours, 33 (34 %) sont passés en réanimation dont 21 (21,6 %) intubés et 7 (7,2 %) sont décédés. En analyse univariée, les facteurs associés au passage en réanimation étaient l’âge (OR = 1,03, IC95 % [1,003 ; 1,058] p = 0,05), le sexe masculin (OR = 3,79, IC95 % [1,55 ; 9,56] p = 0,004), un antécédent d’HTA (OR = 2,67, IC95 % [1,10 ; 6,89], p = 0,03), ainsi que la lymphopénie 100 mg/L (OR = 4,74, IC95 % [1,96 ; 12,03] p 100 mg/L (OR = 4,2 IC95 % [1,7 ; 10,8] p = 0,002), et la lymphopénie

Introduction Pour garder un lien clinique avec les patients atteints de COVID-19 maintenus a domicile en respectant le confinement, de nombreux centres ont deploye en urgence des dispositifs de tele-suivi. Cote usager une application permet l’acces a des conseils, la saisie reguliere de questionnaires predefinis visant a decrire l’evolution de leur infection ou de celles de leurs proches, le tchat avec des equipes soignantes. Cote soignant, des tableaux de bord permettent de concentrer les appels sur les situations les plus problematiques. L’objectif de notre communication est de presenter la perception du service rendu et l’impact sur le parcours patient de ce dispositif mis en place par le CHU, incluant infectiologues, medecins generalistes, hygienistes, psychologues, psychiatres et gynecologues-obstetriciens volontaires. Materiels et methodes Tous les patients depistes (+) en ambulatoire au CHU du 10/03 au 01/06/2020 presentant des criteres de maintien possible a domicile et ayant accepte un tele-suivi ont ete inclus. Outre les questionnaires de saisie de l’evolutions des symptomes, un questionnaire HADS depistant les symptomes anxieux et depressifs etait presente par l’application tous les 2 jours, jusqu’a decision d’arret du patient. Chaque evaluation se terminait par une proposition de rappel. A la fin de la periode un questionnaire d’evaluation de la perception du dispositif a ete envoye. Resultats Deux cent cinquante-cinq unites epidemiologiques (UE) ont ete tele-suivies pour une duree mediane de 11 jours (IQ3 : 8–15) soit 135 familles et 120 individus seuls avec un ratio F/H a 0,64 et un âge median de l’utilisateur de l’application de 42 ans (IQ3 : 30–55). Trente-sept pour cent des patients presentaient des comorbidites, 18 femmes enceintes et 11 sujets immunodeprimes ont ete suivis. Au pic d’activite, 5 ETP 7/7 j (heures ouvrables) ont supervise 125 UE simultanees. Quarante-quatre suivis ont ete realises en post-hospitalisations. Le tele-suivi a genere 17 consultations et 14 hospitalisations directes en unite COVID (dont une a abouti a un deces a j7). Quarante-huit patients presentant un score HADS > 10 ont beneficie d’un avis psychiatrique et 13 ont entame un suivi, une personne a ete hospitalisee a la fin du confinement. Parmi les 127 repondants au questionnaire final, 93,6 % ont declare avoir ete rassure par le dispositif, 93,6 % ont considere qu’ils ont pu facilement obtenir les informations necessaires et suffisantes pour gerer leur situation medicale et le confinement ; 69,9 % ont estime qu’ils auraient consulte aux urgences en l’absence du dispositif. Conclusion Ce dispositif multidisciplinaire a apporte la preuve de son utilite percue en situation de crise pour toutes les parties prenantes.

Summary Background: The DNA repair protein O 6 -alkylguanine-DNA alkyl transferase (AT) mediates resistance to chloroethylnitrosoureas. Agents depleting AT such as DTIC and its new analogue temozolomide (TMZ) can reverse resistance to chloroethylnitrosoureas. We report the results of a dose finding study of TMZ in association with fotemustine. Patients and methods: Twenty-four patients with metastatic melanoma or recurrent glioma were treated with escalating dose of oral or intravenous TMZ ranging from 300 to 700 mg/m 2 , divided over two days. Fotemustine 100 mg/m 2 was given intravenously on day 2, 4 hours after TMZ. AT depletion was measured in peripheral blood mononuclear cells (PBMCs) and in selected cases in melanoma metastases and was compared to TMZ pharmacokinetics. Results: The maximum tolerated dose (MTD) of TMZ was 400 mg/m 2 (200 mg/m 2 /d) when associated with fotemustine the 2nd day with myelosuppression as dose limiting toxicity. The decrease of AT level in PBMCs was progressive and reached 34% of pretreatment values on day 2. There was however wide interindividual variability. AT reduction was neither dose nor route dependent and did not appear to be related to TMZ systemic exposure (AUC). In the same patients, AT depletion in tumour did not correlate with the decrease of AT observed in PBMCs. Conclusions: PBMCs may not be used as a surrogate of tumour for AT depletion. Further study should concentrate on the pharmacokinetic pharmacodynamic relationship in tumour to provide the basis for individually tailored therapy.

Unrelated cord blood transplantation (UCBT) after a reduced intensity conditioning regimen (RIC) has extended the use of UCB in elderly patients and those with co-morbidities without an HLA-identical donor, although post-transplant relapse remains a concern in high-risk acute myeloid leukemia (AML) patients. HLA incompatibilities between donor and recipient might enhance the alloreactivity of natural killer (NK) cells after allogeneic hematopoietic stem-cell transplantation (HSCT). We studied the reconstitution of NK cells and KIR-L mismatch in 54 patients who underwent a RIC-UCBT for AML in CR in a prospective phase II clinical trial. After RIC-UCBT, NK cells displayed phenotypic features of both activation and immaturity. Restoration of their polyfunctional capacities depended on the timing of their acquisition of phenotypic markers of maturity. The incidence of treatment-related mortality (TRM) was correlated with low CD16 expression (P=0.043) and high HLA-DR expression (P=0.0008), whereas overall survival was associated with increased frequency of NK-cell degranulation (P=0.001). These features reflect a general impairment of the NK licensing process in HLA-mismatched HSCT and may aid the development of future strategies for selecting optimal UCB units and enhancing immune recovery.

Conversion disorder is a psychiatric disorder often encountered in neurology services. This condition without organic lesions was and still is sometimes referred as an imaginary illness or feigning. However, the absence of organic lesions does not exclude the possibility of cerebral dysfunction. The etiologic mechanisms underlying this disorder remain uncertain even today.The advent of cognitive and functional imaging opens up a field of exploration for psychiatry in understanding the neurobiological mechanisms underlying mental disorders and especially the conversion disorder. This article reports several neuroimaging studies of conversion disorder and attempts to generate hypotheses about neurobiological mechanisms.Le trouble de conversion est une pathologie psychiatrique fréquemment rencontrée dans les services de neurologie. Cette pathologie «sans substrat» a été et est encore parfois qualifiée de maladie imaginaire ou de simulation. Cependant, l’absence de substrat «organique» n’exclut pas la possibilité d’un dysfonctionnement cérébral. Les mécanismes étiopathogéniques qui sous-tendent ce trouble sont longtemps restés incertains, encore aujourd’hui. L’avènement des sciences cognitives et de l’imagerie fonctionnelle ouvre un champ d’exploration pour la psychiatrie dans la compréhension des mécanismes neurobiologiques qui sous-tendent les troubles mentaux et, en particulier, le trouble de conversion. Cet article reprend plusieurs études de neuroimagerie sur le trouble de conversion et tente d’en dégager des hypothèses sur ses mécanismes neurobiologiques.

Background It has been shown that androgens are immunosuppressive. Androgen deprivation with GnRH agonists regenerates the thymus and its functions in adults, leading to increase in blood and lymphoid organ lymphocytes, in naive lymphocytes with expansion of TCR Vbeta repertoire, and in Tumour Infiltrating Lymphocytes (TILs) in prostate tumours. This phase I study evaluated the safety of triptorelin in combination with nivolumab, as well as its potential to reverse resistance to PD-1 inhibitors in male melanoma patients. Methods Treatment consisted of triptorelin 3.75 mg i.m. every 4 weeks and nivolumab 3 mg/kg i.v. every 2 weeks. Bicalutamide 50 mg p.o. QD was added for the first 28 days. Evaluation of response was performed after 3 months. Triptorelin PK was assessed and various PDy markers were measured in blood and tumour samples. Planned treatment duration was 48 weeks. Results Fourteen male patients were included, of whom 11 were white and 3 were black, with mean age 65 years (range 45-82). At screening 4 were locally advanced while 10 had distant metastases (2 with M1a, 1 with M1b, 6 with M1c and 1 with M1d). Ten patients had cutaneous melanoma, 2 patients had mucosal melanoma, and 2 had an unknown primary. Safety: No grade 4 AEs were reported. Five grade 3 AEs were reported in 4 patients, of which one (abdominal pain) was attributed to triptorelin and resolved after 39 days (causing no treatment interruption as it started on the day treatment was discontinued due to progression), and one (neutropenia) was considered related to nivolumab and resolved following treatment interruption for 14 days. Efficacy: BOR (RECIST 1.1) was assessed as 2 PR, 5 SD, and 7 PD. The two patients with PR showed reductions from baseline in Target Lesions of 76% (one pancreas metastasis) and32% (two inguinal lymph nodes), following an initial pseudoprogression. Conclusion The association of triptorelin to nivolumab was well tolerated and yielded partial response in two patients. Legal entity responsible for the study Debiopharm International S.A. Funding Debiopharm International S.A. Disclosure C. Robert: Advisory / Consultancy: Novartis, Bristol-Myers Squibb, MSD, Roche, Sanofi, Amgen, Pierre Fabre. F.J. Lejeune: Honoraria (self): Debiopharm International SA. C. Lebbe: Honoraria (self): Roche, Bristol-Myers Squibb, Novartis, MSD, Amgen, Pierre Fabre, Pfizer, Incyte; Advisory / Consultancy: Roche, Bristol-Myers Squibb, Novartis, MSD, Amgen; Travel / Accommodation / Expenses: Bristol-Myers Squibb, MSD; Speaker Bureau / Expert testimony: Roche, Bristol-Myers Squibb, Novartis ,Amgen; Advisory / Consultancy: Aventis. T. Lesimple: Research grant / Funding (self): Roche; Advisory / Consultancy: MSD, Novartis, Pierre Fabre. E. Lundstrom: Full / Part-time employment: Debiopharm International SA. V. Nicolas: Full / Part-time employment: Debiopharm International SA. B. Gavillet: Full / Part-time employment: Debiopharm International SA. V. Gregoire: Full / Part-time employment: Debiopharm International SA. P. Crompton: Full / Part-time employment: Debiopharm International SA.

A survey of state mental health agencies found that a majority have no specific policy or procedure regarding how to provide mental health services to persons who are deaf or who are deaf-blind. Agency representatives report that staff lack knowledge of how to provide mental health services to persons who are deaf-blind and the agencies lack qualified interpreters. They recommend training for social workers and counselors to address best practices in working with people who are deaf-blind concerning communication methods and strategies, physical interaction, cultural issues, everyday life, sensory deprivation, ethics, use of an interpreter, and other general issues.

Introduction Le purpura thrombopenique immunologique (PTI) est une etiologie de thrombopenie frequemment rencontree en medecine interne. Les formes secondaires a une pathologie infectieuse (notamment virale), immunologique (lupus ou deficit immunitaire) ou neoplasique (lymphoproliferation) doivent etre systematiquement recherchees. Observation Nous rapportons ici le cas d’une femme de 30 ans se presentant avec un purpura petechial des quatre membres, associe a des bulles hemorragiques endobuccales, survenant a quelques jours d’un episode de myalgies. Ses antecedents principaux consistaient en une malformation pyelo-calicielle gauche (compliquee d’infections locales et de lithiase) et un tabagisme actif. A son arrivee, le score hemorragique de Khellaf etait a 8, ne necessitant pas la prescription d’immunoglobulines intraveineuses (IgIV). Les examens initiaux faisaient etat d’une thrombopenie inferieure a 10 G/L ; il y avait egalement une anemie normocytaire (Hb 11,9 g/dL ; VGM 96 fL ; reticulocytes 124 G/L). Le taux de leucocytes etait de 9,08 G/L (hyper-lymphocytose a 4,81 G/L ; PNN 2,72 G/L). Une haptoglobine indosable, un taux de LDH augmente a 347 UI/L temoignaient d’un processus hemolytique malgre la negativite du test de Coombs. On notait egalement une discrete cytolyse hepatique (ALAT 40 UI/L ; ASAT 30 UI/L) sans cholestase. Le myelogramme, sans anomalie, comportait des megacaryocytes. Le scanner thoraco-abdomino-pelvien injecte mettait en evidence une hepatomegalie homogene a 19 cm, des adenopathies axillaires et latero-aortique gauche juxta-centimetrique ; la rate etait evaluee a 12 cm. Devant cette bi-cytopenie peripherique d’allure auto-immune, un traitement par methylprednisolone a ete debute a la dose de 250 mg/j pendant 3 jours mais n’a pas permis, dans un premier temps, de controler le syndrome hemorragique clinique (persistance du purpura), ni la thrombopenie. Les tests serologiques complementaires demandes devant cette bicytopenie precedee d’un episode de myalgies, ne repondant pas aux criteres stricts de PTI, associee a une hyperlymphocytose et a une cytolyse hepatique, ont alors mis en evidence une positivite des IgM anti-CMV (> 140 U/L). Les IgG etaient a 25 U/L, et le test d’avidite etait en faveur d’une primo-infection datant de moins de 3 mois. La PCR CMV etait positive a 30 300 copies/mL. Un traitement par gangiclovir a ete debute a la dose de 5 mg/kg pendant 5 jours, relaye par du valganciclovir (900 mg 2 fois par jour par voie orale) pour une duree totale de traitement de 21 jours. La corticotherapie a ete diminuee progressivement pendant la meme periode. Une amelioration clinique (regression du purpura petechial et des bulles hemorragiques endo-buccales), et biologique (plaquettes 21 G/L, charge virale 1890 copies/mL) a ete observee a partir de j3 du traitement antiviral. Six semaines apres le debut des symptomes, la patiente a ete reevaluee : elle etait asymptomatique, les plaquettes dosees a 181 G/L ; la recherche de deficit immunitaire etait negative, et les anomalies scannographiques etaient en amelioration. Discussion La recherche d’une infection par le CMV ne fait pas partie du bilan systematique face a un tableau evoquant un PTI. Cependant, devant certaines atypies comme un syndrome pseudo-grippal, un syndrome mononucleosique initial, une cortico-resistance, il peut etre interessant de la demander afin de cibler la strategie therapeutique. Dans notre cas, le traitement antiviral, conjugue a une corticotherapie degressive, a permis une amelioration clinico-biologique durable. Nous n’avons pas retrouve dans la litterature de cas de bi-cytopenies auto-immunes lie a une primo-infection CMV chez l’adulte immunocompetent. En revanche, cela a ete decrit chez des patients immunodeprimes ou des enfants [1] . Un PTI refractaire isole secondaire a une primo infection a CMV a egalement ete decrite chez des adultes immunocompetents [2] . Conclusion Notre observation nous rappelle que les maladies auto-immunes peuvent avoir des facteurs declenchants infectieux, notamment viraux. Les atypies dans un dossier de PTI, ou l’echec du traitement de reference pourront faire evoquer ce diagnostic.

Aims: European starlings (Sturnus vulgaris) are an invasive species in the United States and are considered a nuisance pest to agriculture. The goal of this study was to determine the potential for these birds to be reservoirs and/or vectors for the human pathogen Escherichia coli O157:H7. Materials and Results: Under biosecurity confinement, starlings were challenged with various doses of E. coli O157:H7 to determine a minimum infectious dose, the magnitude and duration of pathogen shedding, and the potential of pathogen transmission among starlings and between starlings and cattle. Birds transiently excreted E. coli O157:H7 following low-dose inoculation; however, exposure to greater than 105.5 colony-forming units (CFUs) resulted in shedding for more than 3 days in 50% of the birds. Colonized birds typically excreted greater than 103 CFU g−1 of faeces, and the pathogen was detected for as long as 14 days postinoculation. Cohabitating E. coli O157:H7-positive starlings with culture-negative birds or 12-week-old calves resulted in intra- and interspecies pathogen transmission within 24 h. Likewise, E. coli O157:H7 was recovered from previously culture-negative starlings following 24-h cohabitation with calves shedding E. coli O157:H7. Conclusions: European starlings may be a suitable reservoir and vector of E. coli O157:H7. Significance and Impact of the Study: Given the duration and magnitude of E. coli O157:H7 shedding by European starlings, European starlings should be considered a public health hazard. Measures aimed at controlling environmental contamination with starling excrement, on the farm and in public venues, may decrease food-producing animal and human exposure to this pathogen.

Gynandroblastoma is a rare ovarian tumor, derived sex cord-stromal, malignant, with low scalable potential. Clinical investigations include endocrinology or gynecological troubles, or pelvic mass syndrome. After pelvic MRI of reference, optimum surgery is the treatment of gynandroblastoma. Fragile X syndrome is the most common inherited cause of mental retardation, and females are more affected. Association of both is totally new.

Background and Objectives Isolated limb perfusion with TNF-alpha and melphalan (TM-ILP) is a limb salvage therapy for non-resectable soft tissue sarcomas (STS) of the extremities. It is indicated for patients for whom amputation or debilitating surgery is the only alternative. It can be used either as an exclusive therapy (in palliation) or as a neo-adjuvant treatment, followed by marginal resection of tumor remnants with minimal functional impairment. Methods Between February 1992 and March 2006, 57 TM-ILPs were performed on 51 patients with 88% high grade and 84% advanced stage tumors. Results Mean follow-up is 38.9 months (4–159, median 22 months). Twenty-one percent patients had significant early complications, with 3 major re-operations, and 23% suffered long-lasting complications. Complete response was observed in 25%, partial response in 42%, stable disease in 14% and progressive disease in 14%. Resection of the tumor remnants was possible in 65%. A complementary treatment was necessary in 31%, mostly radiation therapy. A local recurrence was observed in 35%, after a mean of 20.3 months (2–78), and distant relapse was seen in 45%, after a mean of 13.4 months (5–196). Mean Disease-free survival was 14.9 months, and overall 5-year-survival 43.5%. Amputation rate at 5 years was 24%. Conclusions TM-ILP is a conservative treatment with a high complications rate, but it can be successful even for the most severe STS of extremities. As a consequence the limb can be spared from amputation or debilitating surgery on the long term in about 75% of patients. J. Surg. Oncol. 2008;98:148–155. © 2008 Wiley-Liss, Inc.

This exploratory study provides detailed information about the employment status and experiences of a group of older adults with combined hearing and vision loss. Data were obtained from two sources: primary data collected through a survey and secondary data obtained from a nationally representative sample. Results indicate that many older adults with combined hearing and vision loss do work or want to work, and that accommodations, assistive technology, higher education levels, and changing jobs or type of work are associated with continued employment for this population. Based on the results, suggestions for vocational rehabilitation counselors in working with older adults with combined hearing and vision loss are provided.

Three enzymes intervening in de novo purine synthesis, as well as cystathionine B-synthetase, have been mapped to chromosome 21. In order to gain a better understanding of purine synthesis anomalies in Down's syndrome, the present authors studied the variations in mitotic index of lymphocyte cultures to which various inhibitors or metabolites of purine synthesis had been added. In spite of common gene dosage effects, unexpected and highly significant differences were noted between Down's syndrome patients without complications and those presenting with additional psychotic features. In Down's syndrome patients without complications, a highly significant decrease in mitotic index was noted in the presence of exogenous inosine. A significant decrease in the presence of adenosine and guanosine was also noted. These findings are in keeping with the expected metabolic repercussions of genes mapped to chromosome 21. In Down's syndrome patients with psychotic complications, the in vitro reactions were quite different. A paradoxal increase in mitotic index was noted in the presence of inosine and of adenosine, but the response to guanosine did not differ from that observed in normal controls. These findings were unexpected and seem to indicate that, in spite of the gene dosage effect, psychotic Down's syndrome patients are unable to compensate abnormal purine synthesis and resulting imbalances. Furthermore, a marked difference in purine metabolic reactions was noted between Down's syndrome patients receiving supplemental folic/folinic acid and those on no therapy. This suggests that some modulation of the gene dosage effect may be possible.

Classical metastatic melanoma therapy is disappointing but important progress has been made in the understanding of melanoma biology. Genetic lesions and several intracellular signaling pathways that could serve as targets for novel therapy have been identified and a number of new agents are under evaluation. Promising tumor cell targets were identified in the cell membrane, cytoplasm and nucleus. New therapeutic approaches, besides monoclonal antibodies and vaccination, include an increasing number of small molecules that have been shown to interfere restrictively with intracellular signaling pathways in melanoma and decrease proliferation, survival, migration or invasion. Other agents can interfere with stromal components of melanoma, such as angiogenesis and components of the immune system.

International audience; Tumor necrosis factor (TNF) is a pro-inflammatory cytokine exerting pleiotropic effects on endothelial cells. Depending on the vascular context it can induce endothelial cell activation and survival or death. The microenvironmental cues determining whether endothelial cells will survive or die, however, have remained elusive. Here we report that integrin ligation acts permissive for TNF-induced protein kinase B (PKB/Akt) but not nuclear factor (NF)-kappaB activation. Concomitant activation of PKB/Akt and NF-kappaB is essential for the survival of endothelial cells exposed to TNF. Active PKB/Akt strengthens integrin-dependent endothelial cell adhesion, whereas disruption of actin stress fibers abolishes the protective effect of PKB/Akt. Integrin-mediated adhesion also represses TNF-induced JNK activation, but JNK activity is not required for cell death. The alphaVbeta3/alphaVbeta5 integrin inhibitor EMD121974 sensitizes endothelial cells to TNF-dependent cytotoxicity and active PKB/Akt attenuates this effect. Interferon gamma synergistically enhanced TNF-induced endothelial cell death in all conditions tested. Taken together, these observations reveal a novel permissive role for integrins in TNF-induced PKB/Akt activation and prevention of TNF-induced death distinct of NF-kappaB, and implicate the actin cytoskeleton in PKB/Akt-mediated cell survival. The sensitizing effect of EMD121974 on TNF cytotoxicity may open new perspectives to the therapeutic use of TNF as anticancer agent.Oncogene (2007) 26, 5722-5732; doi:10.1038/sj.onc.1210354; published online 19 March 2007.

Clinical oncologists have not been paying enough attention to the fact that poor tumor penetration represents a major impediment to the efficiency of cancer chemotherapeutics. The cytokine tumor necrosis factor (TNF) was the first treatment shown to affect tumor vessel destruction and improve vascular permeability of drugs in a clinical setting. TNF produces an early increase of vessel permeability followed by a dual targeting: TNF induces apoptosis of intratumoral angiogenic endothelial cells and melphalan during the apoptosis of tumor cells. Given the systemic toxicity, TNF has to be administered by regional therapy. However, experimental data indicate that a systemic approach will be possible, thanks to TNF targeting. Three fusion proteins with TNF were shown to target tumors: anti-EDB fibronectin/TNF, Asn-Gly-Arg-TNF, and anti-gp240/TNF. Current approaches to blocking angiogenesis include strategies that target vascular endothelium growth factor (VEGF)-A. However, little attention has been paid to possible drawbacks, which may include vessel destruction and reduced penetration by chemotherapeutic agents administered simultaneously or subsequently. An antiangiogenic treatment is optimal when it is given at a critical dose and at a critical time. Current protocols seem not to take these prerequisites into consideration. Other new approaches to increased tumor vessel permeability include histamine and combretastatin analog. The current paradigm of antitumor strategy based on the synergism of empirical drug combinations is obsolete. Instead, the design of protocols based on new pharmacodynamic concepts should provide better efficiency of cancer treatment as exemplified in the use of TNF and anti-VEGF antibody.

This article compares the development of print and braille reading in children who are blind and sighted in relation to Chall's stage model of reading development. Chall's model includes a prereading period, in which concepts are developed; middle stages, in which skills that are necessary for decoding text are developed; and later stages, which distinguish skilled readers on the basis of their highly developed schemata and cognitive skills that are necessary for effective comprehension and integration. The relevance of a developmental theory for directing training methods that facilitate braille literacy instruction is discussed. The process of reading may be said to begin when a sensory modality picks up encoded information from the world. Typically, reading is discussed in relation to the visual and cognitive processing that occurs with printed text. During visual reading, light from the printed page is reflected onto the retinas, where it is transferred to the brain for further processing. The brain applies higher cognitive functions that combine and transform arbitrary symbols into meaningful words and sentences that can represent most concrete and abstract thoughts. Thus, reading is an important cultural invention because it creates an effective medium for sharing information. When vision is not available to readers, information must be accessed using some other sensory modality.

This paper reports on the scientific session on sentinel node biopsy, surgery and locoregional treatments that took place during the Third Research Meeting on Melanoma, Milan, Italy, held in May 2003. It provides an overview of contributions presented at the meeting grouped according to subject - ultrasound scanning, sentinel node biopsy, mini-invasive surgery and stop-flow limb perfusion. The main comments made by the respective rapporteurs are also summarized.

General Additive Model (GAM) fitting techniques have been employed to understand and predict cephalopod abundance variations in the north-east Atlantic using data on commercial fisheries and geographic and climatic variables. Spatial patterns were studied for general average, seasonal average and monthly recruitment abundance. The capability of this method to model abundance in time and space was tested by comparing observed and calculated Catch per Unit of Eff ort for a1 longitude by 0.5 latitude rectangular grid. The influence of the explanatory variables on Loliginid abundance was clearly shown. Climatic variable effects change with time scale. They vary during the year and are mainly important during the pre-recruitment month. GAM allows explanation of the main part of seasonal abundance variations of these species in time and space. GAM also provides the first means of predicting the main recruitment peak area by using previous-month climatic variables. This article demonstrates the advantages of using commercial-fisheries data for ecological studies. 2002 Published by Elsevier Science Ltd on behalf of International Council for the Exploration of the Sea

To elucidate the functional heterogeneity of Ag-specific T lymphocyte populations, we combined labeling of lymphocytes with MHC/peptide tetramers and a cell surface affinity matrix for IFN-γ. Magnetic cell sorting of IFN-γ-positive lymphocytes allowed the selective enrichment and identification of live Ag-specific cytokine-secreting cells by flow cytometry. Naive, memory, and effector Ag-specific populations were evaluated in healthy HLA-A2 individuals. Significant fractions of influenza- and CMV-specific cells secreted IFN-γ upon challenge with cognate peptide, consistent with an effector/memory status. The sensitivity of the approach allowed the detection of significant numbers of CMV-specific IFN-γ-secreting cells ex vivo (i.e., without Ag stimulation). This was not apparent when using previously described assays, namely, ELISPOT or intracellular IFN-γ staining (cytospot). CD8+ T cells specific for the melamoma-associated Ag Melan-A/MART-1 did not produce IFN-γ upon challenge with cognate peptide, reminiscent with their naive functional state in healthy individuals. In contrast, CD45RAlow Melan-A/MART-1 tumor-specific cells from three of three melanoma patients presented levels of activity similar to those found for influenza- or CMV virus-specific lymphocytes, compatible with a functional differentiation into competent effector/memory T lymphocytes in vivo. Notably, a sizable fraction of Melan-A/MART-1-specific cells from a patient secreted IFN-γ ex vivo following peptide-based vaccination. Thus, the high sensitivity of the assay provides a valuable tool to monitor effector T cell responses in different clinical situations.

A flameless atomic absorption spectrometric (AAS) method has been developed and validated for the determination of platinum (Pt) in human plasma, plasma ultrafitrate and urines from cancer patients receiving the orally available platinum derivative, JM216. Sample pretreatment is minimal for urine, which is diluted with 10% HCl prior to AAS analysis. Pt analysis in plasma requires the application of the matrix modifier 5% Triton X-100 directly onto the integrated L'vov platform of the graphite furnace prior to the addition of plasma samples. For Pt in ultrafiltrates, enhanced sensitivity is achieved by pre-concentrating ultrafiltrate samples onto the platform prior to the ashing/atomisation step. The AAS program was set specifically for each considered matrix enabling to achieve limit of quantitations as low as 50, 10 and 5 ng Pt ml(-1) for urine, plasma and plasma ultrafiltrate, respectively. The calibration was linear (r(2)>0.993) over the working range 5-150 ng Pt ml(-1). The method has been validated according to the Recommendations on Bioanalytical Methods Validation. The stability of Pt in samples has been explored, as well as the specificity of the method. In the urine intra-assay precision of control samples at 60, 90 and 140 ng Pt ml(-1) is always lower than 3.0, 1.3 and 4.7%, respectively, with concentrations not deviating more than -5.5 to -1.0% from their nominal values, while inter-assay precision is within 5.7-7.7% and inter-assay deviation within the -1.9 to +4.3% range. Intra-assay precision of plasma control samples at 20, 70 and 140 ng Pt ml(-1) is always lower than 8% and concentrations never deviating more than 7.1% from their nominal values. Inter-assay precision of plasma control samples is always lower than 9% with inter-assay deviation from their nominal concentrations within the -3.9 to +1.8% range. In plasma ultrafiltrate, intra-assay CVs of control samples at 12, 25 and 45 ng Pt ml(-1) are always lower than 2.6, 1.7 and 6.8%, respectively, with concentrations not deviating more than -2.6 to -0.2% from their nominal values, while inter-assay CVs are within 5.1-9.5% and inter-assay deviation within the -1.6 to +5.3% range. The proposed method has, therefore, the required performance to measure Pt in biological samples and has been successfully applied to the determination of Pt in samples from cancer patients receiving JM216 in a phase I (daily administration for 14 days, dose escalation 10-50 mg m(-2)) and a phase II (fixed dose 120 mg m(-2) over 5 days) clinical study. In phase I study, both total and ultrafiltrable Pt accumulated upon repetitive dosings, showed long elimination half-lives (t(1/2)) and were measurable 2 weeks after the end of JM216 administration.

According to the Centers for Disease Control (Langlois, Rutland-Brown, & Thomas, 2006), traumatic brain injury (TBI) affects more than 1.4 million persons annually in the United States. Those who are most affected are children and adolescents, aged 0-4 and 15-19, young adults aged 19-25 (among military personnel in war zones), and persons aged 60 and older (Brain Injury Association of America, 2010). These incidences include shaken baby and child abuse cases, automobile accidents, sports injuries, war injuries, and falls. We do know that older persons with vision loss are more likely to fall and that falls among this age group are one of the major causes of TBI. We also know that older persons often have strokes and other neurological conditions, known as acquired brain injury (ABI), that have an impact on cognition and independence in much the same way as does TBI. Unfortunately, the wars in Iraq and Afghanistan have added to the number of young adults with TBI and vision loss, but the related work of the Department of Veterans Affairs has also given us more empirical information on how to work with this population. One of the roles of universities is to conduct research and integrate the results of research into the preparation of professionals in a given program of study. As a result, I believe that vision-related personnel preparation programs need to address this issue. Mississippi State University (MSU) has a Vision Specialist in Vocational Rehabilitation Graduate Certificate Program that is designed for vocational rehabilitation counselors with caseloads of persons who are blind or have low vision. Usually about 80% of the students in this program are working vocational rehabilitation counselors, some with many years of experience, and a few are teachers of students with visual impairments, vision rehabilitation teachers, and orientation and mobility (O&M) specialists or graduate students, who are from all over the United States. Over the past 5 years, we have noticed that more and more vocational rehabilitation counselors who serve persons who are blind have persons with brain injuries in their caseloads. In our program, under the general topic of special populations, we have covered vision loss related to ABI and TBI and HIV in a superficial way, but have paid more attention to the visual conditions associated with aging, diabetes, and deaf-blindness. But because of the increase in cases of brain injury in caseloads and my own experience when my husband, who has been legally blind all his life, acquired a TBI three years ago, MSU has increased the attention that is given this area of service. The motivation for the increased attention to brain injury is that specialization brain in jury-related vision loss is not well addressed in our field, and resources for treating this condition vary considerably around the United States. The program at Mississippi State University consists of four hybrid distance education courses with three weeks of intensive residency. In a nutshell, our courses cover the medical aspects of blindness and low vision with implications for employment, low vision, special populations, history and legislation, assistive technology, O&M, vocational rehabilitation therapy, transition, various resources (including organizations and professionals), special education perspectives, career development, job placement, and a field experience practicum. …

Administration of high doses of TNF and IFNγ by isolated limb perfusion to patients affected by in transit melanoma metastases or inoperable soft tissue sarcoma of the limb, results in a high rate of complete response compared to chemotherapy alone. TNF/IFNγ induce apoptosis of angiogenic endothelial cells and selectively disrupt the tumor vasculature. The study of the cellular and molecular events mediating this effect has revealed that TNF and IFNγ inhibit the function of integrin αVβ3, an adhesion receptor expressed on angiogenic endothelial cells and essential for their survival, resulting in impaired endothelial cell adhesion, spreading, focal adhesion formation and cell survival. These and other recent findings may open new perspectives in the clinical use of TNF as anti-tumor agent as well as in the design of new anti-vascular strategies aimed to disrupt the tumor vasculature.

This open, multicentre, randomized phase II trial was conducted to determine the effect of isolated limb perfusion (ILP) with tumour necrosis factor-alpha (TNFalpha) in combination with melphalan with or without interferon-gamma (IFNgamma) in patients with in-transit metastases of melanoma of the limbs (MD Anderson stage IIIA or IIIAB, AJCC stage III). The 64 patients included were randomized to receive either a two- drug regimen consisting of TNFalpha and melphalan (TM-ILP) or a three-drug regimen consisting of TNFalpha, melphalan and INFgamma (TIM-ILP). Patients randomized to receive IFNgamma were pretreated for 2 days before the ILP with once daily 0.2 mg IFNgamma subcutaneously and also received the same amount of IFNgamma during ILP. A total of 47 complete responses (73%) were reported, 22 (69%) of which occurred in the TM-ILP group and 25 (78%) in the TIM-ILP group; the difference was not significant. The 14 partial responses (22%) were split evenly between the treatment groups. In the TM-ILP group, two cases of stable disease and one case of progressive disease were reported. The overall response rate (complete plus partial responses) was 100% in the TIM-ILP group and 91% in the TM-ILP group, yielding an overall response of 95% for this study. In the historical control data, where 103 patients had received melphalan alone (M-ILP), there were 54 records of complete responses (52%) and 80 of complete or partial responses (78%). The median survival time estimated by the Kaplan-Meier method was 819 days for the TM-ILP group, > 705 days for the TIM-ILP group and 873 days for the combined study population; estimates for time to local progression or recurrence were 327 days, in excess of 498 days and 405 days, respectively. The corresponding figure for the historical controls was 338 days. These data suggest that TNFalpha associated with melphalan may be superior to melphalan alone for ILP.