An approach to classifying occupational exposures to endocrine disrupting chemicals by sex hormone function using an expert judgment process.

Endocrine disrupting chemicals (EDCs) are exogenous substances that interfere with the endocrine system and cause adverse effects. We aimed to classify the effects of 24 known EDCs, prevalent in certain occupations, according to four modes of action (estrogenic, antiestrogenic, androgenic, and/or antiandrogenic). A literature search, stratified into four types of literature was conducted (namely: national and international agency reports; review articles; primary studies; ToxCastTM). The state of the evidence of each EDC on sex hormone function was summarized and reviewed by an expert panel. For each mode of action, the experts evaluated the likelihood of endocrine disruption in five categories: "No", "Unlikely", "Possibly", "Probably", and "Yes". Seven agents were categorized as "Yes," or having strong evidence for their effects on sex hormone function (antiandrogenic: lead, arsenic, butylbenzyl phthalate, dibutyl phthalate, dicyclohexyl phthalate; estrogenic: nonylphenol, bisphenol A). Nine agents were categorized as "Probable," or having probable evidence (antiandrogenic: bis(2-ethylhexyl)phthalate, nonylphenol, toluene, bisphenol A, diisononyl phthalate; androgenic: cadmium; estrogenic: copper, cadmium and; anti-estrogenic: lead). Two agents (arsenic, polychlorinated biphenyls) had opposing conclusions supporting both "probably" estrogenic and antiestrogenic effects. This synthesis will allow researchers to evaluate the health effects of selected EDCs with an added level of precision related to the mode of action.

Reversible strain alignment and reshuffling of nanoplatelet stacks confined in a lamellar block copolymer matrix.

We designed a nanocomposite consisting of CdSe nanoplatelets dispersed in the form of short stacks in the polybutadiene domains of a polystyrene-polybutadiene-polystyrene (SBS) thermoplastic elastomer matrix. Under strain, the material displays reversible, macroscopic anisotropic properties, e.g. the fluorescence signal. We present here a structural study of the composite under stretching, by in situ high-resolution X-ray scattering using synchrotron radiation. Modelling the scattering signal allows us to monitor the evolution of both the matrix and the platelets under strain. In particular, we show that the strain "reshuffles" the platelet stacks, which tilt their long axis from parallel to the plane of the microstructure lamellae at rest to perpendicular to this plane at high strain, at the same time breaking into smaller pieces, more easily accommodated in the soft butadiene domains. This reshuffling is fully reversed after strain relaxation. Moreover, it can be prevented by adding free oleic acid, which reinforces the interactions between the platelets in the stacks.

Extra-articular subcutaneous "inverted king post-truss" ligament reconstruction for severe swan neck deformity (snapping finger).

A swan neck deformity (SND) can be well tolerated for a long time, until the appearance of a disabling "snapping finger". In its most advanced condition, the other hand is needed to initiate finger flexion. We propose a technique of extra-articular, subcutaneous ligament reconstruction with an "inverted king post-truss" configuration use in roofs and to reinforce railway bridges. An artificial ligament (MaxBraid™ polyethylene surgical suture, 5 metric, Biomet) makes a figure of eight between transosseous tunnels in the proximal and middle phalanges, crossing over top of the A3 pulley. We limited our series to severe SND cases with "snapping finger". We excluded isolated SNDs without functional disability. Eleven patients were followed for 3.4 years on average. The cause was an acute injury 8 times (7 balloon accidents), rheumatoid arthritis 2 times and overuse once (saxophone). Only one case was a poor outcome of mallet finger. The 11 patients were reassessed by a telephone survey. Two patients underwent reoperation: one for a ligament rupture, the other one for a knot that became untied. One patient had a suspected late rupture but without recurrence of the disabling snapping finger. The 11 patients considered themselves improved by the intervention. Nine patients did not notice any difference between their operated finger and the contralateral side. Return to manual activity was possible once the skin had healed. The technique is simpler than the spiral oblique retinacular ligament (SORL) reconstruction technique described by Thomson-Littler and also less demanding because it does not involve the distal interphalangeal joint. It requires only a short incision in the volar crease of the proximal interphalangeal joint. No tendon or ligament is sacrificed. Neither postoperative immobilization nor lengthy physical therapy is needed. Complications can be avoided by selecting the appropriate artificial ligament material and careful knot tying.

Strain-controlled fluorescence polarization in a CdSe nanoplatelet-block copolymer composite.

By dispersing semi-conducting CdSe nanoplatelets within a styrene-butadiene-styrene block copolymer matrix we form homogeneous fluorescent hybrid films. Reversible orientation control of the nanoplatelets is simply achieved through stretching the film, leading to tuneable fluorescence anisotropy. Such adjustable polarization effects are useful for modulating the optical response in composite materials.

Interventional pulmonology: an update for internal medicine physicians.

Interventional pulmonology is a subspecialty that uses advanced diagnostic and therapeutic procedures to care for patients with benign and malignant diseases of the lung, airways and pleura. There has been a rapid proliferation of new pulmonary procedural technologies over the last decade. Common diagnostic applications include endobronchial ultrasound, guided bronchoscopy and a number of pleural disease interventions. Endobronchial ultrasound is performed with a specially design flexible bronchoscope and allows safe and accurate sampling of intrathoracic structures through the airway wall under direct visualization. Guided bronchoscopy methods are granting significant improvement in the diagnostic yield of flexible bronchoscopy. Virtual bronchoscopy, radial probe endobronchial ultrasound and electromagnetic navigational bronchoscopy are examples of these methods. Interventional pulmonologists can also be trained to perform ultrasound guided thoracentesis, closed-needle pleural biopsy and medical thoracoscopy to help in the diagnosis of different pleural pathologies. Therapeutic applications can be used to efficiently bring symptomatic relief of benign and malignant central airway obstruction by using a myriad of flexible and rigid bronchoscopy techniques. Airway stenting and ablative techniques such as laser, electrocautery, cryosurgery and microdebrider techniques are example of resources that can be used by interventional pulmonologists for therapeutic purposes. A number of effective therapies for the management of malignant pleural disease have been studied in recent years, including chemical pleurodesis and tunnelled pleural catheters, greatly adding to our understanding of which therapy to use in which patient. In addition, flexible bronchoscopy approaches to more common disease, such as asthma and chronic obstructive pulmonary disease are currently available or are being developed. This update aims to provide the internal medicine physician with a brief overview of some of the common clinical procedures performed by interventional pulmonary specialists and the current indications and evidence for their use.

Effect of interfaces on the melting of PEO confined in triblock PS-b-PEO-b-PS copolymers.

Block copolymers form nanostructures that have interesting physical properties because they combine, for a single compound, the complementary features brought by each block. However, in order to fully exploit these properties, the physical state of each kind of domain must be precisely controlled. In this work, triblock PS-b-PEO-b-PS copolymers consisting of a central poly(ethylene oxide) (PEO) block covalently bonded to polystyrene (PS) blocks were synthesized by Atom Transfer Radical Polymerization. Their morphology was investigated by X-ray scattering and TEM experiments whereas their thermodynamic behavior was characterized by DSC. A strong decrease of both the melting temperature and the degree of crystallinity of PEO, due to its confinement between the PS domains, was observed and analyzed with a modified Gibbs-Thomson equation, following the approaches used for fluids confined in porous media. The existence of an amorphous bound layer, a few nanometers thick, at the PEO/PS interface, that does not undergo any phase transition in the temperature range investigated, accounts for both the melting temperature depression and the decrease of crystallinity upon confinement. This interfacial layer may significantly affect the mechanical and transport properties of these block copolymers that find applications as solid polymer electrolytes in batteries for example. Moreover, the value obtained for the solid PEO/liquid PEO surface tension is lower than those previously published but is thermodynamically consistent with the surface tensions of polymers at the solid/vapor and liquid/vapor interfaces.

Sorting vector producer cells for high transgene expression increases retroviral titer.

Vector producer cells are derived from helper cell lines expressing viral proteins that have been transduced to express a transgene-carrying retroviral genome. Vector producing cells express two relevant forms of RNA in their cytoplasm: vector RNA (vRNA) that is packaged as the actual gene transfer agent, and messenger RNA (mRNA) from which transgene is translated. Two premises underlie this study: (1) vRNA is limiting for virus production and (2) mRNA is proportional to vRNA. Together, these premises predict that transgene expression in the vector producing cells will be predictive of the viral titer from those cells. In this case, sorting the vector producing cells for high transgene expression should select for more virus production in vector producing cell supernatants. This prediction was supported, with a greater than fivefold benefit in viral titer. This demonstrates a rapid and simple method by which to obtain significantly increased viral titers from the same vector producing cell preparation.

Chimeric immune receptors (CIRs) specific to JC virus for immunotherapy in progressive multifocal leukoencephalopathy (PML).

Progressive multifocal leukoencephalopathy (PML) is a deadly brain disease caused by the polyomavirus JC (JCV). The aim of this study is to develop 'designer T cells' armed with anti-JCV TCR-based chimeric immune receptors (CIRs) by gene modification for PML immunotherapy. Two T cell lines specific to two dominant CTL epitopes derived from JCV VP1 protein (termed p36 and p100) from an HLA-A0201+ PML survivor were generated for TCR cloning. Two distinct dominant TCR alpha chains (Valpha6 and Valpha12) and a unique TCR beta chain (Vbeta5.1) were cloned from the p36-specific cell line, while only one alpha (Valpha8.6) and one beta (Vbeta2) chains were dominant in the p100-specific line. Retroviral constructs encoding CIRs were created with the extracellular domains of TCR alpha and beta chains fused to the transmembrane and cytoplasmic portions of CD3zeta (ValphaCalphaCD3zeta or VbetaCbetaCD3zeta). Cellular expression and screening for binding specific peptide-HLA-A0201 tetramer confirmed the reactivity of the p100 TCRalphabeta and of one of the two pairs of p36 TCRalphabeta (Valpha12 and Vbeta5.1). Functional tests confirmed CIR-expressing T cells secreted cytokines and expressed potent cytotoxicity on contact with A0201+ B-lymphoblastoid line loaded with peptides and/or with HLA-A0201+ cells expressing native JCV VP1 protein. In conclusion, anti-JCV designer T cells were generated.

A Light Scattering Study of the Association of Hydrophobically alpha- and alpha,omega-End-capped Poly(ethylene oxide) in Water.

Several hydrophobically alpha- and alpha,omega-end-capped poly(ethylene oxide) polymers were studied by light scattering below and above their critical association concentration, in order to understand their association mechanisms. In the case of monofunctionalized PEO, a one-step closed association model well fits the experimental data, with a limit number of aggregation of about 30, consistent with other experimental data and a theoretical approach. In the case of difunctionalized PEO, a good description of the experimental data is obtained by assuming a two-step association process: at low concentration, the formation of "flower-like" micelles is well described by a closed association model, whereas at higher concentration, the progressive bridging of these "flowers" can be modeled by an open association. Copyright 2000 Academic Press.

[Alimentary anaphylactic shock: implication of penicillin residues]. / Choc anaphylactique alimentaire: implication des résidus de pénicilline.

The case of a 64 y.o. female is reported. She experienced formerly four anaphylactic shocks. Two shocks occurred after ingestion of pork and beef meat. Any food allergy to animal proteins was discarded. A high degree of sensitivity to penicillin G was proved by a positive prick test to penicillin G 1 Ul/ml, which induced a systemic reaction. RAST to penicillin G was class 4. The leucocyte histamine release test showed a high level of spontaneous histamine release. A double blind, placebo controlled, oral challenge with penicillin mixed to milk induced wheezing and a fall of blood pressure at the cumulative dose of 20 Ul. The hypothesis of food induced anaphylaxis, linked to penicillin residues in meats, is highly plausible. The significance of the phenomenon of spontaneous histamine release is discussed. It might point to frequent ingestions of hidden penicillin residues in the diet.

Cultivation of the life cycle stages of Trypanosoma brucei sspp.

A culture system was devised for the production of the various stages in the developmental cycle of Trypanosoma brucei brucei and T. b. rhodesiense. The bloodstream forms were grown at 37 degrees C on a feeder layer of fibroblasts from embryos of Microtus montanus or CD-1 mice in HEPES-buffered Minimum Essential Medium with Earle's salts, supplemented with 15% heat-inactivated rabbit serum. When they were transferred to HEPES-buffered Cunningham's medium and incubated at 27 degrees C, they transformed into procyclic trypomastigotes, some of which developed into epimastigote and metacyclic forms in the presence of explants of Glossina morsitans or Phormia regina. Stages infective to mice were produced in cultures of procyclic forms grown with Anopheles gambiae cells in medium consisting of a mixture of 3 volumes of Cunningham's medium and 1 volume of Anopheles cell medium. In vitro-produced metacyclic trypanosomes were used to initiate cultures of bloodstream forms.

Studies on the development of metacyclic Trypanosoma brucei sspp. cultivated at 27 degrees C with insect cell lines.

When transformed procyclic trypanosomes of three stocks of Trypanosoma brucei brucei and one stock of T.b. rhodesiense were grown at 27 degrees C in 25-cm2 flasks containing Anopheles gambiae cells, some of them developed into forms infective for mice. Infectivity titrations on trypanosome suspensions revealed that up to 2.8 X 10(5) metacyclic forms per ml could be produced, and the cultures remained infective for varying periods of up to 72 days when they were terminated. Of the various culture media tested, a mixture of three volumes of trypanosome medium and one volume of Anopheles medium was the most successful. Control cultures of trypanosomes grown in medium without cells were generally not infective, but two of the stocks gave rise to a few sporadic infections. Trypanosome populations could be subpassaged in the Anopheles cell cultures without loss of infectivity. Metacyclic forms separated from infective cultures by DEAE-cellulose columns had a surface coat.