Survey of selected pathogens in free-ranging pinnipeds in Uruguay.

Marine mammals, regarded as sentinels of aquatic ecosystem health, are exposed to different pathogens and parasites under natural conditions. We surveyed live South American fur seals Arctocephalus australis and South American sea lions Otaria flavescens in Uruguay for Leptospira spp., canine distemper virus (CDV), Mycobacterium spp., Toxoplasma gondii, and Neospora caninum. Samples were collected from 2007 to 2013. The seroprevalence of Leptospira spp. was 37.6% positive, 50.9% negative, and 11.5% suspect for A. australis (n = 61) while for O. flavescens (n = 12) it was 67% positive, 25% negative, and 8% suspect. CDV RNA was not detected in any of the analyzed samples. Most animals tested seropositive to tuberculosis antigens by WiZo ELISA (A. australis: 29/30; O. flavescens: 20/20); reactivity varied with a novel ELISA test (antigens MPB70, MPB83, ESAT6 and MPB59). Seroprevalence against N. caninum and T. gondii was 6.7 and 13.3% positive for O. flavescens and 0 and 2.2% positive for A. australis respectively. To evaluate possible sources of infection for pinnipeds, wild rats Rattus rattus and semi-feral cats Felis catus were also tested for Leptospira spp. and T. gondii respectively. Water samples tested for Leptospira revealed saprofitic L. bioflexa. Pathogenic Leptospira were detected in the kidneys of 2 rats, and cats tested positive for T. gondii (100%). These results represent a substantial contribution to the study of the health status of wild pinnipeds in Uruguay.

Morphometrical and molecular evidence suggests cryptic diversity among hookworms (Nematoda: Uncinaria) that parasitize pinnipeds from the south-eastern Pacific coasts.

Hookworms of the genus Uncinaria parasitize pinniped pups in various locations worldwide. Four species have been described, two of which parasitize pinniped pups in the southern hemisphere: Uncinaria hamiltoni parasitizes Otaria flavescens and Arctocephalus australis from the South American coast, and Uncinaria sanguinis parasitizes Neophoca cinerea from the Australian coast. However, their geographical ranges and host specificity are unknown. Uncinaria spp. are morphologically similar, but molecular analyses have allowed the recognition of new species in the genus Uncinaria. We used nuclear genetic markers (internal transcribed spacer (ITS) and large subunit (LSU) rDNA) and a mitochondrial genetic marker (cytochrome c oxidase subunit I (COI)) to evaluate the phylogenetic relationships of Uncinaria spp. parasitizing A. australis and O. flavescens from South American coasts (Atlantic and Pacific coasts). We compared our sequences with published Uncinaria sequences. A Generalized Mixed Yule Coalescent (GMYC) analysis was also used to delimit species, and principal component analysis was used to compare morphometry among Uncinaria specimens. Parasites were sampled from A. australis from Peru (12°S), southern Chile (42°S), and the Uruguayan coast, and from O. flavescens from northern Chile (24°S) and the Uruguayan coast. Morphometric differences were observed between Uncinaria specimens from both South American coasts and between Uncinaria specimens from A. australis in Peru and southern Chile. Phylogenetic and GMYC analyses suggest that south-eastern Pacific otariid species harbour U. hamiltoni and an undescribed putative species of Uncinaria. However, more samples from A. australis and O. flavescens are necessary to understand the phylogenetic patterns of Uncinaria spp. across the South Pacific.

Increased carrier mobility in end-functionalized oligosilanes.

We show that a class of oligosilane-arene σ, π-hybrid materials exhibits distinct and enhanced solid-state electronic properties relative to its parent components. In the single crystal structure, the σ-conjugation axis of one molecule points towards the π-face of a neighboring molecule due to an unusual gauche conformation. This organization is hypothesized to be beneficial for charge transport. We show that solution-deposited crystalline films of the hybrid materials show up to a 100-fold increase in space-charge limited current (SCLC) mobility relative to literature reports of photoinduced hole transport in oligosilane films. The discovery that σ, π-hybrids are more than the sum of their parts offers a design opportunity for new materials.

Urocanic acid suppresses induction of immunity in human skin.

BACKGROUND/PURPOSE: Trans-urocanic acid is isomerized to cis-urocanic acid (C-UCA) by ultraviolet radiation. C-UCA suppresses immunity in vitro and in vivo in animals; its effect on human skin is unknown. We sought to determine whether its topical application to normal skin suppresses induction of immunity to dinitrochlorobenzene (DNCB). METHODS: Forty subjects applied C-UCA (0%, 0.02%, 0.2%, or 2%) for 17 days. A 40-mcg dose of DNCB was then applied to induce immunity. Subjects were challenged for immunity at 6-week follow-up by occluding doses of DNCB (0, 3.125, 6.25, or 12.5 mcg) on untreated normal skin. Induced immunity was measured by area of erythema and induration 2 and 4 days postchallenge. RESULTS: No significant differences were found in incidence of sensitization by C-UCA concentration (P=.59). DNCB sensitization developed in all 10 subjects induced through 0% C-UCA (placebo); only 23 of 30 patients were sensitized through skin treated with C-UCA. Mean areas of erythema and induration induced through C-UCA-treated skin were less than those in controls (P < 0.05). The number of Langerhans cells in C-UCA-treated skin was unaffected. Laboratory tests of immune function and lymphocyte numbers were unchanged. CONCLUSION: Topically applied C-UCA blunts normal induction responses to a cutaneous sensitizer.

Promising thermoelectric properties of commercial PEDOT:PSS materials and their bi2Te3 powder composites.

Newly commercialized PEDOT:PSS products CLEVIOS PH1000 and FE-T, among the most conducting of polymers, show unexpectedly higher Seebeck coefficients than older CLEVIOS P products that were studied by other groups in the past, leading to promising thermoelectric (TE) power factors around 47 µW/m K(2) and 30 µW/m K(2) respectively. By incorporating both n and p type Bi(2)Te(3) ball milled powders into these PEDOT:PSS products, power factor enhancements for both p and n polymer composite materials are achieved. The contact resistance between Bi(2)Te(3) and PEDOT is identified as the limiting factor for further TE property improvement. These composites can be used for all-solution-processed TE devices on flexible substrates as a new fabrication option.

Topical corticosteroids in psoriasis: strategies for improving safety.

Corticosteroids are a mainstay of topical therapy for psoriasis. While efficacious and relatively safe when used carefully, the potential for side effects, notably skin atrophy and adrenal suppression, have been associated with excesses in potency, prolonged or widespread use. The International Psoriasis Council Working Group on Topical Therapy has reviewed the efficacy and safety of topical corticosteroids and recommends strategies for safe, long-term use of these agents.

Histomorphology of prepuberal ovaries in the South American fur seal (Arctocephalus australis Zimmerman, 1783).

The South American fur seal reproductive histophysiology is scarcely described. This study provides a histological description of prepuberal South American fur seal (Arctocephalus australis) ovaries as well as three-dimensional reconstructions of subcapsular crypts and primordial follicles. Ovaries from fresh dead animals were processed for histology and sliced into serial sections. A portion of the superficial cortex was photographed, and the images were processed using BioVis3d software in order to generate 3-dimensional reconstructions. A. australis prepuberal ovaries conform to the basic structure of pinnipedian species, with a subcapsular crypts system made up of interconnecting cisternae and tubules with multiple openings to the surface. Generally, the primordial follicles were arranged in a monolayer beneath the tunica albuginea and were closely associated with subcapsular crypts. The large number of interstitial cells distributed throughout the cortex was the main histological feature in comparison with previous reports in other seals. Three-dimensional reconstructions modelled the subcapsular crypts microarchitecture and showed the close spatial relationship between the crypts and the primordial follicles. Despite the fact that the general ovarian histological structure was similar to that of other pinnipeds, the large number of interstitial cells is a distinctive feature that raises the question about the origin and function in A. australis with regard to the steroidogenic activity reported in other seal species.

Tunability of mobility and conductivity over large ranges in poly(3,3'''-didodecylquaterthiophene)/insulating polymer composites.

Semiconducting polymers are currently being considered as active layers in field-effect transistors, in which high charge carrier mobility and low off conductivity are important. For other applications, such as certain spintronic mechanisms, the opposite characteristics are desirable. Blending such polymers with insulating polymers would be expected to lower the mobility. In this paper, we report that the use of hydrocarbon polymers such as polystyrene as insulators generally raises the mobility when the semiconducting polymer is poly(bisdodecylquaterthiophene). A high mobility value of nearly 0.1 cm(2)/V.s was obtained for an optimal blend. While this is counterintuitive, it is consistent with a few other recent reports. In order to lower the mobility significantly, a much more polar and irregular blending agent is needed. The further addition of tetrafluorotetracyanoquinodimethane as a dopant gave a rare low mobility/high conductivity combination of properties, with a charge carrier density on the order of 10(19) cm(-3). Thus, mobility and conductivity were tuned somewhat independently over 3 and 4 orders of magnitude, respectively.

Histology of lamb epididymal development.

To describe the distribution of the histological regions and their morphometry during epididymal development, 10 Corriedale lambs were castrated monthly from 90 to 180 days of age (n = 24), and their testes and epididymides were weighed. All animals were weighed monthly. Epididymides were divided into caput, corpus and cauda, and cut sagitally so that sections included all the length of the organ. The diameter of the epididymal duct, the smooth muscle depth and the epididymal epithelium height were measured. The quantitative histology of the ovine epididymal development was described. Epididymal development advanced from caput to cauda. The distribution of the histological regions varied according to epididymal weight. Transient histological regions were found during epididymal development. The present results indicate a new way of epididymal development in sheep, which courses from caput to cauda with transient histological regions appearing, varying in location and disappearing during ovine epididymis development.

Results of a randomized, double-blind, vehicle-controlled efficacy trial of pimecrolimus cream 1% for the treatment of moderate to severe facial seborrheic dermatitis.

BACKGROUND: Seborrheic dermatitis is commonly treated with anti-inflammatory products, including topical corticosteroids. Pimecrolimus cream 1% also exerts anti-inflammatory activity by inhibiting T-cell cytokine production. OBJECTIVE: We sought to compare the efficacy and safety of twice-daily pimecrolimus for treatment of moderate to severe facial seborrheic dermatitis. METHODS: This double-blind, vehicle-controlled, 4-week trial randomized patients with seborrheic dermatitis to pimecrolimus or vehicle (1:1). Clinical assessments (erythema [0-3] and scaling [0-3] combined for a total area score [0-6]) were performed at weeks 0, 2, and 4. Inclusion criteria included total area score 4 or greater and erythema 2 or greater. The prespecified primary variable, change from baseline in total area score at week 4, was analyzed using a two-sample t test for intent-to-treat and per protocol populations. RESULTS: In all, 96 adults of mean age 59.6 years, 88.5% male, were randomized (n = 47 pimecrolimus; 49 vehicle). At week 4, the mean change from baseline in total area score was 3.7 versus 3.3 for pimecrolimus and vehicle groups, respectively (intent-to-treat: P = .1913; 95% confidence interval (CI) for difference [-0.195, 0.961]). Per protocol analysis (n = 41 pimecrolimus; 46 vehicle) indicated a significant difference between groups (mean change 3.9 pimecrolimus vs 3.2 vehicle; P = .0156; CI [0.129, 1.197]). The superiority of pimecrolimus was observed as early as week 2 (intent-to-treat: P = .0062; CI [0.132, 0.777]; per protocol: P = .0012; CI [0.410, 1.593]). No drug-related serious adverse events occurred. The most frequent drug-related adverse events were local, mild, and transient (pimecrolimus = 26%; vehicle = 12%). LIMITATIONS: Generalizability is limited by the elderly male study population. CONCLUSION: This study suggests that pimecrolimus cream 1% is an effective and well-tolerated treatment for moderate to severe facial seborrheic dermatitis.

Characterization of the molecular parameters determining charge transport in anthradithiophene.

The molecular parameters that govern charge transport in anthradithiophene (ADT) are studied by a joint experimental/theoretical approach involving high-resolution gas-phase photoelectron spectroscopy and quantum-mechanical methods. The hole reorganization energy of ADT has been determined by an analysis of the vibrational structure of the lowest ionization band in the gas-phase photoelectron spectrum as well as by density-functional theory calculations. In addition, various dimers and clusters of ADT molecules have been considered in order to understand the effect of molecular packing on the hole and electron intermolecular transfer integrals. The results indicate that the intrinsic electronic structure, the relevant intramolecular vibrational modes, and the intermolecular interactions in ADT are very similar to those in pentacene.

Oral antifungal drug interactions: a mechanistic approach to understanding their cause.

Oral antifungal drugs are generally regarded as effective and safe when used according to their manufacturer's recommendation. However, when an oral antifungal agent is administered with certain interacting agents or classes of drugs, rare severe iatrogenic adverse experiences including death may occur. This article alerts and demystifies some of the clinically significant oral antifungal drug interactions by exploring their underlying pharmacological basis.

Ciclopirox gel for seborrheic dermatitis of the scalp.

BACKGROUND: Seborrheic dermatitis is a common inflammatory skin disorder that usually occurs in patients with pre-existing seborrhea. The etiology of seborrheic dermatitis is uncertain. Typically, sites dense with sebaceous glands support growth of the lipophilic yeast Malassezia furfur. Ciclopirox (Loprox) gel is a hydroxypyridone, broad-spectrum antifungal agent proven effective against the yeast M. furfur. OBJECTIVE: A multicenter, randomized, double-blind, vehicle controlled study of 178 subjects evaluated the efficacy of ciclopirox gel in treating seborrheic dermatitis of the scalp. METHODS: One hundred and seventy-eight subjects were randomized to apply either ciclopirox gel 0.77% twice daily, or vehicle twice daily for 28 days. Subjects' signs and symptoms of severity (erythema, scaling, pruritus and burning) were rated on a scale of 0-3 (none to severe); for inclusion, a minimum score of 4, for the sum of the individual ratings was required. Efficacy evaluations were performed at baseline, days 4, 8, 15, 22, 29, and at end-point (final visit, up to day 33). The primary efficacy variable was clinical response assessed by a global improvement, based on a scale of 0-5 (100% clearance to flare of treatment area). Changes in signs/symptoms severity scores within the target lesion were also evaluated. RESULTS: Global evaluation scores demonstrated that significantly more ciclopirox-treated subjects achieved over 75% improvement compared with vehicle at days 22, 29, and endpoint (P < 0.01). Change-from-baseline mean score for total signs and symptoms was significantly greater in ciclopirox subjects compared with vehicle subjects at the same time points as above (P < 0.001), as well as day 15 (P < 0.01). Twenty-nine percent of subjects rated ciclopirox as having excellent cosmetic acceptability. There were only mild adverse events, with the most common being burning sensation in 13% of ciclopirox subjects and 9% of vehicle subjects. CONCLUSION: Ciclopirox gel is effective and safe in the treatment of seborrheic dermatitis of the scalp.

Late partial dislocation of a laser in situ keratomileusis flap.

We report an apparently atraumatic asymptomatic flap dislocation 4 months after uneventful laser in situ keratomileusis (LASIK) in the right eye of a 43-year-old woman. The patient developed partial dislocation of the LASIK flap during the week after the 4 month examination. The LASIK flap was subsequently lifted to perform an enhancement, and the postenhancement course has been unremarkable. This case illustrates the potential susceptibility of LASIK flaps to dislocation either spontaneously or, more likely, after presumed minor trauma as late as 4 months after the original procedure.

Increased severity of local and systemic anaphylactic reactions in gp49B1-deficient mice.

gp49B1 is an immunoglobulin (Ig) superfamily member that inhibits FcstraightepsilonRI-induced mast cell activation when the two receptors are coligated with antibodies in vitro. The critical question of in vivo function of gp49B1 is now addressed in gene-disrupted mice. gp49B1-deficient mice exhibited a significantly increased sensitivity to IgE-dependent passive cutaneous anaphylaxis as assessed by greater tissue swelling and mast cell degranulation in situ. Importantly, by the same criteria, the absence of gp49B1 also resulted in a lower threshold for antigen challenge in active cutaneous anaphylaxis, in which the antigen-specific antibody levels were comparable in gp49B1-deficient and sufficient mice. Moreover, the absence of gp49B1 resulted in a significantly greater and faster death rate in active systemic anaphylaxis. These results indicate that gp49B1 innately dampens adaptive immediate hypersensitivity responses by suppressing mast cell activation in vivo. In addition, this study provides a new concept and target for regulation of allergic disease susceptibility and severity.

Synthetic chemistry for ultrapure, processable, and high-mobility organic transistor semiconductors.

An essential aspect of the development of organic-based electronics is the synthetic chemistry devised for the preparation of the semiconductor materials responsible for the activity of organic field-effect transistors. Access to organic semiconductors in sufficient purity and variety has led to breakthroughs in solid-state physics and circuit realization. In this Account, we review the synthetic methods that have been most useful for preparing a range of semiconductors, including thiophene-based oligomers, several kinds of fused rings, and polymers. The tradeoff between process efficiency and target purity is emphasized.

Treatment of male infertility due to spinal cord injury using rectal probe electroejaculation: the Israeli experience.

STUDY DESIGN: Male infertility caused by anejaculation is common among patients with spinal cord injury (SCIP). The fertility options for SCIP have improved impressively over the past 10 years. We present the Israeli experience in the treatment of infertility in a large series of SCIP. The issues which are addressed include the treatment of ejaculatory dysfunction, seminal quality and fertility management in SCIP. SETTING: Sexual rehabilitation clinic, Neuro-Rehabilitation department, Sheba Medical Center, Israel. METHODS: Between June 1992 and May 1998, a total of 84 consecutive SCIP were treated in our clinic with electro-ejaculation (EEJ), representing a sample of the SCIP population, composed mostly of young men traumatically injured. The patients have sustained different levels and completeness of spinal injury. Among the patients 33 were interested in achieving pregnancy (39.3%), while the rest were interested in determining fertility potential for family. With EEJ, a low-current stimulation of the ejaculatory organs via a rectal probe is done. The collected semen is used for fertility determination or for fertilization. RESULTS: Eighty-four patients were treated by EEJ. Mean age was 31.3 and mean age at injury was 21.7. There were 29 cervical, 50 thoracic and five lumbar lesions. Sixty-three had complete injury (ASIA A) and 21 incomplete (ASIA B -15, ASIC C -5, ASIA D -1). Fifty-nine had upper motor neuron lesions, and 25 had lower motor neuron. A total of 355 stimulations were performed. Ejaculate was obtained in all patients in 350 stimulations (98.6%), and sperm was present in 74 patients (88.1%) in 296 of the stimulations (83.4%). Fairly good numbers of spermatozoa were obtained, whereas sperm motility and morphology of spermatozoa were low in most cases. A significant difference in sperm count, motility and morphology was noted between antegrade and retrograde samples. No significant improvement in sperm quality after four repeated consecutive stimulations was noted in 38 SCIP. Side effects were minor and encountered in 16 patients (19.1%). Out of 33 couples who wished to achieve pregnancy, 26 reached the stage of insemination. Four pregnancies were achieved after 33 cycles of In-Uterine-Insemination (pregnancy rate 28.6% per couple), and 15 after 68 cycles of In-Vitro-Fertilization (micromanipulation) (pregnancy rate of 68.75% per couple). In all, of 101 conception attempts 23 were successful, resulting in pregnancies in 18 couples, and accounting for an overall pregnancy rate of 70% per couple. CONCLUSION: The high percentage of pregnancies imply that, despite the typically poor sperm motility noted in EEJ, rectal probe EEJ combined with assisted reproductive techniques, and performed by a team approach, is an efficient and safe technique for treating infertility among SCIP.

gp49B1-alpha(v)beta3 interaction inhibits antigen-induced mast cell activation.

We have identified the integrin alpha(v)beta3 as a ligand for mouse gp49B1, thus identifying a new class of ligand for a member of the family of inhibitory immunoreceptors that bear C2-type immunoglobulin-like domains. The specific interaction was shown by both cell-protein and cell-cell binding assays. In addition, we found that the interaction of alpha(v)beta3 with gp49B1 on bone marrow-derived mouse mast cells inhibited antigen-induced immunoglobulin E-mediated cell activation. Because neither gp49B1 nor alpha(v)beta3 exhibit substantive allelic variation, their newly appreciated interaction may reflect an innate pathway for down-regulating the activity of mast cells.

Paper-like electronic displays: large-area rubber-stamped plastic sheets of electronics and microencapsulated electrophoretic inks.

Electronic systems that use rugged lightweight plastics potentially offer attractive characteristics (low-cost processing, mechanical flexibility, large area coverage, etc.) that are not easily achieved with established silicon technologies. This paper summarizes work that demonstrates many of these characteristics in a realistic system: organic active matrix backplane circuits (256 transistors) for large ( approximately 5 x 5-inch) mechanically flexible sheets of electronic paper, an emerging type of display. The success of this effort relies on new or improved processing techniques and materials for plastic electronics, including methods for (i) rubber stamping (microcontact printing) high-resolution ( approximately 1 microm) circuits with low levels of defects and good registration over large areas, (ii) achieving low leakage with thin dielectrics deposited onto surfaces with relief, (iii) constructing high-performance organic transistors with bottom contact geometries, (iv) encapsulating these transistors, (v) depositing, in a repeatable way, organic semiconductors with uniform electrical characteristics over large areas, and (vi) low-temperature ( approximately 100 degrees C) annealing to increase the on/off ratios of the transistors and to improve the uniformity of their characteristics. The sophistication and flexibility of the patterning procedures, high level of integration on plastic substrates, large area coverage, and good performance of the transistors are all important features of this work. We successfully integrate these circuits with microencapsulated electrophoretic "inks" to form sheets of electronic paper.