A combined physicochemical approach towards human tenocyte phenotype maintenance.

During in vitro culture, bereft of their optimal tissue context, tenocytes lose their phenotype and function. Considering that tenocytes in their native tissue milieu are exposed simultaneously to manifold signals, combination approaches (e.g. growth factor supplementation and mechanical stimulation) are continuously gaining pace to control cell fate during in vitro expansion, albeit with limited success due to the literally infinite number of possible permutations. In this work, we assessed the potential of scalable and potent physicochemical approaches that control cell fate (substrate stiffness, anisotropic surface topography, collagen type I coating) and enhance extracellular matrix deposition (macromolecular crowding) in maintaining human tenocyte phenotype in culture. Cell morphology was primarily responsive to surface topography. The tissue culture plastic induced the largest nuclei area, the lowest aspect ratio, and the highest focal adhesion kinase. Collagen type I coating increased cell number and metabolic activity. Cell viability was not affected by any of the variables assessed. Macromolecular crowding intensely enhanced and accelerated native extracellular matrix deposition, albeit not in an aligned fashion, even on the grooved substrates. Gene analysis at day 14 revealed that the 130 kPa grooved substrate without collagen type I coating and under macromolecular crowding conditions positively regulated human tenocyte phenotype. Collectively, this work illustrates the beneficial effects of combined physicochemical approaches in controlling cell fate during in vitro expansion.

[Citohistologic and colposcopic correlation in perimenopausal women]. / Correlación histocitológica y colposcópica en pacientes en transición a la menopausia.

OBJECTIVE: This study was conducted to compare the correlation between the Pap smear and colposcopy findings in postmenopausal Mexican women. MATERIAL AND METHODS: Observational, Retroelective, longitudinal, descriptive study, all menopausal women who consulted for pap smears and colposcopy performed was studied. RESULTS: 119 patients were evaluated. 72 % of pap smears were negative to human papilloma virus, 29 (24%) had a low-grade lesion and 4 (4%) had a high-grade lesions. In the colposcopic study: 31 studies (26%) report low-grade intraepithelial lesion and 2 cases (2%) high-grade lesion. The histopathological biopsy reported one invasive cervical cancer (2.43%) and 20 cases of low-grade lesions (48.7%). cytology had a sensitivity of 85.3% and specificity of 56.09% with a false negative rate of 14.3%, a positive predictive value of 66.03 % and a negative predictive value of 79.31%. Colposcopy: sensitivity= 82.92%, specificity = 56.09% with a false negative rate of 17.07% positive predictive value of 65.38% and a negative predictive value of 76.66%. CONCLUSIONS: The correlation between Pap smear and colposcopy shows that the diagnosis of low and high grade lesions differs only by 2%, therefore indicates adequate sensitivity for diagnosis. In this population of women routine gynecological tests most be performed.

A Quality by design (QbD) approach on starch-based nanocapsules: A promising platform for topical drug delivery.

Exploring novel applications for approved excipients with a history of safe use in therapeutics is a smart strategy to obtain improved pharmaceutical products. The present study aimed at developing a novel starch-based nanoparticulate carrier system (StNC) for topical delivery of lipophilic bioactive molecules. The role of the different factors that affect the particle size distribution and zeta potential of StNC prepared by the emulsification-solvent evaporation method was assessed using a quality by design approach. An optimal formulation was selected and fully characterized in terms of molecular interactions (DSC and FTIR), morphology (TEM and AFM), as well as in vitro and in vivo biological properties, including biological sensitivity/irritation studies performed in human volunteers. Results show the surfactant and lipid contents play a major role in StNC particle size distribution. In addition, all tested formulations presented a zeta potential of ca. +33.6±6.7 mV, indicating a good physical stability, while revealing an excellent compromise between stability, safety and cosmeticity, evidencing that StNC are suitable nanocarriers for topical use. Finally, the design planning methodology has clearly shown its usefulness for optimizing the formulation, being also crucial for the understanding of StNC formation process. The StNC proved to be a promising formulation strategy and a potential nanocarrier for topical lipophilic bioactive molecules.

Reversible morphological changes of assembled supramolecular amphiphiles triggered by pH-modulated host-guest interactions.

Reversible template-directed micellar-size and shape modulation by virtue of host-guest reversible docking of molecular templates at the micellar-solvent interface was achieved in water. By combining a π-electron deficient bipyridinium-based gemini amphiphile which is capable of binding and aligning with a π-electron rich tri(ethylene glycol)-disubstituted 1,5-diaminonaphthalene, a switchable detergent system which operates through the pH-responsive formation of bisammonium dications was realised. The binding of the 1,5-diaminonaphthalene guest to the bipyridinium-based micellar aggregate superstructure can be actuated by the addition of acid and base. Upon the addition of acid, protonation of the guest forming the dication deactivates molecular recognition with the charged head groups of the micellar aggregate by Coulombic repulsion. This process is completely reversible upon the addition of base, whereby the guest reintercalates into the superstructure -again forming donor-acceptor π-π stacks at the micellar-solvent interface amongst contiguous surfactant head groups. Synchrotron small angle X-ray scattering and dynamic laser light scattering confirm that this form of reversible directionally-templated micellisation results in an oblate spheroid-to-lamellar micelle morphological transition with a stabilising net decrease in the free energy of micellisation of 1.4 kcal mol(-1) per hydrophobic tail.

Carpal tunnel and median nerve volume changes after tunnel release in patients with the carpal tunnel syndrome: a magnetic resonance imaging (MRI) study.

PURPOSE: Our aim was to study the dynamics of the post-surgical canal and nerve volumes and their relationships to objective [electromyoneurography (EMNG)] and subjective (pain) outcomes. METHODS: Forty-seven patients with carpal tunnel syndrome (CTS) (median age 52, range 23-75 years) with a prominent narrowing of the median nerve within the canal (observed during carpal tunnel release) were evaluated clinically using EMNG and magnetic resonance imagining (MRI) before and at 90 and 180 days post-surgery. RESULTS: Canal and nerve volumes increased, EMNG findings improved and pain resolved during the follow-up. Increase in tunnel volume was independently associated with increased nerve volume. A greater post-surgical nerve volume was independently associated with a more prominent resolution of pain, but not with the extent of EMNG improvement, whereas EMNG improvement was not associated with pain resolution. CONCLUSIONS: Data confirm that MRI can detect even modest changes in the carpal tunnel and median nerve volume and that tunnel release results in tunnel and nerve-volume increases that are paralleled by EMNG and clinical improvements. Taken together, these observations suggest that MRI could be used to objectivise persistent post-surgical difficulties in CTS patients. Level of evidence 3 (follow-up study).

The influence of fibril composition and dimension on the performance of paper gated oxide transistors.

Paper electronics is a topic of great interest due the possibility of having low-cost, disposable and recyclable electronic devices. The final goal is to make paper itself an active part of such devices. In this work we present new approaches in the selection of tailored paper, aiming to use it simultaneously as substrate and dielectric in oxide based paper field effect transistors (FETs). From the work performed, it was observed that the gate leakage current in paper FETs can be reduced using a dense microfiber/nanofiber cellulose paper as the dielectric. Also, the stability of these devices against changes in relative humidity is improved. On other hand, if the pH of the microfiber/nanofiber cellulose pulp is modified by the addition of HCl, the saturation mobility of the devices increases up to 16 cm(2) V(-1) s(-1), with an ION/IOFF ratio close to 10(5).

Nanocrystalline cellulose applied simultaneously as the gate dielectric and the substrate in flexible field effect transistors.

Cotton-based nanocrystalline cellulose (NCC), also known as nanopaper, one of the major sources of renewable materials, is a promising substrate and component for producing low cost fully recyclable flexible paper electronic devices and systems due to its properties (lightweight, stiffness, non-toxicity, transparency, low thermal expansion, gas impermeability and improved mechanical properties).Here, we have demonstrated for the first time a thin transparent nanopaper-based field effect transistor (FET) where NCC is simultaneously used as the substrate and as the gate dielectric layer in an 'interstrate' structure, since the device is built on both sides of the NCC films; while the active channel layer is based on oxide amorphous semiconductors, the gate electrode is based on a transparent conductive oxide.Such hybrid FETs present excellent operating characteristics such as high channel saturation mobility (>7 cm(2) V (-1) s(-1)), drain-source current on/off modulation ratio higher than 10(5), enhancement n-type operation and subthreshold gate voltage swing of 2.11 V/decade. The NCC film FET characteristics have been measured in air ambient conditions and present good stability, after two weeks of being processed, without any type of encapsulation or passivation layer. The results obtained are comparable to ones produced for conventional cellulose paper, marking this out as a promising approach for attaining high-performance disposable electronics such as paper displays, smart labels, smart packaging, RFID (radio-frequency identification) and point-of-care systems for self-analysis in bioscience applications, among others.

Influence of the layer thickness in plasmonic gold nanoparticles produced by thermal evaporation.

Metallic nanoparticles (NPs) have received recently considerable interest of photonic and photovoltaic communities. In this work, we report the optoelectronic properties of gold NPs (Au-NPs) obtained by depositing very thin gold layers on glass substrates through thermal evaporation electron-beam assisted process. The effect of mass thickness of the layer was evaluated. The polycrystalline Au-NPs, with grain sizes of 14 and 19 nm tend to be elongated in one direction as the mass thickness increase. A 2 nm layer deposited at 250°C led to the formation of Au-NPs with 10-20 nm average size, obtained by SEM images, while for a 5 nm layer the wide size elongates from 25 to 150 nm with a mean at 75 nm. In the near infrared region was observed an absorption enhancement of amorphous silicon films deposited onto the Au-NPs layers with a corresponding increase in the PL peak for the same wavelength region.

Preferential cell response to anisotropic electro-spun fibrous scaffolds under tension-free conditions.

Anisotropic alignment of collagen fibres in musculoskeletal tissues is responsible for the resistance to mechanical loading, whilst in cornea is responsible for transparency. Herein, we evaluated the response of tenocytes, osteoblasts and corneal fibroblasts to the topographies created through electro-spinning and solvent casting. We also evaluated the influence of topography on mechanical properties. At day 14, human osteoblasts seeded on aligned orientated electro-spun mats exhibited the lowest metabolic activity (P < 0.001). At day 5 and at day 7, no significant difference was observed in metabolic activity of human corneal fibroblasts and bovine tenocytes respectively seeded on different scaffold conformations (P > 0.05). Osteoblasts and corneal fibroblasts aligned parallel to the direction of the aligned orientated electro-spun mats, whilst tenocytes aligned perpendicular to the aligned orientated electro-spun mats. Mechanical evaluation demonstrated that aligned orientated electro-spun fibres exhibited significant higher stress at break values than their random aligned counterparts (P < 0.006) and random orientated electro-spun fibres exhibited significant higher strain at break values than the aligned orientated scaffolds (P < 0.006). While maintaining fibre structure, we also developed a co-deposition method of spraying and electro-spinning, which enables the incorporation of microspheres within the three-dimensional structure of the scaffold.

Screening of medicinal plants for antibacterial activities on Staphylococcus aureus strains isolated from bovine mastitis / Screening de plantas medicinais com atividade antimicrobiana contra cepas de Staphylococcus aureus isoladas de mastite bovina

Staphylococcus aureus is the main causative agent of bovine mastitis. The activity of several extracts from ten medicinal plants traditionally used in Brazil as antiseptic was investigated against fifteen strains of Staphylococcus aureus isolated from animals with mastitis manifestation by the disc diffusion method and broth microdilution assay. The interference of the extracts on cell in the form of adherent colonies was also evaluated. MIC values ranged from 0.5 mg/mL to 1.0 mg/mL and biofilm inhibitory concentration (BIC) were between 0.25 mg/mL and 0.8 mg/mL. Results revealed the potential of extracts of Senna macranthera, Artemisia absinthium, Cymbopogon nardus and Baccharis dracunculifolia as antibacterial agents against S. aureus strains isolated from bovine mastitis and support the possible use of these phytotherapic agents in the clinical management of the disease.

Staphylococcus aureus é o principal agente causador de mastite bovina. A atividade de diversos extratos de dez plantas medicinais tradicionalmente usadas no Brasil como anti-sépticas foi investigada contra quinze cepas de Staphylococcus aureus isoladas de animais com manifestação de mastite pelo método de difusão em ágar e ensaio de microdiluição. A interferência dos extratos na célula bacteriana em forma de colônias aderidas também foi avaliada. Os valores de MIC variaram de 0.5 mg/mL a 1.0 mg/mL e a concentração inibitória de biofilme (BIC) variou de 0.25 mg/mL a 0.8 mg/mL. Os resultados revelaram o potencial dos extratos de Senna macranthera, Artemisia absinthium, Cymbopogon nardus e Baccharis dracunculifolia como agentes antibacterianos contra cepas de S. aureus isolados de mastite bovina e suportam o possível uso destas plantas no manejo clínico da doença.

Application of surface chemical analysis tools for characterization of nanoparticles.

The important role that surface chemical analysis methods can and should play in the characterization of nanoparticles is described. The types of information that can be obtained from analysis of nanoparticles using Auger electron spectroscopy (AES), X-ray photoelectron spectroscopy (XPS), time-of-flight secondary-ion mass spectrometry (TOF-SIMS), low-energy ion scattering (LEIS), and scanning-probe microscopy (SPM), including scanning tunneling microscopy (STM) and atomic force microscopy (AFM), are briefly summarized. Examples describing the characterization of engineered nanoparticles are provided. Specific analysis considerations and issues associated with using surface-analysis methods for the characterization of nanoparticles are discussed and summarized, with the impact that shape instability, environmentally induced changes, deliberate and accidental coating, etc., have on nanoparticle properties.

Stabilization of high-order solutions of the cubic nonlinear Schrödinger equation.

In this paper we consider the stabilization of nonfundamental unstable stationary solutions of the cubic nonlinear Schrödinger equation. Specifically, we study the stabilization of radially symmetric solutions with nodes and asymmetric complex stationary solutions. For the first ones, we find partial stabilization similar to that recently found for vortex solutions while for the later ones stabilization does not seem possible.

Dieulafoy lesion: endoscopic and surgical management.

Dieulafoy lesion is characterized by exteriorization of a large pulsatile arterial vessel through a minimal mucosal tear surrounded by normal mucosa, causing massive and recurrent upper digestive bleeding in previously healthy patients. More frequently presented than diagnosed, with the increase of its knowledge among endoscopists, a large number of cases are expected in the literature. Data from patients with upper gastrointestinal bleeding submitted to endoscopy at the Federal University of São Paulo, Gastrointestinal Endoscopy Unit from 1991 through 2002 were reviewed for Dieulafoy lesion. We found 15 patients with typical Dieulafoy gastric lesion. Their ages ranged from 18 to 78 years (mean age 49.9); 5 patients were female and 10 were male. Bleeding presented as hematemesis and melena in 7 cases (46.6%), hematemesis alone in 4 cases (26.6%), and melena alone in the other 4 cases (26.6%). Initial hemostatic approaches employed were: alcoholization (2 cases), epinephrine associated with alcohol injection (5 cases), sclerosis in 7 cases and surgery in 1 case. Dieulafoy lesion is a distinct nosologic entity that must be suspected in patients with massive digestive bleeding. Endoscopy became the procedure of choice for diagnosis and treatment of this disease.

n-body dynamics of stabilized vector solitons.

In this work we study the interactions between stabilized Townes solitons. By means of effective Lagrangian methods, we have found that the interactions between these solitons are governed by central forces, in a first approximation. In our numerical simulations we describe different types of orbits, deflections, trapping, and soliton splitting. Splitting phenomena are also described by finite-dimensional reduced models. All these effects could be used for potential applications of stabilized solitons.

Stabilized vortices in layered Kerr media.

In this paper, we demonstrate the possibility of stabilizing beams with angular momentum propagating in Kerr media against filamentation and collapse. Very long propagation distances can be achieved by combining the choice of an appropriate layered medium with alternating focusing and defocusing nonlinearities with the presence of an incoherent guiding beam which is itself stabilized in this medium. The applicability of the results to the field of matter waves is also discussed.

Stabilized two-dimensional vector solitons.

In this Letter, we introduce the concept of stabilized vector solitons as nonlinear waves constructed by the addition of mutually incoherent fractions of Townes solitons that are stabilized under the effect of a periodic modulation of the nonlinearity. We analyze the stability of these new kinds of structures and describe their behavior and formation in Manakov-like interactions. Potential applications of our results in Bose-Einstein condensation and nonlinear optics are also discussed.

Evidence that BCL3 plays a role in the etiology of nonsyndromic oral clefts in Brazilian families.

The BCL3 gene has been considered a susceptibility locus for nonsyndromic cleft lip with or without cleft palate (NSCL/P), based on association and linkage studies in some populations. We evaluated an intragenic marker at the BCL3 gene and the microsatellite D19S178 (1.1 cM distant from the BCL3 gene) among 98 infants born with NSCL/P and their parents, using the transmission disequilibrium test (TDT) and a method for haplotype analysis. Our analysis, based on BCL3 alleles, revealed the existence of a marginal association of allele 135pb of the BCL3 gene with NSCL/P (chi(2)=3.60; P=0.058; 1 df), with a major effect in female (chi(2)=5.77; P=0.016; 1 df) and in familial cases (chi(2)=3.79; P=0.051; 1 df). However, the haplotype analysis detected no significant segregation distortion, even if the alleles of the D19S178 were grouped into two classes. These findings support previous findings that BCL3 plays a role in the etiology of NSCL/P as an allele of low penetrance or as a modifier locus. We hypothesize that there might be more than one mutation in this gene associated with NSCL/P, or alternatively, that more than one mutation has arisen associated with the 135-bp allele. Genet. Epidemiol. 23:364-374, 2002

Answering funding preferences for medical school graduates in underserved areas.

We describe here a feasible and data-based approach for obtaining important information about the percentage of our medical school graduates who primarily provide health care to the medically underserved. The logic and data used in our methodology have been acceptable to funding agencies. After making the initial investment in developing this approach, we can execute it at low cost to respond to relevant inquiries about the practice activities of our graduates. Other programs that can produce a computerized listing of post-residency graduates' practice locations can follow the procedure outlined above to demonstrate qualification for funding preferences.