Hyaluronan biofilms reinforced with partially deacetylated chitin nanowhiskers: Extraction, fabrication, in-vitro and antibacterial properties of advanced nanocomposites.

Fabrication of nanocomposite biofilms with enhanced mechanical and antibacterial properties was successfully achieved from hyaluronan (HA) and partially deacetylated chitin nanowhiskers (ChNWs) by a casting-evaporation method. The hydrolysis process of chitin showed an important role in the dimensions, stability, and the crystallinity of extracted ChNWs in a time-dependent manner. The volume fraction of ChNWs nanofiller varying from (0.001 to 0.5) exhibited a great influence on the mechanical properties of the biofilms (young modulus, strength) was enhanced by the high load-bearing capacity of NWs compared with net HA film. The antibacterial activity of the nanocomposite biofilms exhibited significant bactericidal activity against different types of bacteria (-/+ gram). HA/ChNWs Nanocomposite biofilms did not show any toxicity against normal human dermal fibroblasts (NHDF) and human primary osteogenic sarcoma (Saos-2) cell lines. The new biofilms with unique properties like edibleness, environmental friendliness, high mechanical properties, antibacterial performance, and non-cytotoxicity that could be used in skin tissue regenerations, and drug delivery applications.

Soft and flexible poly(ethylene glycol) nanotubes for local drug delivery.

Nanotubes are emerging as promising materials for healthcare applications but the selection of clinically relevant starting materials for their synthesis remains largely unexplored. Here we present, for the first time, the synthesis of poly(ethylene glycol) (PEG) based nanotubes via the photopolymerization of poly(ethylene glycol) diacrylate and other diacrylate derivatives within the pores of anodized aluminum oxide templates. Template-assisted synthesis allowed the manufacture of a diverse set of polymeric nanotubes with tunable physical characteristics including diameter (∼200-400 nm) and stiffness (405-902 kPa). PEG nanotubes were subjected to cytotoxicty assessment in cell lines and primary stem cells and showed excellent cytocompatability (IC50 > 120 µg ml-1). Nanotubes were readily drug loaded but released the majority of the drug over 5 days. Direct administration of drug loaded nanotubes to human orthotopic breast tumors substantially reduced tumor growth and metastasis and outperformed i.v. administration at the equivalent dose. Overall, this nanotube templating platform is emerging as a facile route for the manufacture of poly(ethylene glycol) nanotubes.

Polymer dynamics under cylindrical confinement featuring a locally repulsive surface: A quasielastic neutron scattering study.

We investigated the effect of intermediate cylindrical confinement with locally repulsive walls on the segmental and entanglement dynamics of a polymer melt by quasielastic neutron scattering. As a reference, the corresponding polymer melt was measured under identical conditions. The locally repulsive confinement was realized by hydrophilic anodic alumina nanopores with a diameter of 20 nm. The end-to-end distance of the hydrophobic infiltrated polyethylene-alt-propylene was close to this diameter. In the case of hard wall repulsion with negligible local attraction, several simulations predicted an acceleration of segmental dynamics close to the wall. Other than in attractive or neutral systems, where the segmental dynamics is slowed down, we found that the segmental dynamics in the nanopores is identical to the local mobility in the bulk. Even under very careful scrutiny, we could not find any acceleration of the surface-near segmental motion. On the larger time scale, the neutron spin-echo experiment showed that the Rouse relaxation was not altered by confinement effects. Also the entanglement dynamics was not affected. Thus at moderate confinement conditions, facilitated by locally repulsive walls, the dynamics remains as in the bulk melt, a result that is not so clear from simulations.

Pharmaceutical nanocrystals confined in porous host systems--interfacial effects and amorphous interphases.

DSC and NMR results prove the existence of an amorphous acetaminophen nanolayer between acetaminophen nanocrystals (form I and form III) and pore walls in controlled porous glasses. This nanolayer controls the surface energy. This finding is highly relevant for approaches towards crystal engineering in nanopores and indicates similarities to the situation during the early stages of crystallization in polymorphic bulk samples.

Size-dependent growth of polymorphs in nanopores and Ostwald's step rule of stages.

More than 100 years after Ostwald postulated his step rule of stages, predictive understanding as to early crystallization stages of polymorphic materials is still premature. We studied crystallization of the polymorphic pharmaceutical acetaminophen in nanoporous glasses as a model for early stages of bulk crystallization since the surface energy significantly contributes to the total Gibbs free energy of nanosized crystals in both cases. Systematic studies of transitions between different polymorphs inside nanoporous glasses show that the thermodynamic stability of the polymorphs depends on the crystal size. Accordingly, the transient occurrence of different polymorphs during crystal growth in bulk systems can be related to surface energy contributions to the total Gibbs free energy of the developing crystals. In nanosized early-stage crystals with high surface-to-volume ratios other polymorphs may be stable than in large crystals with low surface-to-volume ratios. Improved control of the crystallization of polymorphic materials by imposing well-defined confinement is a promising strategy to tailor release of polymorphic drugs and to optimize optical, electronic, magnetic and ferroelectric properties of polymorphic materials.

Three-dimensional to two-dimensional crossover in the hydrodynamic interactions between micron-scale rods.

Moving micron-scale objects are strongly coupled to each other by hydrodynamic interactions. The strength of this coupling decays with the inverse particle separation when the two objects are sufficiently far apart. It has been recently demonstrated that the reduced dimensionality of a thin fluid layer gives rise to longer-ranged, logarithmic coupling. Using holographic tweezers we show that microrods display both behaviors interacting like point particles in three dimensions at large distances and like point particles in two dimensions for distances shorter then their length. We derive a simple analytical expression that fits our data remarkably well and further validate it with finite element analysis.

Calibration of optically trapped nanotools.

Holographically trapped nanotools can be used in a novel form of force microscopy. By measuring the displacement of the tool in the optical traps, the contact force experienced by the probe can be inferred. In the following paper we experimentally demonstrate the calibration of such a device and show that its behaviour is independent of small changes in the relative position of the optical traps. Furthermore, we explore more general aspects of the thermal motion of the tool.

Anisotropic propagation and confinement of high frequency phonons in nanocomposites.

We show that self-ordered anodic aluminum oxide containing hexagonal arrays of cylindrical nanopores with submicron periodicity is a versatile model system for the exploration of rich phononic phenomena at gigahertz frequencies, which are intimately linked to fluids located in the nanopores and their interactions with the pore walls. Using high-resolution Brillouin spectroscopy we report the first realization of directional flow of elastic energy parallel and perpendicular to the pore axes, phonon localization, and tunability of the phononic band structure.

Manipulating the crystalline state of pharmaceuticals by nanoconfinement.

We show that nanoconfinement is a handle to rationally produce and stabilize otherwise metastable or transient polymorphs of pharmaceuticals, as required for controllable and efficient drug delivery. The systematic investigation of crystallization under confinement unveils thermodynamic properties of metastable polymorphs not accessible otherwise and may enhance the understanding of the crystallization behavior of pharmaceuticals in general. As an example in this case, we studied acetaminophen confined to inexpensive and biocompatible nanoporous host systems. Calorimetric and X-ray scattering data clearly evidence that either the stable polymorph form I or the metastable polymorph form III can be stabilized in high yields. Thermodynamic parameters for form III of acetaminophen are reported, and strategies to manipulate the crystalline state in pores by thermal treatments are presented.

SAXS investigation on aggregation phenomena in supercritical CO2.

Synchrotron Small-Angle X-Ray scattering (SAXS) measurements on aggregate formation of a Polyvinyl acetate- b-Perfluoro octyl acrylate (PVAc- b-PFOA) block copolymer in supercritical CO(2) are here reported. Experiments were carried out for a series of different thermodynamic conditions, changing the solvent density by profiling both the pressure at constant temperature and the temperature at constant pressure. This block copolymer and in general fluorocarbon-hydrocarbon di-blocks form aggregates depending on the value of CO(2) density. A sharp transition between monomers dissolved as random coils and micelles characterized by a solvophilic shell and a solvophobic core occurs when the CO(2) density reaches a critical value. Results of critical micellization density (CMD) derived from pressure and temperature ramps experiment along with the comparison with previous SANS results are here reported to give additional experimental support to the solvent density-driven aggregation process.

Irritable bowel syndrome. How to relieve symptoms enough to improve daily function.

Irritable bowel syndrome is a symptom complex that appears to have multiple causes. In those patients with diagnosable psychiatric illness, treating the psychiatric illness often leads to considerable improvement of the symptoms of irritable bowel syndrome. For almost all symptomatic patients, a caring, thoughtful physician can be very therapeutic by educating the patient, being supportive, offering realistic reassurance and adequate time, and prescribing a minimum of medication judiciously. As in many areas of medicine, a physician can succeed in "taking the hurt out of the pain," thereby vastly improving the patient's quality of life.

Depression and chronic fatigue in the patient with heart disease.

Depression and chronic fatigue are frequently associated with heart disease. They may precede the onset of myocardial infarction, singly or together, and increase the morbidity and mortality of patients with a history of MI. Virtually all such patients have a transient depression, usually accompanied by anxiety, with onset soon after hospitalization. Although this depression is transient and usually abates spontaneously, it frequently warrants therapeutic intervention. Psychosocial and personality factors play a significant role in the recovery of a patient with a cardiac condition. The clinician must be alert for the effects of changing roles within the family and behaviors that may lead to chronic invalidism. Anxiety disorders, often combined with depression, may mimic cardiac disease and may result from it, leading to chronic fatigue and weakness. Proper diagnosis usually leads to considerable improvement. Cardiac drugs, in addition to many others, may produce depression and fatigue that may be misdiagnosed. Often, discontinuing or changing a medication will lead to marked diminution of such symptoms. Observational and listening skills are key ingredients of the "art" of medicine; they can lead to interventions that are not only therapeutic, but which improve the "quality" of life.

Demographic, cognitive and experiential predictors of presurgical anxiety.

A heterogeneous sample completed a demographic survey, a measure of internal-external locus of control (I-E), the Hospital Stress Rating Scale (HSRS), and a state anxiety measure on the eve of major surgery. Three sets of variables (demographic, cognitive, and experiential) together significantly accounted for one-quarter of the variance in state anxiety. However, only the cognitive set (I-E and the HSRS) was uniquely significant, supporting the view of presurgical anxiety as a patient's response to interpretation of a life-threatening event. Higher levels of anxiety were associated with more anticipated stressful experiences, stronger beliefs that powerful others and chance influence events, and weaker beliefs that events are caused by one's own efforts. Implications are presented for identifying patients at risk for presurgical anxiety and for designing interventions to enhance the patient's sense of control.

A survey of attitudes on the use of electroconvulsive therapy.

Electroconvulsive therapy in recent years has received extensive coverage in the mass media, much of it negative. However, little can be found in either the professional literature or the popular press on the attitudes of professionals, patients, and the general public toward ECT. A questionnaire study of 587 individuals drawn from these three categories shows an over-all favorable response to the use of ECT, despite the presence of significant differences in response among members of each category. The implications of the findings for current practice and research are discussed.

Therapeutic usefulness of amitriptyline in spastic colon syndrome.

The therapeutic efficacy of amitriptyline in irritable bowel was studied in a cross-over double-blind trial, employing fourteen patients whose symptoms were rated as Class II or worse on an arbitrarily-defined interval scale and who had not benefited from previous trials of anticholinergics, anticholinergic-sedative combinations, and bulk-forming agents. During the study, patients rated their own symptoms and the interviewer rated their symptoms using the same scale. Average scores for the patients while on drug showed significant improvement compared to pre-test level. No placebo or drug carry-over effects could be demonstrated. Inasmuch as amitriptyline is effective in this context at dosages subtherapeutic with regard to depression, the authors suggest that a central (perhaps anticholinergic) mechanism of action is responsible.

Ganser state: a case of hysterical pseudodementia.

This case history shows the clinical features of a Ganser-like syndrome, in which two basic dilemmas readily present themselves to the clinician. First, careful neurologic, psychiatric, and psychosocial investigation is essential for differential diagnosis. And second, criteria must be established to distinguish a true Ganser syndrome from Ganser symptoms. Ultimately, one must ask where this "syndrome" or constellation of symptoms belongs on the spectrum of psychosis and hysteria.

Conversion hysteria.

Conversion hysteria differs from hysteria in that it arises suddenly, rather than being a lifelong disorder. It is monosymptomatic rather than polysymptomatic, and is seen in men almost as frequently as in women. La belle indifférence, when present, is a useful clue to diagnosis. Other clues are ambiguity in reporting of the symptoms, medically inconsistent symptoms and hysterical personality features. Treatment may include removing the patient from a stressful environment and removing the "payoff" yielded by the illness. A confrontation with the patient is generally to be avoided.