Biological active matter aggregates: Inspiration for smart colloidal materials.

Aggregations of social organisms exhibit a remarkable range of properties and functionalities. Multiple examples, such as fire ants or slime mold, show how a population of individuals is able to overcome an existential threat by gathering into a solid-like aggregate with emergent functionality. Surprisingly, these aggregates are driven by simple rules, and their mechanisms show great parallelism among species. At the same time, great effort has been made by the scientific community to develop active colloidal materials, such as microbubbles or Janus particles, which exhibit similar behaviors. However, a direct connection between these two realms is still not evident, and it would greatly benefit future studies. In this review, we first discuss the current understanding of living aggregates, point out the mechanisms in their formation and explore the vast range of emergent properties. Second, we review the current knowledge in aggregated colloidal systems, the methods used to achieve the aggregations and their potential functionalities. Based on this knowledge, we finally identify a set of over-arching principles commonly found in biological aggregations, and further suggest potential future directions for the creation of bio-inspired colloid aggregations.

Two-photon absorption measurements of deep UV transmissible materials at 213 nm.

We report on two-photon absorption measurements at 213 nm of deep UV transmissible media, including LiF, MgF2, CaF2, BaF2, sapphire (Al2O3), and high-purity grades of fused-silica (SiO2). A high-stability 24 ps Nd:YAG laser operating at the 5th harmonic (213 nm) was used to generate a high-intensity, long-Rayleigh-length Gaussian focus inside the samples. The measurements of the fluoride crystals and sapphire indicate two-photon absorption coefficients between 0.004 and 0.82 cm/GW. We find that different grades of fused silica performed near identically for two-photon absorption; however, there are differences in linear losses associated with purity. A low two-photon absorption cross section is measured for MgF2, making it an ideal material for the propagation of high-intensity deep UV lasers.

Oxygen carrying microbubbles for enhanced sonodynamic therapy of hypoxic tumours.

Tumour hypoxia represents a major challenge in the effective treatment of solid cancerous tumours using conventional approaches. As oxygen is a key substrate for Photo-/Sono-dynamic Therapy (PDT/SDT), hypoxia is also problematic for the treatment of solid tumours using these techniques. The ability to deliver oxygen to the vicinity of the tumour increases its local partial pressure improving the possibility of ROS generation in PDT/SDT. In this manuscript, we investigate the use of oxygen-loaded, lipid-stabilised microbubbles (MBs), decorated with a Rose Bengal sensitiser, for SDT-based treatment of a pancreatic cancer model (BxPc-3) in vitro and in vivo. We directly compare the effectiveness of the oxygen-loaded MBs with sulphur hexafluoride (SF6)-loaded MBs and reveal a significant improvement in therapeutic efficacy. The combination of oxygen-carrying, ultrasound-responsive MBs, with an ultrasound-responsive therapeutic sensitiser, offers the possibility of delivering and activating the MB-sensitiser conjugate at the tumour site in a non-invasive manner, providing enhanced sonodynamic activation at that site.

Tungsten filament material and cesium dynamic equilibrium effects on a surface converter ion source.

We present results on two different aspects that affect surface converter H(-) ion source performance: tungsten filament material and converter/wall temperature control. On the tungsten material aspect, evidence that filament grain size affects the source performance as well as filament failure modes is shown. Materials with impurity contents that hinder grain growth during conditioning or operation are to be avoided in order to increase the filament lifetime. Regarding the temperature control of the converter and plasma chamber walls, we present results of increased current output of up to 2.5 mA (15%). This is explained by generating increased cesium vapor pressure leading to enhanced sputtering of H(-) ions.

Tissue-engineered bone formation in vivo using a novel sintered polymeric microsphere matrix.

We have evaluated in vivo a novel, polymer-based, matrix for tissue engineering of bone. A segmental defect of 15 mm was created in the ulna of New Zealand white rabbits to determine the regenerative properties of a porous polylactide-co-glycolide matrix alone and in combination with autogenous marrow and/or the osteoinductive protein, BMP-7. In this study four implant groups were used: 1) matrix alone; 2) matrix with autogenous marrow; 3) matrix with 20 microg of BMP-7; and 4) matrix with 20 microg of BMP-7 and autogenous marrow. The results showed that the degree of bone formation was dependent on the properties of the graft material. The osteoconductive sintered matrix structure showed significant formation of bone at the implant-bone interface. The addition of autogenous marrow increased the penetration of new bone further into the central area of the matrix and also increased the degree of revascularisation. The osteoinductive growth factor BMP-7 induced penetration of new bone throughout the entire structure of the implant. The most effective treatment was with the combination of marrow cells and osteoinductive BMP-7.

Structural and human cellular assessment of a novel microsphere-based tissue engineered scaffold for bone repair.

The limitations of current grafting materials have driven the search for synthetic alternatives for the regeneration of trabecular bone. A variety of biodegradable polymer foams composed of 85/15 poly(lactide-co-glycolide) (PLAGA) have been evaluated for such uses. However, structural limitations may restrict the clinical use of these scaffolds. We have developed a novel sintered microsphere scaffold with a biomimetic pore system equivalent to the structure of trabecular bone. By modifying processing parameters, several different sintered microsphere structures were fabricated. Optimization of the structure dealt with modifications to sphere diameter and heating time. Compressive testing illustrated a trend between microsphere diameter and modulus, where increased microsphere diameter resulted in decreased modulus. In addition, evaluation of the pore system showed a positive correlation between sphere diameter and pore diameter. Mercury porosimetry showed increased median pore size with an increased microsphere diameter. Heating time modifications showed that compressive modulus was dependent on the period of heating with longer heating times resulting in higher moduli. It was also shown that heating time did not affect the pore structure. Analysis of the structural data indicated that the microsphere matrix sintered for 4h at a temperature of 160 degrees C with a microsphere diameter of 600-710 microm resulted in an optimal, biomimetic structure with range in pore diameter of 83-300 microm, a median pore size of 210 microm, 35% porosity, and a compressive modulus of 232 MPa. An in vitro evaluation of human osteoblasts seeded onto the sintered matrix indicated that the structure was capable of supporting the attachment and proliferation of cells throughout its pore system. Immunofluorescent staining of actin showed that the cells were proliferating three-dimensionally through the pore system. The stain for osteocalcin was used and showed that cells maintained phenotypic expression for this bone specific protein. Through this work, it was shown that an osteoconductive PLAGA scaffold with a pore system used as a reverse template to the structure of trabecular bone could be fabricated through the sintered microsphere method.

Antimalarial drugs in systemic lupus erythematosus: use in pregnancy.

The 4-aminoquinoline radical containing antimalarial drugs are also used in the management of various connective tissue diseases including systemic lupus erythematosus (SLE) and rheumatoid arthritis. These agents are particularly useful for the management of inflammatory polyarthritis and skin disease. By raising the pH in intracellular compartments, these drugs interfere with normal phagocytic function which consequently enables them to interfere with antigen processing. Other actions include inhibition of platelet aggregation, this is advantageous in patients with phospholipid antibodies (aPL) which are known to predispose patients to recurrent arterial and venous clinical thrombotic events. Hydroxychloroquine has also been demonstrated to reduce serum lipid levels including cholesterol, triglycerides and low density lipoproteins. As it is now known that patients with SLE are at risk for accelerated artherogenesis and premature heart disease, this action may be an added benefit for these patients. The use of the 4-aminoquinoline radical containing antimalarial drugs during pregnancy is controversial. It is known that these agents can cross the placenta and are deposited in fetal pigmented tissues. These findings have led to the recommendation that these agents should be discontinued in pregnancy for patients with connective tissue diseases even though they have long been recommended for malarial prophylaxis in pregnant women travelling to malarial infested areas. Flares of SLE disease have been documented when these agents are discontinued and as flares of SLE disease activity are known to be detrimental to pregnancy outcome in patients with SLE, it is our opinion that these drugs should not be discontinued during pregnancy in a patient with lupus, particularly when the known terminal elimination half life is 1 to 2 months.

Poly(lactide-co-glycolide)/hydroxyapatite delivery of BMP-2-producing cells: a regional gene therapy approach to bone regeneration.

Currently, functional treatment of fracture non-unions and bone loss remains a significant challenge in the field of orthopaedic surgery. Tissue engineering of bone has emerged as a new treatment alternative in bone repair and regeneration. Our approach is to combine a polymeric matrix with a cellular vehicle for delivery of bone morphogenetic protein-2 (BMP-2), constructed through retroviral gene transfer. The objective of this study is to develop an osteoinductive, tissue-engineered bone replacement system by culturing BMP-2-producing cells on an osteoconductive, biodegradable, polymeric-ceramic matrix. The hypothesis is that retroviral gene transfer can be used effectively in combination with a biodegradable matrix to promote bone formation. First, we examined the in vitro attachment and growth of transfected BMP-producing cells on a PLAGA-HA scaffold. Second, the bioactivity of the produced BMP in vitro was evaluated using a mouse model. It was found that the polymer-ceramic scaffold supported BMP-2 production, allowing the attachment and growth of retroviral transfected, BMP-2-producing cells. In vivo, the scaffold successfully functioned as a delivery vehicle for bioactive BMP-2, as it induced heterotopic bone formation in a SCID mouse model.

Regional drug delivery with radiation for the treatment of Ewing's sarcoma. In vitro development of a taxol release system.

Recently, several studies have suggested the radiosensitizing effect of taxol, a microtubular inhibitor. Our overall hypothesis is that a combination of radiation and taxol may demonstrate therapeutic efficacy over doses of either individually. Studies examining taxol use have mostly focused on systemic administration, which can lead to undesired effects. To circumvent these side effects, we propose a locally administered polymeric microsphere delivery system combined with radiation therapy for the treatment of Ewing's sarcoma. The present study focuses on the in vitro ability of taxol when present as a microencapsulated drug delivery system, and delivered locally at the site of the sarcoma/tumor, to block cells in the G2/M phase of the cell cycle and potentially enhance the radiation sensitivity of cells. Using the bioresorbable poly(anhydride-co-imide), poly[pyromellityl-imidoalanine-1,6-bis(carboxy-phenoxy)hexane] (PMA-CPH), and the radiosensitizing agent taxol, a microsphere based delivery system was fabricated. A solvent evaporation technique was used to encapsulate taxol at doses of 1%, 5%, and 10% in PMA-CPH microspheres. Release kinetics studies demonstrated that the total amount of taxol released and the release rate were directly dependent on loading percentage. Taxol's bioactivity and radiosensitizing ability were measured using flow cytometry. Co-culture of Ewing's sarcoma cells with and without taxol-loaded microspheres demonstrated that released taxol retained its bioactivity and effectively blocked cells in the radiosensitive G2/M phase of mitosis. The taxol-radiation delivery system studied achieved an 83% decrease in tumor cell count compared to control. Taxol effectively sensitized Ewing's sarcoma cells to radiation with radiosensitivity shown to be independent of radiation dose at levels of dosages studied. This work has demonstrated that taxol can be effectively released from a biodegradable PMA-CPH microsphere delivery system while maintaining potent combined cytotoxic and radiosensitizing abilities.

Tissue engineering: orthopedic applications.

Because of an aging population and increased occurrence of sports-related injuries, musculoskeletal disorders have become one of the major health concerns in the United States. Current treatments, although fairly successful, do not provide the optimum therapy. These treatments typically rely on donor tissues obtained either from the patient or from another source. The former raises the issue of supply, whereas the latter poses the risk of rejection and disease transfer. This has prompted orthopedic surgeons and scientists to look for viable alternatives. In recent years, tissue engineering has gained increasing support as a method to treat orthopedic disorders. Because it uses principles of engineering, biology, and chemistry, tissue engineering may provide a more effective approach to the treatment of musculoskeletal disorders than traditional methods. This chapter presents a review of current methods and new tissue-engineering techniques for the treatment of disorders affecting bone, ligament, and cartilage.

Prevention of the spread of rabies to wildlife by oral vaccination of raccoons in Massachusetts.

OBJECTIVE: To evaluate the use of bait containing rabies vaccine to create a barrier of rabies-vaccinated raccoons in Massachusetts and to determine the effectiveness of various bait distribution strategies in halting the spread of rabies. DESIGN: Prospective study. SAMPLE POPULATION: Free-ranging raccoons. PROCEDURE: Baits were distributed twice yearly in a 207-km2 (80-mi2) area in the vicinity of the Cape Cod Canal. Bait density and distribution strategy varied among 3 treatment areas. Raccoons were caught in live traps after bait distribution and anesthetized; blood samples were obtained to measure serum antibody titers to rabies virus. Vaccination rates were determined by the percentage of captured raccoons with antibody titers to rabies virus > or = 1:5. In addition, raccoons with clinical signs of illness inside the vaccination zone and adjacent areas were euthanatized and submitted for rabies testing. RESULTS: The percentage of vaccinated raccoons differed significantly among the following 3 areas with various bait densities: high-density area with uniform bait distribution (103 baits/km2 [267 baits/mi2]) = 37%; low-density area with additional targeted bait distribution (93 baits/km2 [240 baits/mi2]) = 67%; and, high-density area with additional targeted bait distribution (135 baits/km2 [350 baits/mi2]) = 77%. Nineteen animals with rabies (15 raccoons, 3 skunks, 1 cat) were reported in the area just outside of the vaccination zone, but only 1 raccoon with rabies was reported from inside the vaccination zone. CLINICAL IMPLICATIONS: In this suburban study area, an approximate vaccination rate of 63% was sufficient to halt the spread of rabies in free-ranging raccoons. Compared with uniform bait distribution, targeting raccoon habitats increased vaccination rates.

Suicidal behavior in children and adolescents with mental retardation.

Despite increasing attention to psychiatric disorders in the mentally retarded, suicidal behavior remains an underreported phenomenon in this population, particularly in children and adolescents. This study was aimed at documenting the existence of suicidal behavior among 90 consecutive admissions to a specialty unit for dually diagnosed children and adolescents in a medical school-affiliated children's psychiatric hospital. Archival chart review yielded a total of 19 patients, or 21%, for whom suicidal behavior was a presenting complaint upon admission or during hospitalization. Suicidality was distributed across gender, level of mental retardation, and psychiatric diagnosis. Additional findings of note with regard to family dysfunction and/or abuse history are summarized. Clearly, in this sample, children and adolescents with mental retardation were capable of formulating and engaging in potentially fatal acts. Results of this study suggest that suicidal behavior is an underrecognized, yet significant phenomenon in children and adolescents with mental retardation and psychiatric disorder.

An examination of the validity of social subtypes in autism.

The validity of a social subtyping scheme forwarded by Wing and her colleagues is examined in a sample of 53 autistic individuals. Clinical ratings of subtype (aloof, passive, active-but-odd), IQ estimates, and measures of adaptive functioning and level of autism were obtained. Subjects were individually administered the Autism Diagnostic Observation Schedule (ADOS) by the principle examiner, who was blind to subtype assignment. The general findings supported the validity of aloof and active-but-odd subtypes as predictors of behavior across language/communication, reciprocal social interaction, and stereotyped behavior/restricted interest domains and suggested that individuals assigned to these respective groups differed in a number of important ways (e.g., level of autism, IQ, adaptive behavior). Partial support for an intermediate, passive subtype was garnered. The clinical utility of social subtypes is discussed as an important implication of this work.

Hawkinsinuria in two families.

Hawkinsinuria, a disorder of tyrosine metabolism has been documented in two families in the United States, in one of which there was clear evidence of autosomal dominant inheritance. Metabolic acidosis and failure to thrive appear to be confined to infancy. Tyrosyl metabolites and 5-oxoproline are also found only in infancy, while 4-hydroxycyclohexylacetic acid was present only with time. The disease may be detected by organic acid analysis or by staining an electropherogram for sulfur containing compounds.

Sociometric status and academic, behavioral, and psychological adjustment: a five-year longitudinal study.

Six hundred fourth-graders rated how much they liked to play with each of their classmates and then nominated their three best friends; 296 of the 600 children were assigned sociometric classifications of popular, neglected, average, controversial, or rejected status (the remaining 304 children failed to meet inclusion criteria). Five years later, 267 of the 296 classified children (90.2%) were evaluated on measures of academic performance, social behavior, and psychological adjustment. The number and type of contacts with the juvenile justice system were also determined. In general, children classified as rejected or controversial tended to fare more poorly on indices of long-term adjustment than did children classified as popular, neglected, or average. Results are discussed in terms of the predictive validity of sociometric rating and nomination procedures and their utility in identifying children at risk for later maladjustment.

Glomerulonephritis with absent glomerular basement membrane antigens.

This is a report of a child with glomerulonephritis and no family history of renal disease. On renal biopsy there was splitting and thinning of glomerular basement membrane antigens. These findings are similar to those seen in patients with familial nephritis and may be part of a spectrum of primary glomerular basement membrane defects.