Design of a mechanical larynx with agarose as a soft tissue substitute for vocal fold applications

Mechanical and computational models consisting of flow channels with convergent and oscillating constrictions have been applied to study the dynamics of human vocal fold vibration. To the best of our knowledge, no mechanical model has been studied using a material substitute with similar physical properties to the human vocal fold for surgical experimentation. In this study, we design and develop a mechanical larynx with agarose as a vocal fold substitute, and assess its suitability for surgical experimentation. Agarose is selected as a substitute for the vocal fold as it exhibits similar nonlinear hyperelastic characteristics to biological soft tissue. Through uniaxial compression and extension tests, we determined that agarose of 0.375% concentration most closely resembles the vocal fold mucosa and ligament of a 20-year old male for small tensile strain with an R(2) value of 0.9634 and root mean square error of 344.05±39.84?Pa. Incisions of 10 mm lengthwise and 3 mm in depth were created parallel to the medial edge on the superior surface of agar phantom. These were subjected to vibrations of 80, 130, and 180 Hz, at constant amplitude of 0.9 mm over a period of 10 min each in the mechanical larynx model. Lateral expansion of the incision was observed to be most significant for the lower frequency of 80 Hz. This model serves as a basis for future assessments of wound closure techniques during microsurgery to the vocal fold.     

Panax quinquefolium saponins protects low density lipoproteins from oxidation

Oxidized low-density lipoprotein (Ox-LDL) is believed to be involved in the pathogenesis of atherosclerosis. Panax quinquefolium saponins (PQS) are extracted from the stems and leaves of the North American form of ginseng, Panax quinquefolium. Earlier studies have suggested that this extract improves the lipid profile of hyperlipidemic rats and has antioxidant properties in cultured rat cardiac myocytes. The aims of the present study were to investigate the potential of PQS in reducing LDL oxidation as well as limiting the ability of Ox-LDL to impair endothelium-dependent relaxation in rat aortic rings. LDL was isolated from the plasma of healthy human donors by sequential ultracentrifugation. Native LDL (0.2 or 0.3 mg/ml) was incubated with PQS (0.25-1 mg/ml) for 30 min at 20 degrees C. For comparison, vitamin C (50 microM) was added in place of PQS. Oxidative modification was initiated with 5 microM CuSO4 at 37 degrees C for 0-24 h. In our hands, PQS concentration-dependently reduced lipid peroxide levels as measured by the amount of thiobarbituric acid reactive substances formed. This range of PQS also retarded the alterations in relative electrophoretic mobility of Ox-LDL in a similar manner. Furthermore, measurement of phospholipid fractions content indicated that PQS could reduce the conversion of phosphatidylcholine to lysophosphatidylcholine in Ox-LDL. Functional studies demonstrated that PQS-pretreated Ox-LDL was less potent than untreated Ox-LDL at impairing endothelium-dependent relaxation in rat aortic rings. In conclusion, our results suggest that PQS has antioxidant properties and that reduction of LDL oxidation by PQS may provide a protective effect against the detrimental actions of Ox-LDL.     

Extending the reach of the heterodigital arterialized flap by vein division and repair

The heterodigital arterialized flap is ideal for nonsensory reconstruction of sizable soft-tissue defects in the proximal fingers, web spaces, and the hand. The inclusion of a dorsal vein augments the venous drainage of this digital island flap and avoids the problem of postoperative venous congestion, which is a common problem in digital island flaps. However, the presence of a dorsal vein pedicle inhibits flap mobility somewhat, and the reach of the flap is mainly limited to adjacent fingers. In situations that demand a transfer from a nonadjacent donor finger or when the reach from the adjacent donor finger is inadequate, the dorsal vein pedicle can be temporarily divided and then anastomosed microsurgically after flap transfer is performed. This enables the reach of the flap to be extended up to two fingers from the donor finger. The authors performed this "partially free" heterodigital arterialized flap in 11 consecutive patients between 1991 and 2001. The average size of the defects was 4.4 x 2.3 cm. All of the flaps survived completely, without any evidence of postoperative flap congestion. Healing of all of the flaps was primary and did not result in any scarring. All of the donor fingers had "normal" two-point discrimination of 3 to 5 mm. All of the donor fingers retained excellent or good total active motion, as graded by the criteria of Strickland and Glogovac.     

Ku86 variant expression and function in multiple myeloma cells is associated with increased sensitivity to DNA damage

Ku is a heterodimer of Ku70 and Ku86 that binds to double-stranded DNA breaks (DSBs), activates the catalytic subunit (DNA-PKcs) when DNA is bound, and is essential in DSB repair and V(D)J recombination. Given that abnormalities in Ig gene rearrangement and DNA damage repair are hallmarks of multiple myeloma (MM) cells, we have characterized Ku expression and function in human MM cells. Tumor cells (CD38(+)CD45RA(-)) from 12 of 14 (86%) patients preferentially express a 69-kDa variant of Ku86 (Ku86v). Immunoblotting of whole cell extracts (WCE) from MM patients shows reactivity with Abs targeting Ku86 N terminus (S10B1) but no reactivity with Abs targeting Ku86 C terminus (111), suggesting that Ku86v has a truncated C terminus. EMSA confirmed a truncated C terminus in Ku86v and further demonstrated that Ku86v in MM cells had decreased Ku-DNA end binding activity. Ku86 forms complexes with DNA-PKcs and activates kinase activity, but Ku86v neither binds DNA-PKcs nor activates kinase activity. Furthermore, MM cells with Ku86v have increased sensitivity to irradiation, mitomycin C, and bleomycin compared with patient MM cells or normal bone marrow donor cells with Ku86. Therefore, this study suggests that Ku86v in MM cells may account for decreased DNA repair and increased sensitivity to radiation and chemotherapeutic agents, whereas Ku86 in MM cells confers resistance to DNA damaging agents. Coupled with a recent report that Ku86 activity correlates with resistance to radiation and chemotherapy, these results have implications for the potential role of Ku86 as a novel therapeutic target.     

Giardia lamblia rearranges F-actin and alpha-actinin in human colonic and duodenal monolayers and reduces transepithelial electrical resistance

The mechanisms of epithelial injury in giardiasis remain unknown. The effects of live Giardia lamblia on cellular G-actin, F-actin, alpha-actinin, and electrical resistance of human intestinal epithelial monolayers were investigated using SCBN and Caco2 cell lines grown on chamber slides or Transwell filter membranes. In separate experiments, some monolayers were also exposed to sonicated trophozoites, some to supernatant from live G. lamblia cultures, and some with or without the Ca2+ channel blocker verapamil. After 2, 24, or 48 hr of coincubation with G. lamblia, monolayers were assessed for cytoskeletal arrangement under fluorescence and confocal laser microscopy, and transepithelial electrical resistance was measured. Exposure to live G. lamblia trophozoites induced localized condensation of F-actin and loss of perijunctional alpha-actinin while G-actin remained unchanged. Confocal laser microscopy indicated that F-actin rearrangement was not affected by verapamil and was localized within the terminal web area. Coincubation of monolayers with G. lamblia lysates or with spent medium alone similarly rearranged F-actin. Verapamil alone did not alter F-actin. Electrical resistance of SCBN and Caco2 monolayers exposed to G. lamblia was significantly decreased versus controls regardless of whether live or lysed trophozoite samples were used. The results indicate that G. lamblia-induced epithelial injury is associated with F-actin and alpha-actinin rearrangements in the terminal web area via mechanisms independent of extracellular Ca2+. These alterations are associated with reduced transepithelial electrical resistance and are due at least in part to trophozoite products.     

Shifting Baselines on a Tropical Forest Frontier: Extirpations Drive Declines in Local Ecological Knowledge

The value of local ecological knowledge (LEK) to conservation is increasingly recognised, but LEK is being rapidly lost as indigenous livelihoods change. Biodiversity loss is also a driver of the loss of LEK, but quantitative study is lacking. In our study landscape in SW China, a large proportion of species have been extirpated. Hence, we were interested to understand whether species extirpation might have led to an erosion of LEK and the implications this might have for conservation. So we investigated peoples'' ability to name a selection of birds and mammals in their local language from pictures. Age was correlated to frequency of forest visits as a teenager and is likely to be closely correlated to other known drivers of the loss of LEK, such as declining forest dependence. We found men were better at identifying birds overall and that older people were better able to identify birds to the species as compared to group levels (approximately equivalent to genus). The effect of age was also stronger among women. However, after controlling for these factors, species abundance was by far the most important parameter in determining peoples'' ability to name birds. People were unable to name any locally extirpated birds at the species level. However, contrary to expectations, people were better able to identify extirpated mammals at the species level than extant ones. However, extirpated mammals tend to be more charismatic species and several respondents indicated they were only familiar with them through TV documentaries. Younger people today cannot experience the sights and sounds of forest animals that their parents grew up with and, consequently, knowledge of these species is passing from cultural memory. We suggest that engaging older members of the community and linking the preservation of LEK to biodiversity conservation may help generate support for conservation.