An integrated biomarker approach: Non-monotonic responses to cadmium exposure in the suckermouth catfish Hypostomus plecostomus.

Environmental risk assessment in aquatic ecosystems typically uses biomarkers to detect interactions between potential hazards and biological systems. Next to knowing environmental contaminant levels in tissues and the environment, it is important to link to potentially deleterious effects at higher levels of biological organization such as biochemistry, physiology, and overall health status. In this laboratory study we assessed the toxicity of waterborne cadmium (Cd) over an exposure range of 0 - 100 µg l-1 for nine days to the loricariid suckermouth catfish Hypostomus plecostomus. We evaluated the integrated response of the fish at the biochemical to physiological level by means of a suite of tissue biomarkers of exposure and effects, including Cd concentrations in gills, liver metallothioneins (MT) and cholinesterase activity (ChE) in brain, before and after the inhibition of the alkaloid eserine, as well as whole-fish resting oxygen consumption rates and ingestion rate. Tissue biomarkers (MT and ChE) showed a non-monotonic relationship, with maximum/minimum responses at intermediate doses. i.e. 10 and 50 µg l-1, whereas biomarker responses of fish exposed at 100 µg l-1 more closely resembled biomarker responses seen at lower concentrations (< 10 µg l-1). Conversely, the oxygen consumption rate peaked at 100 µg l-1, suggesting a higher metabolic cost for higher metal exposure, with no significant correlation with fish body condition and food intake. Integrated Biomarker Response (IBR) values peaked at the intermediate exposure concentration of 50 µg l-1 Cd. The non-monotonic dose-response of the biochemical biomarkers of exposure, together with the higher metabolic rates of fish exposed to 50 - 100 µg l-1 of Cd and the non-significant effects on the more relevant physiological and histological variables suggests that H. plecostomus is capable of biochemically and physiologically regulating moderately high Cd concentrations, thus representing a suitable indicator organism to monitor metal pollution by Cd.

Monitoring metallothionein-like protein concentrations and cholinesterase activity in tropical cup oysters as biomarkers of exposure to metals and pesticides in the southern Caribbean, Colombia.

Metallothionein-like protein concentrations (MT) and three functionally defined fractions of cholinesterase activity (ChE) were quantified in gill and digestive gland homogenates of tropical cup oysters from 5 nearshore locations in the Colombian Caribbean and correlated with sediment and tissue metal (9 metals) and pesticide (22 organophosphates, OPs, and 20 organochlorines-OCPs), as well as water physical-chemical parameters (salinity, pH, temperature, and dissolved oxygen). Tissue and sediment pesticide concentrations were below detection limits in all samples, whereas sediment and tissue metal concentrations exceeded environmental thresholds at several locations. Tissue MT and ChE biomarkers varied by a factor of 5-6 between locations. Inhibition of cholinesterase activity was negligible for all 5 sites, despite spatial-temporal variation in ChE activity, consistent with below-detection OP concentrations. Tissue MT and ChE biomarkers correlated with tissue and metal sediment concentrations, yet, statistically significant covariance between biomarkers and water chemistry parameters was also observed, indicating that both, metal concentrations and physical-chemical variables, are likely to be responsible for generating the observed spatial-temporal variations in biomarker patterns.

Chalcogen Bonding Ion-Pair Cryptand Host Discrimination of Potassium Halide Salts.

A series of chalcogen, halogen and hydrogen bonding heteroditopic macrobicyclic cryptands are reported and their potassium halide ion-pair recognition properties investigated. Saliently, the co-bound potassium cation was determined to be crucial in switching on the bromide and iodide recognition properties of the respective cryptand receptor. Importantly, the nature of the sigma-hole mediated interaction employed in the anion recognition component is demonstrated to significantly augment the ion-pair binding behaviour, markedly so for the halogen bonding analogue. Most notably the incorporation of a chelating chalcogen bonding donor motif significantly improves the selectivity towards KBr over KI, relative to halogen and hydrogen bonding analogues.

Long-Term Outcomes Following Lumbar Nucleus Replacement.

BACKGROUND: Nucleus replacement devices are designed to replace the native pain-generating lumbar nucleus while preserving the annulus fibrosus, endplates, and natural motion. The DASCOR Disc Arthroplasty Device seemed to perform well clinically but was discontinued in 2009. While there are no commercially available NRDs today, the potential advantages of using such devices have prompted a renewed interest in further developing the technology and assessing long-term outcomes for the DASCOR device. METHODS: A retrospective review of hospital records from a single institution was performed to identify all patients that underwent implantation of a DASCOR device between 2006 and 2009. Clinical outcome and imaging data were gathered to assess device performance of the DASCOR device over an extended period of time. Clinical data were assessed using a visual analog scale for back pain (VAS), Oswestry Disability Index (ODI) scores, and analgesic medication use score (ANS). Magnetic resonance images were systematically evaluated at the index and adjacent disc levels: disc height, Modic changes, Pfirrmann grade, and any implant-associated findings. RESULTS: Twenty-six patients received DASCOR implants. Follow-up data were available for 22 patients. The mean age at time of implantation was 34.9 years. Long-term data were available for 14 patients (mean, 11.5 years) with a mean improvement in VAS of 4.0 +/- 2.8 (P < 0.0001), ODI 33.4 +/- 18.4 (P < 0.0001), and ANS 0.5 (P = 0.07) compared to baseline values, while 46% developed radiological adjacent segment degeneration on MRI and 54% did not. In total, 6 patients underwent revision surgery at the index level and 3 underwent surgery at adjacent lumbar levels. CONCLUSIONS: While any conclusions should be interpreted with caution, there was a subgroup of patients that had excellent clinical and radiological outcomes. Additional studies on this device or other similar devices would add to our knowledge regarding ideal treatment of discogenic low back pain in younger patients. CLINICAL RELEVANCE: Treatment of discogenic low back pain. LEVEL OF EVIDENCE: 4.

A new species of Bestiolina (Crustacea, Copepoda, Calanoida, Paracalanidae) from coastal waters of the Colombian Pacific, including a worldwide key for the identification of the species.

Plankton samples obtained from estuarine waters of the Colombian Pacific yielded adults specimens of an undescribed species of a paracalanid copepod of the genus Bestiolina. It most closely resembles two Asian species; B.sinica (Shen & Lee, 1966) from China and B.arabica (Ali, Al-Yamani & Prusova, 2007) from the Arabian Gulf. These three species share the absence of spinules on the posterior surfaces of exopod segments of legs 2, 3 and 4. Bestiolinasarae Dorado-Roncancio & Gaviria, sp. n. can be easily separated from B.sinica by the number of spinules on the anterior surface of endopod 2 of legs 2 and 3, and by the absence of spinules on the posterior surface of second endopod of leg 4. It can be distinguished from B.arabica by the presence of spinules on the posterior surface of endopod 2 of same legs (absent in B.arabica), and the size of spinules on the anterior surface of the same segments. The only other species known from the Americas, B.mexicana (Suárez-Morales & Almeyda-Artigas, 2016), can be distinguished from Bestiolinasarae Dorado-Roncancio & Gaviria, sp. n. by the presence of spinules on the posterior surface of the leg 2 first exopodal segment and the morphology of the mandible blade. The morphological and meristic differences to the eight known species of the genus are presented. An identification key to the species of Bestiolina is provided.

Cholinesterase activity in the cup oyster Saccostrea sp. exposed to chlorpyrifos, imidacloprid, cadmium and copper.

In the present study, the sensitivity and concentration dependence of three functionally-defined components of cholinesterase activity (total: T-ChE; eserine-sensitive: Es-ChE; and eserine-resistant: Er-ChE) were quantified in the gill, digestive gland and adductor muscle of the tropical cup oyster Saccostrea sp., following acute (96h) aqueous exposure to commercial formulations of the organophosphate (OP) insecticide chlorpyrifos and the neonicotinoid (NN) imidacloprid (concentration range: 0.1-100mg/L), as well as to dissolved cadmium and copper (concentration range: 1-1000µg/L). Oysters (1.5-5.0cm shell length), field-collected from a boating marina in Santa Marta, Colombia (Caribbean Sea) were exposed in the laboratory to each substance at five concentrations. T-ChE, Es-ChE, and Er-ChE activity were quantified in the three tissues in pools of 5 individuals (3 replicates per concentration), before and after inhibition with the total cholinesterase inhibitor eserine (physostigmine, 100µM). Oysters exposed to chlorpyrifos, imidacloprid and Cd showed reduced T-ChE and Es-ChE activity in gills at highest exposure concentrations, with Es-ChE activity being inhibited proportionally more so than T-ChE, whereas Er-ChE activity showed no significant concentration-response. Digestive gland also showed diminished T-ChE, Es-ChE and Er-ChE activity for highest chlorpyrifos and Cd concentrations relative to controls, but an increase of T-ChE and Er-ChE activity at the highest imidacloprid concentration (100mg/L). For Cu, T-ChE, Es-ChE and Er-ChE activities in gills and digestive gland were elevated relative to controls in oysters exposed to Cu concentrations > 100µg/L. In adductor muscle, T-ChE, Es-ChE and Er-ChE activity showed no apparent pattern for any of the four xenobiotics and concentration levels tested. Although this study confirms acute (96h) concentration-dependent reduction of tissue T-ChE and Es-ChE activity in gills and digestive glands of Saccostrea sp. exposed to high concentrations of chlorpyrifos (100mg/L), significant changes in T-ChE, Es-ChE and Er-ChE were also caused by exposure to Cd and Cu at concentrations > 100µg/L and by exposure to imidacloprid (100mg/L), indicating that cholinesterase activity is not a specific biomarker of organophosphate exposure in this species, but, rather, a biomarker of diverse xenobiotic exposure.

Chemical contamination assessment in mangrove-lined Caribbean coastal systems using the oyster Crassostrea rhizophorae as biomonitor species.

This paper aims to contribute to the use of mangrove cupped oyster, Crassostrea rhizophorae, as a biomonitor species for chemical contamination assessment in mangrove-lined Caribbean coastal systems. Sampling was carried out in eight localities (three in Nicaragua and five in Colombia) with different types and levels of contamination. Oysters were collected during the rainy and dry seasons of 2012-2013 and the tissue concentrations of metals, polycyclic aromatic hydrocarbons (PAHs), and persistent organic pollutants (POPs) were determined. Low tissue concentrations of metals (except Hg) and PAHs; moderate-to-high tissue concentrations of Hg, hexachlorocyclohexanes (HCHs), and dichlorodiphenyl-trichloroethanes (DDTs); detectable levels of chlorpyrifos, polychlorinated biphenyls (PCBs) (mainly CB28, CB118, CB138 and CB 153) and brominated diphenyl ethers 85 (BDE85); and negligible levels of musks were recorded in Nicaraguan oysters. A distinct profile of POPs was identified in Colombia, where the tissue concentrations of PCBs and synthetic musk fragrances were low to moderate, and Ag, As, Cd, Pb, and PAHs ranged from moderate to extremely high. Overall, the values recorded for HCHs, DDTs and PCBs in Nicaraguan mangrove cupped oysters greatly exceeded the reference values in tissues of C. rhizophorae from the Wider Caribbean Region, whereas only the levels of PCBs were occasionally surpassed in Colombia. Different contaminant profiles were distinguished between oysters from Nicaragua and Colombia in radar plots constructed using the main groups of contaminants (metals, PAHs, musks, PCBs, and organochlorine pesticides (OCPs)). Likewise, integrated pollution indices revealed differences in the levels of contaminants. Moreover, the profiles and levels in oyster tissues also varied with season. Thus, principal component analysis clearly discriminated Nicaraguan and Colombian localities and, especially in Colombia, seasonal trends in chemical contamination and differences amongst localities were evidenced. The geographical and environmental disparity of the studied scenarios may represent to a large extent the diversity of mangrove-lined Caribbean coastal systems and therefore the present results support the use of C. rhizophorae as suitable biomonitor species at Caribbean regional scale, where seasonal variability is a major factor controlling pollutant mobility and bioavailability.

Alterations of tissue metallothionein and vitellogenin concentrations in tropical cup oysters (Saccostrea sp.) following short-term (96h) exposure to cadmium.

Metallothioneins and vitellogenins are low molecular weight proteins that have been used widely in environmental monitoring as biomarkers of exposure and damage to metals and estrogenic compounds, respectively. In the present study, the responses of metallothionein and vitellogenin tissue concentrations were measured following acute (96h) aqueous exposures to cadmium in Saccostrea sp., a tropical cup oyster native to the Western Pacific Ocean that has recently established itself in the Caribbean Sea. Adult oysters (1.5-5.0cm shell length) collected from the municipal marina of Santa Marta, Colombia (Caribbean Sea) and acclimated for 5days in the laboratory, were exposed to Cd at five concentrations (0, 1, 10, 100 and 1000µg/L) and their tissues (gills, digestive gland and adductor muscle) were analyzed in pools of 5 individuals (3 replicates per concentration). Metallothioneins in digestive glands of oysters exposed to Cd concentrations≥100µg/L showed a significant increase, from 8.0 to 14.8µg MT/mg total protein, whereas metallothionein concentrations in gills increased to lesser extent, and no differences were observed in adductor muscle. Metallothionein concentrations in digestive gland and gills correlated directly with whole soft tissue Cd concentrations (ranging from 2 to 297µg/g dw Cd). Vitellogenin in homogenates of oyster gonad tissue, after 96h of exposure to 1000µg/L Cd, were significantly lower (0.04mg P/g gonad) compared to control oysters (0.68mg P/g gonad), suggestive of an anti-estrogenic effect of Cd at high concentrations, whereas no significant changes in vitellogenin concentrations were observed at intermediate Cd exposure concentrations. This study confirms acute responses of metallothionein and vitellogenin concentrations in tissues of Saccostrea sp. exposed to high concentrations of cadmium (Cd≥100µg/L, 96h). The present results are first step towards validating the use of these two proteins as biomarkers of metal exposure in this species.

Cuantificación eel carbón mineral en las playasdel caribe Colombiano (departammento del magdalena) / Quantification of Coal on Colombian Caribbean Beaches (Department of Magdalena)

Con el fin de cuantificar el porcentaje de carbón mineral en playas del departamento del Magdalena, (Colombia) se llevó a cabo un procedimiento sencillo para separar el sedimento en fracciones sedimentológicas de acuerdo a su densidad. Se utilizaron sedimentos provenientes de seis playas del departamento colectadas de dos niveles mareales en noviembre de 2012 y febrero de 2013, antes y después de un derrame de una barcaza de carbón, que ocurrió el 12 de enero de 2013. Los sedimentos fueron secados, suspendidos en una solución de sodio politungstato (densidad: 2,0 g*cm-3) y centrifugados. Ya que el carbón tiene una densidad menor (1,2-1,9 g*cm-3) que otros minerales inorgánicos, cualquier partícula de carbón presente en una muestra se concentró en la fracción ligera, mientras que las partículas más densas se sedimentaron. Para eliminar materia orgánica no correspondiente a carbón mineral, se sometió la fracción ligera después a una oxidación leve con peróxido de hidrógeno. Adicionalmente, para estimar un límite máximo del contenido de carbón mineral, se determinó la pérdida de peso de sedimentos enteros a partir de combustión a 550 °C. En las seis playas evaluadas, la pérdida máxima de peso por combustión fue de 2,4 % y el porcentaje máximo de la fracción ligera (densidad < 2 g*cm-3) y resistente a oxidación por H2O2 fue de 0,07 % para noviembre 2012 y el 0,02 % para febrero 2013. No se observaron diferencias significativas en el porcentaje de carbón mineral entre los dos muestreos, sugiriendo que el derrame de carbón que ocurrió en el área en enero 2013 no resultó en un aumento del carbón en las playas, muy probablemente debido a la baja densidad que caracteriza al carbón. Se concluye que el porcentaje de carbón en todas las playas examinadas es menor al 0,1 % y que el aspecto negro en los sedimentos se debe a minerales inorgánicos, poco combustibles a 550 °C, con densidad >3 g*cm-3 y que constituyen entre 10 y 70 % del peso seco total de las muestras.

To quantify the percentage of unburnt coal in beach sediments from the department of Magdalena (Colombia) a simple procedure was devised to separate the sediment mineral phases according to their density. Sediments were collected from six beaches, at two tidal heights, in November 2012 and February 2013, before and after a spill from a coal barge that occurred on 12 January 2013. Sediments were dried, suspended in an aqueous solution of sodium polytungstate (density: 2.0 g*cm-3) and centrifuged. Because coal has a lower density (1.2-1.9 g*cm-3) than other inorganic minerals and rocks, any coal particle present in a sample concentrated in the suspended fraction, whereas more dense particles settled. To remove organic matter not corresponding to coal, the light fraction was subsequently subjected to a weak oxidation with hydrogen peroxide. To estimate an upper limit for any coal present, weight loss on ignition at 550 °C was determined for whole sediments. For the six beaches examined, the maximum weight loss on ignition was 2.4 % and the weight percentage of the light fraction (with a density < 2 g*cm-3) and resistant to oxidation by H2O2 was 0.07 % in November 2012 and 0.02 % in February 2013. No significant differences in coal content were found between the two sampling events, suggesting that the coal spill that occurred in January 2013 did not result in an increase in coal accumulation on the beaches, probably due to coal's characteristic low density. We conclude that the weight percentage of carbon in the six beaches investigated is less than 0.1 % and that sediments owe their black appearance to inorganic minerals, poorly-combustible at 550 °C, with a density > 3 g*cm-3, which comprise between 10-70 % of the total sediment dry weight.

PSA enzymatic activity: a new biomarker for assessing prostate cancer aggressiveness.

BACKGROUND: With the advent of widespread prostate-specific antigen (PSA) testing in recent decades, prostate cancer (PCa) has emerged as the most frequently diagnosed non-skin cancer among men in the U.S. and Europe. Greater screening rates coupled with improved detection methods have caused a controversial upsurge in the number of men undergoing prostate biopsy and subsequent treatment. However, current diagnostic techniques generally suffer from limited ability to identify which seemingly indolent cancers are biologically aggressive. METHODS: We collected prostatic fluid from 778 post-radical prostatectomy specimens and randomly selected samples from both the clinically confirmed aggressive (n = 50) and non-aggressive (n = 50) prostate cancer populations. We measured the level of proteolytic enzyme activity of PSA (aPSA) in each sample and used receiver operating characteristic (ROC) analysis to correlate aPSA levels with prostate cancer aggressiveness. RESULTS: We found aPSA in prostatic fluid to be inversely proportional to disease stage, such that patients with the most aggressive PCa have on average significantly reduced aPSA compared to those with less aggressive disease. Significantly, our results suggest that many (22% in our study population) of the diagnosed patients with non-aggressive PCa could have averted or delayed radical prostatectomy. CONCLUSIONS: Given the high level of debate surrounding PSA screening effectiveness [3-5] and the recent U.S. Preventative Services Task Force recommendation to discontinue PSA screening [6], our results provide renewed hope that a clinical monitoring tool may emerge that truly refines PCa treatment decision-making.

Spectroscopic and redox properties of amine-functionalized K2[OsII(bpy)(CN)4] complexes.

We report the first examples of amine-functionalized K(2)[Os(II)(bpy)(CN)(4)] (bpy = 2,2'-bipyridine) complexes. The tetracyanoosmate complexes were prepared by UV irradiation (λ = 254 nm) of K(4)[Os(II)(CN)(6)] and primary amine-functionalized bpy ligands in acidic aqueous media. The aqueous solution pH dependences of the spectroscopic and redox properties of 4,4'- and 5,5'-substituted complexes have been investigated. The pendant amine functional groups and coordinated cyanide ligands are basic sites that can be sequentially protonated, thereby allowing systematic tuning of electrochemical and optical spectroscopic properties.

A source mixing model to apportion PAHs from coal tar and asphalt binders in street pavements and urban aquatic sediments.

Present-day and more than 30 years old road and footpath pavements from Auckland, New Zealand were analysed for PAHs to test the hypothesis that coal tar based pavement binders contribute to unusually high PAH concentrations in adjacent stream and estuarine sediments. Total PAH (∑(28)PAH) concentrations in the dichloromethane-soluble fraction ("binder"), comprising 5-10% of pavement mass, were as high as 200,000 mgkg(-1) (10,000 mgkg(-1) in binder+aggregate). Older and deeper pavement layers were strongly pyrogenic, whereas pavement layers from recently sealed roads had a more petrogenic composition and more than 1000 times lower ∑(28)PAH concentrations. Source identification analysis using three PAH isomer ratio pairs (benz(a)anthracene/(benz(a)anthracene+chrysene); benzo(a)pyrene/(benzo(a)pyrene+benzo(e)pyrene); and indeno(1,2,3-cd)pyrene/(indeno(1,2,3-cd)pyrene+benzo(g,h,i)perylene) revealed low PAH (bitumen) pavements to have consistently lower isomer ratios than high PAH (coal tar) samples. Moreover, pavement data for one isomer ratio (e.g. benzo(a)pyrene/(benzo(a)pyrene+benzo(e)pyrene) were highly correlated with those of another isomer ratio (e.g. benz(a)anthracene/(benz(a)anthracene+chrysene) and were bounded at their lower and higher extremes by the characteristics of pure bitumen and coal tar, respectively, suggesting that PAH composition of a given pavement sample could be accounted for by conservative mixing between coal tar and bitumen as source materials. A concentration-weighted mixing model, with coal tar and bitumen as source materials, explained more than 80% of the variance in isomer ratios and enveloped the entire PAH compositional and concentration range encountered. PAH composition and concentrations in adjacent stream sediments (> 15 mgkg(-1) dry weight) were consistent with diluted coal tar material as a principal PAH source. Due to the very high PAH concentrations of coal tar, a coal tar content of as little as 0.01% of total sediment mass can account for more than 90% of PAH concentrations in adjacent stream sediments.

Ferrocene and maleimide-functionalized disulfide scaffolds for self-assembled monolayers on gold.

A series of ferrocene-based electroactive molecules (EAMs) containing maleimide and disulfide groups in different asymmetric and branched architectures were designed and synthesized. Stable monolayers of each EAM on gold electrodes were confirmed by cyclic voltammetry. Importantly, these EAMs expand the repertoire of monolayer building blocks amenable to modular biofunctionalization for applications in electrochemical biosensor fabrication.

The restoration of lumbar intervertebral disc load distribution: a comparison of three nucleus replacement technologies.

STUDY DESIGN: A validated L3-L4 nonlinear finite element model was used to evaluate strain and pressure in the surrounding structures for 4 nucleus replacement technologies. OBJECTIVE: The objective of the current study was to compare subsidence and anular damage potential between 4 current nucleus replacement technologies. It was hypothesized that a fully conforming nucleus replacement would minimize the risk of both subsidence and anular damage. SUMMARY OF BACKGROUND DATA: Nucleus pulposus replacements are emerging as a less invasive alternative to total disc replacement and fusion as a solution to degenerative intervertebral discs. Multiple technologies have been developed and are currently undergoing clinical investigation. METHODS: The testing conditions were applied by excavating the nucleus of the intact model and virtually implanting models representing the various nucleus replacement technologies. The implants consisted of a conforming injectable polyurethane (E = 4 MPa), soft hydrogel (E = 4 MPa), stiff hydrogel (E = 20 MPa), and polyether-etherketone (PEEK) on PEEK articulating designs. The model was exercised in flexion, extension, lateral bending, axial rotation (7.5 Nm with 450 N preload), and compression (1000 N). Vertebral body strain, anular maximum shear strain, endplate contact pressure, anulus-implant contact pressure, and bone remodeling stimulus were reported. RESULTS: The PEEK implant induced strain maxima in the vertebral bodies with associated endplate contact pressure concentrations. For the PEEK and hydrogel implants, areas of nonconformity with the endplate indicated adjacent bone resorption. Lack of conformity between the implant and inner anulus for the PEEK and hydrogel implants resulted in inward anular bulging with associated increased maximum shear strain. The conforming polyurethane implant maintained outward bulging of the inner anular wall and indicated no bone resorption or stress shielding adjacent to the implant. CONCLUSION: A fully conforming nucleus replacement resulted in a decreased propensity for subsidence, anular bulging, and further degeneration of the anulus when compared with nonconforming implants.

Nucleus replacement with the DASCOR disc arthroplasty device: interim two-year efficacy and safety results from two prospective, non-randomized multicenter European studies.

STUDY DESIGN: A prospective, nonrandomized multicenter study of lumbar disc nucleus replacement using the DASCOR Disc Arthroplasty Device. An interim analysis of clinical results is presented, obtained from European patients enrolled in 2 studies. OBJECTIVE: To determine the safety and efficacy of the DASCOR Device for the treatment of symptomatic single-level degenerative disc disease (DDD). SUMMARY OF BACKGROUND DATA: Patients suffering from DDD have been limited to a choice between nonoperative therapies or invasive surgical treatments such as total disc replacement or spinal fusion. The DASCOR Device was developed to provide an alternative treatment with a less invasive surgical intervention. METHODS: A total of 85 patients from 11 European centers were enrolled in 1 of 2 studies between February 2003 and July 31, 2007. Data were collected before surgery and after surgery at 6 weeks and at 3, 6, 12, and 24 months. The clinical outcome measures were obtained from the Visual Analog Scale (VAS) for back pain, the Oswestry Disability Index (ODI), radiographic assessments, and records of analgesic medication use. RESULTS: Mean VAS and ODI scores improved significantly after 6 weeks and throughout the 2 years. Radiographic results demonstrated, at a minimum, maintenance of disc height with no device expulsion and, despite Modic-Type 1 changes, no subsidence. Fourteen patients had serious adverse events including device explants in 7 patients (7 of 85), in which the main complication was resumed back pain after time. Patients' rate of analgesic medication decreased dramatically over time, with all patients experiencing significant improvements after 3 months and nearly no analgesic medication or narcotic drug use at 2 years. CONCLUSION: The interim outcomes showed significant improvements in mean ODI and VAS scores. The results of these European studies suggest that the DASCOR Device may be a safe and effective less-invasive surgical option for patients with DDD.

Electroactive self-assembled monolayers on gold via bipodal dithiazepane anchoring groups.

Novel dithiazepane-functionalized ferrocenyl-phenylethynyl oligomers 1 and 2 have been synthesized. Self-assembled monolayers (SAMs) of these ferrocene derivatives have been studied by X-ray photoelectron spectroscopy, ellipsometry, and cyclic voltammetry. It has been shown by XPS that monolayers of the dithiazepane-anchored molecules on gold electrodes contain gold-thiolate species. Cyclic voltammetry of the SAMs were characteristic of stable electroactive monolayers even for single-component SAMs of 1 and 2, with the more ideal responses recorded for the two-component SAMs diluted with undecanethiol. The small variation in peak splittings at progressively higher scan rates in these SAMs makes dithiazepane-bridged redox species promising candidates for further studies on molecular wires with bipodal anchoring.

Direct observation of the preference of hole transfer over electron transfer for radical ion pair recombination in donor-bridge-acceptor molecules.

Understanding how the electronic structures of electron donor-bridge-acceptor (D-B-A) molecules influence the lifetimes of radical ion pairs (RPs) photogenerated within them (D+*-B-A-*) is critical to designing and developing molecular systems for solar energy conversion. A general question that often arises is whether the HOMOs or LUMOs of D, B, and A within D+*-B-A-* are primarily involved in charge recombination. We have developed a new series of D-B-A molecules consisting of a 3,5-dimethyl-4-(9-anthracenyl)julolidine (DMJ-An) electron donor linked to a naphthalene-1,8:4,5-bis(dicarboximide) (NI) acceptor via a series of Phn oligomers, where n = 1-4, to give DMJ-An-Phn-NI. The photoexcited charge transfer state of DMJ-An acts as a high-potential photoreductant to rapidly and nearly quantitatively transfer an electron across the Phn bridge to produce a spin-coherent singlet RP 1(DMJ+*-An-Phn-NI-*). Subsequent radical pair intersystem crossing yields 3(DMJ+*-An-Phn-NI-*). Charge recombination within the triplet RP then gives the neutral triplet state. Time-resolved EPR spectroscopy shows directly that charge recombination of the RP initially produces a spin-polarized triplet state, DMJ-An-Phn-3*NI, that can only be produced by hole transfer involving the HOMOs of D, B, and A within the D-B-A system. After the initial formation of DMJ-An-Phn-3*NI, triplet-triplet energy transfer occurs to produce DMJ-3*An-Phn-NI with rate constants that show a distance dependence consistent with those determined for charge separation and recombination.

Photoinduced charge separation in self-assembled cofacial pentamers of zinc-5,10,15,20-tetrakis(perylenediimide)porphyrin.

A bichromophoric electron donor-acceptor molecule composed of a zinc tetraphenylporphyrin (ZnTPP) surrounded by four perylene-3,4:9,10-bis(dicarboximide)(PDI) chromophores (ZnTPP-PDI(4)) was synthesized. The properties of this molecule were compared to a reference molecule having ZnTPP covalently bound to a single PDI (ZnTPP-PDI). In toluene, ZnTPP-PDI(4) self-assembles into monodisperse aggregates of five molecules arranged in a columnar stack, (ZnTPP-PDI(4))(5). The monodisperse nature of this assembly contrasts sharply with previously reported ZnTPP-PDI(4) derivatives having 1,7-bis(3,5-di-t-butylphenoxy) groups (ZnTPP-PPDI(4)). The size and structure of this assembly in solution was determined by small angle X-ray scattering (SAXS) using a high flux synchrotron X-ray source. The ZnTPP-PDI reference molecule does not aggregate. Femtosecond transient absorption spectroscopy shows that laser excitation of both ZnTPP-PDI and (ZnTPP-PDI(4))(5) results in quantitative formation of ZnTPP(+*)-PDI(-*) radical ion pairs in a few picoseconds. The transient absorption spectra of (ZnTPP-PDI(4))(5) suggest that the PDI(-*) radicals interact strongly with adjacent PDI molecules within the columnar stack. Charge recombination occurs more slowly within (ZnTPP-PDI(4))(5)(tau= 4.8 ns) than it does in ZnTPP-PDI (tau= 3.0 ns) producing mostly ground state as well as a modest yield of the lowest triplet state of PDI ((3*)PDI). Formation of (3*)PDI occurs by rapid spin-orbit induced intersystem crossing (SO-ISC) directly from the singlet radical ion pair as evidenced by the electron spin polarization pattern exhibited by its time-resolved electron paramagnetic resonance spectrum.

Time-resolved EPR studies of photogenerated radical ion pairs separated by p-phenylene oligomers and of triplet states resulting from charge recombination.

Photoexcitation of a series of donor-bridge-acceptor (D-B-A) systems, where D = phenothiazine (PTZ), B = p-phenylene (Phn), n = 1-5, and A= perylene-3,4:9,10-bis(dicarboximide) (PDI) results in rapid electron transfer to produce 1(PTZ+*-Phn-PDI-*). Time-resolved EPR (TREPR) studies of the photogenerated radical pairs (RPs) show that above 150 K, when n = 2-5, the radical pair-intersystem crossing mechanism (RP-ISC) produces spin-correlated radical ion pairs having electron spin polarization patterns indicating that the spin-spin exchange interaction in the radical ion pair is positive, 2J > 0, and is temperature dependent. This temperature dependence is most likely due to structural changes of the p-phenylene bridge. Charge recombination in the RPs generates PTZ-Phn-3*PDI, which exhibits a spin-polarized signal similar to that observed in photosynthetic reaction-center proteins and some biomimetic systems. At temperatures below 150 K and/or at shorter donor-acceptor distances, e.g., when n = 1, PTZ-Phn-3*PDI is also formed from a competitive spin-orbit-intersystem crossing (SO-ISC) mechanism that is a result of direct charge recombination: 1(PTZ+*-Phn-PDI-*) --> PTZ-Phn-3*PDI. This SO-ISC mechanism requires the initial RP intermediate and depends strongly on the orientation of the molecular orbitals involved in the charge recombination as well as the magnitude of 2J.

Bis(n-octylamino)perylene-3,4:9,10-bis(dicarboximide)s and their radical cations: synthesis, electrochemistry, and ENDOR spectroscopy.

1,6- and 1,7-bis(n-octylamino)perylene-3,4:9,10-bis(dicarboximide) were synthesized by reaction of n-octylamine with the corresponding dibromo compounds. These compounds display intense charge-transfer optical transitions in the visible spectrum (approximately 550-750 nm) and fluoresce weakly (Phi(F) < 0.06). Cyclic voltammetry reveals that each chromophore undergoes facile and reversible oxidation and reduction. Spectroelectrochemical studies show that the radical cations of these chromophores are stable and show no signs of deprotonation of the secondary amines. Electron paramagnetic resonance (EPR) and electron-nuclear double resonance (ENDOR) studies of the chemically generated radical cations of these chromophores corroborate the spectroelectrochemical data by showing that the radical cations persist for days at room temperature in methylene chloride solution. These experiments and complementary density functional theory (DFT) calculations provide a comprehensive picture of the molecular orbitals, spin density distributions, and geometries of the radical cations. The redox properties and stability of these alkylamino-functionalized perylene compounds make them a valuable addition to the family of robust perylene-based chromophores that can be used to develop new photoactive charge transport materials.