Ultra-soft X-ray system for imaging the early cellular responses to X-ray induced DNA damage.

The majority of the proteins involved in processing of DNA double-strand breaks (DSBs) accumulate at the damage sites. Real-time imaging and analysis of these processes, triggered by the so-called microirradiation using UV lasers or heavy particle beams, yielded valuable insights into the underlying DSB repair mechanisms. To study the temporal organization of DSB repair responses triggered by a more clinically-relevant DNA damaging agent, we developed a system coined X-ray multi-microbeam microscope (XM3), capable of simultaneous high dose-rate (micro)irradiation of large numbers of cells with ultra-soft X-rays and imaging of the ensuing cellular responses. Using this setup, we analyzed the changes in real-time kinetics of MRE11, MDC1, RNF8, RNF168 and 53BP1-proteins involved in the signaling axis of mammalian DSB repair-in response to X-ray and UV laser-induced DNA damage, in non-cancerous and cancer cells and in the presence or absence of a photosensitizer. Our results reveal, for the first time, the kinetics of DSB signaling triggered by X-ray microirradiation and establish XM3 as a powerful platform for real-time analysis of cellular DSB repair responses.

How does injury compensation affect health and disability in patients with complaints of whiplash? A qualitative study among rehabilitation experts-professionals.

PURPOSE: To explore rehabilitation professionals' opinions about the influence and the pathways of injury compensation (IC) on health and disability in patients with whiplash associated disorder (WAD). METHODS: Semi-structured interviews were performed among a purposeful selected sample of Dutch expert-professionals in the field of rehabilitation of patients with WAD. Inclusion continued until saturation was reached. Inductive and deductive thematic analyses were performed. RESULTS: Ten rehabilitation expert-professionals (five females), working as physician, psychologist or physiotherapist, were interviewed. All expert-professionals acknowledged that IC can influence rehabilitation, health and disability. The expert-professionals provided three causal pathways; a pathway through prolonged distress, a behavioral pathway, and patient characteristics that may either attenuate or worsen their response. They assess the influence of IC mainly with interview techniques. Most professionals discuss the potential influence of IC with their patients, because they want to give clear information to the patient. Some emphasize that their role is neutral in relation with the IC. Others mention that financial consequences can accompany functional improvement. CONCLUSIONS: Rehabilitation expert-professionals believe that IC may affect rehabilitation, health and disability in patients with WAD. Three pathways are mentioned by the experts-professionals. IMPLICATIONS FOR REHABILITATION: According to rehabilitation expert-professionals, an injury compensation (IC) can lead to distress, by creating a (conscious or unconscious) conflict of interests within a patient between striving for compensation on one hand, and recovery on the other hand. Patient characteristics can either attenuate or worsen IC-related distress. Reliable and valid tools need to be developed to assess the influence of IC on health, disability and rehabilitation, and to limit the negative effects. Rehabilitation professionals can discuss the possible unintended effects of IC with their patients to clarify their current situation.

The association of clinical and microbiologic parameters with histologic observations in relatively healthy peri-implant conditions- a preliminary short-term in vivo study.

PURPOSE: To determine whether clinical findings-bleeding on probing, pocket depth, recession, and bacterial sampling-correlate with histologic outcomes in relatively healthy peri-implant soft tissues in people. MATERIALS AND METHODS: In this cross-sectional study, a convenience sample of 20 edentulous subjects received two endosseous mandibular implants each. The abutments were either zirconia (ZrO2) or titanium (Ti) (nonsubmerged implant placement, within-subject comparison, leftright randomization). Sulcular bacterial sampling and assessment of probing pocket depth, recession, and bleeding on probing were performed 3 months postsurgery. Mucosal biopsy specimens were obtained, and the blood vessel density and a score on an inflammation grading scale were determined. RESULTS: Simple linear and linear regression models revealed that the clinical or microbiologic parameters were not associated with either of the histologic parameters. The soft tissues impressed as healthy, regardless of the abutment material. CONCLUSIONS: The peri-implant mucosa around ZrO2and Ti abutments was considered healthy in most situations when examined histologically after 3 months but showed variation in clinical and microbiologic parameters.

Relationship between self-reported disability and functional capacity in patients with whiplash associated disorder.

PURPOSE: Patients with chronic Whiplash Associated Disorders (WAD) report symptoms and disability. Neither the relationship between self-reported disability and functional capacity, nor its predictors have been investigated in patients with WAD. This was the purpose of this study. METHOD: This was a cross-sectional study. Participants were patients with WAD on sick leave. Self-reported disability was assessed with the Neck Disability Index (NDI). Functional capacity was assessed with a six-item neck functional capacity evaluation (FCE). Correlation coefficients were used to express the relationship between NDI (total and items) and FCE. Multivariate linear regression analyses were performed to identify independent predictors of NDI and FCE. RESULTS: Forty patients were measured, of whom 18 (45 %) were male. Mean age was 33 years, median duration of complaints was 12 months, and 75 % had a pending insurance claim. Correlations between NDI and FCE tests varied from -0.39 to -0.70. Independent predictors of NDI were pain intensity and a pending claim, explaining 43 % of the variance. independent predictors of fce were ndi, gender, and pain intensity, explaining 20-55 % of the variance. CONCLUSIONS: Self-reported disability and functional capacity are related but different. Both can part be predicted by pain intensity. A pending claim can predict higher self-reported disability. Both constructs are complementary and are recommended to determine disability in patients with WAD comprehensively.

Which instruments can detect submaximal physical and functional capacity in patients with chronic nonspecific back pain? A systematic review.

STUDY DESIGN: Systematic review. OBJECTIVE: To evaluate the validity of instruments that claim to detect submaximal capacity when maximal capacity is requested in patients with chronic nonspecific musculoskeletal pain. SUMMARY OF BACKGROUND DATA: Several instruments have been developed to measure capacity in patients with chronic pain. The detection of submaximal capacity can have major implications for patients. The validity of these instruments has never been systematically reviewed. METHODS: A systematic literature search was performed including the following databases: Web of Knowledge (including PubMed and Cinahl), Scopus, and Cochrane. Two reviewers independently selected the articles based on the title and abstract according to the study selection criteria. Studies were included when they contained original data and when they objectified submaximal physical or functional capacity when maximal physical or functional capacity was requested. Two authors independently extracted data and rated the quality of the articles. The included studies were scored according to the subscales "Criterion Validity" and "Hypothesis Testing" of the COSMIN checklist. A Best Evidence Synthesis was performed. RESULTS: Seven studies were included, 5 of which used a reference standard for submaximal capacity. Three studies were of good methodological quality and validly detected submaximal capacity with specificity rates between 75% and 100%. CONCLUSION: There is strong evidence that submaximal capacity can be detected in patients with chronic low back pain with a lumbar motion monitor or visual observations accompanying a functional capacity evaluation lifting test.

Structural properties of subnanometer thick Y layers in extreme ultraviolet multilayer mirrors.

We studied the structure and optical properties of B(4)C/Mo/Y/Si multilayer systems. Using extended x-ray absorption fine structure measurements at the Y and Mo K-edge, the structure of the subnanometer thick Y layer and the underlying Mo layer were analyzed. It was found that even a 0.2 nm thick Y layer significantly reduced silicon diffusion toward Mo, thus reducing Mo silicide formation. Hard x-ray reflectometry showed that the difference in average interface roughness of the B(4)C/Mo/Y/Si multilayer structure compared to Mo/Si and B(4)C/Mo/B(4)C/Si multilayer structures was negligible. Soft x-ray reflectometry showed optical improvement of B(4)C/Mo/Y/Si with respect to Mo/Si and B(4)C/Mo/B(4)C/Si multilayer structures.

Soft tissue response to zirconia and titanium implant abutments: an in vivo within-subject comparison.

AIM: To compare the health of the soft tissues towards zirconia and titanium abutments in man, as observed using histological data. MATERIAL AND METHODS: Twenty patients received two mandibular implants with either a zirconia or titanium abutment (split mouth study design, left-right randomization). After 3 months soft tissue biopsies were prepared for histological evaluation. They were subjected to blind evaluation. The number of blood vessels per surface unit and an inflammation grading scale score ranging from 1 to 4 were determined. RESULTS: Paired samples from 17 patients were suitable for analysis, 3 with unsevered implant-abutment connections and 14 solely containing soft tissue. All showed a well-keratinized stratified squamous epithelium which was continuous with the barrier (junctional) epithelium that faced the abutment surface. The normal epithelial build-up could be recognized with little signs of inflammation. No statistically significant difference in tissues adjacent to zirconia and titanium abutment surfaces were seen with respect to vascular density (20.5 SD 4.4 and 20.7 SD 3.2) or inflammation grading scale scores (3.2 SD 0.7 versus 3.1 SD 0.7). CONCLUSION: No differences in soft tissue health were seen in peri-implant mucosa adjacent to zirconia and titanium abutment surfaces.

Radiographic features of mandibular trabecular bone structure in hypodontia.

PURPOSE: Radiographic parameters of mandibular trabecular bone structure between 67 subjects having hypodontia and those without were studied on digital panoramic radiographs. MATERIALS AND METHODS: Three regions of interest (ROI) were defined: the ascending ramus, apical of the mandibular molar and mesial of the first mandibular molar. The effects of the presence of hypodontia and the ROI on the mandibular trabecular bone structure were tested for statistical significance by means of multivariate analysis. RESULTS: Radiographic parameters of trabecular bone architecture were found to differ between various regions of the mandible (p = 0.000), but not between the group of hypodontia subjects and their controls (p = 0.23). There was no interaction effect between the ROIs and the two groups (p = 0.79). For people having hypodontia, some directional parameters of trabecular bone have a reverse correlation with the number of missing teeth. The fractal dimension and the number and perimeter of white segments in the binarized image correlate positively with the number of congenitally missing teeth. CONCLUSIONS: A limited number of parameters of radiographic mandibular trabecular bone structure correlate with the number of missing teeth. However, a markable difference in radiographic parameters of mandibular trabecular bone structure between hypodontia and non-hypodontia subjects could not be demonstrated.

Early bacterial colonization and soft tissue health around zirconia and titanium abutments: an in vivo study in man.

AIM: To compare the early bacterial colonization and soft tissue health of mucosa adjacent to zirconia (ZrO(2)) and titanium (Ti) abutment surfaces in vivo. MATERIALS AND METHODS: Twenty edentulous subjects received two endosseous mandibular implants. The implants were fitted with either a ZrO(2) or a Ti abutment (non-submerged implant placement, within-subject comparison, left-right randomization). Sulcular bacterial sampling and the assessment of probing pocket depth, recession and bleeding on probing were performed at 2 weeks and 3 months post-surgery. Wilcoxon matched-pairs, sign-rank tests were applied to test differences in the counts of seven marker bacteria and the clinical parameters that were associated with the ZrO(2) and Ti abutments, at the two observation time points. RESULTS: ZrO(2) and Ti abutments harboured similar counts of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, Peptostreptococcus micros, Fusobacterium nucleatum and Treponema denticola at 2 weeks and 3 months. Healthy clinical conditions were seen around both ZrO(2) and Ti abutments at all times, without significant differences in most clinical parameters of peri-implant soft tissue health. Mean probing depths around Ti abutments were slightly deeper than around ZrO(2) abutments after 3 months (2.2 SD 0.8 mm vs. 1.7 SD 0.7 mm, P=0.03). CONCLUSIONS: No difference in health of the soft tissues adjacent to ZrO(2) and Ti abutment surfaces or in early bacterial colonization could be demonstrated, although somewhat shallower probing depths were observed around ZrO(2) abutments after 3 month.

Bone structure changes in iliac crest grafts combined with implants.

BACKGROUND: Remodeling of onlay grafts combined with implants to the mandible results in predictable changes in the graft's radiographic density. We studied the relationship between changes in radiographic density and trabecular structure during the first year after onlay grafting with simultaneous implant placement to the mandible. PURPOSE: The aim of this study was to evaluate changes in bone structure after onlay grafting. MATERIALS AND METHODS: Standardized extraoral radiographs were taken regularly of 16 mandibular sides. Bone structure was measured using the Carl Zeiss Vision KS 400 3.0 imaging system. The parameters studied were trabecular area and perimeter, cavity area and perimeter, end points, branching points, skeleton length, branch angle and direction, and texture. RESULTS: No differences were found between measurements ventrally versus dorsally of the implant, nor close to versus away from the implant. Early cortical changes suggest partial resorption and formation of a more complex structure. In the fourth quarter after surgery, progressive resorption is seen in the graft's upper cortex. In the graft's upper spongiosa, most parameters indicate bone formation during the first postoperative year. Loading-induced structure changes could not yet be found. CONCLUSION: The technique can be used to study changes in the architecture of bone grafts. Changes found in the graft's architecture are in accordance with changes in bone density.

Dental implants in persons with severe epilepsy and multiple disabilities: a long-term retrospective study.

PURPOSE: A retrospective study on the performance of endosseous implants in a population of patients with severe epilepsy and additional motor and/or intellectual impairments was performed. MATERIALS AND METHODS: All residents of an inpatient center for persons affected by severe, refractory epilepsy and multiple disabilities who received endosseous implants between 1991 and April 2007 were included in the study. Implant survival was analyzed using the Kaplan-Meier method. A subset of patients who were treated between 1991 and 2004 was invited to participate in a clinical and radio?graphic evaluation in 2004 and 2005. RESULTS: A total of 61 patients were treated between 1991 and April 2007 (n=134 implants). Three of these implants in three different patients failed during the observation period, demonstrating an estimated probability of functional implant survival of 97.6% (SE 1.4%) after 16 years. In patients who were seen during the clinical evaluation in 2004 (n=76 implants), only mild inflammation of the peri-implant mucosa was generally observed (Gingival-Bleeding Index=1), despite the fact that the level of oral hygiene was considered inadequate around 55 of 76 implants (72%). Obvious signs of drug-induced gingival hyperplasia in relation to the implants were not observed. Probing depths averaged approximately 2 mm. Stable marginal bone levels were observed on the radiographs. CONCLUSIONS: Dental implant treatment in a population of patients with severe epilepsy and additional disabilities seems to be a viable treatment option. Implant loss is rare. Although adequate plaque control was not feasible in all patients, marginal bone levels remained stable.

An ultrasoft X-ray multi-microbeam irradiation system for studies of DNA damage responses by fixed- and live-cell fluorescence microscopy.

Localized induction of DNA damage is a valuable tool for studying cellular DNA damage responses. In recent decades, methods have been developed to generate DNA damage using radiation of various types, including photons and charged particles. Here we describe a simple ultrasoft X-ray multi-microbeam system for high dose-rate, localized induction of DNA strand breaks in cells at spatially and geometrically adjustable sites. Our system can be combined with fixed- and live-cell microscopy to study responses of cells to DNA damage.

Comment: Electron-transfer reactions in the 9-mesityl-10-methylacridinium ion: impurities, triplet states and infinitely long-lived charge-shift states?

The likelihood of an infinitely long-lived, charge-shift state being formed by the target compound is re-assessed in light of persistent claims that such chemistry is both viable and observable.

Ultrafast intersystem crossing in 9,10-anthraquinones and intramolecular charge separation in an anthraquinone-based dyad.

Femtosecond transient absorption spectroscopy was employed to determine quantitatively the ultrafast S1-T1 intersystem crossing in a 2-substituted 9,10-anthraquinone derivative (3), kisc = 2.5 x 10(12) s-1. Notwithstanding this rapid process, photoexcitation of dyad 1 is followed by competition between intersystem crossing and intramolecular charge separation, the latter leading to a short-lived (2 ps) singlet charge-transfer (CT) state. The local triplet state itself undergoes slower charge separation to populate a relatively long-lived (130 ns) triplet CT state. An earlier report about the formation of an extremely long-lived CT state (> 900 micros) in 1 was found to be erroneous and was related to the sacrificial photo-oxidation of the dimethylsulfoxide solvent used in that study. Finally, some important criteria have been formulated for future experimental validation of "unusually long-lived" CT states.

Permucosal implants combined with iliac crest onlay grafts used in extreme atrophy of the mandible: long-term results of a prospective study.

Thirteen patients received an onlay bone-graft augmentation to their severely atrophic mandible in combination with simultaneous implant insertion. This treatment modality was studied in a long-term prospective clinical and radiographic study. A reproducible measurement method, consisting of oblique lateral cephalometric radiographs, in combination with an image analysis system, was used to accurately assess the graft resorption rate. On average, 51% (95% confidence interval 42-61%) of the grafted bone height remained after 10-11 years. Resorption of the graft occurred mainly during the first years and showed a marked degree of individual variance. In the following years, the resorption rate followed a predictable pattern in most of our patients. Ventral and dorsal sites exhibited a similar degree of resorption. Peri-implantitis occurred in nine patients. Ten muco-gingival surgical interventions were necessary in four of these nine patients. No implants were lost and 12 patients indicated that they were satisfied. It is concluded that the described surgical technique should be used on stringent indication only, and alternative techniques are discussed.

Long-lived charge-transfer states in compact donor-acceptor dyads.

Photoinduced electron transfer is a widely applied method to convert photon energy into a useful (electro)chemical potential, both in nature and in artificial devices. There is a continuing effort to develop molecular systems in which the charge-transfer state, populated by photoinduced electron transfer, survives sufficiently long to tap the energy stored in it. In general this has been found to require the construction of rather complex molecular systems, but more recently a few approaches have been reported that allow the use of much more simple and relatively small electron donor-acceptor dyads for this purpose. The most successful examples of such systems seem to be those that apply "electron spin control" to slow down the spontaneous decay of the charge-transfer state, and these are reviewed in this minireview, with a discussion of the underlying principles and a critical evaluation of some of the claims made with regard to using a pronounced "inverted-region effect" as an alternative method to prolong the lifetime of charge-transfer states.

Charge shift and triplet state formation in the 9-mesityl-10-methylacridinium cation.

The target donor-acceptor compound forms an acridinium-like, locally excited (LE) singlet state on illumination with blue or near-UV light. This LE state undergoes rapid charge transfer from the acridinium ion to the orthogonally sited mesityl group in polar solution. The resultant charge-transfer (CT) state fluoresces in modest yield and decays on the nanosecond time scale. The LE and CT states reside in thermal equilibrium at ambient temperature; decay of both states is weakly activated in fluid solution, but decay of the CT state is activationless in a glassy matrix. Analysis of the fluorescence spectrum allows precise location of the relevant energy levels. Intersystem crossing competes with radiative and nonradiative decay of the CT state such that an acridinium-like, locally excited triplet state is formed in both fluid solution and a glassy matrix. Phosphorescence spectra position the triplet energy well below that of the CT state. The triplet decays via first-order kinetics with a lifetime of ca. 30 micros at room temperature in the absence of oxygen but survives for ca. 5 ms in an ethanol glass at 77 K. The quantum yield for formation of the LE triplet state is 0.38 but increases by a factor of 2.3-fold in the presence of iodomethane. The triplet reacts with molecular oxygen to produce singlet molecular oxygen in high quantum yield. In sharp contradiction to a recent literature report, there is no spectroscopic evidence to indicate the presence of an unusually long-lived CT state.

Electron transfer at the single-molecule level in a triphenylamine-perylene imide molecule.

Photoinduced electron transfer (ET) processes in a donor-acceptor system based on triphenylamine and perylene imide have been studied at the single-molecule (SM) and ensemble levels. The system exists as two isomers, one of which undergoes forward and reverse ET in toluene with decay constants of 3.0 and 2.2x10(9) s(-1), respectively, resulting in the dual emission of quenched and delayed fluorescence while the other isomer remains ET-inactive. The fluorescence of both isomers is heavily quenched in the more polar solvent, diethyl ether, by ET. A broad range of ET dynamics is seen at the SM level in polystryene with the two isomers nonresolvable indicating that the local nanoenvironment of the SMs varies considerably throughout the polymer matrix. Both the electronic coupling and the driving force for ET are shown to influence the ET dynamics. Many fluorescence trajectories of SMs show long periods (tens of milliseconds to seconds) where the count rate is attenuated either partly (a "dim" state) or to the background level (an "off-time"). During these periods, the reduction or interruption of emission is attributed to cycles of rapid charge separation followed by charge recombination to the ground state reducing the fluorescence quantum yield of the SM.

Illumination of the 9-mesityl-10-methylacridinium ion does not give a long-lived photoredox state.

Photolysis of the 9-mesityl-10-methylacridinium cation in benzonitrile forms an acridinyl radical, detected by EPR and UV-visible spectroscopy, by way of a sacrificial process.