Effect of femtosecond laser interaction with human fibroblasts: a preliminary study.

In in vitro methods and cell culture models, femtosecond (fs) laser interaction has been employed to assess its effect on the proliferation and morphology of human skin fibroblasts. We cultured a primary human skin fibroblast cell line on a glass plate, passages 17-23. The cells were irradiated with a 90-fs laser at a wavelength of 800 nm and a repetition rate of 82 MHz. The target received an average power of 320 mW for 5, 20, and 100 s, corresponding to the radiation exposures of 22.6, 90.6, and 452.9 J/cm2, respectively. Using a laser scanning microscopy technique, the photon densities were measured to be 6.4 × 1018, 2.6 × 1019, and 1.3 × 1020 photons/cm2 in a spot area of 0.07 cm2; the recorded spectra were obtained from the laser interaction after 0.00, 1.00, 25.00, and 45.00 h. The cell count and morphological changes showed that the cultured cells were affected by laser irradiation under photon stress; some fibroblasts were killed, while others were injured and survived. We discovered evidence of the formation of several coenzyme compounds, such as flavin (500-600 nm), lipopigments (600-750 nm), and porphyrin (500-700 nm). This study is motivated by the future development of a novel, ultra-short fs laser system and the need to develop a basic in vitro understanding of photon-human cell interaction. The cell proliferation indicated that cells are partly killed or wounded. The exposure of fibroblasts to fs laser fluence up to 450 J/cm2 accelerates cell growth of the viable residual cell.

Effect of high-flow vs. low-flow nasal plus mouthguard oxygen therapy on hypoxaemia during sedation: a multicentre randomised controlled trial.

Whether high-flow vs. low-flow nasal oxygen reduces hypoxaemia for sedation during endoscopic retrograde cholangiopancreatography is currently unknown. In this multicentre trial, 132 patients ASA physical status 3 or higher, BMI > 30 kg.m-2 or with known or suspected obstructive sleep apnoea were randomly allocated to high-flow nasal oxygen up to 60 l.min-1 at 100% FI O2 or low-flow nasal oxygen at 4 l.min-1 . The low-flow nasal oxygen group also received oxygen at 4 l.min-1 through an oxygenating mouthguard, totalling 8 l.min-1 . Primary outcome was hypoxaemia, defined as Sp O2 < 90% regardless of duration. Hypoxaemia occurred in 7.7% (5/65) of patients with high-flow and 9.1% (6/66) with low-flow nasal oxygen (percentage point difference -1.4%, 95%CI -10.9 to 8.0; p = 0.77). Between the groups, there were no significant differences in frequency of hypoxaemic episodes; lowest Sp O2 ; peak transcutaneous carbon dioxide; hypercarbia (transcutaneous carbon dioxide > 2.66 kPa from baseline); requirement of chin lift/jaw thrust; nasopharyngeal airway insertion; bag-mask ventilation; or tracheal intubation. Following adjustment for duration of the procedure, the primary outcome remained non-significant. In high-risk patients undergoing endoscopic retrograde cholangiopancreatography, oxygen therapy with high-flow nasal oxygen did not reduce the rate of hypoxaemia, hypercarbia or the need for airway interventions, compared with combined oral and nasal low-flow oxygen.

Use of Imaging in Children With Witnessed Physical Abuse.

OBJECTIVE: Physicians are occasionally asked to evaluate children who are reported to have been victims of witnessed abuse, but who have no injuries noted on examination. The rate of injury in these patients is presently unknown. This is important because abuse allegations are brought for both altruistic and other reasons. This study compares the use of skeletal survey and neuroimaging in well-appearing and clearly injured children reported to be victims of witnessed child abuse. METHODS: Retrospectively planned secondary analysis of the Examination of Siblings to Recognize Abuse cohort of children referred to a child abuse pediatrician with concerns for physical abuse. Children were selected who presented to a medical provider with a history of witnessed child abuse including shaking. Rates of radiographically evident injuries are noted among children with and without injuries noted on physical examination. RESULTS: Among 2890 children evaluated by a child abuse pediatrician, 90 children (3.1%) presented with a history of witnessed abuse. Among these, 51 children (57%) had injuries noted on physical examination; 9 (29%) of 31 skeletal surveys and 9 (35%) of 26 neuroimaging studies revealed injuries. Of 39 children (43%) with witnessed abuse and normal examination, 3 (10%) of 30 skeletal surveys and 2 (8%) of 25 neuroimaging studies revealed an injury. CONCLUSIONS: A significant minority of children evaluated for allegations of witnessed abuse will have occult injuries identified radiographically. Absence of injury on examination should not deter physicians from obtaining otherwise indicated skeletal surveys and neuroimaging in children reported to have experienced witnessed abuse.

Cesarean delivery is not associated with decreased at-birth fracture rates in osteogenesis imperfecta.

PURPOSE: Osteogenesis imperfecta (OI) predisposes to recurrent fractures. Patients with the moderate to severe forms of OI present with antenatal fractures, and the mode of delivery that would be safest for the fetus is not known. METHODS: We conducted systematic analyses of the largest cohort of individuals with OI (n = 540) enrolled to date in the OI Linked Clinical Research Centers. Self-reported at-birth fracture rates were compared among individuals with OI types I, III, and IV. Multivariate analyses utilizing backward-elimination logistic regression model building were performed to assess the effect of multiple covariates, including method of delivery, on fracture-related outcomes. RESULTS: When accounting for other covariates, at-birth fracture rates did not differ based on whether delivery was by vaginal route or by cesarean delivery (CD). Increased birth weight conferred higher risk for fractures irrespective of the delivery method. In utero fracture, maternal history of OI, and breech presentation were strong predictors for choosing CD. CONCLUSION: Our study, the largest to analyze the effect of various factors on at-birth fracture rates in OI, shows that CD is not associated with decreased fracture rate. With the limitation that the fracture data were self-reported in this cohort, these results suggest that CD should be performed only for other maternal or fetal indications, not for the sole purpose of fracture prevention in OI.Genet Med 18 6, 570-576.

Consensus conference on best practices in live kidney donation: recommendations to optimize education, access, and care.

Live donor kidney transplantation is the best treatment option for most patients with late-stage chronic kidney disease; however, the rate of living kidney donation has declined in the United States. A consensus conference was held June 5-6, 2014 to identify best practices and knowledge gaps pertaining to live donor kidney transplantation and living kidney donation. Transplant professionals, patients, and other key stakeholders discussed processes for educating transplant candidates and potential living donors about living kidney donation; efficiencies in the living donor evaluation process; disparities in living donation; and financial and systemic barriers to living donation. We summarize the consensus recommendations for best practices in these educational and clinical domains, future research priorities, and possible public policy initiatives to remove barriers to living kidney donation.

A cross-sectional multicenter study of osteogenesis imperfecta in North America - results from the linked clinical research centers.

Osteogenesis imperfecta (OI) is the most common skeletal dysplasia that predisposes to recurrent fractures and bone deformities. In spite of significant advances in understanding the genetic basis of OI, there have been no large-scale natural history studies. To better understand the natural history and improve the care of patients, a network of Linked Clinical Research Centers (LCRC) was established. Subjects with OI were enrolled in a longitudinal study, and in this report, we present cross-sectional data on the largest cohort of OI subjects (n = 544). OI type III subjects had higher prevalence of dentinogenesis imperfecta, severe scoliosis, and long bone deformities as compared to those with OI types I and IV. Whereas the mean lumbar spine area bone mineral density (LS aBMD) was low across all OI subtypes, those with more severe forms had lower bone mass. Molecular testing may help predict the subtype in type I collagen-related OI. Analysis of such well-collected and unbiased data in OI can not only help answering questions that are relevant to patient care but also foster hypothesis-driven research, especially in the context of 'phenotypic expansion' driven by next-generation sequencing.

Zolpidem test and catatonia.

WHAT IS KNOWN AND OBJECTIVE: There is no consensus regarding treatment of catatonia and the main recent therapeutic progress has been the development of the zolpidem diagnostic and therapeutic test. We report on the use of this test in one of our patients. CASES SUMMARY: Mr. S. suffered from a paranoid schizophrenia. Three episodes of catatonia are described to illustrate the effect of zolpidem in a patient for whom lorazepam was ineffective or inadequate. WHAT IS NEW AND CONCLUSION: Zolpidem with appropriate testing appears to be a credible alternative to electroconvulsive therapy or increased lorazepam dosing and allows continuation of antipsychotic administration.

Estimating risks of de novo kidney diseases after living kidney donation.

De novo post donation renal diseases, such as glomerulonephritis or diabetic nephropathy, are infrequent and distinct from the loss of GFR at donation that all living kidney donors experience. Medical findings that increase risks of disease (e.g. microscopic hematuria,borderline hemoglobin A1C) often prompt donor refusal by centers. These risk factors are part of more comprehensive risks of low GFR and end-stage renal disease (ESRD) from kidney diseases in the general population that are equally relevant. Such data profile the ages of onset, rates of progression, prevalence and severity of loss of GFR from generically characterized kidney diseases. Kidney diseases typically begin in middle age and take decades to reach ESRD, at a median age of 64. Diabetes produces about half of yearly ESRD and even more lifetime near-ESRD. Such data predict that (1) 10- to 15-year studies will not capture the lifetime risks of post donation ESRD; (2)normal young donors are at demonstrably higher risk than normal older candidates; (3) low-normal predonation GFRs become risk factors for ESRD when kidney diseases arise and (4) donor nephrectomy always increases individual risk. Such population-based risk data apply to all donor candidates and should be used to make acceptance standards and counseling more uniform and defensible.

Inflammation and atrial remodeling after a mountain marathon.

Endurance athletes have an increased risk of atrial fibrillation. We performed a longitudinal study on elite runners of the 2010 Jungfrau Marathon, a Swiss mountain marathon, to determine acute effects of long-distance running on the atrial myocardium. Ten healthy male athletes were included and examined 9 to 1 week prior to the race, immediately after, and 1, 5, and 8 days after the race. Mean age was 34.9 ± 4.2 years, and maximum oxygen consumption was 66.8 ± 5.8 mL/kg*min. Mean race time was 243.9 ± 17.7 min. Electrocardiographic-determined signal-averaged P-wave duration (SAPWD) increased significantly after the race and returned to baseline levels during follow-up (128.7 ± 10.9 vs. 137.6 ± 9.8 vs. 131.5 ± 8.6 ms; P < 0.001). Left and right atrial volumes showed no significant differences over time, and there were no correlations of atrial volumes and SAPWD. Prolongation of the SAPWD was accompanied by a transient increase in levels of high-sensitivity C-reactive protein, proinflammatory cytokines, total leucocytes, neutrophil granulocytes, pro atrial natriuretic peptide and high-sensitivity troponin. In conclusion, marathon running was associated with a transient conduction delay in the atria, acute inflammation and increased atrial wall tension. This may reflect exercise-induced atrial myocardial edema and may contribute to atrial remodeling over time, generating a substrate for atrial arrhythmias.

Serum vitamin D concentrations in rabbits (Oryctolagus cuniculus) are more affected by UVB irradiation of food than irradiation of animals.

Rabbits kept under ultraviolet B (UVB)-irradiation respond with increasing serum vitamin D (25(OH)D) concentrations, but it is unknown whether irradiation of the animals or their feed contributes more. Twenty-four New Zealand White rabbits were divided into three groups for a four-week period: the control group (C) received no UVB-exposure and non-irradiated hay (ergocalciferol (vitamin D2) concentration 2.22 µg/100 g dry matter). The direct exposure group (D) was provided with 12 h of UVB-irradiation daily and fed the same hay as group C in shaded areas to prevent UVB-irradiation thereof. The indirect exposure group (I) did not receive direct UVB-irradiation but was fed hay of the same batch that was exposed to 12 h of UVB-irradiation (vitamin D2 6.06 µg/100 g dry matter). Serum 25(OH)D2, 25(OH)D3, ionised calcium, total calcium, phosphorus, and magnesium concentrations were measured weekly. There was no systematic effect on serum mineral concentrations. The serum 25(OH)D2 concentrations were significantly higher in group I compared to groups C and D from the second week onwards. 25(OH)D3 concentrations increased only in group D, with significant differences to both other groups from the third week onwards, yet at lower magnitudes than the noted increase of 25(OH)D2 in group I. Total 25(OH)D concentrations were highest in group I, intermediate in group D and lowest in group C. Serum total 25(OH)D concentration was more affected by UVB-irradiation of rabbits' feed than by direct irradiation of the animals themselves. If rabbit serum total 25(OH)D concentrations should be managed, diet manipulation rather than animal UVB-exposure appears to be more effective.

Research challenges in central nervous system manifestations of inborn errors of metabolism.

The Research Challenges in CNS Manifestations of Inborn Errors of Metabolism workshop was designed to address challenges in translating potential therapies for these rare disorders, and to highlight novel therapeutic strategies and innovative approaches to CNS delivery, assessment of effects and directions for the future in the treatment of these diseases. Therapies for the brain in inborn errors represent some of the greatest challenges to translational research due to the special properties of the brain, and of inborn errors themselves. This review covers the proceedings of this workshop as submitted by participants. Scientific, ethical and regulatory issues are discussed, along with ways to measure outcomes and the conduct of clinical trials. Participants included regulatory and funding agencies, clinicians, scientists, industry and advocacy groups.

Apical surgery: endoscopic findings at the resection level of 168 consecutively treated roots.

AIM: Endoscopic evaluation of the cut root face after root-end resection during apical surgery. METHODOLOGY: Consecutive cases undergoing apical surgery from June 2006 to May 2008 were enrolled. After root-end resection, the cut root face was inspected with a rigid endoscope and the following findings were assessed: number of canals, presence of isthmus, presence and location of craze lines/cracks, frosted dentine, and gaps between root filling material and dentine. Craze lines/cracks, frosted dentine and gaps were further correlated with the age group of the patient (<45 vs. ≥ 45 years), the type of treated tooth and the presence or absence of a post/screw. RESULTS: The final material included 168 resected roots. The highest frequency of isthmuses was found in mesial roots of mandibular first molars (88.5%). A craze line/crack was seen in 9.5%, frosted dentine in 79.8% and gaps in 83.3% at the cut root faces. Significant differences were observed for the location of the microfindings at the resected root surfaces (buccal vs. mesial vs. lingual vs. distal, P > 0.0001). Premolars had significantly more craze lines/cracks than anterior teeth (P = 0.006) and molars (P = 0.000). Frosted dentine was significantly more frequently seen in premolars (P = 0.027) and molars (P = 0.001) compared to anterior teeth. The age groups and the presence or absence of a post/screw did not significantly influence the findings. CONCLUSIONS: Frosted dentine and gaps were frequently observed with endoscopy at the resected root surfaces. The type of tooth appeared to affect the occurrence of a craze line/crack and of frosted dentine.

Bidirectional reflectance measurement of tungsten samples to assess reflection model in WEST tokamak.

This paper presents the measurement of the bidirectional reflectance distribution function of tungsten (W) samples and the resulting reflection models in the nuclear fusion device WEST (tokamak). For this, an experimental gonio-spectrophotometer was developed to fully characterize the material's optical and thermal-radiative properties of metallic samples with different roughnesses. Ray-tracing photonic simulation was then carried out to predict the photon behavior in a fully metallic environment as a function of reflectance measurement. Low emissivity (0.1 at 4 µm) and highly specular reflectance (fitting with a Gaussian distribution around the specular direction with a small width lower than 10°) are found for W samples. These measurements have been used as input for the photonic simulation, and the resulting synthetic image reproduced the reflection features well on the upper divertor, detected in WEST infrared experimental images.

'Normal for now' or 'at future risk': a double standard for selecting young and older living kidney donors.

Transplant centers medically evaluate potential living kidney donors in part to determine their baseline remaining lifetime risk for end stage renal disease (ESRD). If baseline risk is increased by the presence of a risk factor for ESRD, donation is often refused. However, as only about 13% of ESRD occurs in the general population by age 44, a normal medical evaluation cannot be expected to significantly reduce the 7% lifetime risk for a 'normal' 25-year-old black donor or the 2-3% risk for a similar white donor. About half of newly diagnosed ESRD in the United States occurs by age 65, and about half of that is from diabetic nephropathy, which takes about 25 years to develop. Therefore, the remaining baseline lifetime risk for ESRD is significantly lower in the normal, nondiabetic 55-year-old donor candidate. Some older donors with an isolated medical abnormality such as mild hypertension will be at lower or about the same overall baseline lifetime risk for ESRD as are young 'normal' donor candidates. Transplant centers use a 'normal for now' standard for accepting young donors, in place of the long-term risk estimates that must guide selection of all donors.

Rhodium and silicon system: I. Glassy metallic alloy formation.

Detailed characterizations of rhodium/silicon films prepared by co-deposition using magnetron sputtering have been carried out on silicon substrates at room temperature. Effects of the silicon content incorporated in the film on the chemical bonding state and crystallinity were investigated using XPS/UPS, XRD and SEM. It should be emphasized that XPS/UPS measurements are carried out without breaking the vacuum to avoid any contamination of the film. All x-ray diffraction patterns revealed a high degree of amorphization. There is only a weak Rh pattern and a weak Rh(2)Si pattern for 20 and 37 at.% of Si, respectively, i.e. showing a formation of glassy metallic alloy. A negative shift in the Rh core level binding energy for rhodium-rich alloys is mainly referred to relaxation effects due to a high density of d-states near the Fermi level. The filling of the d-states is completed between 25 and 40 atomic concentration of Si. Valence orbital transformation due to the Si-Rh interactions is causing the progressive positive shift in the binding energy for higher silicon content.

Rhodium and silicon system: II. Rhodium silicide formation.

Detailed characterizations of rhodium/silicon films prepared by co-deposition using magnetron sputtering have been carried out on silicon substrates at room temperature up to 900 degrees C. The properties of the films were investigated using XPS/UPS, XRD, SIMS, SEM and AFM techniques. It should be emphasized that XPS/UPS measurements are carried out without breaking the vacuum to avoid any contamination of the film. Up to 500 degrees C an interdiffusion between the oxidized silicon wafer and the deposited Rh/Si film occurred leading to hole formation in the entire film at 900 degrees C. Diffraction patterns for the compounds Rh(2)Si, Rh(5)Si(3), RhSi and Rh(3)Si(4) were measured. Upon annealing the covalent character is increased and for the samples forming the compound RhSi the valence band structure is markedly changed. Depth profiling (XPS and SIMS) reveals a stable composition in the bulk of the film. For these measurements the silicon-rich alloy in the interfacial layer is probably an effect of sputtering, by implanting the Rh atoms into the silicon substrate. A previously reported negative shift for the compound Rh(5)Si(3) could be connected to the sample preparation, as sputtering of the surface is reducing the silicon content and inducing a glassy state. For the first phase Rh(2)Si formed on the rhodium-rich side the shift in binding energy is unclear, for all the other compounds encountered in this work a positive shift relative to pure rhodium was found.