bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis, characterization of calcium phosphates/polyurethane composites for weight‐bearing implants
Authors: Yoshii Toshitaka , Dumas Jerald E. , Okawa Atsushi , Spengler Dan M. , Guelcher Scott A.
Published: September 2011

Calcium phosphate (CaP)/polymer composites have been studied as an alternative graft material for the treatment of bone defects. In this study, lysine‐triisocyanate‐based polyurethane (PUR) composites were synthesized from both hydroxyapatite (HA) and β‐tricalcium phosphate (TCP) to reduce the brittleness of CaP and increase the bioactivity of the polymer. The mechanical properties and in vitro cellular response were investigated for both HA/PUR and TCP/PUR composites. The composites were implanted in femoral defects in rats, and in vivo bioactivity was evaluated by X‐rays, micro‐computed tomography (μCT), and histological sections. In biomechanical testing, PUR improved the mechanical properties of the CaP, thus rendering it potentially suitable for weight‐bearing applications. In vitro cell culture studies showed that CaP/PUR composites are biocompatible, with β‐TCP enhancing the cell viability and proliferation relative to HA. CaP/PUR composites also supported the differentiation of osteoblastic cells on the materials. When implanted in rat femoral defects, the CaP/PUR composites were biocompatible and osteoconductive with no adverse inflammatory response, as evidenced by X‐rays, μCT images, and histological sections. Additionally, a histological examination showed evidence of cellular infiltration and appositional remodeling. These results suggest that CaP/PUR composites could be potentially useful biomaterials for weight‐bearing orthopaedic implants. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
Characterization of worn alumina hip replacement prostheses
Authors: Zeng Peng , Rainforth W. Mark. , Inkson Beverley J. , Stewart Todd. D.
Published: September 2011

Alumina hip replacement prostheses have been analyzed following in vitro simulated microseparation. The worn surfaces of the alumina acetabular cup and femoral head were investigated using scanning electron microscopy (SEM) and atomic force microscopy (AFM) which identified four different wear zones. Focused ion beam (FIB) cross‐sectioning was used to section the worn surface and produce 3D reconstructions of the subsurface damage. This showed that the subsurface fracture was predominantly intergranular, with occasional intragranular fracture. Significantly, in all cases, fracture was restricted to the outer layer of grains. The wear mechanisms leading to the generation of the stripe wear region on the worn alumina hip prostheses are proposed and microseparation is believed to play a critical role. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
Circulating γδ T cells and the risk of acute-phase response after zoledronic acid administration
Authors: Rossini Maurizio , Adami Silvano , Viapiana Ombretta , Ortolani Riccardo , Vella Antonio , Fracassi Elena , Gatti Davide
Published: September 2011

The use of intravenous nitrogen-containing bisphosphonates (N-BPs) is associated with the appearance of an acute phase response (APR) in a proportion of the patients for reasons that are poorly understood. The APR was attributed to the indirect activation of γδ T cells with the release of interferon-γ and tumor necrosis factor (TNF). Forty patients with postmenopausal or senile osteoporosis (age range = 53–91 years) never previously treated with intravenous (iv) bisphosphonate, received a single 5-mg zoledronic acid (ZOL) iv infusion over 15 minutes. White blood cells were counted and analyzed with an automated hematology analyzer (ADVIA 2120i Siemens, New York, USA) and by flow cytometer (BD FACSCanto, Becton Dickinson). The occurrence of APR was defined by the occurrence of fever (>37 °C) during the next 2 days. Forty-two percent of patients (17 of 40) receiving the infusion of ZOL experienced an APR. Compared with the others they were younger (69 ± 7 years versus 74 ± 8 years; p = 0.06), and both the proportion and absolute number of γδ T cells were significant higher (p = 0.02 and p = 0.013, respectively). Nonsignificant differences were found between the two groups for white blood cells and for the other circulating lymphocyte subpopulations. Age was inversely correlated with circulating γδ T cells (p = 0.003) but the difference between the two groups in circulating γδ T cells persisted for age-adjusted values and vice versa. In conclusion, the results of this study indicate that the number of circulating γδ T cells, together with age, are important determinant of the occurrence of APR after intravenous infusion of ZOL and possibly of any other N-BPs. © 2012 American Society for Bone and Mineral Research
A case of hypophosphatemic osteomalacia secondary to deferasirox therapy
Authors: Milat Frances , Wong Phillip , Fuller Peter J , Johnstone Lillian , Kerr Peter G , Doery James CG , Strauss Boyd J , Bowden Donald K
Published: September 2011

Patients with β-thalassemia major require iron-chelation therapy to avoid the complication of iron overload. Until recently, deferoxamine (DFO) was the major iron chelator used in patients requiring chronic hypertransfusion therapy, but DFO required continuous subcutaneous therapy. The availability of deferasirox (Exjade®), an orally active iron chelator, over the past 4 years represented a necessary alternative for patients requiring chelation therapy. However, there have been increasing reports of proximal renal tubular dysfunction and Fanconi Syndrome associated with deferasirox in the literature. We report a case of hypophosphataemic osteomalacia secondary to deferasirox therapy. © 2012 American Society for Bone and Mineral Research
Rare coding variants in ALPL are associated with low serum alkaline phosphatase and low bone mineral density
Authors: Nielson Carrie M , Zmuda Joseph M , Carlos Amy S , Wagoner Wendy J , Larson Emily A , Orwoll Eric S , Klein Robert F
Published: September 2011

Alkaline phosphatase (ALP) plays an essential role in the regulation of tissue mineralization, and its activity is highly heritable. Guided by genetic associations discovered in a murine model, we hypothesized a role for rare coding variants in determining serum ALP level and bone mineral density (BMD) in humans. We sequenced the coding regions of the ALP gene (ALPL) in men with low and normal serum ALP activity levels. Single-nucleotide ALPL variants, including 19 rare nonsynonymous variants (minor allele frequency <1%), were much more frequent among the low ALP group (33.8%) than the normal group (1.4%, p = 1 × 10−11). Within the low ALP group, men with a rare, nonsynonymous variant had 11.2% lower mean serum ALP (p = 3.9 × 10−4), 6.7% lower BMD (p = 0.03), and 11.1% higher serum phosphate (p = 0.002) than those without. In contrast, common nonsynonymous variants had no association with serum ALP, phosphate, or BMD. Multiple rare ALPL coding variants are present in the general population, and nonsynonymous coding variants may be responsible for heritable differences in mineralization and thus BMD. © 2012 American Society for Bone and Mineral Research
A murine model of neurofibromatosis type 1 tibial pseudarthrosis featuring proliferative fibrous tissue and osteoclast-like cells
Authors: El-Hoss Jad , Sullivan Kate , Cheng Tegan , Yu Nicole YC , Bobyn Justin D , Peacock Lauren , Mikulec Kathy , Baldock Paul , Alexander Ian E , Schindeler Aaron , Little David G
Published: September 2011

Neurofibromatosis type 1 (NF1) is a common genetic condition caused by mutations in the NF1 gene. Patients often suffer from tissue-specific lesions associated with local double-inactivation of NF1. In this study, we generated a novel fracture model to investigate the mechanism underlying congenital pseudarthrosis of the tibia (CPT) associated with NF1. We used a Cre-expressing adenovirus (AdCre) to inactivate Nf1 in vitro in cultured osteoprogenitors and osteoblasts, and in vivo in the fracture callus of Nf1flox/flox and Nf1flox/− mice. The effects of the presence of Nf1null cells were extensively examined. Cultured Nf1null-committed osteoprogenitors from neonatal calvaria failed to differentiate and express mature osteoblastic markers, even with recombinant bone morphogenetic protein-2 (rhBMP-2) treatment. Similarly, Nf1null-inducible osteoprogenitors obtained from Nf1 MyoDnull mouse muscle were also unresponsive to rhBMP-2. In both closed and open fracture models in Nf1flox/flox and Nf1flox/− mice, local AdCre injection significantly impaired bone healing, with fracture union being <50% that of wild type controls. No significant difference was seen between Nf1flox/flox and Nf1flox/− mice. Histological analyses showed invasion of the Nf1null fractures by fibrous and highly proliferative tissue. Mean amounts of fibrous tissue were increased upward of 10-fold in Nf1null fractures and bromodeoxyuridine (BrdU) staining in closed fractures showed increased numbers of proliferating cells. In Nf1null fractures, tartrate-resistant acid phosphatase–positive (TRAP+) cells were frequently observed within the fibrous tissue, not lining a bone surface. In summary, we report that local Nf1 deletion in a fracture callus is sufficient to impair bony union and recapitulate histological features of clinical CPT. Cell culture findings support the concept that Nf1 double inactivation impairs early osteoblastic differentiation. This model provides valuable insight into the pathobiology of the disease, and will be helpful for trialing therapeutic compounds. © 2012 American Society for Bone and Mineral Research
Amphiphilic peptides with arginine and valine residues as siRNA carriers
Authors: Ryu Dong‐Wook , Kim Hyun Ah , Ryu Jae Hwan , Lee Dong Yun , Lee Minhyung
Published: September 2011

An efficient and safe delivery carrier is required for the therapeutic application of siRNA. In this research, amphiphilic peptides with arginine and valine residues were evaluated as siRNA carriers. The peptides were composed of 1–4 arginine‐blocks and 6 valine‐blocks. In the aqueous solution, the arginine–valine peptides (RV peptides) formed micelles with hydrophobic cores comprised of a valine block and a cationic surface comprised of an arginine block. In a gel retardation assay, the RV peptides completely retarded siRNA at a 1:10 weight ratio (siRNA:peptide). A heparin competition assay suggested that the RV peptides formed more stable complexes with siRNA than they did with polyethylenimine (25 kDa, PEI25k). In an in vitro silencing assay, a dual luciferase expression (Renilla and firefly luciferases) vector, psiCHECK2, was co‐transfected into human embryonic kidney 293 cells with Renilla‐siRNA using the RV peptides. The specific silencing effect of Renilla luciferase was analyzed in reference to firefly luciferase. The results showed that the R3V6 peptide was more efficient than the R1V6, R2V6, and R4V6 peptides in silencing Renilla luciferase. In the flow cytometry and in vitro silencing studies, the R3V6 peptide delivered Renila‐siRNA as efficiently as PEI25k. The siVEGF/R3V6 peptide also reduced endogenous vascular endothelial growth factor (VEGF) expression in CT27 cells as efficiently as PEI25k. A cytotoxicity assay showed that RV peptides did not cause any cytotoxicity. Therefore, RV peptides may be useful for the development of a safe and efficient delivery carrier of siRNA. J. Cell. Biochem. 113: 619–628, 2012. © 2011 Wiley Periodicals, Inc.
Microarray analysis of 1,25(OH)2D3 regulated gene expression in human primary osteoblasts
Authors: Tarroni Paola , Villa Isabella , Mrak Emanuela , Zolezzi Francesca , Mattioli Michela , Gattuso Claudio , Rubinacci Alessandro
Published: September 2011

Though extensive studies have been conducted, questions regarding the molecular effectors and pathways underlying the regulatory role of 1,25(OH)2D3 in human osteoblasts other than cell differentiation and matrix protein production remain unanswered. This study aims to identify genes and pathways that are modulated by 1,25(OH)2D3 treatment in human osteoblasts. Primary osteoblast cultures obtained from human bone tissue samples were treated with 1,25(OH)2D3 (10−7 M) for 24 h and their transcritptomes were profiled by microarray analysis using the Affymetrix GeneChip®. Statistical analysis was conducted to identify genes whose expression is significantly modulated following 1,25(OH)2D3 treatment. One hundred and fifty‐eight genes were found to be differentially expressed. Of these, 136 were upregulated, indicating clear transcriptional activation by 1,25(OH)2D3. Biostatistical evaluation of microarray data by Ingenuity Pathways Analysis (IPA) revealed a relevant modulation of genes involved in vitamin D metabolism (CYP24), immune functions (CD14), neurotransmitter transporters (SLC1A1, SLC22A3), and coagulation [thrombomodulin (THBD), tissue plasminogen activator (PLAT), endothelial protein C receptor (PROCR), thrombin receptor (F2R)]. We identified a restricted number of highly regulated genes and confirmed their differential expression by real‐time quantitative PCR (RT qPCR). The present genome‐wide microarray analysis on 1,25(OH)2D3‐treated human osteoblasts reveals an interplay of critical regulatory and metabolic pathways and supports the hypothesis that 1,25(OH)2D3 can modulate the coagulation process through osteoblasts, activates osteoclastogenesis through inflammation signaling, modulates the effects of monoamines by affecting their reuptake. J. Cell. Biochem. 113: 640–649, 2012. © 2011 Wiley Periodicals, Inc.
Hydrogen abstraction reactions of OH radicals with CH3CH2CH2Cl and CH3CHClCH3: A mechanistic and kinetic study
Authors: Wang Li , Li Yanjie , He Hongqing , Zhang Jinglai
Published: September 2011

The hydrogen abstraction reactions of OH radicals with CH3CH2CH2Cl (R1) and CH3CHClCH3 (R2) have been investigated theoretically by a dual‐level direct dynamics method. The optimized geometries and frequencies of the stationary points are calculated at the B3LYP/6‐311G(d,p) level. To improve the reaction enthalpy and potential barrier of each reaction channel, the single point energy calculation is performed by the BMC‐CCSD method. Using canonical variational transition‐state theory (CVT) with the small‐curvature tunneling correction, the rate constants are evaluated over a wide temperature range of 200–2000 K at the BMC‐CCSD//B3LYP/6‐311G(d,p) level. For the reaction channels with the negative barrier heights, the rate constants are calculated by using the CVT. The calculated total rate constants are consistent with available experimental data. The results show that at lower temperatures, the tunneling correction has an important contribution in the calculation of rate constants for all the reaction channels with the positive barrier heights, while the variational effect is found negligible for some reaction channels. For reactions OH radicals with CH3CH2CH2Cl (R1) and CH3CHClCH3 (R2), the channels of H‐abstraction from –CH2– and –CHCl groups are the major reaction channels, respectively, at lower temperatures. With temperature increasing, contributions from other channels should be taken into account. Finally, the total rate constants are fitted by two models, i.e., three‐parameter and four‐parameter expressions. The enthalpies of formation of the species CH3CHClCH2, CH3CHCH2Cl, and CH2CH2CH2Cl are evaluated by isodesmic reactions. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Electronic structure and low temperature thermoelectric properties of In24 M8 O48 (M = Ge4+, Sn4+, Ti4+, and Zr4+)
Authors: Yan Yu Li , Wang Yuan Xu
Published: September 2011

The electronic structure and transport properties of In24M8O48 (M = Ge4+, Sn4+, Ti4+, and Zr4+) have been studied by using the full‐potential linearized augmented plane‐wave method and the semiclassical Boltzmann theory, respectively. It is found that the magnitude of powerfactor with respect to relation time follows the order of In24Sn8O48 > In24Zr8O48 > In24Ge8O48 > In24Ti8O48. The largest powerfactor is 2.7 × 1012 W/K2ms for In24Sn8O48 at 60 K, which is nearly thirty times larger than those of conventional n‐type thermoelectric materials. The origin of the different thermoelectric behavior for these compounds is discussed from the electronic structure level. It is found that, at low temperature, the dopant strongly affect the bands near the Fermi level, which consequently leads to their different thermoelectric properties. The electronic configuration and the difference in atomic number between the dopant and the host atom also play an important role on the thermoelectric properties of In24M8O48. Our calculations give a valuable insight on how to enhance the thermoelectric performance of In32O48. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Sonographic detection of transient gas in the portal vein in an infant following abdominal surgery: A possible sign of adhesive small bowel obstruction
Authors: Tritou Ioanna , Megremis Stylianos , Stefanaki Evangelia , Goumenakis Michalis , Sfakianaki Evangelia
Published: September 2011

We present a case of sonographically detected transient gas in the portal vein in a 4.5‐month‐old infant who had a history of two consecutive jejunectomies due to jejunal stenoses and was admitted to our hospital with clinical and laboratory findings consistent with a subacute small bowel obstruction and dehydration. Sonography excluded other pathologies and the patient was treated conservatively with success. The presence of gas in the portal vein could be a sign of an underlying mechanical obstacle, as another episode of small bowel obstruction 1 month later required surgical treatment of adhesive intestinal obstruction. © 2011 Wiley Periodicals, Inc. J Clin Ultrasound 2012
Transmission of parental care behavior in African striped mice, Rhabdomys Pumilio
Authors: Rymer Tasmin , Pillay Neville
Published: September 2011

The expression of behavior, including parental care behavior, is influenced by complex interactions of the genes of an organism and the prevailing environmental conditions. Previously, we showed that the development of paternal, but not maternal, care in the African striped mouse, Rhabdomys pumilio, has a significant nongenetic maternal component. Here, we investigate the genetic component of parental care behavior from parents to offspring. We first measured the duration of parental care behavior of mothers and fathers every second day for 11 days postnatally. Subsequently, one son and one daughter from each of these litters were paired with unrelated mates when they were adults and their parental care behavior scored. Using regression models, we then compared parental care behavior of parents and their adult offspring. The transmission of parental care behavior from striped mouse fathers to sons and from mothers to both sons and daughters did not indicate a genetic component. Instead, we found a patrilineal genetic component for parental care in daughters. The reason for this unusual pattern of inheritance is not known, but this finding complements that of our other studies, showing that the expression of maternal care behavior in adult daughters is also not nongenetically influenced by their mothers. We suggest that, although females are constrained to provide maternal care in different social contexts, maternal care behavior may be influenced genetically by the father. J. Exp. Zool. 315:631–638, 2011. © 2011 Wiley Periodicals, Inc.
Comparison of surgical outcomes between endoscopic and robotic thyroidectomy
Authors: Yoo Ho , Chae Byung Joo , Park Hyung Seok , Kim Ki Ho , Kim Shin Hyuk , Song Byung Joo , Jung Sang Seol , Bae Ja Seong
Published: September 2011

Objectives

Gasless transaxillary endoscopic thyroidectomy offers a distinct advantage over the conventional open operation because it leaves no visible neck scar. Indications have expanded with the development of new surgical techniques and instruments. However, because of the two‐dimensional view and the nonflexible instruments, this procedure is not easily amenable for total thyroidectomy. So, robotic surgery has been introduced and offers improved visualization and dexterity. But, it remains unclear whether robotic thyroidectomy offers any potential benefits over endoscopic thyroidectomy. The aim of this present study was to determine whether robotic surgery is superior to endoscopic surgery through a comparison of surgical outcomes.

Methods

Between May 2009 and February 2011, 165 patients underwent endoscopic thyroidectomy (endoscopy group) and 46 patients underwent robotic thyroidectomy (robot group). A gasless transaxillary approach was used in both groups. The two groups were compared in terms of patient characteristics, perioperative clinical results, pathologic findings, and postoperative complication.

Results

Both patient groups were similar in terms of patient characteristics, mean number of retrieved central lymph nodes, pathological features, length of hospital stays, postoperative complication rate, and serum Tg level. However, the mean total operation time for thyroidectomy was 126.2 ± 37.84 min in the endoscopy group and 179.6 ± 44.34 min in the robot group (P < 0.001). Postoperative total drainage for lobectomy was 153.3 ± 45.64 for the endoscopy group and 179.9 ± 49.15 for the robot group (P = 0.031). Cost effectiveness is also an important consideration when evidence for predominance of two surgical techniques is lacking. The mean cost of robotic thyroidectomy was $6,655, compared with $829 for endoscopic thyroidectomy (P < 0.001). There was no significant difference in postoperative complications as hypocalcemia, recurrent laryngeal nerve injury, chyle leakage and tracheal injury in the two groups (P = 0.332).

Conclusion

Robotic thyroidectomy was lengthier in duration than endoscopic thyroidectomy, more costly, and associated with increased postoperative drainage with no improvement in oncologic outcomes or complication rates. Therefore our data do not support any advantage of robotic surgery over endoscopic surgery. J. Surg. Oncol. 2012; 105:705–708. © 2011 Wiley Periodicals, Inc.
Retrospective LC‐QTOF‐MS analysis searching for pharmaceutical metabolites in urban wastewater
Authors: Hernández Félix , Ibáñez María , Gracia‐Lor Emma , Sancho Juan V.
Published: September 2011

The presence of pharmaceuticals in the environment is a matter of major concern because of their wide consumption and their potential negative effect on the water quality and living organisms. After human and/or veterinary consumption, pharmaceuticals can be excreted in unchanged form as the parent compound and/or as free or conjugated metabolites. These compounds seem not to be completely removed during wastewater treatments and might finally arrive to surface and ground waters. Consequently, both parent pharmaceuticals and metabolites are target analytes to be considered in analytical methodologies. The satisfactory sensitivity in full‐acquisition mode, high‐resolution, exact mass measurements and MS/MS capabilities of hybrid quadrupole time‐of‐flight (QTOF) mass spectrometry make of this technique a powerful analytical tool for the identification of organic contaminants. In this study, the use of QTOF‐MS with the aid of specialised processing‐data application managers has allowed the retrospective analysis of pharmaceuticals metabolites in urban wastewater without the need for additional injection of sample extracts. Around 160 metabolites have been investigated in wastewater samples previously analysed only for parent compounds using LC‐QTOF under MSE mode (simultaneous recording of two acquisition functions, at low and high collision energy). The retrospective analysis was applied to search for pharmaceutical metabolites in parent‐positive effluent wastewaters from the Spanish Mediterranean region. Five metabolites, such as clopidogrel carboxylic acid or N‐desmethyl clarithromycin, were identified in the samples.
Hierarchical multi‐scale occupancy estimation for monitoring wildlife populations
Authors: Pavlacky David C. , Blakesley Jennifer A. , WHITE GARY C. , Hanni David J. , Lukacs Paul M.
Published: September 2011

Occupancy estimation is an effective analytic framework, but requires repeated surveys of a sample unit to estimate the probability of detection. Detection rates can be estimated from spatially replicated rather than temporally replicated surveys, but this may violate the closure assumption and result in biased estimates of occupancy. We present a new application of a multi‐scale occupancy model that permits the simultaneous use of presence–absence data collected at 2 spatial scales and uses a removal design to estimate the probability of detection. Occupancy at the small scale corresponds to local territory occupancy, whereas occupancy at the large scale corresponds to regional occupancy of the sample units. Small‐scale occupancy also corresponds to a spatial availability or coverage parameter where a species may be unavailable for sampling at a fraction of the survey stations. We applied the multi‐scale occupancy model to a hierarchical sample design for 2 bird species in the Black Hills National Forest: brown creeper (Certhia americana) and lark sparrow (Chondestes grammacus). Our application of the multi‐scale occupancy model is particularly well suited for hierarchical sample designs, such as spatially replicated survey stations within sample units that are typical of avian monitoring programs. The model appropriately accounts for the non‐independence of the spatially replicated survey stations, addresses the closure assumption for the spatially replicated survey stations, and is useful for decomposing the observation process into detection and availability parameters. This analytic approach is likely to be useful for monitoring at local and regional scales, modeling multi‐scale habitat relationships, and estimating population state variables for rare species of conservation concern. © 2011 The Wildlife Society.
Enhanced uptake and photoactivation of topical methyl aminolevulinate after fractional CO2 laser pretreatment
Authors: Hædersdal M. , Katsnelson J. , Sakamoto F.H. , Farinelli W.A. , Doukas A.G. , Tam J. , Anderson R.R.
Published: September 2011

Background and Objectives

Photodynamic therapy (PDT) of thick skin lesions is limited by topical drug uptake. Ablative fractional resurfacing (AFR) creates vertical channels that may facilitate topical PDT drug penetration and improve PDT‐response in deep skin layers. The purpose of this study was to evaluate whether pre‐treating the skin with AFR before topically applied methyl aminolevulinate (MAL) could enable a deep PDT‐response.

Materials and Methods

Yorkshire swine were treated under general anesthesia with a fractional CO2 laser using stacked single pulses of 3 milliseconds, 91.6 mJ per pulse and subsequent topical MAL application for 3 hours (Metvix®). Red light (LED arrays) was then delivered at fluences of 37 and 200 J/cm2. Fluorescent photography and microscopy was used to quantify MAL‐induced porphyrin distribution and PDT‐induced photobleaching at the skin surface and five specific depths down to 1,800 µm.

Results

Laser‐ablated channels were approximately 1,850 µm deep, which significantly increased topical MAL‐induced porphyrin fluorescence (hair follicles, dermis, P < 0.0001) and PDT response, both superficially and deep, versus topical MAL application alone. The fraction of porphyrin fluorescence lost by photobleaching was slightly less after 37 J/cm2 than after 200 J/cm2 (overall median values 67–90%; 37 vs. 200 J/cm2, P > 0.05 for all but one comparison). Photobleaching was steady throughout skin layers and did not vary significantly with skin depth at either LED fluence (P > 0.05).

Conclusions

AFR greatly facilitates topical MAL‐induced porphyrins and the fraction of photobleached porphyrins is similar for superficial and deep skin. These observations are consistent with AFR‐enhanced uptake of MAL, increased porphyrin synthesis, and photodynamic activation of deep porphyrins even at the lower fluence of 37 J/cm2, widely used in clinical practice. AFR appears to be a clinically practical means for improving PDT deep into the skin. Clinical studies are suggested to evaluate selectivity in targeting dysplastic cell types. Lasers Surg. Med. © 2011 Wiley‐Liss, Inc.
When not to treat cutaneous vascular lesions with the pulsed dye laser
Authors: Shofner Joshua D. , Lipworth Adam , Tannous Zeina , Avram Mathew M.
Published: September 2011

The availability of effective laser treatment for cutaneous vascular lesions has risen dramatically in recent years. At the same time, there has been a proliferation of laser providers with varying amounts of training—both medical and nonmedical. We report a series of four cases where patients presented for cosmetic evaluation of vascular lesions and were discovered to have more significant pathologic disease. In presenting these cases, we hope to illuminate a basic differential diagnosis that exists for cutaneous vascular lesions and remind healthcare providers that not all “cosmetic” concerns are benign in origin. There is a differential diagnosis that exists for cutaneous vascular lesions that is worth reviewing, and it should be considered in all patients presenting for laser treatment. Lasers Surg. Med. © 2011 Wiley‐Liss, Inc.
Nonmotor versus motor symptoms: How much do they matter to health status in Parkinson's disease?
Authors: Hinnell Claire , Hurt Catherine S. , Landau Sabine , Brown Richard G. , Samuel Michael ,   on behalf of the PROMS‐PD Study Group
Published: September 2011

Evidence suggests that both motor and nonmotor symptoms contribute to health status in Parkinson's disease. Less clear is how much change in health status can be expected if these clinical variables change. In addition, anxiety, separate from depression, has rarely been examined as a predictor of health status. We used hierarchical multiple regression analysis and standardized beta coefficients in a prevalent cohort of 462 patients with Parkinson's disease to explore the relative impact on health status (measured using the Parkinson's Disease Questionnaire) of 5 well‐recognized symptom domains in Parkinson's disease: motor signs, depression, anxiety, cognition, and other nonmotor symptoms. In the health status scores, 19.6% of variance was explained by age, number of comorbidities, disease duration, and levodopa equivalent dose. Younger age predicted worse health status. A full regression model containing baseline variables and all 5 symptom domains explained 56% of the variance in health status. The standardized beta coefficient for depression was 2.1, 1.6, and 1.3 times that of motor signs, anxiety, and other nonmotor symptoms, respectively. Our findings provide a ranking order of clinical variables for their relative impact on health status in Parkinson's disease and show that depression has more than twice the impact of motor signs on health status. Anxiety and other nonmotor symptoms are also important separate determinants of poor health status in Parkinson's disease. Our results will help to guide the development of individual care and service planning for patients with Parkinson's disease. © 2011 Movement Disorder Society
Weekly exercise does not improve fatigue levels in Parkinson's disease
Authors: Winward Charlotte , Sackley Cath , Meek Charmaine , Izadi Hooshang , Barker Karen , Wade Derick , Dawes Helen
Published: September 2011

Background:

Fatigue is one of the most disabling non‐motor symptoms for people with Parkinson's disease. Exercise may modify fatigue. This study examines prescribed exercise effects on physical activity levels, well‐being, and fatigue in Parkinson's disease.

Methods:

In this single‐blinded trial, participants were randomly assigned to either a 12 week community exercise program or control group. Primary outcome measures were fatigue (Fatigue Severity Scale) and physical activity.

Results:

Thirty‐nine people with Parkinson's disease were included: 20 in exercise and 19 in control. Sixty‐five percent of the study group were fatigued (n = 24, mean 4.02, SD 1.48). Increased fatigue was associated with lower mobility and activity (P < .05). Individuals participated in a mean of 15 (SD 10) exercise sessions with no significant change in fatigue, mobility, well‐being, or physical activity after exercise (P ≥ .05).

Conclusion:

Participation in weekly exercise did not improve fatigue in people with Parkinson's Disease. © 2011 Movement Disorder Society
Quantitative analysis of tumor burden in mouse lung via MRI
Authors: Tidwell Vanessa K. , Garbow Joel R. , Krupnick Alexander S. , Engelbach John A. , Nehorai Arye
Published: September 2011

Lung cancer is the leading cause of cancer death in the United States. Despite recent advances in screening protocols, the majority of patients still present with advanced or disseminated disease. Preclinical rodent models provide a unique opportunity to test novel therapeutic drugs for targeting lung cancer. Respiratory‐gated MRI is a key tool for quantitatively measuring lung‐tumor burden and monitoring the time‐course progression of individual tumors in mouse models of primary and metastatic lung cancer. However, quantitative analysis of lung‐tumor burden in mice by MRI presents significant challenges. Herein, a method for measuring tumor burden based upon average lung‐image intensity is described and validated. The method requires accurate lung segmentation; its efficiency and throughput would be greatly aided by the ability to automatically segment the lungs. A technique for automated lung segmentation in the presence of varying tumor burden levels is presented. The method includes development of a new, two‐dimensional parametric model of the mouse lungs and a multi‐faceted cost function to optimally fit the model parameters to each image. Results demonstrate a strong correlation (0.93), comparable with that of fully manual expert segmentation, between the automated method's tumor‐burden metric and the tumor burden measured by lung weight. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
Self‐refocused adiabatic pulse for spin echo imaging at 7 T
Authors: Balchandani Priti , Khalighi Mohammad Mehdi , Glover Gary , Pauly John , Spielman Daniel
Published: September 2011

Spin echo pulse sequences are used to produce clinically important T2 contrast. However, conventional 180° radiofrequency pulses required to generate a spin echo are highly susceptible to the B1 inhomogeneity at high magnetic fields such as 7 Tesla (7 T), resulting in varying signal and contrast over the region of interest. Adiabatic 180° pulses may be used to replace conventional 180° pulses in spin echo sequences to provide greater immunity to the inhomogeneous B1 field at 7 T. However, because the spectral profile of an adiabatic 180° pulse has nonlinear phase, pairs of these pulses are needed for proper refocusing, resulting in increased radiofrequency power deposition and long minimum echo times. We used the adiabatic Shinnar Le‐Roux method to generate a matched‐phase adiabatic 90°–180° pulse pair to obviate the need for a second adiabatic 180° pulse for phase refocusing. The pulse pair was then reformulated into a single self‐refocused pulse to minimize the echo time, and phantom and in vivo experiments were performed to validate pulse performance. The self‐refocused adiabatic pulse produced transmit profiles that were substantially more uniform than those achieved using a conventional spin echo sequence. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.
Triple‐quantum‐filtered sodium imaging of the human brain at 4.7 T
Authors: Tsang Adrian , Stobbe Robert W. , Beaulieu Christian
Published: September 2011

The limited signal‐to‐noise ratio of triple‐quantum‐filtered MRI of sodium is a major hurdle for its application clinically. Although it has been shown that short 90° radiofrequency pulses in combination with sufficiently long repetition time for full T1 recovery (labelled “standard” parameters) produce the maximum signal through the triple‐quantum‐filter, and in this work, simulation and images of agar phantoms and human brain demonstrate that the use of longer radiofrequency pulses and reduced repetition time (optimized parameters to accommodate more averages for a constant specific absorption rate, reducing noise variance for a given scan length) results in signal‐to‐noise ratio improvement (22 ± 5% in brain tissue of five healthy volunteers—images created in 11 min with nominal resolution of 8.4 mm isotropic). However, residual intensity was observed in the ventricular space on triple‐quantum‐filtered images acquired with either optimized or standard parameters, contrary to the expectation of complete single‐quantum signal suppression. Further simulation and experimentation suggest that this is likely due to the combination of triple‐quantum‐passed signal from surrounding brain tissue being spatially smeared into the ventricular space and single‐quantum‐signal breakthrough from sodium nuclei in the fluid space. It is shown that the latter can be eliminated with judicious first flip angle selection. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.
Integration of diffusion‐weighted MRI data and a simple mathematical model to predict breast tumor cellularity during neoadjuvant chemotherapy
Authors: Atuegwu Nkiruka C. , Arlinghaus Lori R. , Li Xia , Welch E. Brian , Chakravarthy Bapsi A. , Gore John C. , Yankeelov Thomas E.
Published: September 2011

Diffusion‐weighted magnetic resonance imaging data obtained early in the course of therapy can be used to estimate tumor proliferation rates, and the estimated rates can be used to predict tumor cellularity at the conclusion of therapy. Six patients underwent diffusion‐weighted magnetic resonance imaging immediately before, after one cycle, and after all cycles of neoadjuvant chemotherapy. Apparent diffusion coefficient values were calculated for each voxel and for a whole tumor region of interest. Proliferation rates were estimated using the apparent diffusion coefficient data from the first two time points and then used with the logistic model of tumor growth to predict cellularity after therapy. The predicted number of tumor cells was then correlated to the corresponding experimental data. Pearson's correlation coefficient for the region of interest analysis yielded 0.95 (P = 0.004), and, after applying a 3 × 3 mean filter to the apparent diffusion coefficient data, the voxel‐by‐voxel analysis yielded a Pearson correlation coefficient of 0.70 ± 0.10 (P < 0.05). Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.
Analytical model for the beam action of a tunnel lining during construction
Authors: Talmon A.M. , Bezuijen A.
Published: September 2011

Measurements on a 14.5‐m diameter bored tunnel have shown that the mechanised assembly of a segmented tunnel lining results in a permanent longitudinal bending moment in the tunnel lining. An analytical model for the beam action of the tunnel lining during the construction phase of bored tunnels is presented. The model incorporates many of the essentials in staged beam construction. It takes into account the influence of forces from the TBM, the loading of the tunnel lining by the grout in the liquid phase, and linear elastic properties of the tunnel lining and soil. Calculations are compared with measurements at the Groene Hart Tunnel (GHT), 20 km south of Amsterdam: the bending moment curve and vertical inclination of tunnel lining segments were compared. The measured bending moment curve is well reproduced. The measured vertical inclination of the lining segments is found to be governed by the beam action of the tunnel lining plus the influence of shear force in the lining. Copyright © 2011 John Wiley & Sons, Ltd.
Mechanisms involved in endothelin‐1‐induced contraction of the pig urinary bladder neck
Authors: Arteaga José Luis , Orensanz Luis M. , Martínez María Pilar , Barahona María Victoria , Recio Paz , Martínez‐Sáenz Ana , Fernandes Vítor S. , Ribeiro Ana S. F. , García‐Sacristán Albino , Prieto Dolores , Hernández Medardo
Published: September 2011

Aims

There is no information about the signaling pathways involved in the endothelin‐1 (ET‐1)‐induced contraction of bladder neck. The current study investigates the mechanisms involved in the ET‐1‐elicited contraction in the pig bladder neck.

Methods

Bladder neck strips were mounted in organ baths containing physiological saline solution at 37°C and gassed with 95% O2 and 5% CO2, for isometric force recording to endothelin receptor agonists, noradrenaline (NA), and electrical field stimulation. Endothelin ETA receptor expression was also determined, by both immunohistochemistry and Western blot.

Results

ETA receptor expression (Western blot) was observed in the muscular layer and urothelium. A strong ETA‐immunoreactivity (ETA‐IR) was identified within nerve fibers among smooth muscle bundles. ET‐1 and ET‐2 evoked similar concentration‐dependent contractions of urothelium‐denuded preparations. ET‐3 produced a slight response, whereas the ETB receptor agonist BQ3020 failed to promote contraction. BMS182874, an ETA receptor antagonist, reduced ET‐1‐induced contraction whereas BQ788, an ETB antagonist, did not change such responses. ET‐1 contractions were reduced by extracellular Ca2+ removal and by inhibition of voltage‐gated Ca2+ (VOC) (L‐type) and non‐VOC channels, Rho/Rho‐kinase pathway, and neuronal VOC channels. NA produced contractions which were enhanced by ET‐1 threshold concentrations. ETA receptor blockade enhanced nitric oxide‐dependent nerve‐mediated relaxations.

Conclusions

These results suggest that ET‐1 produces contraction via muscular ETA receptors coupled to extracellular Ca2+ entry via VOC (L‐type) and non‐VOC channels. Intracellular Ca2+ mobilization and a Rho/Rho‐kinase pathway could also be involved in these responses. ET‐1‐evoked potentiation on noradrenergic contraction, and neuronal ETA receptors modulating nitrergic inhibitory neurotransmission, are also demonstrated. Neurourol. Urodynam. 31:156–161, 2012. © 2011 Wiley Periodicals, Inc.
Nuclear lamins and laminopathies
Authors: Worman Howard J.
Published: September 2011

Nuclear lamins are intermediate filament proteins that polymerize to form the nuclear lamina on the inner aspect of the inner nuclear membrane. Long known to be essential for maintaining nuclear structure and disassembling/reassembling during mitosis in metazoans, research over the past dozen years has shown that mutations in genes encoding nuclear lamins, particularly LMNA encoding the A‐type lamins, cause a broad range of diverse diseases, often referred to as laminopathies. Lamins are expressed in all mammalian somatic cells but mutations in their genes lead to relatively tissue‐selective disease phenotypes in most cases. While mutations causing laminopathies have been shown to produce abnormalities in nuclear morphology, how these disease‐causing mutations or resultant alterations in nuclear structure lead to pathology is only starting to be understood. Despite the incomplete understanding of pathogenic mechanisms underlying the laminopathies, basic research in cellular and small animal models has produced promising leads for treatments of these rare diseases. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Fanconi anaemia pathway orchestrates incisions at sites of crosslinked DNA
Authors: Crossan Gerry P , Patel Ketan J
Published: September 2011

Fanconi anaemia (FA) is a rare, autosomal recessive, genetically complex, DNA repair deficiency syndrome in man. Patients with FA exhibit a heterogeneous spectrum of clinical features. The most significant and consistent phenotypic characteristics are stem cell loss, causing progressive bone marrow failure and sterility, diverse developmental abnormalities and a profound predisposition to neoplasia. To date, 15 genes have been indentified, biallelic disruption of any one of which results in this clinically defined syndrome. It is now apparent that all 15 gene products act in a common process to maintain genome stability. At the molecular level, a fundamental defect in DNA repair underlies this complex phenotype. Cells derived from FA patients spontaneously accumulate broken chromosomes and exhibit a marked sensitivity to DNA‐damaging chemotherapeutic agents. Despite complementation analysis defining many components of the FA DNA repair pathway, no direct link to DNA metabolism was established until recently. First, it is now evident that the FA pathway is required to make incisions at the site of damaged DNA. Second, a specific component of the FA pathway has been identified that regulates nucleases previously implicated in DNA interstrand crosslink repair. Taken together, these data provide genetic and biochemical evidence that the FA pathway is a bona fide DNA repair pathway that directly mediates DNA repair transactions, thereby elucidating the specific molecular defect in human Fanconi anaemia. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Epiphyseal growth plate and secondary peripheral chondrosarcoma: the neighbours matter
Authors: de Andrea Carlos E , Hogendoorn Pancras CW
Published: September 2011

Chondrocytes interact with their neighbours through their cartilaginous extracellular matrix (ECM). Chondrocyte–matrix interactions compensate the lack of cell–cell contact and are modulated by proteoglycans and other molecules. The epiphyseal growth plate is a highly organized tissue responsible for long bone elongation. The growth plate is regulated by gradients of morphogens that are established by proteoglycans. Morphogens diffuse across the ECM, creating short‐ and long‐range signalling that lead to the formation of a polarized tissue. Mutations affecting genes that modulate cell–matrix interactions are linked to several human disorders. Homozygous mutations of EXT1/EXT2 result in reduced synthesis and shortened heparan sulphate chains on both cell surface and matrix proteoglycans. This disrupts the diffusion gradients of morphogens and signal transduction in the epiphyseal growth plate, contributing to loss of cell polarity and osteochondroma formation. Osteochondromas are cartilage‐capped bony projections arising from the metaphyses of endochondral bones adjacent to the growth plate. The osteochondroma cap is formed by cells with homozygous mutation of EXT1/EXT2 and committed stem cells/wild‐type chondrocytes. Osteochondroma serves as a niche (a permissive environment), which facilitates the committed stem cells/wild‐type chondrocytes to acquire secondary genetic changes to form a secondary peripheral chondrosarcoma. In such a scenario, the micro‐environment is the site of the initiating processes that ultimately lead to cancer. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.