bluuebunny/crossref_metadata_2025 huggingface dataset:
Carpal tunnel syndrome and keyboard use at work: A population‐based study
Authors: Atroshi Isam , Gummesson Christina , Ornstein Ewald , Johnsson Ragnar , Ranstam Jonas
Published: October 2007

Objective

To investigate the relationship between carpal tunnel syndrome (CTS) and keyboard use at work in a general population.

Methods

A health status questionnaire was mailed to 2,465 persons of working age (25–65 years) who were randomly selected from the general population of a representative region of Sweden. The questionnaire required the subjects to provide information about the presence and severity of pain, numbness and tingling in each body region, employment history, and work activities, including average time spent using a keyboard during a usual working day. Those reporting recurrent hand numbness or tingling in the median nerve distribution were asked to undergo a physical examination and nerve conduction testing. The prevalence of CTS, defined as symptoms plus abnormal results on nerve conduction tests, was compared between groups of subjects that differed in their intensity of keyboard use, adjusting for age, sex, body mass index, and smoking status.

Results

Eighty‐two percent responded to the questionnaire, and 80% of all symptomatic persons attended the examinations. Persons who had reported intensive keyboard use on the questionnaire were significantly less likely to be diagnosed as having CTS than were those who had reported little keyboard use, with a prevalence that increased from 2.6% in the highest keyboard use group (≥4 hours/day), to 2.9% in the moderate use group (1 to <4 hours/day), 4.9% in the low use group (<1 hour/day), and 5.2% in the no keyboard use at work group (Pfor trend = 0.032). Using ≥1 hour/day to designate high keyboard use and <1 hour/day to designate low keyboard use, the prevalence ratio of CTS in the groups with high to low keyboard use was 0.55 (95% confidence interval 0.32, 0.96).

Conclusion

Intensive keyboard use appears to be associated with a lower risk of CTS.
Pattern and distribution of myocardial fibrosis in systemic sclerosis: A delayed enhanced magnetic resonance imaging study
Authors: Tzelepis George E. , Kelekis Nikolaos L. , Plastiras Sotiris C. , Mitseas Panayiotis , Economopoulos Nikolaos , Kampolis Christos , Gialafos Elias J. , Moyssakis Ioannis , Moutsopoulos Haralampos M.
Published: October 2007

Objective

To assess the prevalence and pattern of myocardial fibrosis as detected by delayed enhanced magnetic resonance imaging (DE‐MRI) in patients with systemic sclerosis (SSc), and to evaluate a possible association between myocardial fibrosis and cardiac arrhythmias.

Methods

Forty‐one patients with SSc underwent 24‐hour Holter monitoring, Doppler echocardiography, and DE‐MRI following gadolinium administration.

Results

Technically acceptable DE‐MRIs were obtained in 36 patients with SSc. Enhancement on DE‐MRI, consistent with myocardial fibrosis, was observed in 24 of these patients (66%), and it was invariably midwall with a linear pattern, mostly involving basal and midcavity segments of the left ventricle. The volume of enhancement (total volume percentage index [TVPI]) did not differ between patients with diffuse SSc and those with limited SSc (mean ± SD 1.46 ± 1.73% versus 1.44 ± 1.77%; P = 0.98). Patients with a long duration (≥15 years) of Raynaud's phenomenon had a greater number of enhancing segments (mean ± SD 6.55 ± 4.93 versus 2.96 ± 3.46; P = 0.017) and a greater TVPI (mean ± SD 2.44 ± 1.97% versus 1.02 ± 1.43%; P = 0.02) than those with a duration of Raynaud's phenomenon <15 years. Nineteen patients with SSc (53%) had abnormal Holter study results. Compared with patients with normal Holter study results, those with abnormal results had a greater number of enhancing segments (mean ± SD 5.4 ± 4.8 versus 2.5 ± 2.9; P < 0.05) and a greater TVPI (mean ± SD 2.1 ± 1.9% versus 0.8 ± 1.2%; P < 0.05).

Conclusion

DE‐MRI can identify myocardial fibrosis in a significant percentage of patients with SSc and may be a useful noninvasive tool for determining cardiac involvement.
The aminobisphosphonate risedronate preserves localized mineral and material properties of bone in the presence of glucocorticoids
Authors: Balooch Guive , Yao Wei , Ager Joel W. , Balooch Mehdi , Nalla Ravi K. , Porter Alexandra E. , Ritchie Robert O. , Lane Nancy E.
Published: October 2007

Objective

Glucocorticoids (GCs) alter bone strength such that patients receiving these medications have a high rate of fragility‐related fractures. The purpose of this study was to assess whether concurrent treatment with GCs (prednisolone) and risedronate (an aminobisphosphonate) would prevent the reduction in bone strength induced by GCs, in a mouse model of GC‐induced bone loss and in patients enrolled in a clinical study.

Methods

We evaluated mice treated with prednisolone pellets alone, GCs plus risedronate, or placebo alone and iliac crest biopsy specimens obtained from patients who were treated with GCs plus placebo or GCs plus risedronate for 1 year. We measured the mass, architecture, and physical and material properties of bone (subject to therapeutic treatments) at nanoscale to macroscopic dimensions, using synchrotron x‐ray tomography, elastic modulus mapping, transmission electron microscopy, and small‐angle x‐ray scattering techniques.

Results

GC treatment reduced trabecular bone mass, microarchitecture, and the degree of bone mineralization and elastic modulus within the trabeculae. Concurrent treatment with GCs and risedronate prevented the deterioration of trabecular bone architecture, reduced the degree of mineralization, and preserved elastic modulus within the trabeculae, in both mouse and human bone. In addition, treatment with risedronate plus GCs in mice appeared to preserve bone crystal orientation, compared with treatment with GCs alone.

Conclusion

Risedronate prevented the localized changes in mineral and material properties of bone induced by GCs, which may ultimately improve bone strength.
Overexpression of human decoy receptor 3 in mice results in a systemic lupus erythematosus–like syndrome
Authors: Han Bing , Moore Paul A. , Wu Jiangping , Luo Hongyu
Published: October 2007

Objective

Decoy receptor 3 (DcR3), a tumor necrosis factor receptor family member, is a secreted protein that can enhance cell survival by interfering with multiple apoptosis pathways. This study was undertaken to investigate the role of DcR3 in the pathogenesis of autoimmune disease.

Methods

We generated transgenic mice with actin promoter–driven expression of human DcR3 and investigated the development of autoimmune disease in these mice.

Results

T cell immune responses were compromised in young DcR3‐transgenic mice. Beyond 5–6 months of age, transgenic mice developed a systemic lupus erythematosus (SLE)–like syndrome, with numerous features of the disease. They produced autoantibodies against double‐stranded DNA. Their kidneys showed pathologic changes indicative of glomerular nephritis and IgG and C3 deposition, and proteinuria, leukocyturia, and hematuria, were evident. Aged transgenic mice also developed skin lesions and lymphocyte infiltration in the liver, and exhibited leukopenia, anemia, and thrombocytopenia. The SLE‐like syndrome penetrance in DcR3‐transgenic mice was sex associated, occurring in ∼60% of females versus 20% of males. Exogenous recombinant DcR3 or endogenous DcR3 produced by transgenic T cells effectively protected T cells against activation‐induced apoptosis in vitro. Probably as a consequence of this, CD4 cells with a phenotype of previous activation were increased in the peripheral blood of transgenic mice beyond 6 months of age.

Conclusion

These results show that DcR3 overexpression could lead to an SLE‐like syndrome in mice.
Early identification of radiographic osteoarthritis of the hip using an active shape model to quantify changes in bone morphometric features: Can hip shape tell us anything about the progression of osteoarthritis?
Authors: Gregory Jennifer S. , Waarsing Jan H. , Day Judd , Pols Huibert A. , Reijman Max , Weinans Harrie , Aspden Richard M.
Published: October 2007

Objective

Few methods exist to measure the progression of osteoarthritis (OA) or to identify people at high risk of developing OA. Striking radiographic changes include deformation of the femoral head and osteophyte growth, which are usually measured semiquantitatively following visual assessment. In this study, an active shape model (ASM) of the proximal femur was used to determine whether morphologic changes to the bone could be quantified and used as a marker of hip OA.

Methods

One hundred ten subjects who had no signs of radiographic hip OA at baseline (Kellgren/Lawrence [K/L] scores 0–1) were selected from the Rotterdam Study cohort of subjects ages ≥55 years. To measure the progression of OA, subjects were followed up with radiographic assessment after 6 years. At the 6‐year followup, 55 subjects had established OA (K/L score 3), and in 12 of these OA subjects, the progression of the disease required a total hip replacement (THR). Age‐ and sex‐matched control subjects had a K/L score of 0 at followup. Using the ASM, subjects were assessed for shape changes in the femoral head and neck before, during, and after the development of radiographic OA. Scores of shape variance, or mode scores, were assigned for 10 modes of variation in each subject, and differences in mode scores were determined.

Results

During followup, significant changes in shape of the proximal femur occurred within the OA group from baseline to followup (P < 0.0001 for mode 1 and P = 0.002 for mode 6) but not within the control group. At baseline (all subjects having K/L scores 0–1), there were significant differences in mode 6 between the OA group and the control group (P = 0.020), and in modes 3 and 6 between the OA subjects who underwent THR and the remaining OA subjects (P = 0.012 and P = 0.019, respectively).

Conclusion

Compared with traditional scoring methods, the ASM can be used more precisely to quantify the deforming effect of OA on the proximal femur and to identify, at an earlier stage of disease, those subjects at highest risk of developing radiographic OA or needing a THR. The ASM may therefore be useful as an imaging biomarker in the assessment of patients with hip OA.
Mechanotransduction of bovine articular cartilage superficial zone protein by transforming growth factor β signaling
Authors: Neu Corey P. , Khalafi Afshin , Komvopoulos Kyriakos , Schmid Thomas M. , Reddi A. Hari
Published: October 2007

Objective

Mechanical signals are key determinants in tissue morphogenesis, maintenance, and restoration strategies in regenerative medicine, although molecular mechanisms of mechanotransduction remain to be elucidated. This study was undertaken to investigate the mechanotransduction process of expression of superficial zone protein (SZP), a critical joint lubricant.

Methods

Regional expression of SZP was first quantified in cartilage obtained from the femoral condyles of immature bovines, using immunoblotting, and visualized by immunohistochemistry. Contact pressure mapping in whole joints was accomplished using pressure‐sensitive film and a load application system for joint testing. Friction measurements on cartilage plugs were acquired under boundary lubrication conditions using a pin‐on‐disk tribometer modified for reciprocating sliding. Direct mechanical stimulation by shear loading of articular cartilage explants was performed with and without inhibition of transforming growth factor β (TGFβ) signaling, and SZP content in media was quantified by enzyme‐linked immunosorbent assay.

Results

An unexpected pattern of SZP localization in knee cartilage was initially identified, with anterior regions exhibiting high levels of SZP expression. Regional SZP patterns were regulated by mechanical signals and correlated with tribological behavior. Direct relationships were demonstrated between high levels of SZP expression, maximum contact pressures, and low friction coefficients. Levels of SZP expression and accumulation were increased by applying shear stress, depending on location within the knee, and were decreased to control levels with the use of a specific inhibitor of TGFβ receptor type I kinase and subsequent phospho‐Smad2/3 activity.

Conclusion

These findings indicate a new role for TGFβ signaling in the mechanism of cellular mechanotransduction that is especially significant for joint lubrication.
Vascular endothelial damage and repair in antineutrophil cytoplasmic antibody–associated vasculitis
Authors: de Groot K. , Goldberg C. , Bahlmann F. H. , Woywodt A. , Haller H. , Fliser D. , Haubitz M.
Published: October 2007

Objective

Antineutrophil cytoplasmic antibody–associated vasculitis (AAV) is characterized by necrotizing vessel wall inflammation, paralleled by the detachment of endothelial cells. The repair of such endothelial defects is crucial for the maintenance of regular structure and function of the injured vessels. Bone marrow–derived endothelial progenitor cells (EPCs) are thought to play a pivotal role in the regeneration of damaged endothelium. The aim of this study was to investigate whether EPCs are involved in vascular repair in AAV.

Methods

We assessed disease activity, CD34+ hematopoietic progenitor cells (HPCs) using flow cytometry, EPCs using an in vitro assay, and circulating endothelial cells (CECs) by immunomagnetic isolation from the peripheral blood of 31 patients with active AAV at 1, 3, and 6 months after the initiation of immunosuppressive therapy.

Results

In patients with untreated active disease, HPC and EPC numbers were comparable with those in healthy control subjects (n = 64). With the induction of remission, the number of HPCs and EPCs increased significantly, from a median of 1.5 cells/μl (range 0.0–7.0) to a median of 3.2 cells/μl (range 0.76–9.2) (P < 0.001) and from a median of 261 cells/high‐power field (range 171–643) to a median of 470 cells/high‐power field (range 168–996) (P < 0.021), respectively. In contrast, the initially elevated number of CECs decreased significantly (P < 0.001). We observed no correlation between the number of HPCs or EPCs and the leukocyte count, the thrombocyte count, or kidney function.

Conclusion

In patients with AAV, the numbers of circulating CD34+ HPCs and EPCs increased significantly after the institution of immunosuppressive therapy and disease remission. This finding points to a role of circulating CD34+ HPCs and EPCs in endothelial repair in vasculitis. Targeted stimulation of these cells might represent a new possibility of improving vascular healing in AAV.
Fetal thermal dose considerations during the obstetrician's watch: Implications for the pediatrician's observations
Authors: Miller Morton W. , Church Charles C. , Miller Richard K. , Edwards Marsh J.
Published: October 2007

There are a number of seemingly “usual” thermal episodes during pregnancy for which it is relatively easy to determine a rudimentary aspect of thermal dose; these episodes include fever, labor, labor plus epidural, and the normally‐occurring 0.5°C temperature elevation above maternal core temperature of the fetus during the entirety of the third trimester. Complications can involve, for instance, fever during the third trimester. We consider the thermal doses of five different but “usual” or “normal” hyperthermic episodes during human pregnancy and compare those doses with the thermal doses involved with both single and cohort exposures of pregnant guinea pigs throughout their gestational period. The end‐point studied in the guinea pigs was microencephaly. In nine of the 10 comparisons (human fetal thermal dose vs. guinea pig fetal thermal dose) the human dose is substantially larger than that of the guinea pig thermal dose, which was substantially teratogenic. This situation is essentially the inverse of the type of information contained in the Physician's Desk Reference (PDR) on drugs, in which it is not unusual to discern that at high drug levels there may be teratogenic effects in laboratory animals, but such effects were not observed at “clinical” drug levels in animals or subsequent clinical trials. With hyperthermic events, however, it appears that the teratogenically‐effective thermal dose levels associated with animal testing are quite low relative to those thermal doses associated with relatively “normal” obstetric observations during a pregnancy. Birth Defects Research (Part C) 81:135‐143, 2007. © 2007 Wiley‐Liss, Inc.
Air pollutant effects on fetal and early postnatal development
Authors: Wang Lei , Pinkerton Kent E.
Published: October 2007

Numerical research on the health effects of air pollution has been published in the last decade. Epidemiological studies have shown that children's exposure to air pollutants during fetal development and early postnatal life is associated with many types of health problems including abnormal development (low birth weight [LBW], very low birth weight [VLBW], preterm birth [PTB], intrauterine growth restriction [IUGR], congenital defects, and intrauterine and infant mortality), decreased lung growth, increased rates of respiratory tract infections, childhood asthma, behavioral problems, and neurocognitive decrements. This review focuses on the health effects of major outdoor air pollutants including particulates, carbon monoxide (CO), sulfur and nitrogen oxides (SO2, NOx), ozone, and one common indoor air pollutant, environmental tobacco smoke (ETS). Animal data is presented that demonstrate perinatal windows of susceptibility to sidestream smoke, a surrogate for ETS, resulting in altered airway sensitivity and cell type frequency. A study of neonatal monkeys exposed to sidestream smoke during the perinatal period and/or early postnatal period that resulted in an altered balance of Th1‐/Th2‐cytokine secretion, skewing the immune response toward the allergy‐associated Th2 cytokine phenotype, is also discussed. Birth Defects Research (Part C) 81:144–154, 2007. © 2007 Wiley‐Liss, Inc.
Radiation effects on development
Authors: De Santis Marco , Cesari Elena , Nobili E. , Straface Gianluca , Cavaliere Anna Franca , Caruso Alessandro
Published: October 2007

It has been widely reported that prenatal exposure to ionizing radiation can interfere with embryonic and fetal development, depending on dose and gestational age in which exposure occurs. According to several studies on animal models, different well‐defined stages during prenatal life can be distinguished in relation to teratogenic effects. During the preimplantation stage, elevated doses of radiation can result in abortion, while lower doses may produce genomic damage that is usually repaired. On the other hand, during the organogenesis stage in mice (embryonic day 6.5 [E6.5] to E13.5), irradiation is associated with increased incidence of malformation and intrauterine growth restriction (IUGR). Later exposure is linked to brain damage. Doses used in animal studies are generally higher than those used for diagnostic procedures in humans. Usually, radiation exposure to diagnostic range (<0.05 Gy = 5 rads) is not associated with an increased risk of congenital anomalies. In human studies, elevated doses produce adverse outcomes, depending on stage of development, as in animal studies. Blastogenesis (up to two weeks) is associated with failure to implant or no significant health effects. An increased risk of malformation and growth retardation can be observed for two to seven weeks exposure (organogenesis stage), while exposure at later stages (fetogenesis) is mainly associated with brain damage. In this review we focus on the relevance of estimating the cumulative dose of radiation to the fetus and the gestational age in which exposure occurs, to provide appropriate counseling to pregnant women. Birth Defects Research (Part C) 81:177–182, 2007. © 2007 Wiley‐Liss, Inc.
The effect of hypoxia in development
Authors: Webster William S. , Abela Dominique
Published: October 2007

There is increasing evidence that the oxygen supply to the human embryo in the first trimester is tightly controlled, suggesting that too much oxygen may interfere with development. The use of hypoxia probes in mammalian embryos during the organogenic period indicates that the embryo is normally in a state of partial hypoxia, and this may be essential to control cardiovascular development, perhaps under the control of hypoxia‐inducible factor (HIF). A consequence of this state of partial hypoxia is that disturbances in the oxygen supply can more easily lead to a damaging degree of hypoxia. Experimental mammalian embryos show a surprising degree of resilience to hypoxia, with many organogenic stage embryos able to survive 30–60 min of anoxia. However, in some embryos this degree of hypoxia causes abnormal development, particularly transverse limb reduction defects. These abnormalities are preceded by hemorrhage/edema and tissue necrosis. Other parts of the embryo are also susceptible to this hypoxia‐induced damage and include the genital tubercle, the developing nose, the tail, and the central nervous system. Other frequently observed defects in animal models of prenatal hypoxia include cleft lip, maxillary hypoplasia, and heart defects. Animal studies indicate that hypoxic episodes in the first trimester of human pregnancy could occur by temporary constriction of the uterine arteries. This could be a consequence of exposure to cocaine, misoprostol, or severe shock, and there is evidence that these exposures have resulted in hypoxia‐related malformations in the human. Exposure to drugs that block the potassium current (IKr) can cause severe slowing and arrhythmia of the mammalian embryonic heart and consequently hypoxia in the embryo. These drugs are highly teratogenic in experimental animals. There is evidence that drugs with IKr blockade as a side effect, for example phenytoin, may cause birth defects in the human by causing periods of embryonic hypoxia. The strongest evidence of hypoxia causing birth defects in the human comes from studies of fetuses lacking hemoglobin (Hb) F. These fetuses are thought to be hypoxic from about the middle of the first trimester and show a range of birth defects, particularly transverse limb reduction defects. Birth Defects Research (Part C) 81:215–228, 2007. © 2007 Wiley‐Liss, Inc.
Effect of statins on proteolytic activity in the wall of abdominal aortic aneurysms
Authors: Abisi S , Burnand K G , Humphries J , Waltham M , Taylor P , Smith A
Published: October 2007

Background

The aim of this study was to examine the effect of statin treatment on the activity of proteases in the wall of abdominal aortic aneurysms (AAAs).

Methods

The activities of matrix metalloproteinases (MMPs) 9 and 3, cathepsins B, H, K, L and S, and the cystatin C level were measured in extracts of AAA wall taken from 82 patients undergoing AAA repair; 21 patients were receiving statin treatment before surgery. All values were standardized against soluble protein (SP) concentration in the extract, and reported as median (interquartile range) or mean(s.e.m.).

Results

The two groups had similar demographics. Reduced activity of MMP-9 (43 (34–56) versus 80 (62–110) pg per mg SP; P < 0·001), cathepsin H (183 (117–366) versus 321 (172–644) nmol 4-methylcoumarin-7-amide released per mg SP; P = 0·016) and cathepsin L (102 (51–372) versus 287 (112–816) µmol 7-amino-4-trifluoromethylcoumarin released per mg SP; P = 0·020) was found in the statin-treated aortas compared with AAAs from patients not taking a statin. The statin-treated group had lower MMP-3 activity, but this did not reach statistical significance (P = 0·053). Cystatin C levels were higher in statin-treated aortas than in controls (41·3(3·1) versus 28·9(2·1) ng per mg SP; P = 0·003).

Conclusion

Statins decreased the activity of proteases that have been implicated in aneurysm disease.
Randomized clinical trial of moxonidine in patients undergoing major vascular surgery
Authors: Bolliger D , Seeberger M D , Lurati Buse G A L , Christen P , Gürke L , Filipovic M
Published: October 2007

Background

Myocardial ischaemia is the leading cause of perioperative morbidity and mortality after surgery in patients with coronary artery disease. The aim of this study was to evaluate the effects of moxonidine, a centrally acting sympatholytic agent, on perioperative myocardial ischaemia and 1-year mortality in patients undergoing major vascular surgery.

Methods

In this double-blind, placebo-controlled two-centre trial, 141 patients were randomly assigned to receive moxonidine or placebo on the morning before surgery and on the following 4 days. Levels of cardiac troponin I (cTnI) were analysed before surgery and on days 1, 2, 3 and 7 thereafter. Holter electrocardiograms were recorded for 48 h starting before the administration of the study drug. Patients were followed daily during admission and by telephone interview 12 months after surgery.

Results

The incidence of raised perioperative cTnI levels or alteration in the ST segment in the Holter electrocardiogram or both was 40 per cent in the moxonidine group and 37 per cent in the placebo group (P = 0·694). All-cause mortality rates within 12 months were 10 per cent in the moxonidine group and 11 per cent in the placebo group (P = 0·870).

Conclusion

Small oral doses of moxonidine did not reduce the incidence of perioperative myocardial ischaemia and had no effect on mortality in patients undergoing vascular surgery. Registration number: NCT00244504 (http://www.clinicaltrials.gov).
Lasp‐2 expression, localization, and ligand interactions: A new Z‐disc scaffolding protein
Authors: Zieseniss Anke , Terasaki Asako G. , Gregorio Carol C.
Published: October 2007

The nebulin family of actin‐binding proteins plays an important role in actin filament dynamics in a variety of cells including striated muscle. We report here the identification of a new striated muscle Z‐disc associated protein: lasp‐2 (LIM and SH3 domain protein‐2). Lasp‐2 is the most recently identified member of the nebulin family. To evaluate the role of lasp‐2 in striated muscle, lasp‐2 gene expression and localization were studied in chick and mouse tissue, as well as in primary cultures of chick cardiac and skeletal myocytes. Lasp‐2 mRNA was detected as early as chick embryonic stage 25 and lasp‐2 protein was associated with developing premyofibril structures, Z‐discs of mature myofibrils, focal adhesions, and intercalated discs of cultured cardiomyocytes. Expression of GFP‐tagged lasp‐2 deletion constructs showed that the C‐terminal region of lasp‐2 is important for its localization in striated muscle cells. Lasp‐2 organizes actin filaments into bundles and interacts directly with the Z‐disc protein alpha‐actinin. These results are consistent with a function of lasp‐2 as a scaffolding and actin filament organizing protein within striated muscle Z‐discs. Cell Motil. Cytoskeleton 2008. © 2007 Wiley‐Liss, Inc.
Emerging molecular mechanisms that power and regulate the anastral mitotic spindle of flowering plants
Authors: Bannigan Alex , Lizotte‐Waniewski Michelle , Riley Margaret , Baskin Tobias I.
Published: October 2007

Flowering plants, lacking centrosomes as well as dynein, assemble their mitotic spindle via a pathway that is distinct visually and molecularly from that of animals and yeast. The molecular components underlying mitotic spindle assembly and function in plants are beginning to be discovered. Here, we review recent evidence suggesting the preprophase band in plants functions analogously to the centrosome in animals in establishing spindle bipolarity, and we review recent progress characterizing the roles of specific motor proteins in plant mitosis. Loss of function of certain minus‐end‐directed KIN‐14 motor proteins causes a broadening of the spindle pole; whereas, loss of function of a KIN‐5 causes the formation of monopolar spindles, resembling those formed when the homologous motor protein (e.g., Eg5) is knocked out in animal cells. We present a phylogeny of the kinesin‐5 motor domain, which shows deep divergence among plant sequences, highlighting possibilities for specialization. Finally, we review information concerning the roles of selected structural proteins at mitosis as well as recent findings concerning regulation of M‐phase in plants. Insight into the mitotic spindle will be obtained through continued comparison of mitotic mechanisms in a diversity of cells. Cell Motil. Cytoskeleton 2008. © 2007 Wiley‐Liss, Inc.
Fluency remediation in dyslexic children: does age make a difference?
Authors: Tressoldi Patrizio E. , Lorusso Maria Luisa , Brenbati Federica , Donini Roberta
Published: October 2007

This study tested the hypothesis whether older dyslexic children may obtain fewer gains on fluency and accuracy with respect to their younger peers after specific remediation.

Changes in accuracy and fluency of a group of children with a diagnosis of dyslexia attending third and fourth grades were compared with those obtained by a group of children attending the sixth, seventh or eighth grade in two different treatments, one based on the Balance model (Bakker) and the second based on the automatization of syllable recognition (sublexical).

Among all comparisons between the gains in accuracy and fluency obtained by the two groups, only the younger group in the sublexical treatment obtained a statistically significant gain with respect to their older peers' accuracy in reading words.

These outcomes suggest that, at least for the chronological ages and types of treatments considered in this study, older children with dyslexia may obtain comparable gains to their younger peers, suggesting that ‘it is never too late’ to remediate reading fluency and accuracy. Copyright © 2007 John Wiley & Sons, Ltd.
The tripartite influence model of body image and eating disturbance: A replication with a Japanese sample
Authors: Yamamiya Yuko , Shroff Hemal , Thompson J. Kevin
Published: October 2007

Objective:

To examine the tripartite influence model of body image and eating disturbance as a viable sociocultural explanation for the development of eating and body image problems with young Japanese females.

Method:

A sample of 289 Japanese female undergraduates completed a variety of measures designed to index family, peer, and media influences, as well as levels of body dissatisfaction, eating disturbances, and self‐esteem.

Results:

The data were evaluated with structural equation modeling to test the tripartite model. Fit indices indicated a moderate fit to the overall tripartite model, replicating previous findings.

Conclusion:

This study suggests that the sociocultural variables found to influence body image and eating disturbances in Japan are similar to those observed with US samples. The implications for prevention and intervention programs are discussed. © 2007 by Wiley Periodicals, Inc. Int J Eat Disord 2008
Carbohydrate‐Based VEGF Inhibitors
Authors: Haag Tobias , Hughes Richard A. , Ritter Gerd , Schmidt Richard R.
Published: October 2007

Cyclic peptide–carbohydrates (compounds 1a–c, 2, 33, 34) were designed and synthesized to act as mimetics of loop 2 of the proangiogenic molecule vascular endothelial growth factor D (VEGF‐D). The mimetics were designed to inhibit dimerization of the receptors (VEGFR‐2 and VEGFR‐3) by VEGF‐D, and thus have the potential to inhibit angiogenesis. To this end, in the previously described cyclic octapeptide CNEESLIC and the cyclic nonapeptide CGNEESLIC inhibitors derived from VEGF‐D loop 2, the NEES tetrapeptide residue was replaced by a carbohydrate scaffold having the amino acid side chain mimics in positions proposed by modeling studies. Attachment of the additional amino acids using the Fmoc technology, then formation of the cyclic disulfides, and finally total deprotection afforded the target molecules of which 2 and 34 showed an ability to inhibit the biological activity of VEGF‐D through VEGFR‐2 in cell‐based assays, albeit at high mimetic concentration.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Incorporation of covariates into multipoint linkage disequilibrium mapping in case‐control studies
Authors: Chiu Yen‐Feng , Liang Kung‐Yee , Chuang Lee‐Ming , Beaty Terri H.
Published: October 2007

Case‐control designs are commonly adopted in genetic epidemiological studies because they are cost effective and offer powerful tests for genetic and environmental risk factors, as well as their interactions. Previously, we proposed an association mapping approach to estimate the position of an unobserved disease locus as well as measuring its genetic effect on risk. The method provides a confidence interval for the estimated map position to help narrow the chromosomal region potentially harboring a disease locus. However, concerns often rise about case‐control designs including possible false positives or bias due to confounders, heterogeneity or interactions among genes and between genes and environments. In the present work, we extended the multipoint linkage disequilibrium mapping approach for case‐control studies to incorporate information about factors influencing the effect of causal genes to improve precision and efficiency of the estimated location. The efficiency, bias and coverage probability of this extended approach for locating a disease locus using case‐control data with and without additional information on a covariate were compared through simulation. An example of a case‐control study for type 2 diabetes was used to illustrate this extended method. In this study, a strong association between diabetes and a candidate gene, SCL2A10, was detected among nonobese subjects, whereas no evidence of association was found for either obese subjects or the whole sample when obesity was ignored. Simulation studies and these diabetes data both demonstrate how the efficiency of the estimated location of a disease gene can be improved substantially by incorporating information on covariates. Genet. Epidemiol. 2008. © 2007 Wiley‐Liss, Inc.
A support vector machine approach for detecting gene‐gene interaction
Authors: Chen Shyh‐Huei , Sun Jielin , Dimitrov Latchezar , Turner Aubrey R. , Adams Tamara S. , Meyers Deborah A. , Chang Bao‐Li , Zheng S. Lilly , Grönberg Henrik , Xu Jianfeng , Hsu Fang‐Chi
Published: October 2007

Although genetic factors play an important role in most human diseases, multiple genes or genes and environmental factors may influence individual risk. In order to understand the underlying biological mechanisms of complex diseases, it is important to understand the complex relationships that control the process. In this paper, we consider different perspectives, from each optimization, complexity analysis, and algorithmic design, which allows us to describe a reasonable and applicable computational framework for detecting gene‐gene interactions. Accordingly, support vector machine and combinatorial optimization techniques (local search and genetic algorithm) were tailored to fit within this framework. Although the proposed approach is computationally expensive, our results indicate this is a promising tool for the identification and characterization of high order gene‐gene and gene‐environment interactions. We have demonstrated several advantages of this method, including the strong power for classification, less concern for overfitting, and the ability to handle unbalanced data and achieve more stable models. We would like to make the support vector machine and combinatorial optimization techniques more accessible to genetic epidemiologists, and to promote the use and extension of these powerful approaches. Genet. Epidemiol. 2008. © 2007 Wiley‐Liss, Inc.
The triggering of debris flow due to channel‐bed failure in some alpine headwater basins of the Dolomites: analyses of critical runoff
Authors: Gregoretti C. , Fontana G. Dalla
Published: October 2007

The debris deposits at the bottom of very steep natural channels and streams in high mountain areas can be mobilized by runoff, triggering a water–sediment mixture flow known as debris flow. The routing of debris flow through human settlements can cause damage to civil structures and loss of human lives. The prediction of such an event, or the runoff discharge that triggers it, assumes an interest in risk analyses and the planning of defence measures. The object of this study is to find a method to determine the critical runoff value that triggers debris flow as a result of channel‐bed failure. Historical and rainfall data on 30 debris flows that occurred in six watersheds of the Dolomites (north‐eastern Italian Alps) were collected from different sources. Field investigations at the six sites, together with the hydrologic response to the rainfalls that triggered the events, were performed to obtain a realistic scenario of the formation of the debris flow there occurred. Field observations include a survey along the channel of the triggering reach of debris flow, with measurements of the channel slope and cross‐section and sampling of debris deposits for grain size distribution. Simulated runoff discharge values based on the rainfall recorded by pluviometers were then compared with values obtained through experimental criteria on the initiation and formation of debris flow by bed failure. The results are discussed to provide a plausible physical‐based method for the prediction of the triggering of debris flow by channel‐bed failure. Copyright © 2007 John Wiley & Sons, Ltd.
Effect of antecedent rainfall on pore‐water pressure distribution characteristics in residual soil slopes under tropical rainfall
Authors: Rahardjo H. , Leong E. C. , Rezaur R. B.
Published: October 2007

Characteristics of changes in pore‐water pressure distribution are the main parameters associated with slope stability analysis involving unsaturated soils, which are directly affected by the flux boundary conditions (rainfall infiltration, evaporation and evapo‐transpiration) at the soil–atmosphere interface. Four slopes were instrumented in two major geological formations in Singapore to provide real‐time measurements of pore‐water pressures and rainfall events on the slopes. The field monitoring results were analysed to characterize pore‐water pressure distributions under various meteorological conditions and to study the effect of antecedent rainfall on pore‐water pressure distributions in typical residual soil slopes under tropical climate. Slope stability analyses were also conducted for the best and worst pore‐water pressure distributions recorded in each slope to determine the range of factor of safety for the slopes. Results indicate that, antecedent rainfall, initial pore‐water pressures prior to a significant rainfall event as well as the magnitude of the rainfall event play a crucial role in the development of the worst pore‐water pressure condition in a slope. The role of antecedent rainfall in the development of the worst pore‐water pressure condition was found to be more significant in residual soils with low permeability as compared with that in residual soils with high permeability. Pore‐water pressure variation due to rainfall was found to take place over a wide range in residual soils with higher permeability as compared to residual soils with lower permeability. The worst pore‐water pressure profiles occurred when the total rainfall including the 5‐day antecedent rainfall (in most cases) reached a maximum value during a wet period. The factor of safety of residual soils with low permeability was found to be unaffected by the worst pore‐water pressure condition. Copyright © 2007 John Wiley & Sons, Ltd.
Representation of agricultural conservation practices with SWAT
Authors: Arabi Mazdak , Frankenberger Jane R. , Engel Bernie A. , Arnold Jeff G.
Published: October 2007

Results of modelling studies for the evaluation of water quality impacts of agricultural conservation practices depend heavily on the numerical procedure used to represent the practices. Herein, a method for the representation of several agricultural conservation practices with the Soil and Water Assessment Tool (SWAT) is developed and evaluated. The representation procedure entails identifying hydrologic and water quality processes that are affected by practice implementation, selecting SWAT parameters that represent the affected processes, performing a sensitivity analysis to ascertain the sensitivity of model outputs to selected parameters, adjusting the selected parameters based on the function of conservation practices, and verifying the reasonableness of the SWAT results. This representation procedure is demonstrated for a case study of a small agricultural watershed in Indiana in the Midwestern USA. The methods developed in the present work can be applied with other watershed models that employ similar underlying equations to represent hydrologic and water quality processes. Copyright © 2007 John Wiley & Sons, Ltd.
Chitosan/gelatin blends for biomedical applications
Authors: Pulieri Ettore , Chiono Valeria , Ciardelli Gianluca , Vozzi Giovanni , Ahluwalia Arti , Domenici Claudio , Vozzi Federico , Giusti Paolo
Published: October 2007

Blends between chitosan (CS) and gelatin (G) with various compositions (CS/G 0/100 20/80, 40/60, 60/40, 100/0 w/w) were produced as candidate materials for biomedical applications. Dehydro‐thermal crosslinking was adopted to promote the formation of amide and ester bonds between the macromolecules ((CS/G)‐t). The effect of composition and crosslinking on the physico‐chemical properties of the samples was evaluated by scanning electron microscopy, thermogravimetry, contact angle measurements, dissolution and swelling tests. Mechanical properties of (CS/G)‐t samples were also determined through stress–strain and creep‐recovery tests. The elastic moduli of dry blend samples showed a positive deviation from the additive law of the in‐series model, because of interactions and/or chemical bonds between components. The comparison between the elastic moduli of wet samples and those of different human tissues showed that (CS/G)‐t substrates can be suitable for soft‐tissue reconstruction. (CS/G)‐t two‐dimensional scaffolds were fabricated by micro‐molding, based on the use of a polydimethylsiloxane mould to create patterns with micro‐scale resolution on cast films. Biocompatibility of (CS/G)‐t samples was studied by means of cell tests using NIH‐3T3 fibroblasts. Finally, the evaluation of the affinity of (CS/G)‐t samples towards neuroblastoma cells adhesion and proliferation was performed, showing promising results for the blend containing 80 wt % gelatin. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Lactoyl‐poloxamine/collagen matrix for cell‐containing tissue engineering modules
Authors: Sosnik Alejandro , Leung Brendan M. , Sefton Michael V.
Published: October 2007

Collagen‐containing crosslinked, remodelable poloxamine derivatives were produced by introducing very short oligo(lactic acid) segments through the reaction of poloxamine with L‐lactide and the later addition of unsaturated bonds by the reaction of modified poloxamine with methacryloyl chloride. Degradation studies on discs indicated a faster weight loss in comparison to the stability of lactoyl‐free samples. Cell‐containing modules (both HepG2 cells and two different umbilical vein smooth muscle cell (UVSMC) cell‐types) were produced. Live/Dead assay showed high survival levels for both HepG2 and UVSMC cell types after crosslinking. While nondegradable modules did not change shape over time, lactoyl‐poloxamine matrices showed a gradual shrinkage and size decrease and an increase in the roughness of the surface. These findings were consistent with the expected degradability of the lactoyl derivative. A UVSMC cell line (CRL‐2481) embedded in a LA‐poloxamine/collagen matrix showed the characteristic elongated shape at day 9. UVSMC primary cells behaved in a manner similar to that seen in collagen gels: these cells formed isolated clusters through the matrix that gradually lost viability. On tissue culture polystyrene the same cells aggregated and did not reach confluence. Modules with embedded CRL‐2481 UVSMC led to a better initial adhesion of endothelial cells and a higher extent of surface coverage than seen with the UVSMC‐free system. With embedded primary UVSMC, some EC attachment and formation of gap junctions was seen. The pattern was not well organized. With further improvement (and characterization), the lactoyl poloxamine derivative is potentially useful as a scaffold for modular tissue engineering, when tissue remodeling is an important consideration. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Platelet adhesion studies on nanostructured poly(lactic‐co‐glycolic‐acid)–carbon nanotube composite
Authors: Koh Li Buay , Rodriguez Isabel , Zhou Jijie
Published: October 2007

Design of blood‐compatible surfaces is required to minimize platelet–surface interactions and increase the thromboresistance of foreign surfaces. Poly(lactic‐co‐glycolic‐acid)–carbon nanotube (PLGA‐CNT) composite is studied as a building material to fabricate artificial blood prostheses. This nanocomposite‐based biomaterial is prepared by an electrostatic Layer‐by‐Layer (LbL) deposition technique, in which layers of CNTs are adsorbed onto a PLGA film. Before incubation in nonstimulated platelet‐rich plasma (PRP) for platelet studies, fibrinogen is immobilized on PLGA‐CNT composite. Interactions between the plasma proteins, e.g. fibrinogen and PRP, are investigated on the prepared PLGA‐CNT composite. Contact angle measurements on the PLGA‐CNT composite displayed a good resistance of platelets adhesion on a hydrophilic surface with an angle of 64.94° as compared to pristine PLGA control with an angle of 93.43°. A significant reduction of adhesion is observed on the PLGA‐CNT composite, as well as the absence of platelet activation. On the contrary, both platelet adhesion and activation are observed on control samples. We inferred this suppression in secretion of granule contents in the platelet by the presence of the CNTs that resulted in the absence of platelet activation and its subsequent inhibition in the release of adhesive membrane receptors on the PLGA‐CNT composite. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Effects of fluid flow and calcium phosphate coating on human bone marrow stromal cells cultured in a defined 2D model system
Authors: Scaglione S. , Wendt D. , Miggino S. , Papadimitropoulos A. , Fato M. , Quarto R. , Martin I.
Published: October 2007

In this study, we investigated the effect of the long‐term (10 days) application of a defined and uniform level of fluid flow (uniform shear stress of 1.2 × 10−3 N/m2) on human bone marrow stromal cells (BMSC) cultured on different substrates (i.e., uncoated glass or calcium phosphate coated glass, Osteologic™) in a 2D parallel plate model. Both exposure to flow and culture on Osteologic significantly reduced the number of cell doublings. BMSC cultured under flow were more intensely stained for collagen type I and by von Kossa for mineralized matrix. BMSC exposed to flow displayed an increased osteogenic commitment (i.e., higher mRNA expression of cbfa‐1 and osterix), although phenotype changes in response to flow (i.e., mRNA expression of osteopontin, osteocalcin and bone sialoprotein) were dependent on the substrate used. These findings highlight the importance of the combination of physical forces and culture substrate to determine the functional state of differentiating osteoblastic cells. The results obtained using a simple and controlled 2D model system may help to interpret the long‐term effects of BMSC culture under perfusion within 3D porous scaffolds, where multiple experimental variables cannot be easily studied independently, and shear stresses cannot be precisely computed. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008